Differential Diagnosis in Neurology

1.1. Ischemic Stroke

General Features of the Differential Diagnosis of Ischemic Stroke, Embolus, and Intracranial Hemorrhage

Cerebral thrombosis occurs most frequently in the early morning hours during sleep. Patients frequently awaken and fall as they are unaware of their deficits. Transient ischemic episodes occur prior to thrombotic stroke in approximately 30% of patients and TIA's precede 50% of strokes in the posterior circulation. They are almost always atherosclerotic in origin. TIA's are usually emboli that arise either from the heart or intra-arterial vessels (carotid, arch of the aorta or vertebral arteries to distal smaller branches). They occasionally occur from distal field ischemia due to compromised vessels and decreased cerebral perfusion or vasospasm (migraine). They may cause symptoms at each level of the brain as they progress through the circulation. They often occur in showers so that a number of vessels may be occluded simultaneously. The symptoms of intra-arterial vessel to vessel emboli are usually less than 2 minutes. Longer TIA's suggest a cardiac origin. TIA's may occur only a few times or up to several times a day or on rare occasions in a rapid series (crescendo TIA). They often are stereotypical, but careful exam may reveal a new sign or symptom with each TIA. If an infarction follows the first TIA, it will be within one month in 20% of patients and within one year in 50%. Anterior TIA's involve the cerebral hemisphere and the eye. Visual loss in the ipsilateral eye is usually characterized by transient monocular blindness. A shade may descend over the eye uniformly or more rarely there is a wedge of visual loss, sudden blurring or bright scotomata (This finding is often noted with concomitant carotid stenosis). The visual deficit clears painlessly and uniformly. Often ocular attacks precede hemispheric attacks. Hollenhorst plaques (yellow, birefringent, cholesterol particles) are rarely noted and occur at branch points of the retinal arterioles. Rarely the pupil is paralyzed from ischemia of the ciliary body. Hemispheric attacks are most often characterized by face and arm weakness with concomitant sensory loss. The face and lips may be involved together or singly, a cheiro-oral presentation. The sensory loss involves the corner of the mouth and usually the C6 and C8 hand sensory root distribution: Most hemispheric TIA's cause aphasia, heaviness, weakness and numbness of the face and arm (brachiocephalic) or of the arm, face and leg (internal capsule distribution). Rarely dysarthria leg weakness may predominate. A pseudo radial palsy of the arm suggests ischemia of the "knuckle" of the motor cortex. Simultaneous eye and hand involvement from a carotid embolus is extremely rare. Anterior TIA's may cause: dizziness, confusion, both anterior or posterior aphasia, higher cortical sensory and cognitive deficits, and neglect to contralateral space with nondominant hemispheric involvement. Headaches are common and usually ipsilateral. The usual manifestation of TIA's in the posterior circulation (includes the vertebral, basilar and posterior cerebral arteries) are: bilateral visual field loss, dizziness, perioral numbness, ataxia, diplopia, dysphagia, dysarthria and bilateral motor or sensory symptoms. A crural hemisensory deficit (ipsilateral face and contralateral body below the clavicle) is pathognomic of brainstem involvement but is extremely rare. Dizziness alone is rare as a posterior TIA symptom but has been described with posterior inferior cerebellar artery involvement. Unusual signs and symptoms of posterior circulation TIA's are: veering to one side (PICA at the level of the inferior olive), staggering (PICA territory), lateral pulsion (PICA territory, medial branch), a feeling of crossed eyedness, bilateral dark vision, noise or pounding in the head or ear, unusual cephalic sensations, pain in the face or head. Drop attacks, sudden loss of tone with falling may occur and are unaccompanied by loss of consciousness. The patients are stunned or slightly confused. Impaired hearing (sounds are faint or distant); deafness, forced eye deviation, hemiballismus, and a feeling of moving of a part and choreoathetosis have rarely been described. Peduncular hallucinosis has recently been demonstrated to occur from hippocampal formation ischemia. Forced eye deviation is encountered from unilateral para pontine reticular formation ischemia. Basilar artery ischemia may cause alternate hemiparesis. The affected extremities may be simultaneously weak or there is spread of weakness over 10 to 60 seconds which is much longer than expected from seizure activity. A basilar TIA may resolve suddenly or gradually. Posterior TIA's have a higher incidence of headache than anterior TIA's. In general, ipsilateral carotid disease causes face and parietal headache. Vertebral artery involvement refers pain to the retroauricular area whereas basilar artery disease produces occipital and C2 distribution (forehead) pain. Posterior cerebral artery ischemia refers to the lateral eyebrow.

The major risk factors for thrombotic stroke are an important diagnostic feature. Hypertension, diabetes mellitus, cigarette smoking, prior stroke, heart and peripheral vascular disease are most common in older patients. Stroke in the young is embolic from the heart or secondary to dissection, collagen vascular disease, hypercoagulable states, genetic diseases or associated medical conditions.

Development of neurological deficits in thrombotic strokes occurs in several ways:

• single attack with the full deficit evolving over hours
• stuttering or intermittent progression that may continue over hours to 1–2 days
• a partial deficit that may improve and then progress to a completed stroke
• fleeting deficits may be followed by a longer episode and then a major stroke that occurs within days

The deficits may be regional at onset or evolve in a step-like pattern. Intermittent progression is a characteristic of thrombotic stroke. Rarely there is an apparent gradual progression of the deficit over 1–2 weeks which is most common in pure motor strokes.

In general, thrombotic strokes of the large conducting vessels of the middle cerebral artery (M1 and M2 components) reach maximum disability in three days which is dependent on consequent edema. Carotid occlusion, particularly if there is a fetal origin of the posterior cerebral artery (from the carotid artery) results in maximum edema and disability within 24 hours. Death is usually from transtentorial herniation at midbrain levels. Posterior fossa strokes, particularly of the vertebral artery, (the most common site of origin of PICA), may have delayed cerebral edema (4–7 days) and produce tonsillar herniation at this time (tonsillar coning).

Particular arteries thrombose with different diseases. Diabetic patients suffer infarction of PICA and the thalamogeniculate and thalamoperforate arteries from the PCA to a greater extent than expected. Young hypertensive women on birth control pills infarct PICA. Lipohyalinosis and focal atheromatous plaques at the origin of penetrating arteries (lacunar strokes) occur most frequently in diabetic hypertensive patients. Dissection of the vertebral or carotid arteries usually causes stroke by emboli from the site of dissection but less commonly by decreased flow. Dissection of the vertebral artery is common in the horizontal component of the artery at C2. This frequently causes neck pain and may be followed by chiropractic manipulation which extends the dissection.

Diabetes accelerates atherosclerosis by approximately 10 years. Radiation therapy in the neck induces a vasculopathy that accelerates atherosclerosis and causes proliferative endarteritis over long segments of the artery. If the brain is involved, small vessels occlude in the cortex with focal deficits and strokes. In the spinal cord, the perforating sulcal arteries are involved which produces a Brown Sequard Syndrome. Polycythemia most often affects the posterior circulation. The vasculopathy of sickle cell disease affects large and small vessels.

The usual sites of atherosclerotic disease are the carotid bifurcation, siphon and the intracavernous portion of the artery. Rarely there may be isolated stenosis of superficial branches as well as the M1 and M2 segments of the middle cerebral artery. In the posterior circulation, the origin of the vertebral arteries, mid and top of the basilar artery, as well as the junction of the vertebral and basilar arteries, are major sites of disease. Stenosis may be seen singly or in tandem.

Anomalies of arteries from their embryological origin may be important in determining the extent of thrombotic stroke. Poor development of the anterior and posterior communicating arteries may isolate one cerebral hemisphere. In general, the right vertebral artery is atretic or smaller than the left. Atherosclerosis of the left vertebral artery may induce severe basilar symptoms because of lack of circulatory support from the right vertebral artery. Occlusion of a vertebral artery may occur with prolonged abnormal head positions during surgical procedures as the artery on the side of the ipsilaterally turned head is occluded. If it is the predominant artery, there is no effective basilar flow. Similarly, a single thalamic peduncle (Percheron's artery) at the top of the basilar may cause bilateral thalamic infarction as it will be the origin of the paired interpeduncular arteries that usually arise separately from the top of the basilar artery. Failure of regression of the 4 major embryologic connections between the carotid and basilar artery (persistent trigeminal, otic, hypoglossal and pro-atlantal) may allow an embolus from the anterior circulation to infarct posterior circulation territory or vice versa. A fetal origin of the posterior cerebral artery arising from the carotid may be the cause of complete hemispheric infarction following carotid occlusion.

A lacune is an area of infarction within the territory of a single perforating artery. The basic clinical syndromes associated with these lesions are: pure motor stroke, pure sensory stroke, homolateral ataxia and crural paresis, dysarthria – clumsy hand syndrome, ataxic hemiparesis and sensorimotor stroke. Approximately 80% of lacunes may be clinically silent. The temporal profile of a lacunar infarct may evolve over hours or rarely days in contradistinction to a cortical infarct. Lacunar strokes do not present with loss or impairment of consciousness, headache, seizure or higher cognitive deficits. Approximately 20% have TIA's at the time of incipient occlusion and may be embolic. Often several perforating arteries are occluded in the latter circumstance. The capsular warning syndrome describes a crescendo of lacunar TIA attacks prior to completion of internal capsule infarction.

A cerebral embolus strikes suddenly during wakefulness and frequently has a suggestive underlying cause. It may involve superficial surface cortical vessels giving pure cortical symptoms such as aphasia or hemianopia, or it may occlude stem arteries such as the M1 segment of the middle cerebral artery. This location causes deep internal capsular as well as surface hemispheric symptoms. Seizures occur in at least 15% of patients, and a similar number appear stunned and mute (stem MCA territory and rarely supplementary motor area). A small percentage of patients lose consciousness. Smaller emboli characteristically are cholesterol-platelet-fibrin in origin and give shorter symptoms (minutes). Larger red emboli from the heart clear more slowly (hours). The deficit following an embolus is most severe at onset and then clears over time. Most emboli occur in the MCA territory as this vascular territory receives the most blood flow. There may be evidence at presentation of prior embolic events in other vascular territories. Approximately 30% of cerebral emboli are associated with blood in the CSF(100 RBC/mm³).

The setting for a cerebral embolus is a cardiac arrhythmia of which atrial fibrillation is by far the most common. A patient with AF that has the onset of an acute isolated Wernicke's aphasia has almost certain embolization to the temporo-occipital branch of the inferior division of the MCA. Brady-tachy arrhythmia is the second most common arrhythmia causing cerebral embolus (usually during the tachy phase). A myocardial infarction, subacute bacterial endocarditis, artifical heart valve, perforated foramen ovale (20% of patients), aneurysm of the atrial septum, cardiomyopathy, lower extremity thrombophlebitis (paradoxical emboli) and cancer (nonbacterial thrombotic endocarditis) all suggest an embolus as the cause of stroke. Newer transthoracic echo-cardiographic techniques have demonstrated the importance of the aortic arch as a source of emboli (approximately 15–25%).

The brain is the first clinical herald of systemic emboli from the heart in the overwhelming majority of patients. Recent diffusion/perfusion MRI studies confirm the diagnosis particularly if two circulations are involved.

Arteries to artery emboli are smaller than those from the heart and often involve several territories in the posterior circulation. It is not unusual to have a vertebral artery embolus produce lower brainstem, pontine, midbrain, thalamic and cortical symptoms and signs as it moves up the posterior circulation. Carotid artery emboli to ophthalmic and central retinal arteries frequently produce amaurosis fugax, a shade descending in the involved eye that lasts for 1–2 minutes. It is coincident with a Hollenhorst plaque at a retinal artery bifurcation. The embolic deficit from a carotid or vertebral artery dissection may be associated with sympathetic ocular paralysis in the former and lateral neck pain in the latter. The clinical deficits caused from these events are from emboli at the site of dissection rather than CBF limitation. Embolic disease both from artery to artery and from the heart may occur as a shower with several circulations affected. Characteristically, emboli may affect the same territory with each event, which is thought to be due to laminar flow characteristics of that circulation. In the vertebrobasilar system, the top of the basilar artery is narrowest and is most often occluded from emboli. Rarely, emboli occur in a stepwise fashion that simulates distal field ischemia. The use of transesophageal echocardiography has demonstrated the root of the aorta as a rich source of emboli (15–25% of all emboli). Grade V (pedunculated) atherosclerosed material is most likely to cause a clinical problem. The recent application of transcranial Doppler techniques during carotid endarterectomy and other procedures has demonstrated that emboli may be asymptomatic. The from high frequency "hits" noted are smaller platelet fibrin emboli while lower frequency "hits" clots favor the heart. Lacunar disease of the basal ganglia and subcortical white matter are most often due to lipohyalinosis or atheromatous plaques at the origin of the penetrating vessels. If a group of these small penetrating vessels is occluded simultaneously emboli are the most likely cause. Persistent embryological arteries (trigeminal, otic, and hypoglossal) may allow an anterior embolus to infarct the posterior circulation or vice-versa.

Hemorrhagic vascular disease can easily be divided by location, age of the patient, underlying medical disease, iatrogenic factors and clinical features.

In general, hemorrhagic vascular disease occurs when the patient is awake and active. The exceptions may be aneurysms and cavernous hemangiomas that may rupture while the patient is asleep. The usual pattern of cerebral hemorrhage is the apoplectic onset of severe neurologic deficits with gradual headaches. Occasionally, the headache is severe, the patient vomits once (pressure on the floor of the IV ventricle followed by compensating mechanisms), and there are focal neurologic deficits and loss of consciousness. Specific clinical points allow differentiation of the location and the most likely pathogenesis of the hemorrhage. Hypertensive hemorrhages occur in the setting of sustained hypertension that is then exacerbated by Kocher–Cushing reflexes (increased activity of the vasomotor center) which come into play to insure cerebral perfusion. The most common locations for hypertensive hemorrhages are the basal ganglia (40%), the thalamus (20%), the cerebellum 10%, lobar 10%, the pons 5%, and infrequently the medulla 1%. Hemorrhages in the white matter of the centrum semiovale suggest platelet and clotting disorders. Several areas of hemorrhage in different lobes that have mixed MRI signals (old and new blood surrounded by a dark hemosiderin ring) are suggestive of cavernous hemangioma. Blood in the suprachiasmatic cistern is often noted with P-COM, carotid and anterior communicating artery aneurysms. Blood tracking anteriorly between the hemispheric fissures is most characteristic of A-Com aneurysms. Blood in the Sylvian fissure on one side suggests MCA aneurysm. Perimesencephalic prepontine blood in a patient with little or no focal abnormality is probably venous. Cavernous sinus aneurysms decompress into the sinus and are associated with cranial nerve abnormalities (III, IV, VI). Approximately 50% of aneurysms have a short episode of loss of consciousness at the ictus. A small percentage has seizures. Almost all have EKG changes. The neck is stiff, and Brudzinski's and Kernig's signs are positive. Frequently hydrocephalus is noted on the initial CT scan. Dural irritation from blood may be associated with tender eyes, a retinal hemorrhage on the side of the lesion (Torsten's syndrome) and sore neck and shoulder muscles (meningeal irritation). Rarely, pain in the lower back is the major manifestation. Irritation of lower back meninges without headache should always raise the suspicion of a spinal AVM. Each aneurysm has its own clinical profile. P-COMs are associated with a pupil involving III nerve palsy A-COM show little focal neurological deficit (weak leg) but prominent personality defects. MCA aneurysms may have a prominent hemiparesis. Carotid aneurysms may be associated with a contralateral hemiparesis and III nerve palsy. Ophthalmic artery aneurysms cause unilateral visual loss.

Parenchymal vascular malformations most often present with seizures rather than overt bleeding. These emanate from abnormal glial and neuronal tissue within the malformation. Migraine-like headaches are also common. Hemorrhage clearly can present with focal neurologic signs depending on the affected lobe. Arteriovenous malformations are associated with phakomatoses such as Von Hippel Lindau, Cobb's, Sturge Weber, Wyburn–Mason, Klippel–Feil–Trenaunay, syndromes. There are genetic chromosomal defects with AVMs and cavernous hemangiomas (Krit1gene).

Elderly patients presenting with single or multiple lobar hemorrhages suffer congophilic angiopathy. Gradient Echo MRI sequences demonstrate prior bleeds because this technique is very sensitive to hemosiderin deposition. Traumatic hemorrhages may be associated with blood in the subarachnoid space, a coup contra coup location (frontal lobe coup and contra coup in occipital lobe) with contusion of the crown of the gyrus. They may be delayed for four to seven days after the injury. If severe, the hemorrhage may be associated with loss of autoregulation, severe cerebral edema and "commotio retinae" (an increased light streak from the retinal blood vessels).

Venous hemorrhages occur in association with sinus thrombosis (particularly the superior sagittal sinus). They present with seizures, headache and focal deficits. They are accompanied by bilateral basal ganglia or thalamic hemorrhages. If cortical, they also are frequently seen in the middle cerebral artery territory. In the setting of pre or post-partum, they frequently present with seizures in a lower extremity that generalizes, associated with bloody spinal fluid. Venous malformations are linear and often connect to a ventricle. They seldom bleed spontaneously but will cause infarction and hemorrhage into the drained territory if they are clipped.

The use of TPA causes 6–16% of hemorrhage into the occluded territory. Hyperextension, the size of the infarcted area and age are risk factors similar to that which is seen with anticoagulation. Transformed hemorrhage which occurs in a previously infarcted area often is petechial but may be massive. Hemorrhage from anticoagulants usually is nonhomogeneous on MRI scan (swirling effect). Arteriograms following infarction may appear to be hemorrhages.

Twenty percent of patients that have suffered a cerebral hemorrhage from cocaine abuse have an underlying vascular malformation. Rarely, propanethanolamine and Dexedrine may cause cerebral hemorrhage from hypertensive mechanisms.

Hereditary congophilic superficial hemorrhages are noted in Dutch, Swedish and Icelandic patients. Cavernous hemangiomas may be most common in Mexican Americans. The history and physical examination should localize vascular disease. The medical setting and this localization generates the differential diagnosis. Imaging proves the diagnosis, uncovers unsuspected pathology and allows insight into the basic mechanisms that are involved. There is no substitute for the history, physical examination, interpretation of the imaging studies and clinical judgment. The rapid advance of interventional radiological techniques, thrombolytic and possibly neuroprotective agents have made stroke neurology very therapeutic.

Differential Diagnosis of Risk Factors for Ischemic Stroke

Specific risk factors determine which form of vascular disease is most likely in a given clinical circumstance. Primary risk factors of age (accumulating atherosclerotic lesions), African American and Asian ancestry (intracranial greater than extra cranial vascular disease) and family history are immutable.

Specific secondary risk factors are associated with specific arterial size and distribution of infarction. Hypertension is associated with accelerated atherosclerosis of large extracranial vessels particularly the arch of the aorta, the carotid bifurcation, systemic and intracranial large vessel stenosis as well as atheromata at the mouth of penetrating small vessels of the brain. The lacunar hypothesis is generally, but not totally, accepted. Diabetes mellitus is concomitant with atherosclerosis but also is a risk factor for infarction of the posterior inferior cerebellar arteries, the thalamogeniculate and the thalamoperforate arteries. It is also associated with the lacunar state. Smoking is a clear risk factor for cerebral and extracranial atherosclerosis. Most patients with extracranial carotid disease from atherosclerosis associated with smoking die of coronary artery disease.

The major risk factors for embolic stroke are cardiac and intravascular (artery to artery). Cardiac arrhythmia, particularly atrial fibrillation and tachybrady arrhythmias are the most serious. Ejection fractions of less than 30% from dilated cardiomyopathy of any cause are highly associated with embolic disease. Mitral valve disease from rheumatic involvement, prolapse, valve replacement or infection is the most common valvular cause of embolic stroke. The aortic valve is more prone to calcification from a bicuspid congenital defect than rheumatic disease (in the present era). Patent foramen ovale with or without atrial septal aneurysm is gaining increasing attention as a cause of embolic disease. Valve lesions are now very well visualized by transesophageal echocardiography. Thickening of valve cusps and myxomatous degeneration of the chordae tendinea are now being evaluated as a source of emboli. Left ventricular aneurysms and thrombi, as well as akinetic heart segments, have clearly been identified as risk factors for stroke following myocardial infarction.

The arch of the aorta is now visualized with TEE and is a source of artery to artery emboli in approximately 30% of posterior circulation embolic strokes.

Special risk factors for ischemic stroke include asymptomatic large vessel atherosclerosis (particularly the carotid bifurcation), but also the origin of the great vessels from the aorta and initial segments of the anterior cerebral, middle and posterior cerebral arteries. This stenosis can now be addressed by angioplasty and stenting. Catheter related emboli are special risks of CABG surgery.

Risk Factors for Ischemic Stroke

Primary Risk Factors

The nonmodifiable primary risk factors for ischemic stroke are male sex, age, African-American or Asian ethnicity and family history. The modifiable risk factors are hypertension, smoking, diabetes mellitus, hypercholesterolemia, hyperhomocystinemia, excessive alcohol and drug abuse.

Secondary Risk Factors for Stroke

Hypertension

There is a positive linear relationship between both systolic and diastolic pressure and the incidence of stroke, at any age in both sexes. After one year of therapy, there is evidence for a reduction of stroke risk and coronary artery disease in hypertensive patients, treated with diuretics and betablockers but not with either ACE inhibitors or calcium channel blockers. If the diastolic blood pressure is reduced 5–6 mmHg there is a 42% reduction in the incidence of all strokes and a 45% reduction in the incidence of fatal strokes. In a large series of patients (Medical Research Council Study) 65–73 years of age who were treated with hydrochlorothiazide or atenolol there was a 31% reduction in strokes, a 44% reduction in coronary artery events and a 35% reduction in all cardiovascular events. In the Medical Research Council Study, every 5.8 mm drop in diastolic pressure over a 2–3 year period produced a 42% reduction of stroke rate. Isolated systolic hypertension (systolic blood pressure > 170 mHg) should be treated. An 11 mmHg decrease of systolic blood pressure (The systolic hypertension in the elderly study) and a 3.6 mmHg reduction of diastolic blood pressure produced a 36% reduction in stroke risk.

Diabetes mellitus

The risk of stroke is increased 2.5 to 3.5 times in diabetics compared to controls. Long standing prospective trials with both insulin and hypoglycemic agents to reduce the risk of stroke are not convincing.

Smoking

Cigarette smoking increases the risk of stroke two times from accelerated atherosclerosis as well as effects on α₁-antitrypsin and platelet inhibitory factor. The increased risk is dose dependent. Cessation of smoking reduces the risk of stroke rapidly at any age, whereas it takes 1 year to effect a 50% reduction of coronary artery events and 10 years to decrease the risk of lung cancer compared to controls.

Hyperlipidemia

Elevated total cholesterol and low-density lipoproteins are independent risk factors for stroke.

Oral contraceptives

Studies conducted with high estrogen formulations in the past demonstrated an increased risk of stroke empirically in women older than 35. Lower estrogen formulations in women younger than 35 who do not smoke have the same risk as the general population. The Nurses Health Study revealed that the relative risk of stroke was 1.2 with estrogen formulations, which was directly related to dose. Patients utilizing 50 μg of estrogen had a relative risk of 2.9, while in those utilizing 30–40 μg the relative risk was 1.8. The relative risk of progesterone preparations was 0.9. The problem with the study was that it was done in older women and few patients utilized oral contraceptives.

Postmenopausal hormonal replacement

Two recent studies have demonstrated protective effects of hormonal replacement. Patient estrogen compounds had a relative risk of stroke of 0.72 while combination estrogen progesterone compounds had a relative risk score of 0.61. Less potent estrogen compounds were ineffective in stroke prevention.

Strokes associated with hyperhomocystinemia

Hyperhomocystinemia is a risk factor for premature atherosclerotic peripheral vascular disease, myocardial infarction and stroke. Prevalence of HHC has been noted in approximately 20–42% of stroke cohorts.

Physical activity

Physical exercise correlates with a progressive decrease in stroke rate. There is no evidence that weight reduction without exercise is beneficial for decreasing the risk of stroke.

Cholesterol reduction with statin drugs, risk of stroke and total mortality

A total of 16 trials were evaluated that investigated approximately 29,000 subjects who were followed for more than 3 years. In those taking statin drugs (3-hydroxy-3-methylglutaryl coenzyme) reductase inhibitors (HMG-COA) had an average reduction in total and low density lipoprotein cholesterol of 22% and 30% respectively. Those taking statin drugs had a robust decrease of stroke of 29% and of mortality from stroke of 22%.

Lipoprotein (a) is a low density lipoprotein (LDL) covalently linked by a di-sulfide-bridge to a large glycoprotein called apo(a). Sequencing of apo(a) suggests a high degree of homology with plasminogen. Lp(a) competes with plasminogen for the plasminogen binding site and reduces its cellular binding which may reduce endothelial cell fibrinolysis and thus produce a procoagulant state. Lp(a) accumulates on the endothelium of atherosclerotic coronary arteries but not on normal blood vessels. Lp(a) may be increased in a significant number of patients with acute stroke but has no association with cardiovascular risk factors stroke severity, or ischemic events during follow up.

Silent cerebral infarction associated with coronary artery disease

Silent cerebral infarction is a predictor of symptomatic cerebrovascular disease. Silent cerebral infarction by definition is an infarct demonstrated by CT or MRI without a history of stroke. In the Framingham study, latent, primarily lacunar infarcts were detected in 10% of patients. Silent cerebral infarction occurs in about 80% of patients with significant coronary artery disease. Myocardial infarction and angina pectoris are both associated with a high incidence of lacunar infarction.

Patients who present with their first stroke (symptomatic) may have had a preceding silent infarct 25% of the time. These infarcts are usually small, deep and in the basal ganglia. They are usually less than 1 cm. The occipital lobes may be disproportionately involved. Demographic variables that may be important for silent cerebral infarct (SCI) are age, male gender and African-American ethnicity. Left atrial enlargement may also be a risk factor for SCI.

Characteristics of Silent Cerebral Infarction at First Stroke Presentation

• Advanced age
• Small <1 cm
• Lacunar infarcts of BG
• Higher than expected in the occipital lobe
• In association with significant coronary artery disease
• In association with enlarged left atrium

Alcohol Consumption and Risk of Ischemic Stroke

Systolic blood pressure and high density lipoproteins (HDL) are modified by alcohol. Alcohol increases insulin sensitivity and has an antithrombotic effect on the coagulation system. Beer, wine and spirits have different effects on the risk of cardiovascular disease, due possibly to other substances consumed with the alcohol. Present evidence suggests that there is a small beneficial effect of alcohol (wine particularly) on the risk of ischemic stroke. However, high alcohol consumption may be associated with an increased risk of stroke and intracranial hemorrhage. Wine contains flavonoids and tannins, which may be beneficial.

Infectious Disease and Risk of Ischemic Stroke

A large prospective study of patients with either TIA or completed stroke in a large inner city hospital demonstrated a high seropositivity for syphilitic infection but a low rate of meningovascular syphilis (0.4% was detected by CSF analysis).

The role of infectious agents and occlusive vascular disease has been noted in rapidly progressive coronary atherosclerosis, in cardiac transplant patients (cytomegalo-virus infection) as well as chlamydia pneumoninae for CAD. Antibodies to chlamydia pneumoniae have been detected in chronic coronary artery disease and acute myocardial infarction. There seems to be an association between ischemic vascular disease and chlamydia pneumoniae infection in general and with recurrent infection and acute stroke.

HIV infection also confers a significant risk for ischemic vascular disease.

Major Secondary Risk Factors

• Previous TIA or stroke
• Previous myocardial infarction or angina
• Carotid artery stenosis
• Diffuse vasculopathy
• Irregular heart rhythm
  • Atrial fibrillation
  • Sick sinus syndrome
• Left ventricular hypertrophy

Modifiable Risk Factors

Medical Diseases and Risk of Stroke

Atrial Fibrillation (AF)

• Framingham Heart Study Group – a twenty-two year prospective study
  • New AF incidence of stroke is 2.5/1,000 males and 17.1/1,000 females
• Stroke rate

  	Age 25–34	Age 35–64
  Males	2.6/1,000	37.9/1,000
  Females	2.2/1,000	29.9/1,000

• European Study – a 14 year prospective study
• Stroke rate
  • Patients < 60 years of age 3% year
  • Patients >76 years of age – 5.4% year
  • Inpatients – 5–9% incidence of stroke
  • Outpatient – 1.9–4.8% incidence of stroke

Atrial Fibrillation Alone (Framingham Study Group)

Patients with coronary artery disease, congestive heart failure, and rheumatic heart disease were excluded. Ninety percent of patients were greater than 60 years of age. Patients were included who had nonspecific EKG changes. Patients with AF alone had a four times higher risk of stroke (24%). Mayo Clinic Study Group – 15 year prospective study. This study had the same exclusion factors as the Framingham study but added hypertension and nonspecific EKG changes. The cumulative incidence of stroke was 1.5%.

The Olmsted County Minnesota Study – This study had the same entrance and restrictions criteria as the Mayo Clinic Study and found a 17% incidence of stroke.

Acute Myocardial Infarction (6 studies)

The risk of stroke with anterior wall MI is 6% (4–12%). Inferior wall MI carries a risk of 10%. Most cardiac embolic events occur within 1–2 weeks after the infarction.

Left Ventricular Thrombus After Myocardial Infarction

Forty percent of patients that suffered a stroke after MI had a left ventricular thrombus (LVT), which is usually absent the first 24 hours after a myocardial infarction. Most thrombi develop between 1–14 days after infarction. Transthoracic echocardiography cannot detect thrombi less than 5 mm.

Nonischemic Cardiomyopathy

The incidence of stroke is 4%/year in three studies of cardiomyopathy (0–12%). Echocardiographic detection of LVT ranged from 0–37% in five studies. The risk of emboli is linear with the severity of the cardiomyopathy. It is difficult to determine the true rate of embolic ischemic stroke from these studies because many different causes of myopathy were included.

Mitral Valve Prolapse (MVP)

The prevalence of MVP is approximately 5% in the general population. The most common cause of MVP is a variant of mitral leaflet excursion rather than myomatous degeneration of valve leaflet chordae or the annulus. Five studies revealed an incidence of 4% of stroke with MVP in young adults (2–6%). There are two distinct populations of patients with MVP. It is most common in young women. The complications are most prevalent in older patients and men. Complication prone MVP is most likely with older age, male sex, redundant and thickened leaflets, associated mitral regurgitation, tricuspid valve prolapse and mitral annulus abnormality.

Infective Endocarditis

The prevalence of stroke in infective endocarditis is 15–20%. The majority of strokes occur within 48 hours of diagnosis or at presentation. The risk of stroke after antibiotic treatment is 5%. Staphylococcus aureus, and mechanical valve SBE are positive predictors for stroke whereas valve site is not. Mycotic aneurysms amenable to surgery are seen in 2% of patients. Large and enlarging mycotic aneurysms can be healed by antibiotic therapy. The risk of late rupture of mycotic aneurysms is low. They are invariably found on peripheral vessels rather than at the Circle of Willis. Intracranial hemorrhage carries a high mortality.

Left Ventricular Aneurysm (LVA) and Left Ventricular Thrombi (LVT) Remote from the Site of MI

LVT usually are noted within two weeks of an acute MI and spontaneously resolve or may persist indefinitely. LVT that overlie wall motion abnormalities may have a delay of many months before they are detected after the acute MI.

Left ventricular aneurysm (LVA) after acute MI has a low incidence of associated LVT as determined by cardiac catheterization. Emboli occurred in 3% of patients that were anticoagulated with LVT and 13% of those not anticoagulated.

Nonbacterial Thrombotic Endocarditis (NBTE)

NBTE is frequently unrecognized although it accounts for 27% of ischemic strokes in cancer patients and had a prevalence of 1–5% in one autopsy series. It is associated with the prothrombotic state seen with cancer and has its highest occurrence during chemotherapy.

Special Risk Factors for Ischemic Stroke

Asymptomatic Large Vessel Atherosclerosis

There is a clear-cut benefit for secondary prevention of stroke if the carotid artery is narrowed >70% (NASCET and ECST European Carotid Surgery Trial). The benefit of surgery for 30–69% stenosis of symptomatic arteries is being evaluated. Asymptomatic stenosis surgery in the best surgical centers carries a 1.5–2.7% risk of stroke.

Risk of Stroke with Intra-aortic Atherosclerotic Debris

Atherosclerotic disease of the thoracic aorta is common in elderly patients with coronary artery disease. Emboli arise from thrombi, fibrinous material, and cholesterol crystals that dislodge from complex ulcerated plaques. Transesophageal echocardiography with the high frequency (5MHZ) transducer can resolve intraaortic atherosclerotic debris from a simple atherosclerotic plaque. Autopsy studies have demonstrated a prevalence of 38% of complex atherosclerotic aortic plaques greater than 8 nm in patients with clinical coronary artery disease. Pedunculated and highly mobile plaques have a higher embolic potential than layered and immobile atherosclerotic debris.

Risk of Catheter Related Emboli in Patients with Atherosclerotic Debris in the Thoracic Aorta

Cardiac catheterization or intra-aortic balloon placement in patients with transesophageal echocardiographic evidence of atherosclerotic debris carries a significant risk of embolization (10% and 5% respectively). The strongest predictors of atherosclerotic aortic debris are advanced age and peripheral vascular disease. The classifications of degrees of aortic atherosclerosis are:

• grade 1 – normal aorta
• grade 2 – simple atherosclerotic plaque (intimal calcification)
• grade 3 – plaque protruding <5 mm into the aortic lumen
• grade 4 – plaque protruding >5 mm into the aortic lumen which is layered
• grade 5a – 5 mm plaque that is mobile.

Embolic events occurred following femoral catheterization (17%) while none occur following brachial catheterization. Embolic events from insertion of intra-aortic balloons occur in 40–50% of patients with atherosclerotic aortic debris and are primarily peripheral. The generally accepted incidence of stroke or peripheral embolization from cardiac catheterization is approximately 0.07%. Patients at particularly high risk of catheter related emboli are older than 65 years and have had a prior history of stroke. The incidence of catheter related stroke is 30% in those patients with mobile aortic debris and approximately 6% in those with layered aortic debris.

Stroke Risk with CABG (Coronary Artery Bypass Graft) Surgery

There is approximately a 20% mortality from stroke in the setting of a CABG 6.1% of patients undergoing this procedure suffer a serious adverse cerebral outcome. The high risk features for a type I outcome (fatal cerebral injury and nonfatal strokes) are: advanced age, proximal aortic atherosclerosis, pulmonary disease, neurologic disease and hypertension. The most significant of these risk factors is atherosclerotic emboli released into the circulation by surgical manipulation of the aorta. This condition is found in approximately 20% of patients older than 70 and in approximately 12% of all patients undergoing the procedure. A history of prior TIA or stroke is also a significant risk factor. Increased risk of stroke is also seen with DM, unstable angina, prothrombic state, left ventricular thrombus and use of an intra-aortic balloon pump.

The Risk of Stroke Associated with Cardiac Surgery

In general, patients undergoing coronary artery bypass, valvular surgery or both have a risk of stroke between 2–6%. Patients who suffer stroke are older and have a high rate of prior TIA, congestive heart failure and peripheral vascular disease. Surgical aspects that predispose to stroke are a pump time of greater than 120 minutes. Most strokes occur (approximately 60%) by postoperative day 2, but a significant number of delayed strokes occur (post -operative day 3 to 9). Hemispheric syndromes are seen in approximately 2/3 of patients, brainstem and cerebellar infarction in 10–15% and lacunar syndromes in a similar number. Delayed strokes may occur due to a disrupted embolic source (plaque in the arch of the aorta) or an ongoing hypercoagulable state. Many studies have noted other variables associated with an increased risk of stroke with heart surgery. These include: carotid artery stenosis greater than 50%; repeat heart surgery, valve surgery, prior stroke, and perioperative hypotension.

Late stroke risk factors are possibly:

• anemia
• embolism (calcified atheromatous platelet fibrin complicated plaques)
• decreased platelet number and function are decreased following surgery which increases the risk of bleeding
• reactive thrombocytosis

Risk of Stroke in Cardiac Surgical Patients with a History of Stroke

Patients with deficits from previous strokes have a higher chance of experiencing a new stroke and of suffering reappearance or worsening of old deficits. These patients have a higher mortality rate, take longer to awaken from anesthesia, and to extubate. They are more likely to sustain a depressed level of consciousness and confusion after operation and are more likely to aspirate and require reintubation. Patient age rather than the interval between stroke and surgery is most significant. In general, a recent stroke is associated with reappearance or worsening of the prior deficit and a remote stroke predisposes to a new focal postoperative deficit. Retrospective studies suggest a stroke rate of approximately 13% inpatients with a prior stroke while a large prospective study demonstrated a rate of 43%. The stroke rate of patients with no prior history of stroke undergoing cardiac surgery varies between 1.5% to 5%.

Special Cases of Stroke Risk in Carotid Endarterectomy

Preoperative Risk Factors for Endarterectomy for Asymptomatic Carotid Artery Stenosis

The benefit of carotid endarterectomy (CEA) for significant asymptomatic carotid stenosis (greater than 70%) is dependent on surgical risk (less than 3%). In general, diabetes, contralateral carotid artery stenosis, and never having ingested alcoholic beverages were associated with a higher risk of perioperative complications. Females, age 75 years or older with a history of congestive heart failure are associated with a higher risk of postoperative stroke or death. Patients undergoing CEA and concomitant coronary artery surgery were also at greater risk.

Intraoperative risks

• Cross-clamp time
• Use of a shunt
• Use of glucose solutions

Surgical complications

• Carotid occlusion
• Thrombus
• Ligation
• Tacking sutures
• Patch angioplasty

Preoperative Risks Predict Severity of Carotid Endarterectomy Related Stroke

Advanced age, angina, and myocardial infarction in the past 6 months, congestive heart failure, hypertension, obesity and chronic obstructive lung disease are medical risk factors.

Neurological risk factors are crescendo TIAs (multiple TIAs/day), TIA while anticoagulated with heparin, multiple completed strokes and ischemic symptoms less than 24 hours prior to the surgical procedure.

Angiographic risk factors are: occlusion of the contralateral internal carotid artery, siphon stenosis on the operative side, plaque extension more than 3 cm distal to the origin of the ICA, high bifurcation of the carotid artery, and thrombus extending from the operative lesion.

The higher incidence of poor outcome following stroke occurred in patients with neurological risk factors with or without medical or angiographic risk factors. Patients sustaining a surgical complication are more likely to have a CVA (60%). Surgical complications did not predict poor stroke outcome. The most common surgical complication is carotid thrombus formation. Preventative measures include:

• nonreversal of intraoperative heparin
• avoidance of hypotension
• administration of postoperative dextran

The presence of an intimal flap or vessel kinking after closure may lead to a nidus for vessel thrombus formation.

Carotid Recurrent Stenosis and Risk of Ipsilateral Stroke

The risk of recurrent stenosis is highest in the first years after carotid endarterectomy and lower in later years. A crude post endarterectomy stroke incidence (including perioperative stroke) is 1.6–3% per year. The annual stroke rate for all persons 55 to 64 years is 0.29%. For those 65 to 74 it is 0.55%. For those 75 to 84 years, it is 1.2%/year. After patients have had CEA they are 1.3 to 10 times at higher risk of stroke than the general population. Recurrent stenoses occurring within the first 2 years after operation are due to pseudointimal hyperplasia. Those occurring later are due to recurrent atherosclerosis. Low incidence of stroke early may be due to smooth homogeneous fibrous plaques with minimal ulceration or hemorrhage. Early stenosis has an incidence of 0.45% of stroke whereas restenosis after 36 months is 2.1%. Annualized risk of stroke related to restenosis is 0.15% in the first 36 months period and 0.5%/year after 36 months. Patch angioplasty may be most effective for arteriotomy closure.

Carotid Endarterectomy in Patients with Near Occlusion of the Carotid Artery

Near occlusion of the carotid artery also known as the "string sign", "slim sign", or atherosclerotic "pseudo-occlusion" does not increase the risk of CEA more than that noted for CEA of 70–94% stenosis. In general, patients with anatomically normal but collapsed distal internal carotid arteries do better than those with fibrosis or atherosclerosis of the distal and proximal artery. CEA reduces the risk of stroke in symptomatic near occlusion. Emergency CEA is not necessary.

The Influence of Carotid Siphon Stenosis in Short and Long-Term Outcomes after Carotid Endarterectomy

Early studies suggested that the risk of perioperative stroke and recurrent symptoms was higher in those patients with ipsilateral carotid stenosis and that siphon stenosis increased the severity of cerebral ischemic symptoms. Recent studies demonstrate no change in the short and long term stroke morbidity rates after carotid endarterectomy. Late death (more than 5 years) was caused most frequently by concomitant heart disease and was slightly higher in patients with siphon stenosis.

Moderate siphon stenosis is a 50–79% diameter-reducing lesion. The incidence of ipsilateral carotid siphon stenosis is about 21.4%. Hemodynamically significant ipsilateral carotid siphon stenosis is approximately 14%. In those series that utilized a criterion of carotid siphon stenosis of greater than 20%, than approximately 40% of the ipsilateral carotid (extra-axial) will have concomitant siphon stenosis. Some natural history studies have documented decreased long-term survival of patients with siphon stenosis. The major hypothesis is that intracranial stenosis is a marker of wide spread vascular disease.

Siphon stenosis is found ipsilateral to 20% of stenotic arteries and is usually 20–40%. It may increase the rate of late death (5–7 years), and may slightly lower the stroke free survival rate (from 80% to 50%).

Simultaneous Carotid Endarterectomy and Coronary Bypass Risk of Stroke and Long Term Survival

The association of coronary and carotid atherosclerotic disease is clear. Greater than 50% of patients with carotid endarterectomy have had a previous infarct, angina, or ischemic EKG abnormalities. In patients undergoing coronary bypass, duplex ultrasound studies reveal greater than 50% carotid stenosis in 3.4% to 22% of patients. The incidence of more than 80% stenosis is approximately 6–12%. Stroke complicates 1% to 4% of all coronary artery bypass procedures. It is higher in patients with extracranial carotid disease.

Coronary Bypass Related Stroke Causes

• Emboli from the carotid and aortic arch
• Endocardium (emboli)
• Pump oxygenator (emboli)
• Hypoperfusion (occlusive arterial lesions or hypotension)
• Air embolization
• Extracranial hemorrhage

Carotid lesions of at least 60% will occur in 3% to 15% of patients undergoing a CABG. Selection criteria for the combined CABG-CEA patients versus CEA alone are accounted for by differences in perioperative morbidity and mortality.

Ultrasound Lesion Morphology in Retinal Ischemia

Carotid arterial disease is a significant factor in causing retinal ischemic symptoms. The retinal ischemic symptoms are related to the morphology of the plaque lesion as well as the degree of carotid stenosis. Approximately 10% of patients who present with retinal ischemic symptoms first will develop a stroke. Complex heterogeneous plaques have an uneven distribution of low level and high level ultrasound echoes within the lesion and have an irregular or pitted surface and have been associated with both cerebral and retinal ischemia. In patients who presented with retinal ischemia there is a low incidence of continuing retinal emboli but a 26% rate of cerebrovascular or cardiovascular events. Complex heterogeneous plaque morphology is a significant risk factor for cardiovascular events.

The Risk of Stroke in Patients with First Ever Retinal Transient Ischemic Attacks and High-Grade of Carotid Stenosis

The risk of ipsilateral stroke at 2 years following first ever retinal TIA is approximately 15% whereas it is approximately 40% if the first event was a hemispheric TIA. Most of the 2 year risk for both groups occurred in the first 2 months after the initial event. Patients with hemispheric TIAs as their first ever event were approximately 3 times more likely to suffer an ipsilateral stroke at 2 years than those patients who suffered retinal TIA as their first ever event regardless of stenosis severity within the 70–79% range. Patients with amaurosis fugax from all sources have a yearly stroke rate of 2–4%.

Natural History of Stenosis from Intracranial Atherosclerosis

Atherosclerosis of the intracranial vessels occurs in the setting of widespread vascular disease but may develop selectively in Blacks and Asians. Risk factors for intracranial atherosclerosis are race, hypertension, diabetes, smoking, and hyperlipidemia. These patients have an increased risk of heart disease, stroke and death. In patients who have failed medical therapy (anticoagulation), angioplasty of intracranial vessels carries a risk of stroke of 20–33%, which is secondary to occlusion of small perforating vessels, selection bias, vessel dissection and thromboembolism.

In general, intracranial petrous to supraclinoid carotid lesions were stable while ACA, MCA, PCA and distal vertebral and basilar artery vessels progressively stenosed. In general 40% of stenoses were stable, 20% regressed and 40% progressed. Pathological specimens demonstrate that narrowing is caused by atherosclerosis and at times concomitant thrombosis. Emboli may also cause vessel narrowing and then complete resolution due to clot lysis. Absence of carotid bifurcation disease is associated with lesion progression while duration of tobacco use, hypertension and diabetes were associated with ICA atherosclerosis. Intracranial atherosclerotic lesions like coronary artery atherosclerotic disease are dynamic and both progress and regress over time.

Special Risk Factors for Ischemic Stroke (Summary)

• Asymptomatic stenosis of >70%
• Intra-aortic atherosclerotic debris
• Catheter related emboli with thoracic aorta debris or other material
• Stroke risk of CABG
• Stroke risk with cardiac surgery
• Risk of stroke in cardiac surgery patients with a history of stroke
• Preoperative risks factors for asymptomatic CEA
• Preoperative risks predict severity of CEA related stroke
• Carotid recurrent stenosis and risk of stoke
• Risk of stroke in carotid near occlusion
• Carotid siphon stenosis and risk of stroke
• CEA and CABG stroke risk
• Lesion morphology as risk of retinal stroke
• Stroke risk in first ever retinal TIA vs hemispheric TIA
• Natural history of intracranial stenosis

Ischemic Vascular Disease

The hallmarks of ischemic cerebrovascular disease are the suddenness of the ictal event, the preceding risk factors, the patterns of the deficits and the course of recovery. Transient ischemic attacks precede 70% of ischemic events in the anterior circulation and 50% of those that occur in the posterior circulation. They may be divided into short less than 1 hour or greater than 1 hour ischemic deficits although most last between thirty seconds and 2 minutes. Transient ischemic attacks are overwhelmingly caused by intra-arterial artery to artery emboli, primarily thrombus material or detritus from atherosclerotic plaques, or clots from the atrial appendices, the walls of dyskinetic heart segments or from heart valves. There are a great number of causes of emboli originating from the heart due to intrinsic heart disease, tumor of the valves and systemic disease. Larger TIAs in general are caused by cardiac clots or large vessel emboli whereas those that last less than 1 hour are more after associated with lacunar infarcts or small vessel disease. Lacunar infarction may have a stuttering course. Recent studies demonstrate that atherosclerotic lesions of the aortic arch are associated with 20–25% of emboli to both circulations.

Transient ischemic attacks of the anterior circulation may cause painless loss of vision in one eye (amaurosis fugax). This is frequently described as a shade descending over the eye and may last for 30 seconds to 1 minute; occasionally they may last for 5 minutes to 30 minutes. Rarely, a yellow birefringent cholesterol embolus can be seen at a retinal artery bifurcation (Hollenhorst plaque) and frequently appears to be larger than the vessel wall. The emboli move peripherally as vision clears. Smaller white fibrin platelet emboli are seen at retinal artery bifurcations and originate from complex plaques in the carotid artery or a cardiac valve or annulus source. It is extremely rare for amaurosis fugax to be associated with contralateral weakness or sensory loss. Constriction of the visual field or a monocular visual loss is from marginal or failed perfusion of the retina. TIAs are transient neurologic deficits that frequently precede ischemic stroke.

Clinical Signs and Symptoms of Anterior TIA (Carotid, Anterior, Middle Cerebral Artery Circulation Territories)

• Numbness or heaviness of the contralateral face, arm or leg
• Slurred speech
• Anterior or posterior aphasia
• Weakness of face, arm or leg
• Perioral numbness of one side of the mouth either alone or concomitant with the hand (cheiro-oral pattern)
• Amaurosis fugax in the ipsilateral eye
• Temporal or parietal headache
• Dizziness or light headedness
• Imbalance
• Dominant and nondominant hemispheric parietal deficits
• Unilateral orthostatic clonic tonic jerks (primarily carotid stenosis)

Posterior Circulation TIA (Vertebrobasilar Arteries, Posterior Cerebral Artery Branches)

Clinical Signs and Symptoms

• Bilateral visual loss or blurriness
• Vertigo or dizziness
• Bilateral peri-oral numbness
• Ataxia, imbalance, clumsiness/disequilibrium not associated with vertigo
• Diplopia
• Dysarthria
• Dysphagia
• Bilateral weakness or shifting weakness
• Bilateral sensory loss; shifting numbness
• Dissociated sensory loss (face and contralateral body)
• Medial or lateral spinothalamic tract sensory loss (face)
• Drop attacks corticospinal, cerebral peduncle, pyramidal tracts in the medulla or medial reticular formation ischemia
• Dysgeusia; (nucleus tractus solitarius from posterior circulation; ischemia of the VIIth nerve peripherally (supplied by the inferolateral trunk of the external carotid)
• Numbness of 1/2 of the tongue (patient aware of the deficit)
• Hearing loss (unilateral AICA or bilateral pontine ischemia)
• Persistent vomiting out of proportion to dizziness
• Singultus (hiccoughs)
• Basioccipital headache

Differential Diagnosis of Transient Ischemic Attacks

The differential diagnosis of TIA is best thought of by mechanism. As stated earlier, most TIAs are embolic with the source being artery to artery or clots or other material from the heart of the TIAs are widely separated in time they most likely are from a large artery that is undergoing gradual occlusion. The carotid bifurcation may gradually occlude and during this process cholesterol debris as well as platelet fibrin clots form and dislodge from the area of ulceration. As the artery reaches a critical flow limiting state greater than 95% occlusion the TIAs may come very rapidly and may be a combination of distal field ischemic as well as artery to artery emboli. These may be known as crescendo TIAs and most often present as multiple episodes of amaurosis fugax. Tight stenosis of intracranial proximal conducting vessels (stenosis M1 of the MCA and AI and P1 of the anterior and posterior circulation) and factors combined with lower systemic pressure and CBF flow are causative. MRI scans demonstrate high signal T2 weighted lesions in the affected side periventricularly (vascular stripe). Tandem lesion of the carotid bifurcation siphon and M1 segment also cause susceptibility to fluctuations in blood pressure. Specific stenotic lesions cause stereotypical neurological symptoms as opposed to emboli which are slightly different from attack to attack, but often may lodge in the same or adjacent vessels due to laminar flow characteristics.

Embolic TIAs particularly from the heart occur in specific settings. Some are pathognomonic such as a pure receptive aphasia which is characteristic of obstruction of the temporoparietal branch of the inferior division of the MCA from atrial fibrillation. Patients with dilated cardiomyopathy invariably embolize over time. Emboli may not cause catastrophic symptoms. A sudden headache or dizziness rather than hemiparesis, hemisensory loss or aphasia may be the only symptoms. Visual field loss of the superior quadrants suggests emboli to the lower banks of the calcarine cortex in the setting of atrial fibrillation. Ten percent of cancer patients suffer non-bacterial thrombotic emboli. Cardiac valve lesions even in those patients that are perfectly anticoagulated may embolize. The mitral valve is the most commonly affected followed by the aortic valve. Subacute bacterial endocarditis frequently is announced by an embolus to the middle cerebral artery territory. Atrial myxomas are noted for small embolic strokes but the clinical picture may be clouded by fevers and a remittent course due to an immunological response to the myxomatous material. This diagnosis may be heralded as well by the presence of a peripheral aneurysm. A peripheral aneurysm that has ruptured suggests SBE. Emboli occur during wakefulness. Occasionally, they are seen as a patient gets up to urinate at night or during a Valsalva maneuver suggestive of patent foramen ovale. The characteristic feature is the maximum deficit at ictus with clearing rather than deterioration which is more common with ischemic occlusion. Headache occurs if the dura is involved. There is a small amount of CSF blood (approximately 100 RBC/mm³) and a higher incidence of seizures.

Mobile plaques of the arch of the aorta and associated atherosclerotic detritus account for 30% of emboli to the posterior circulation and can now be evaluated with TEE. Patent foramen ovale with or without atrial septal aneurysms or tunnel emboli account for a large number of formerly cryptogenic emboli in younger patients. Symptoms form extracranial arterial dissections are usually form emboli rather than limitation of flow.

Rarer causes of emboli are myxomatous degeneration of valves noted in mitral valve prolapse, verrucous endocarditis of SLE and air, fat, and calcium.

The only common condition that causes vasospasm and TIS is migraine. The differential points for migraine versus embolism or ischemia as a cause of neurological dysfunction are clear. Migraine is noted for positive visual symptoms of scintillating or fortification scotomata, a gradual evolution over 20 minutes, one somatosensory complaint gradually merging with the next (visual symptoms merging with parietal sensory loss) and a headache after the neurological symptoms. Embolic or ischemic events are characteristic for the association of all deficits simultaneously with primarily negative symptomatology (heaviness, visual loss and weakness). Family history and risk factors are different. However, CADASIL (cerebral AD arteriopathy with subcortical infarction and leukoencephalopathy) as well as mitochondrial disease are noted for concomitant migraine headaches. SLE and other connective tissues have a high incidence of associated migraine.

Emboli may occlude deep penetrating blood vessels mimicking lacunar disease (10–12 penetrators from the lenticulostriate arteries) of the internal capsule or basal ganglia. Congophilic angiopathy patients may suffer repeated small bleeds (noted by gradient Echo MRI) that mimic emboli.

Imaging studies are extremely helpful. CT scan may demonstrate older lesions in two circulations or a dense MCA sign. This is at the site of embolic occlusion. Diffusion weighted MRI demonstrates areas of acute ischemia and in tandem with perfusion studies demonstrates the ischemic penumbra. Occasionally, one see lesions not only in different circulation, but demonstrating different intensities suggesting earlier events.

Transcranial Doppler studies, particularly during carotid surgery, have shown that most emboli are asymptomatic (similar to the lung). The frequency characteristics suggest size of the embolic material. Carotid Doppler characteristics suggest qualities and morphology of the ulcerated plaque or dissection. As Dr. Caplan has pointed out, it is most important to discover the type of bird that has left the nest.

Differential Diagnosis of TIA

• Seizure (including inhibitory seizure)

A shaking TIA from carotid stenosis and hemispheric ischemia (distal field ischaemia) occurs with decreased cerebral blood flow. There are no auras, no loss of consciousness or mental clouding and no post ictal clouding. Bilateral shaking of the upper extremities and lower extremities may occur with internal capsule or cerebral peduncle ischemia (top of the basilar distal field ischemia). Extremely rare, a seizure emanating from the suppressor strip of the motor cortex (area 6) may cause contralateral paralysis of the face and arm. This does not clear for hours. There is no associated loss of consciousness. Todd's paralysis from a focal seizure usually lasts less than one hour, but may persist for one week to ten days. Recently, prolonged Todd's paralysis have been noted in that affect speech areas. They denote focal brain disease. The underlying seizure history and length of the attack differentiate them from TIA.

• Demyelinating disease

The short symptoms of demyelinating disease, those that last for a few minutes are thought to occur from Utoff's phenomena (failure of partially demyelinated axons to conduct with heat) or blocking antibodies. The blocking antibodies may affect the optic nerves or sensory pathways most frequently with scotomata or paresthesia (less than five minutes). Most demyelinating attacks take weeks to clear. Paroxysmal ataxia pain, sensory and motor loss do occur with demyelinating disease. The underlying hyperreflexia, ataxia intranuclear ophthalmoplegia and cortical deficits suggest demyelinating disease rather than TIA.

• Migraine

Bickerstaff migraine with bilateral visual loss, paresthesias of the hands, perioral numbness, bilateral visual disturbance (visual field deficits, scintillating scotomata, teichopsia), dysarthria and loss of consciousness may be confused with brain stem stroke. In general, migraine can be differentiated from ischemic stroke by risk factors, age and hereditary pattern. Most migraine symptoms are positive and the progression is one modality affected seriously. Thus, visual loss slowly melds with parietal sensory loss and other weaknesses. The symptoms frequently precede the headache. The patients with ischemia suffer deficits in several modalities simultaneously. In general, these are negative – loss of vision, numbness and weakness. The headache is usually concomitant.

Surprisingly, headache is suffered more frequently in patients with posterior rather than anterior circulation ischemia. This phenomenon has been ascribed to V1 innervation of the dura and the tentorium.

Several drug intoxications are notable for focal neurologic deficits. Most often distributed cortical or brainstem networks with multiple synapses are affected. Hypoglycemia, hepatic insufficiency and phenobarbital poisoning dose cause focal deficits. If a patient had a prior deficit and then has metabolic compromise, the prior compensated deficit may become manifest.

Diseases that are exacerbated by temperature may demonstrate the onset of new focal symptoms. These include multiple sclerosis, myasthenia gravis, the Lambert–Eaton syndrome and Fabry's Disease. The neuromuscular junction deficits have cranial nerve, fluctuating weakness and maintained reflexes. Lambert–Eaton may at times demonstrate hyporeflexia and myasthenia gravis hyperreflexia (spreading acetylcholine sensitivity of the sarcolemmical membrane). Fabry's Disease patients may present in coma under thermal stress that mimics basilar artery occlusion. The cataracts, skin lesions (bathing suit distribution) family history and painful neuropathy are diagnostic. Stroke and renal disease also occur in Fabry's disease.

Mitochondrial disease particularly MELAS, presents with stroke like episodes. Migraine, fatigue with exercise, short statue, exercise intolerance and VIIIth nerve deficits are characteristics. The MRI demonstrates basal ganglia involvement (probably white matter) within the basal ganglia. Posterior leukoencephalopathy may be present.

Subclavian steal is over diagnosed and rarely is clinically significant as demonstrated by arteriographic studies on young Japanese women with Takayasu's Disease. In general, the patient is vigorously rising the right arm overhead (which further lowers the pressure in the arm by dilating muscle vessels) the subclavian artery is stenosed prior to the origin of the vertebral artery and blood then flows from the ipsilateral brainstem through the vertebral artery and into the exercising arm. Patient's demonstrate brainstem signs and symptoms.

Syncope whether vasovagal (drop of systemic pressure) or vago-vagal and increase of vagal tone from the dorsal vagal nucleus to the nucleus tractus solitarius and then the SA and AV node) non-focal and in less than 15 seconds.

Differential Diagnosis of TIA

• Seizure (including inhibitory seizure)
• Demyelinating disease
• Anterior or posterior migraine (Bickerstaff's)
• Rare metabolic dysfunction (phenobarbital, hepatic failure, drugs)
• Hypoglycemia
• Temperature exacerbated disease (myasthenia gravis, Lambert–Eaton syndrome, Fabry's disease, demyelinating disease)
• Mitochondrial disease (MELAS)
• Subclavian steal
• Syncope

Clinical Symptoms and Signs of Major Vessel Stroke

Carotid Occlusion

A patient that has suffered a complete carotid occlusion is not infrequently asymptomatic if the process has been insidious and has been accompanied by extensive collateralization. Patients have been described with slowly developing complete carotid and vertebral occlusion that are relatively asymptomatic. In the face of acute occlusion without sufficient collateralization patients suffer weakness or paralysis of the contralateral arm, face and leg, the head and eyes are deviated to the side of the lesion (may not be dolled across the midline to the opposite side for 12–24 hrs) and may have a contralateral hemisensory deficit to all modalities. Cerebral edema supervenes within the first 12–24 hours and is manifest by lethargy, Cheyne–Stokes respiration exacerbated (if cardiac or pulmonary disease is present) and slight downward deviation of the eyes (5° below the horizontal). The arm on the contralateral side is pronated and the leg externally rotated. If the infarction is in the dominant hemisphere (90% of dextral and sinistrals are dominant in the left hemispheres) expressive and receptive aphasia is evident. If the occluded carotid affects the nondominant hemisphere (NDH) hemineglect may be associated with episodes of weakness of the contralateral leg which is precipitated by walking or standing. Similarly contralateral coarse shaking or involuntary movements may be seen in the extremities opposite the stenotic carotid artery precipitated by standing, walking, or head hyperextension due to ischemia of the ipsilateral corticospinal pathways.

Severe Preocclusive Carotid Disease

Severe preocclusive carotid disease may present with recurrent TIA's, a stepwise onset, or a pseudotumoral slowly progressive form. Ischemic orbital pain may awaken the patient from sleep and is described as severe, deep and boring. Ischemic oculopathy with a swollen disc, and neovascularization may occur in conjunction with engorgement of conjunctival and episcleral vessels. The intraocular pressure may be extremely low. Optic atrophy on the ischemic side is rare. High grade stenosis may be associated with a unilateral loss of vision in bright light which may persist for seconds to hours and is related to delayed regeneration of visual pigments in the retinal pigment epithelial layer. These phenomena may occur bilaterally if both carotids are severely stenotic. Monocular visual loss may also be described as dimming or blurring of vision or seeing through a fog. The attacks are short, from 1–2 minutes, but occasionally last for 20 to 30 minutes. They are not positionally related.

Bruits are frequently associated with severe stenosis but frequently disappear when the occlusion reaches approximately 90% of the arterial diameter. A diastolic component to the bruit is very significant. A bruit may be heard contralaterally in a minimally affected carotid due to augmented blood flow through the less diseased artery.

Acute Carotid Occlusion

Carotid occlusion at or below the bifurcation may cause a complete Horner's syndrome with ptosis meiosis, facial anhidrosis and apparent enophthalmos. If only the internal carotid is occluded past the branching of the external carotid there, will be no facial anhidrosis. The sympathetics surround the internal carotid artery to innervate the iris whereas the external carotid carries sympathetic innervation to the face. In a few patients, the pupil on the affected side will be dilated (less than 10%) and unresponsive to light due to iris ischemia. Pupillary cortical representation may lie in the motor sensory cortex or the prefrontal eye fields so that unilateral infarction may cause unilateral or bilateral ptosis (cortical innervation to the central caudal nucleus which innervates the levator palpebrae) and ipsilateral meiosis. This constellation is known as a cortical baby Horner's syndrome. If severe carotid stenosis has preceded acute occlusion, the arcus senilis may be less apparent on the affected side. A major motor seizure may occur in a small proportion of patients concomitant with the occlusion. Waxing and waning of consciousness occurs during the first few days and Cheyne–Stokes respiration is common. The anterior 2/3 of the hemisphere is most severely affected. Rarely the affected side demonstrates hyperhidrosis (involvement of the anterior hypothalamus supplied by the meningohypophyseal trunk of the cavernous carotid).

The hemisphere may be more severely involved if it is isolated due to hypoplasia of the anterior or posterior communicating arteries or if there is a fetal origin of the posterior cerebral artery from the carotid (concomitant hypoplastic ipsilateral posterior communicating artery). The stenotic or emboli lesions may extend to occlude the origin of the anterior cerebral artery with its consequent occlusion or in the case of a fetal origin of the posterior cerebral artery it may be occluded along with the middle cerebral artery.

The size of the ICA occlusion may be minimized by collateral circulation through the Circle of Willis, cortical leptomeningeal vessels and those from the external carotid (internal maxillary, superficial temporal artery to meningeal vessels, ophthalmic and external carotid vessels to middle cerebral artery branches).

Clinical correlate of the acute carotid occlusion:

• Lethargy, fluctuating level of consciousness, rare seizures
• Horner's syndrome (ipsilateral)
• 10% dilated unresponsive pupil (iris ischemia)
• Periodic respiratory breathing pattern
• Head and eyes deviated ipsilaterally (frontal eye fields BA 8 and BA 10)
• Hemisensory deficit to all modalities (contralaterally); vibration spared
• Broca's aphasia > Wernicke's (DH)
• Hemineglect contralateral side (NDH)
• Pronated arm, externally rotated leg (contralaterally)
• Depressed reflexes (contralaterally) acutely
• Babinski's sign (contralaterally)

Features of Intracranial Internal Carotid Occlusive Disease

Atherosclerosis of the Carotid Siphon

Calcification of the siphon is common and is coexistent with extracranial disease. There is a high death rate from coronary artery disease and disease in this location is more common in Afro-American than Caucasians. There are frequent concordant lesions in the origins of the internal carotid and vertebral arteries. Tandem ICA and siphon disease is common. There is a higher ratio of stroke to TIA in carotid siphon disease than cervical carotid disease. The major clinical differential points of siphon versus internal carotid diseases are:

• Few episodes of amaurosis fugax
• No ocular retinal pathology
• Retrograde extension of the siphon clot may cause delayed optic ischemia
• Leg is more affected than the arm
• Associated scattered ACA and MCA infarcts are noted. These may involve the foot and face, sparing the arm
• Slowly progressive symptoms
• Worse prognosis than ICA origin disease
• There are no collaterals through the external carotid artery

Occlusion of the Top of the Carotid (T Portion)

A block at the top of the carotid causes infarction of both the anterior cerebral and the internal carotid artery. It is most common with sickle cell disease and with circulating anti-coagulants.

The Anterior Choroidal Artery (ACHA) Syndrome

The anterior choroidal artery is the second branch of the internal carotid artery. It partially supplies the caudal 2/3 of the posterior limb of the internal capsule, the posterior optic tract, the uncus of the temporal lobe, medial GP₁, cerebral peduncle, lateral geniculate body and portions of the thalamus. AchA does not supply the corona radiata or the ventricular wall. Its most consistent branches are to the optic tract, cerebral peduncle and choroid plexus. There are variable anastomosis with branches of the MCA, PCA and posterior communicating artery. This artery supplies territories in both anterior and/or posterior circulations.

• Most Consistent Clinical Presentation
  • Hemiparesis, hemisensory loss, hemianopsia
    • Pure motor hemiplegia (face, arm and leg affected)
    • Bilateral AchA infarcts:
      • pseudo bulbar palsy
      • mutism
      • quadriparesis
    • Hemisensory symptoms: incomplete or temporary and comprise all modalities
• Unusual Sensory Manifestations
  • Hemisensory deficit with spared proprioception
  • Painful thalamic-type syndrome
    • Formication (crawling paraesthesias)
    • Feeling of limb swelling
    • Pain in the arms and legs
  • Hemiataxia with the sensory symptoms
  • Temporary sensory loss
• Clinical Features of the Motor Deficit
  • Face, arm and leg affected
  • Ataxic hemiparesis (thalamic)
  • Hypesthetic ataxic hemiparesis
• Visual Field Deficits and Eye Movement Abnormalities
  • Congruent homonymous visual field deficit sparing the central sector
    • Lateral geniculate body infarcted
    • Known as a quadruple sectoranopic defect
  • Homonymous congruent superior quadrantanopia
    • With or without macular sparing
  • Congruent homonymous hemianopia
  • Ipsilateral conjugate eye deviation
• Higher Cortical Deficits with AchA Infarction (Unusual)
  • Nondominant hemisphere
    • Visual neglect
    • Constructional apraxia
    • Short term visual memory loss
    • Anosognosia
    • Motor impersistence
  • Dominant hemisphere infarction
    • Decreased fluency
    • Semantic paraphasia
    • Perseveration
    • Deficits in language processing
    • Poor understanding of word associations
    • Poor comprehension
    • Short term verbal memory loss
• AchA Infarction of Lateral Thalamus and Posterior Limb of the Internal Capsule
  • Dysarthria
  • Language processing defects
  • Short term verbal memory loss
• Bilateral AchA Infarction
  • Urinary incontinence without dementia
  • Dysarthria
  • Dysphagia
  • Dysphonia
  • Palatal paralysis – (may occur with unilateral stroke)
  • Pseudobulbar affect
  • Depression
  • Blunted affect
  • Mutism
  • Lethargy
• Anatomic Variants of AchA
  • Anastomosis with:
    • MCA
    • Posterior communicating artery
  • Paraventricular areas
    • Watershed between the deep MCA perforators and lateral lenticulostriate arteries
    • Watershed between the posterior choroidal arteries (near the superior portion of the internal capsule)
  • May supply the temporo-occipital lobe (PCA territory)
• Pathogenesis of AchA Occlusion
  • Surgical manipulation
    • Aneurysm (spasm)
    • Seizure surgery
  • Hyperviscosity states
  • Decreased perfusion
  • Embolism
    • Cardiac
    • Often with concomitant MCA embolism
  • Thrombosis
    • Intracranial atherosclerosis

Anterior Cerebral Artery

The anterior cerebral artery arises from the internal carotid artery at the level of the anterior clinoid process to supply the medial surfaces of the frontal and parietal lobes as well as the anterior 4/5 of the corpus callosum, the ventrobasilar frontal cortex (substantia innominata, septal nuclei, and nuclei of the diagonal band) and the anterior thalamus. The A1 segment from the carotid joins the anterior communicating artery (ACoA) in the interhemispheric fissure. There are approximately 8 perforating branches from the A1 segment. Proximal A1 branches perfuse the genu, contiguous areas of the posterior limb of the internal capsule, the anterior hypothalamus, anteroventral putamen and pallidum. Distal A1 segment branches perfuse the optic nerve, chiasm and tract. The perforating branches of the ACoA perfuse the most anterior aspects of the hypothalamus, the basal forebrain, and the medial anterior commissure, fornix and lamina terminalis, corpus callosum and anterior cingulum. A2 branches, part of the ascending segment, perfuse the gyrus rectus, the inferior frontal cortex, the anterior thalamus and the rostrum of the corpus callosum. The recurrent artery of Heubner takes origin near the ACoA and travels backward along the A1 segment to penetrate the brain at the lateral anterior perforating substance, Sylvian fissure or orbitofrontal cortex to supply the head of the caudate and anterior limb of the internal capsule.

The distal A2–A5 segments comprise the pericallosal and callosomarginal arteries. If the callosomarginal artery is absent, all cortical branches originate from the pericallosal artery (18–60%) of patients. The ascending orbitofrontal and the frontopolar arteries arise from the A2 segment and supply the inferior, medial and lateral surfaces of the frontal pole. The superior frontal gyrus is supplied rostrocaudally by A2–A4 segments of the pericallosal artery. The paracentral artery, the superior parietal artery may arise from either the callosal marginal or the A4–A5 segment of the pericallosal artery to supply the superior precuneus while the posterior inferior cuneus is supplied by A5 branches of the inferior parietal artery from the pericallosal artery. There are a great number of normal variations of the anterior cerebral artery and anterior portion of the Circle of Willis.

The usual etiology of ACA-territory infarction is a cardioembolic stroke particularly if there is increased blood flow through the artery due to a contralateral ICA occlusion or a congenital defect of the anterior Circle of Willis. In situ thrombosis of the artery is more common in Asian patients. Extension of thrombus from the ipsilateral carotid is the usual atherosclerotic mechanism. Occlusion by transtentorial herniation, vasospasm from ruptured ACoA aneurysm or embolisms from these aneurysms are particular causes of infarction peculiar to this artery. Bilateral occlusion is rare but has been reported. Approximately 25% of these patients have had an azygous or unilateral supply of both ACAs from one carotid artery, the others having suffered probable emboli from atrial fibrillation or recent myocardial infarction. Bilateral infarction of the ACA causes akinetic mutism with poor recovery. The artery may be infarcted by the angitis of collagen vascular disease, prothrombotic states, lacunar infarction, rare emboli (fat, air, and atrial myxoma), dissection or fibromuscular dysphasia.

Anterior Cerebral Artery (ACA) Stroke: Clinical Signs and Symptoms

The clinical signs and symptoms of ACA are distinct. The artery is involved primarily following vasospasm secondary to anterior communicating aneurysm rupture, damage from neurosurgical procedures, propagation from ICA occlusion and artery-to-artery embolism from more proximal atherosclerotic occlusive disease.

Cortical branch occlusion causes severe weakness of the distal foot and leg, the proximal arm with sparing of the face and tongue. The patient can frequently perform fractional movement of the hand and thumb. Muscle tone is flaccid early and then becomes spastic. The paracentral lobule, upper motor cortex and subcortical fibers from these areas that project into the corona radiata are affected. A few patients may only suffer a crural monoplegia (contralateral weakness of the leg). The pattern of weakness may vary considerably with some patients suffering arm and leg weakness to the same degree, others with hemiparesis and brachial predominance. Distal occlusion of the ACA may also cause pure motor hemiparesis and homolateral ataxia and crural paresis.

Patterns of ACA Weakness

• Paresis of foot and leg > arm; face and tongue spared
• Crural monoplegia (contralateral paralysis of leg and foot)
• Contralateral arm and leg involved equally
• Contralateral hemiparesis with brachial facial predominance
• Homolateral ataxia with crural paresis
• Pure motor hemiparesis

Infarction of the recurrent artery of Heubner from the A1 segments affects the head of the caudate, the putamen and the anterior limb of the internal capsule. This lesion may cause faciobrachial predominance in the observed hemiparesis. The proximal perforators from A1 may also supply the genu and anterior internal capsule. Right-sided > left-sided medial frontal infarction that includes the SMA may cause contralateral motor neglect.

Sensory deficits are most severe in the foot and leg contralaterally. They are most often in discriminative touch but may be severe to all modalities.

Psychomotor Dysfunction

The anterior cerebral artery supplies regions of the limbic system and basal ganglia essential for integration of emotional aspects of movement and frontal lobe function. Transient loss of consciousness may occur with ACA infarction. Bilateral damage to the anterior cingulate gyrus or head of the caudate nucleus may cause akinetic mutism. These patients do not initiate speech or movement and have no emotional expression. They do not respond to sensory stimuli but may follow the examiner with their eyes. Transient abulia may be seen with a unilateral lesion of the caudate head and cingulate gyrus and is characterized by decreased spontaneous speech and delayed response to questions, minimal spontaneous activity and impersistence. These patients may speak almost normally on the telephone.

Infarction of projections from the caudate nucleus to the orbital and dorsolateral prefrontal cortex causes agitation hyperactivity and delirium. If they occur on the dominant side and disrupt connections into the thalamus, aphasia may be noted. Medial frontal lobe infarction causes euphoria, lability of affect and pathological jocularity. Antegrade amnesia may occur from damage to the paramedian basal forebrain during aneurysm surgery that damages perforators from the ACoA. If concomitant mesial frontal damage occurs confabulation may occur with the amnesia.

Aphasia and Language Disorders

Damage to the left supplementary motor area (SMA) may cause decreased spontaneous speech, normal articulation, repetition and comprehension. Transcortical motor or mixed transcortical aphasia have been documented with SMA lesions. Mirror writing can develop with right SMA lesions. Acquired stuttering may occur with anterior callosal or bifrontal lesions. Occlusion of either the right or left anterior cerebral artery may cause muteness.

Anterior Cerebral Artery Speech Disorders

• Muteness
• Transcortical motor aphasia
• Transcortical sensory aphasia
• Acquired stuttering
• Whispered speech
• Reduced spontaneous speech
• Normal comprehension
• Normal articulation

Urinary and Fecal Incontinence

Unilateral or bilateral ACA infarction may cause urinary and fecal incontinence by damaging the midportion of the superolateral and medial superior frontal gyrus and the anterior cingulate gyrus. Damage to the paracentral lobule may induce precipitate micturition that cause patients to urinate uninhibitedly when their bladder is partially full.

The Grasp Reaction of ACA Infarction

The grasp reflex is caused by a contralateral basal ganglia or frontal lesion. This response is flexion and adduction of the hand when an object is gently moved from the palmar hypothenar eminence through the palmar index finger and thumb. This is an involuntary response. The instinctive grasp reaction is elicited by a stationary touch in the same areas of the hand and consists of:

• several grasping movements directed toward the object
• a true grasp is one grasp in response to an object
• the traction response follows stretching of the patient's flexed fingers that he cannot release
• a magnetic response in which the patient shadows the movements of the examiner's hand

A contralateral lesion of the mesial superior frontal and cingulate gyrus or rarely the basal ganglia cause a grasp reflex.

Callosal Disconnection Syndromes Following ACA Infarction

In right-handed patients, a left handed ideomotor apraxia may occur following ACA infarction. The patient is unable to perform a simple command with the left hand such as a military salute. This is due to disconnection of Wernicke's area and the premotor cortex from the premotor and primary motor cortex of the right hemisphere. It may also occur after infarction of the left premotor area (BA 8) , the anterior corpus callosum or the right premotor cortex. The patient may have impaired ability to imitate the examiner's movements with the left hand.

Left-hand agraphia may be seen with ACA infarction. Patients are unable to write readable letters, utilize correct words and often demonstrate substitutions or perseverations both to dictation and with spontaneous writing. No linguistic mistakes are made with the right hand. They are able to write or copy correctly but cannot type or use block letters. In general, ideomotor apraxia and agraphia occur concomitantly with callosal lesions but may be dissociated. The callosal fibers for praxis cross the midline in the rostral portion of the posterior body of the corpus callosum.

Unilateral tactile anomia occurs in the left hand. The patient can manipulate the objects correctly with either hand. He has an associated unilateral left agraphia that is caused by a lesion of the posterior part of the body of the corpus callosum. Right handed constructional dysfunction and crossed pseudoneglect to both visual and tactile line dissection tasks have been noted with callosal posterior body infarction. A crossed visuomotor ataxia results from damage to the dorsal aspect of the posterior callosum. A crossed avoiding reaction (patient unable to move the left hand when an object is placed in the right hemispace) has been seen with a lesion of the genu and body of the corpus callosum.

The alien hand syndrome denotes a patient who has a feeling that the left hand does not belong to them and notes that one hand works at cross purposes with the other. In general, these patients have suffered a mesial frontal lobe and corpus callosum lesion. The patient cannot voluntarily suppress motor perseveration in which the patient compulsively repeats stereotyped movements. These movements are usually associated with a grasp reflex and instinctive grasp reaction. Compulsive manipulation of tools placed in front of the patient is a release of praxis from damage of the left mesial frontal lobe, cingulate gyrus and genu of the corpus callosum. The syndrome occurs with a concomitant grasp reflex and instinctive grasp reaction but no disconnection syndrome. The utilization behavior of Lhermitte differs from compulsive manipulation of tools because it is bilateral and lacks the compulsive quality noted in the compulsive manipulation of tools. Diagnostic dyspraxia is a dissociative movement in which the left hand undoes the actions of the right. Usually the left hand works at cross-purposes to the right. Damage to the body of the corpus callosum is required for this behavior. Damage to the contralateral mesial frontal lobe and genu of the corpus callosum may cause purposeless movements of the contralateral hand such as an updrift, tucking the hand in the axilla or grasping the throat.

Alien Hand Phenomena and Variants

• Le signe de la main étagére "strange hand"
• Intermanual conflict
• Motor perseveration
• Compulsive manipulation of tools
• Diagnostic dyspraxia
• Updrift, hand in the axilla, grasping the throat

Callosal Disconnection Syndromes

• Ideomotor apraxia – left hand
• Agraphia – left hand
• Tactile anomia – left hand

Pathologic Grasp Phenomena

• Grasp reflexes
• Instinctive grasp reaction:
  • True grasp
  • Instinctive groping
  • Traction response
  • Magnetic response

The Middle Cerebral Artery

The middle cerebral artery (MCA) is most commonly affected in ischemic cerebral vascular disease. African-American or Asian patients have a higher incidence of infarction of this artery than white patients.

The TIAs of the MCA disease are less frequent than those stemming from carotid disease and occur over a shorter time period. White patients present with TIAs of the MCA more frequently than with stroke; cigarette smoking is a strong risk factor for all groups that suffer MCA infarction.

Major differential points of MCA occlusive disease from that of the ICA are:

• deficits on awakening
• fluctuation or progression of symptoms over the following 1–7 days
• probable low flow mechanism

Carotid disease is more suggestive of an embolic mechanism. There are no ocular symptoms with MCA disease.

Approximately 2/3 of all first brain infarcts are in the MCA territory. Approximately 1/3 affect the deep MCA territory and 10% occlude both deep and superficial territories. Approximately 50% of MCA infarction are restricted to the superficial pial arteries.

Anatomy of the MCA and Its Patterns

• Pial branches supply:
  • Almost the entire convex surface of the brain
  • Lateral frontal, parietal and temporal lobes
  • Insula, claustrum and extreme capsule
• MCA emerges from the ICA for 1.8–2.6 cm as a single trunk
  • Proximal M1/M2 segments give rise to medial and lateral lenticulostriate arteries
• The stem divides into three patterns:
  • Bifurcation pattern
    • Superior and inferior division – 79%
  • Trifurcation pattern:
    • Superior, middle, inferior division – 12%
  • Four or more trunks – 10%

Bifurcation Pattern (Superior/Inferior Division)

• Superior division (pial branches):
  • Ascending orbitofrontal branch
  • Prefrontal branches
  • Precentral branches
  • Central or central sulcal branches
  • 2–3 anterior parietal branches
  • 1–3 angular branches
• Inferior division (pial branches):
  • Ascending temporopolar branch
  • Anterior temporal branch
  • Middle temporal branch
  • Posterior temporal branch

Trifurcation Pattern

• Superior division:
  • Ascending orbitofrontal branch
  • Prefrontal branches
  • Precentral branches
• Middle division:
  • Central/central sulcal branches
  • Variable origin of:
    • Precentral/anterior and posterior parietal branches
    • Angular/temporo-occipital branches
• Inferior division (pial branches):
  • Ascending temporopolar
  • Anterior temporal branches
  • Middle temporal branches
  • Posterior temporal branches
  • Variable origin of (posterior parietal/angular/temporo-occipital arteries):
    • In both bifurcation and trifurcation patterns superficial branches may come from the stem of the MCA prior to its division:
      • Ascending temporopolar branches
      • Anterior and middle temporal branches

Anomalies of the Middle Cerebral Artery

• Rare: occur in 3% of individuals
• Duplication of the MCA:
  • A second vessel arises from the ICA which supplies the anterior and middle temporal territories
• Variable patterns of ACA and PCA pial terminal anastomosis at hemispheric border zones
• If the main MCA trunk is short the lenticulostriate arteries may arise from the superior division

General Features of Superficial Middle Cerebral Artery Territory Infarction

Patients frequently develop distal MCA trunk occlusions that spare the deep penetrators from the M1 and M2 segments of the proximal MCA. The pathogenesis is most often thrombosis in situ rather than embolic. Complete infarction of the superficial MCA territory of the dominant hemisphere causes head and eye deviation to the side of the lesion, lethargy, global aphasia (often early mutism) and perseveration. The hemiparesis and hemisensory loss is brachiocephalic predominant with an invariant contralateral homonymous hemianopia. Nondominant hemisphere infarction in addition to similar motor and eye signs demonstrate contralateral neglect, constructional apraxia, alloesthesia, anosognosia and multiple nondominant (ND) parietal lobe symptomatologies.

Superior division dominant (D) hemisphere infarction causes brachiofacial predominant motor and sensory symptoms, no visual field deficits, but gaze preference or eye deviation (Brodmann's 8 and 10) to the affected side. Broca's aphasia, ipsilateral ideomotor or limb kinetic apraxia and oral buccal lingual apraxia may be seen. Nondominant infarcts have similar motor and sensory deficits with hemi spatial neglect and emotional aprosody. Inferior division territory infarction causes minimal weakness but usually an up drift can be appreciated acutely. Astereognosis, difficulty with dynamic and static parietal copy, point localization is noted after the ictus. The most common visual field deficit is a contralateral superior quadrantanopsia if Meyer's loop is involved, although a contralateral noncongruent homonymous hemianopsia may also be seen (optic tract). Dominant hemisphere lesions cause a Wernicke's aphasia with an occasional patient demonstrating acute agitation. Characteristics of nondominant lesions are a contralateral predominant sensory hemineglect, anosognosia, constructional apraxia and an agitated confusional state.

Superior Division of the Middle Cerebral Artery (Pial Branches)

Ascending Orbital Frontal Artery

This artery perfuses the orbital portion of the middle and inferior frontal gyrus and the inferior pars orbitalis. Its infarction (emboli or arteritis) causes behavioral disinhibition and a contralateral grasp sign.

Prefrontal Arteries

The territory perfused by these arteries is the middle frontal gyrus, pars triangularis, anterior pars opercularis and superior pars orbitalis. The clinical symptomatology includes apathy, abulia, poor ability to change motor sets, perseveration (DH), impersistence (NDH), poor judgment and abstraction, imitation and utilization behavior, and poor retrieval of short term semantic material. A transcortical motor aphasia may be noted with (DH) lesions and motor neglect with nondominant hemisphere infarction.

Precentral Arteries

This group of arteries supplies the posterior middle frontal gyrus, the posterior pars opercularis and the anterior and midportion of the precentral gyrus. The clinical features of infarction of this branch or branches are proximal upper extremity weakness or distal brachiofacial weakness. Dominant hemisphere lesions may have a concomitant transcortical motor aphasia. Due to infarction of area 8, patients may have bilateral upper extremity ideomotor apraxia. If the infarction involves the posterior left middle frontal gyrus (Exner's area) they may have agraphia out of proportion to hand weakness.

Central Sulcal Artery

The central artery group supplies the posterior bank of the precentral gyrus and the anterior half of the post central gyrus. A pathognomic clinical sign of infarction of this territory is monoparesis of the upper extremity (pseudoradial palsy) although brachiofacial weakness is the most common pattern. Infarction of the motor knuckle anteriorly causes selective weakness of muscles innervated by C5 and C6. Posterior infarction causes C8–T1 innervated muscle weakness. Sensory loss is noted in the same distribution. Rarely a pure motor stroke affecting arm, face, and leg occurs. Infarction of the parietal operculum may cause a cheiro-oral sensory loss (corner of the mouth and hand). Dominant hemisphere infarctions cause Broca's aphasia or dysarthria and dysprosody. Nondominant hemisphere infarction usually causes less severe dysarthria.

Anterior Parietal Artery

This artery or group of arteries supplies the post central gyrus, parasagittal portion of the central sulcus, and the anterior inferior portions of both the inferior and superior parietal lobules.

Anterior parietal branch occlusions may cause a contralateral updrift of the arm with abnormal proprioceptive finger movements (mini myoclonus). Loss of touch, pain and position sense is common in the arm and face distribution. Vibration is usually spared. The distal upper extremity may be most severely affected. Incoordination of the affected hand may be noted. Dominant hemisphere infarction may cause conduction aphasia while nondominant lesions are associated with visual-spatial deficit.

Posterior Parietal Artery

Infarction of this territory involves the posterior portions of the superior and inferior parietal lobules and the supramarginal gyrus. Discriminative sensations such as two point localization, stereognosis and graphesthesia are predominantly involved. Patients may demonstrate an inferior quadrantanopsia or noncongruent homonymous hemianopsia. Dominant hemisphere lesions may cause anomic aphasia (SMG), agraphia, and alexia (BA 39, 40, 41) . Ideational and bilateral representational ideomotor apraxia as well as a posterior alien hand syndrome may occur. Left right confusion, finger agnosia, dyscalculia, inability to cross the midline and dysgraphia (Von Gerstmann syndrome) may be seen singularly or concurrently. Nondominant hemisphere infarction causes contralateral sensory spatial neglect, constructional apraxia and visuospatial deficits.

Differential Diagnosis of Parietal Sensory Loss

In general, parietal sensory symptoms from infarction have a regional pattern. Dramatic involvement of 1/2 of the body is characteristic of thalamic disease. Other thalamic signs are the upper extremity is more severely affected and often the trunk is spared. The deficit may be limited to the finger tips (ventral posterior inferior nucleus) and primarily involves the discriminative aspects of sensation. Vibration loss is a thalamic or dorsal column nuclear deficit. Motor dysfunction with these sensory symptoms occurs in a large majority of patients. This motor deficit first described by Foerster as an afferent paresis or tactile paresis (loathness to move). Partial pseudosegmental, pseudoradicular, cheiro-oral (posterior parietal operculum) pseudospinal patterns may be seen with parietal lesions. The usual pseudoradicular pattern is C6 or C8–T1. A pseudothalamic pattern (SI area) consists of deficits of elementary modalities of sensation with faciobrachial predominance (syndrome of Roussy and Foix). Spinothalamic type of sensory loss (BA 43, part of SMG and the posterior insula) may be seen. Patients may demonstrate asymbolia for pain, if the secondary somatosensory cortex (SII) is infarcted (adjacent to the lower extent of primary somatosensory cortex (SI)). Portions of the cortical sensory syndrome with loss of discriminative touch, position sense, astereognosis, ability to copy posture, sensory hemineglect (NDH) with preserved vibration sense may be seen with both anterior and posterior parietal branch infarctions. Corona radiata and occasionally SI infarction may cause a feeling of heaviness in the contralateral extremities and are associated with difficulty initiating and sustaining movement (disconnection of deep SI, BA 3b and BA 4) in the depths of the central fissure.

Angular Artery Branch

This artery supplies the posterior portion of the superior temporal gyrus, parts of the supramarginal and angular gyri and the superior lateral occipital gyri. The major features of infarction of this branch are the angular gyrus syndrome (Von Gerstmann). Frequently associated is anomic or transcortical aphasia, alexia without agraphia, an inability to cross the midline and constructional apraxia. Nondominant lesions are associated with:

• contralateral spatial neglect
• visuospatial and constructional deficit
• loss of opticokinetic nystagmus (eyes remain toward the ipsilateral side)
• hemianopia or inferior quadrantanopsia
• anosognosia (denial of illness)
• asomatognosia (denial of a limb)
• alloesthesia (perception of sensation on the normal side when the affected side is stimulated are seen)

If there is a short mainstem MCA, the lenticulostriate arteries may originate from the superior trunk. Infarction in this circumstance would involve the basal ganglia and the internal capsule.

Inferior Division of Middle Cerebral Artery

The general characteristics of an inferior division MCA infarction are:

• Wernicke's aphasia (DH)
• contralateral superior quadrantic VF deficit
• poor drawing and copying (NDH)
• agitation (NDH)

Ascending Temporopolar/Anterior Temporal/Middle Temporal Branch Occlusion

The anterior temporal artery supplies the anterior portion of the superior, middle, and inferior temporal gyri. The temporopolar artery complex supplies the anterior pole of the superior middle and inferior temporal gyri. The middle temporal group of arteries supplies the superior gyrus below the pars triangularis and pars opercularis as well as the middle portion of the middle temporal gyrus and posterior portion of the inferior temporal gyrus.

The clinical features of infarction of the anterior temporal branches are a contralateral homonymous superior quadrantanopsia. If on the dominant side, the visual field deficit may be associated with an anomic aphasia with category-predominant naming deficits. Nondominant infarction may cause hemispatial neglect and an acute confusional syndrome.

Temporo-Occipital/Posterior Temporal Branch Occlusion

These arteries supply the posterior half of the superior temporal gyrus and the posterior portions of the middle and inferior temporal gyri and the inferior portion of the lateral occipital gyri. These occlusions cause a contralateral superior quadrantanopsia or hemianopsia. Dominant hemisphere infarction of the posterior superior temporal gyrus causes Wernicke's aphasia. This infarction is frequently embolic and if pure (no other neurologic symptoms) is often caused by atrial fibrillation or another cardiac source. Nondominant hemisphere infarction produces an acute confusional state, contralateral hemispatial neglect and constructional apraxia.

Other Common MCA Occlusions of the Superficial Territory

Insular Branch Occlusion

The insula is supplied by the MCA trunk or proximal portions of its division and is rarely infarcted in isolation. Bilateral infarctions from seriatim strokes cause the Foix–Marie–Chavany syndrome which consists of severe apraxia for all of the muscles of branchial origin. Patients have difficulty swallowing, moving the face and tongue, buccal movements and initiating and articulating speech. This is a cause of aphemia which is a dramatic dysarthria that renders speech unintelligible. It may occasionally occur from unilateral insular branch occlusion.

Long Penetrating Medullary Artery Occlusion

Infarction of a group of long-penetrating arteries cause large infarcts in the centrum semiovale. Their origin is in the MCA pial branches and they usually cause a contralateral motor and sensory deficit as well as a noncongruent hemianopsia. If in the dominant hemisphere, patients are dysphasic while NDH lesions are associated with hemineglect and visuospatial deficits.

Infarcts of less than 1.5 cm in diameter cause pure motor or sensory strokes, ataxic hemiparesis without cognitive impairment or isolated involvement of face, arm or leg (fibers are widely separated). This fractionation is less common than with deep subcortical infarcts. Severe ipsilateral carotid disease produces the lesions by distal field ischemia or embolic disease.

Deep Territory MCA Infarction

The deep territory is composed of penetrating branches from the M1 and M2 proximal segments of the MCA which are known as the lenticulostriate arteries. If these arteries are infarcted, the process is usually embolic and occlusion of many perforators occurs simultaneously. This type of infarction is a striatocapsular infarction rather than a lacunar infarction in which only 1 lenticulostriate perforator is occluded. In general, striatocapsular infarction involves the head of the caudate, the putamen, and the lateral internal and external capsule and may extend into the corona radiata. The insular cortex and the thalamus is spared. Striatocapsular infarcts may involve the territory of Heubner's artery (recurrent branch from A1) or the anterior choroidal artery. In general, the area infarcted is in the range of 2–7 cm, is wedge or comma shaped, and is not ovoid as are the smaller lacunar infarctions. Cortical symptoms are rare and if present resolve quickly. The cortex is not infarcted due to leptomeningeal anastomoses. In situ thrombosis or cranial arteritis involving a segment of M1 that occludes multiple perforators is rare.

Acutely, patients present with predominantly motor or sensory motor hemiparesis with or without dysarthria. Hemiparesis results from damage to the posterior limb (mid 1/3) of the internal capsule (motor cortex corticospinal fibers) or if only the frontal part of the internal capsule is involved (the lateral premotor cortex corticospinal fibers or those from the SMA cortex in the genu) are involved.

The differential diagnosis of striatocapsular infarcts are:

• lacunar syndromes
• pure sensory stroke
• strokes in the basis pontis
• ICH of the striatum

If the leptomeningeal anastomosis fails patients may suffer cortical deficits which add to the underlying deficit and rule out lacunar stroke.

In striatocapsular stroke, cortical deficits such as aphasia or neglect resolve in the face of persistent motor or sensory deficits. In a moderate or large territorial or MCA branch occlusion the cortical deficits are more severe and long lasting. Extended striatocapsular stroke is most often associated with Wernicke's aphasia (involvement of insular or superior temporal gyrus). Rarely focal dystonia, contralateral choreoathetosis, or hemiballismus has been noted. Bilateral striatocapsular infarction may cause tetraplegia and akinetic mutism.

Striatocapsular Stroke

• Predominant motor or sensorimotor hemiparesis
• Minimal cortical signs and symptoms that resolve
• 2 to 7 cm in size
• Wedge or comma shaped
• Involves caudate, putamen, anterior or posterior limb of the internal capsule
• Rare contralateral movement disorder
• Rare tetraplegia with akinetic mutism (if bilateral)

Distal field infarction (or low flow state in the periventricular white matter) between the penetrating cortical branches and the ascending lenticulostriate branches that does not infarct the basal ganglia or internal capsule may mimic some of these findings.

If the head of the caudate nucleus, the putamen and the anterior portion of the internal capsule are infarcted the pattern represents that of occlusion of the recurrent artery of Heubner whose origin is the A1 segment of the ACA aberrant (medial lenticulostriate artery). The resultant hemiparesis has brachiocephalic predominance with tongue involvement. A similar infarction can occur from occlusion of the perforating branches of the most proximal portion of the A1 segment of the ACA artery. If the caudate head and the anterior limb of the internal capsule are involved, the eyes may be deviated ipsilaterally and the face and arm are more severely affected than the leg. Caudate infarction interrupts fibers that project to the frontal and dorsolateral prefrontal cortex and may be associated with an acute confusional, agitated or an abulic state. If the infarction extends anteriorly and destroys fibers that project to the medial dorsal and anteroventral thalamic nuclei, patients may have an expressive aphasia. Rarely with infarctions in this area patients demonstrate a hemisensory defect that affects the face and hand more severely than the leg. Dysarthria is more severe with left sided than right sided capsular lesions (corticobulbar projections to cranial nerves VII, X and XII). A noncongruent homonymous hemianopsias results from optic tract infarction. This may also be accompanied by a Behr's pupil (larger, poorly reactive pupil on the ipsilateral side).

The lateral lenticulostriate group of perforators takes origin from the M2 proximal middle cerebral artery segment and supplies the putamen, claustrum, external and extreme capsule and the insular cortex. Putaminal infarction causes brachiocephalic predominant weakness with increased tone and hyperreflexia but no sensory loss. Rarely putaminal infarction causes contralateral dystonia, choreoathetosis, and abnormal contralateral hand posture. Bilateral insular cortex infarction (insular branches of the MCA) produces the Foix–Chavany–Marie syndrome which causes apraxia of all branchial derived musculature and disrupts speech and swallowing. The dysarthria may be so severe that speech is unintelligible (usually requires bilateral infarction).

The Capsular Warning Syndrome

These are TIA's restricted to the face, arm and leg and are not often seen with severe carotid stenosis accompanied by a low flow state. The major clinical features are:

• Simultaneous sensorimotor involvement of face, arm and leg
• No neglect, dysphasia or dyspraxia
• Three or more clinical events within 24 hours
• Onset over seconds
• Pure motor hemiparesis is most common
• Sensory symptoms clear prior to motor signs
• Capsular infarction follows in approximately 40% of patients

As noted above, the capsule may be predominately involved in specific areas.

Capsular Genu Syndrome

• Contralateral facial, lingual and brachial weakness
• With or without ipsilateral horizontal conjugate eye deviation
• Rare thalamic aphasia

Midpoint Infarction of the Upper Capsule with Lower Corona Radiata Extension (Anterior 1/3 of the Posterior Limb)

Clinical Signs and Symptoms

• Dysarthria
• Contralateral clumsy hand
• Faciolingual weakness
• Blood supply is from the lenticulostriate arteries that concomitantly supply the upper ventricular wall (anastomosis with ependymal vessels)
• Posterior 1/3 limb of internal capsule infarction:
  • Middle third
    • Face < arm < leg weakness
    • Purely motor
  • Posterior 1/3:
    • Pure sensory
    • Arm, face, and leg involved
  • Arterial supply (lenciculostriate)
• Rare behavioral signs and symptoms of striatocapsular stroke are:
  • Fluctuating alertness
  • Inattention
  • Memory loss
  • Apathy
  • Frontal lobe deficits
• These deficits are caused by infarction of:
  • Inferior and anterior thalamic peduncles
  • Anterior limb of internal capsule

The Differential Diagnosis of Striatocapsular Infarctions

• Lacunar infarcts (1–2 perforating vessels)
• Pure sensory stroke (thalamic infarction)
• Infarction of the basis points (penetrating basilar branches)
• Small striatal or intracranial hemorrhage

If leptomeningeal anastomoses fail, or there is a concomitant shower of emboli, patients may suffer cortical deficits. As noted earlier, lack of cortical dysfunction is characteristic of lacunar stroke.

Clinical Differential Diagnosis of Capsular Infarction

• The first of frequent hemiplegic events is more likely capsular than pontine.
• Premonitory events are characteristics of anterior choroidal artery ischemia.
• Capsular ischemia: patients are aware of its onset; it resolves over seconds to minutes.
• Incipient occlusion of the ICA often is accompanied by repetitive events with cortical dysfunction.
• Hemodynamic events are posturally influenced and are shorter than embolic events.
• Artery-to-artery embolic events are more widely separated in time.

Rare Patterns of Stroke in the MCA Territory

Central sulcal branch artery infarction may cause a right pseudothalamic sensory loss (primary sensory modality involvement), ideational apraxia and conduction aphasia. Wernicke's aphasia and hemianopsia often follows embolic occlusion of the temporooccipital branch of the inferior MCA division particularly in the setting of atrial fibrillation. Precentral branch occlusion may cause transcortical motor aphasia, proximal weakness of the arm and ideomotor apraxia.

The anatomical variants of the middle cerebral artery, specifically the origin of the angular artery may determine unusual stroke symptoms following infarction in the MCA territory. Stenosis of the M1 segment of the MCA in conjunction with hypertension may cause periventricular longitudinal infarction.

Double infarcts are those that involve two components of one arterial territory. Aphasia without hemiparesis occurs when Broca's and Wernicke's area are infarcted leaving the motor strip intact. Hemiplegia with visual field deficits occur when the superior division (central sulcal branches) are occluded concomitantly with temporo/occipital branches (inferior division) thus sparing the primary sensory cortex. Conduction aphasia with hemiparesis has been noted with motor cortex and supramarginal gyrus lesions. Fragmentation of emboli at the MCA bifurcation or seriatim strokes are the most likely mechanisms.

Complete MCA Infarction (Superficial and Deep Territory)

Panhemispheric MCA occlusion is often embolic particularly if sudden. If it occurs with a slower or stuttering onset it is most likely due to carotid occlusion. These patients have cerebral swelling usually within 12 hours of infarction that impairs consciousness. Their head and eyes are deviated ipsilaterally, they demonstrate periodic or Cheyne–Stokes respiration, a flaccid contralateral hemiparesis and hemisensory deficit, homonymous hemianopsia and global aphasia (DH), or severe contralateral sensory neglect (NDH). The eyes are usually congruently deviated slightly below the horizontal due to pressure on the center for upgaze (the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF)that is ventral to the superior colliculus. In stem MCA infarction, edema is most severe at 3 days. Prior to herniation, patients may demonstrate an ipsilateral sluggish and oval pupil (pressure on the III nerve) as well as ipsilateral or bilateral ptosis (frontal eye field compromise).

Clinical Summary of Complete Superficial Territory Infarction

• Hemiparesis faciobrachial > leg
• Hemineglect for space and motor activity (NDH)
• Anosognosia (NDH)
• Asomatognosia (NDH)
• Spatial disorientation (internal/external/geographical) NDH
• Disorientation NDH > DH hemisphere
• Depressed reflexes contralaterally (acutely); rarely increased (cortical disinhibition)
• Babinski's sign contralaterally (ipsi or bilaterally if there is increased ICP)
• Angular gyrus syndrome (DH)
• Supra marginal gyrus syndrome (DH)
• Wernicke's aphasia (DH)
• Broca's aphasia (DH)
• Conduction aphasia (motor DH)
• Conduction aphasia (sensory DH)
• Alexia without agraphia (DH)
• Ideomotor/limb-kinetic apraxia D > NDH
• Ideational apraxia (DH)
• Alien hand syndrome (DH > NDH)
• Sympathetic apraxia or callosal apraxia (DH)

Superior Division MCA Occlusion (Bifurcation Pattern)

• Broca's aphasia (DH)
• Exner's area (severe inability to write) DH; Brodmann's area 45
• Parietal hand (updraft; loathness to move)
• Dysarthria
• Motor conduction aphasia (DH)
• Limb kinetic/ideomotor apraxia (DH)
• Alien hand syndrome (area6/DH)
• Brachiofacial pattern of weakness > leg weakness
• Depressed reflexes contralaterally
• Head and eye deviation (ipsilaterally)
• Babinski's sign contralaterally
• Frontal behavioral syndrome
• Apathy and abulia
• Brachiofacial crural weakness (rare)
• Phonemic paraphasia
• Rare cheiro oral sensory loss

Inferior Division MCA Occlusion (Bifurcation Pattern)

• Wernicke's aphasia (DH)
• Sensory conduction aphasia (DH)
• Supramarginal gyrus syndrome (DH)
• Angular gyrus syndrome (DH)
• Hemineglect for space (NDH)
• Depressed opticokinetic nystagmus (ipsilateral hemisphere)
• Depressed optic scanning (contralateral space)
• Constructional apraxia (NDH)

Prosopagnosia (NDH)

• Loss of higher cortical sensory function (contralateral)
• Ideational apraxia
• Posterior type alien hand

Summary of MCA Infarctions

• 2/3 of first brain infarcts involve the MCA
• 1/3 of MCA infarction involves the deep MCA territory
• 1/10 of MCA infarction involves both superficial and deep territory
• 50% are branch occlusions

Sentinel Differential Diagnostic Feature of Large Vessel Stroke of the Anterior Circulation

The hallmark of carotid disease is retinal involvement either embolic from burst plaques or artery to artery. Hollenhorst plaque material at a bifurcation of a retinal artery is pathognomonic. Horner's syndrome associated with a brachycephalic predominant lesion points to the internal carotid artery. Due to the circle of Willis collaterals may save a great deal of the hemisphere. Carotid siphon disease has no ocular pathology, but the anterior cerebral artery may be involved concomitantly with the middle cerebral artery. Emboli from the siphon may occlude the anterior cerebral artery and the inferior branch of the dominant middle cerebral artery sparing the major portions of the motor sensory cortex. This causes a Wernicke's aphasia with shoulder and leg weakness.

The anterior choroidal artery supplies aspects of both anterior and posterior circulations. The hallmark of its infarction is a quadruple sectoranopic defect that spares the central sector. The defect arises from infarction of the lateral geniculate body. Infarction of the uncus and components of its thalamic supply cause a deficit in short term memory and language processing. Hyperesthetic hemiparesis (thalamic) and hyperesthetic ataxic hemiparesis are patterns of infarction.

The usual pattern of anterior cerebral artery infarction is severe weakness and sensory loss of the foot, minimal involvement of the shoulder and face with excellent preservation of hand movement. The patient may be able to wiggle the thumb, but not the arm if the Az section is involved. If the recurrent artery of Heubner is infarcted and the patient demonstrates facio brachial predominant weakness. Involvement of the supplementary motor area (distal ACA) causes transcortical motor aphasia, mirror writing acquired stuttering and muteness. Muteness is often seen as well with sudden occlusion of the stem of the MCA. Medial frontal lobe infarction often causes euphoria, lability and iocularity. Anterior callosal involvement causes sympathetic apraxia (inability to follow commands with the left hand) and the anterior alien hand syndrome (inter manual conflict).

The major differential distinction of middle cerebral artery disease is that from internal carotid artery occlusion. TIAs in the middle cerebral artery distribution occur on awakening, are less frequent than carotid TIAs and once initiated occur over a shorter time period. They frequently fluctuate or progress over 1–7 days. The mechanism often is distal field ischemia so symptoms often vary with posture. There are no monocular symptoms. Characteristic of superficial territory involvement is hemiparesis and hemisensory deficit with brachycephalic predominance. The frontal eye fields are frequently involved (FEF) with no corresponding visual field deficit. Severe motor neglect and parietal visuospatial deficits are noted if the non-dominant parietal lobe is involved. The angular artery syndrome of Van Gerstmann localizes the lesion to posterior parietal territory if the DH is involved. The pre and frontal superficial branches of the superior division supply Broca's area (BA 44). The DLPC (dorsolateral pre frontal cortex) is also frequently involved and causes memory retrieval difficulties. Characteristic of inferior division infarction of the superficial territory is Wernicke's aphasia (pathognomonic of embolus if isolated and concomitant with atrial fibrillation) and agitation.

Deep territory middle cerebral artery territory infarction is characterized by internal capsule and basal ganglia infarction. The important differential point from superficial territory and carotid infarction is involvement of the leg, absence of eye deviation and the transient nature of any cortical deficits. This infarction causes a striatocapsular stroke with persistent motor sensory signs. The medial and lateral lenticulostriate group of arteries from the M1 and M2 segments of the MCA of the lateral group is involved. The putamen may be affected causing motor weakness, increased tone and reflexes without sensory loss. The capsular warning and genu syndromes may be seen prior to stroke.

Differential Diagnosis of Posterior Circulation Stroke

General Features

The posterior circulation can be considered the arch of the aorta, the innominate and subclavian arteries and vertebral, basilar posterior cerebral and their derivative arteries.

The arch of the aorta is a rich source of embolic material to the posterior circulation. Its prominence in this regard has recently been accentuated by transesophageal echo cardiography. A mobile grade V plaque is extremely dangerous as a source of embolus. Approximately 30% of emboli to the posterior circulations arise from this source. Emboli to both anterior and posterior circulations arise from the heart or the arch of the aorta in the great majority of cases. The embryologic connections from the carotid to the basilar artery are rare source of emboli. These include the persistent trigeminal artery, the otic, hypoglossal and pro-at canthal arteries. The most significant of these arteries is the persistent trigeminal which connects this top of the basilar to the carotid artery just below the siphon.

The vertebrobasilar system can be divided into diagnostic thirds. Each major artery has sentinel features that can guide diagnosis. Characteristic of a subclavian stenosis proximal to the origin of the vertebral artery is the subclavian steal syndrome. The patient uses the affected arm (left greater than right) which further lowers pressure in the arm (lower than that in the vertebrobasilar system) and blood flows to the arm from the vertebral supply. Most patients have a clear difference in blood pressure between the two arms and a significant decrease of pulse volume and clear lag of the pulse in the affected side. The syndrome usually causes more claudication in the arm than brainstem symptoms. It is rarely significant clinically.

A rare syndrome of ischemia of the brachial plexus and posterior circulation can occur from ischemia of the vertebral and axillary artery (feeds the plexus) that occurs simultaneously. Patients may complain of arm pain in the lateral or medial cord distribution, hand weakness concomitantly with lower brainstem, and cranial nerve symptoms.

Atheromatous occlusion with or without emboli may cause simultaneous carotid and vertebral artery symptoms on the right side. In general, the left carotid takes origin from the aorta and this will not occur on this side.

The common congential anomaly of the posterior cerebral artery taking origin from the carotid may cause complete hemispheric infarction if that carotid is occluded. The patency of the posterior communicating arteries may determine upper basilar perfusion if there is occlusion of the mid basilar or vertebral arteries.

Proximal vertebral artery disease is most common at the origin from the subclavian artery which is accessible to stenting and angioplasty. The most prominent clinical symptoms are dizziness, diplopia (VIth nerve), dysphagia, oscillopsia, bilateral leg weakness and sensory loss on the trunk. Isolated dizziness especially points to the labyrinth rather than the brainstem. The origin of the posterior inferior cerebellar artery is from the vertebral. It is most commonly involved due to occlusion of the parent artery. The sentinel features of its involvement are dysphagia, nausea and vomiting (out of proportion to dizziness), hoarseness, lateral pulsion to the side of the lesion). These patients have a great deal of difficulty walking which is out of proportion to their ipsilateral ataxia. Seventh nerve weakness (ipsilateral) may occur due to recurrent medullary fibers. Ipsilateral facial pain "salt and pepper" in Vth nerve distribution is characteristic.

Medial medullary infarction is suggested by contralateral flaccid paralysis of arm and leg (infarction above C2) or ipsilateral flaccid hemiparesis if ischemia involves the cervical medullary junction. Spasticity evolves within days to weeks and causes flexion of the upper extremity and extension of the lower extremities. The motor deficit is more severe distally in the upper extremity which is also typical for pontine infarction. Infarction of the pyramidal decussation may cause a crural paresis. The sensory loss is lemniscal, the face may be involved alone and rarely there is dissociation of position severe and vibratory loss. Upbeat nystagmus implies pontomedullary junction infarction. Respiratory dysfunction (Ondine's curse), mild ptosis with hypohidrosis and XIIth nerve involvement may occur.

Bilateral medial medullary infarction is manifest by flaccid quadriplegia, paralysis of the tongue, loss of lemniscal sensation, and cardiorespiratory failure.

Combined medial and lateral medullary infarction is suggest by ipsilateral involvement of IX, X, XI, XII a Horner's syndrome, contralateral lemniscal and spinothalamic sensory loss and hemiparesis. Ipsilateral ataxia is apparent if the patient is hemiparetic.

The most common infarction of the pons is ventral and occurs due to occlusion of the anteromedial or anterolateral branches from the basilar artery. These infarctions are suggested by the constellation of facio-branchial crural hemiparesis, brachiocrural ataxia (homo-lateral to the motor deficit), ataxic hemiparesis and the dysarthria clumsy hand syndrome. Ataxic hemiparesis and dysarthria clumsy hand occur more often in the middle and upper pons or at the ventrotegmental junction. Pontine hemiparesis is greater in the distal upper extremity than the lower extremity.

Pontine tegmental involvement is suggested by cranial nerve involvement (V, VIth) a depressed level of consciousness and an intranuclear ophthalmoplegia or 1 1/2 syndrome.

Tegmental pontine syndrome from occlusion of short circumferential vessels is headed by mild motor deficit, cranial nerve involvement V–VII, and lemniscal (medial) or spinothalamic sensory loss.

The major circumferential artery of the lower pons is the anterior inferior cerebellar artery. Infarction of this artery characteristically causes sudden ipsilateral hearing loss, ipsilateral ataxia arm greater than leg (the reverse of PICA), dizziness, ipsilateral VIIth nerve palsy (small artery to the facial nerve peripherally in the CPA angle) and contra lateral loss of pain and temperature of the limbs and trunk.

Mid basilar branch disease is suggested by the motor deficits with a fluctuating and progressive course, the ocular signs of horizontal gaze dysfunction, ataxic hemiparesis (level of the MCP) the clumsy hand dysarthria syndrome and classic lacunar syndromes.

Basilar artery thrombosis may have dizziness as the most frequent early symptom, a herald hemiparesis, alternating levels of consciousness to stupor or coma. Dysarthria, pseudobulbar symptoms, tongue paralysis are common. Pin point pupils and ocular bobbing are diagnostic. The locked in syndrome with maintained consciousness is pathognomonic of ventral pontine infarction.

The top of the basilar (distal 1/3) is commonly involved from embolic disease. The superior cerebellar artery and specific components of the posterior cerebral artery are involved and determine the specific symptoms and signs of the infarction.

The superior cerebellar artery brainstem territory is most often infracted in conjunction with the posterior cerebral artery. Severe dysarthria with various degrees of appendicular ataxia are characteristic. The associated components of the posterior cerebral artery often suggest the diagnosis.

The posterior cerebral artery supplies the medial temporal lobe, the midbrain (paramedian branches), the medial and lateral motor sensory thalamus, medial parietal lobe and the occipital cortex. Hippocampal formation ischemia from proximal PCA branch occlusion causes transient global amnesia. A similar amnestic syndrome, much longer lasting may also occur from dorsal medial thalamic ischemia from occlusion of the paramedian top of the basilar branch occlusion. Midbrain involvement from paramedian ischemia causes clonic syndromes involving the third nerve. Crossed hemiparesis is webers syndrome, crossed movement disorder is Benedict's, and Claude's is cerebellar ataxia. Disorders of vertical gaze such as 1 1/2 syndrome, dissociation of vertical and horizontal opticokinetic nystagmus and pupillary abnormalities are characteristic. A peduncular hemiparesis from cerebral peduncle infarction may simulate MCA infarction. The IIIrd nerve is not involved and the face may be spared. Rarely a nuclear IIIrd nerve syndrome is noted with bilateral ptosis, pupillary dilatation and failure of upgaze. Nystagmus retractorius may occur from vascular lesions of the periaquaductal ava but is more characteristic of dorsal midbrain pressure. Posterior cerebral artery thalamic involvement is characterized by stricking sensory involvement. The patient is aware of a midline split of sensory deficit. The leg may be involved first (VPL). The fingertip involvement of one hand is diagnostic of thalamic VPI nuclear involvement. Bilateral involvement of intraoral sensation is characteristic of VPM ischemia. Thalamic sensory loss includes vibration. This modality is never lost with a cortical lesion, but may be seen with dorsal column nuclear lesions. Thalamic motor involvement may be suspected from a characteristic thumb in the palm drift. Proprioceptive deficits combine with weakness. Ataxia of stance is characteristic of thalamic lesions that affect zones of proprioceptive and cerebellar input that converges in VL. Rarely dystonic postures are seen after UA/VL thalamic motor lesions.

Occipital lobe posterior cerebral artery involvement should always be suspected in the face of a dense congruent VF deficit of which the patient is aware. If there is visual neglect the patient has parietal lobe involvement. Deficits in optic scanning and visio-coordinative hand function and fixation gaze comprise Balint's syndrome that overlaps parietal and occipital posterior cerebral artery territories. Anton's syndrome of cortical blindness is manifest by visual confabulation euphoria and normal pupillary function. Specific field deficits such as a checkerboard field, quadrantic altitudinal deficits, macular sparing and temporal crescent of spared vision all point to PCA occipital lobe branch occlusions.

Lateral posterior choroidal artery infarction is suggested clinically by a homonymous quadrantanopsia. If the lateral geniculate body is involved, patients demonstrate a homonymous horizontal sectoranopia. There may be a concomitant transcortical aphasia and hemisensory deficit. This infarction is suggested by pulvinar involvement on MRI or CT.

Medial posterior choroidal artery infarction is less common than lateral PchA infarction and is suggested by nystagmus retractorius and a central Horner's syndrome. A mild hemiparesis and lemniscal sensory deficit may occur. CT or MRI of medial pulvinar involvement suggests this atrial territory.

The following is a detailed differential analysis of posterior circulation vascular infarctions.

Posterior Circulation

Occlusion or Severe Stenosis of the Subclavian and Innominate Arteries

Extracranial vertebral arteries (ECVA)

General Features

• Arise from the proximal subclavian arteries
• Subclavian steal syndrome:
  • Obstruction of proximal subclavian artery (prior to the origin of the vertebral artery):
    • Low pressure system within the ipsilateral vertebral artery
    • Blood supply of the ipsilateral arm is deficient. During exercise these blood vessels dilate which further lowers vascular resistance in the exercised arm
    • Higher pressure system:
      • Contralateral vertebral artery
      • Blood flows retrogradely down the ipsilateral VA into the arm (brainstem becomes ischemic)

Clinical symptoms

• Most patients are asymptomatic in the face of arterial demonstration of a steal
• Complaints relate primarily to arm ischemia:
  • Fatigue, achiness with exercise, autonomic dysregulation (coolness)
• Neurologic symptoms are more common with concomitant carotid disease
• 75% of patients are asymptomatic (demonstrated in Takayasu's disease)
• Rare neurologic symptoms (usually brief) occur:
  • Arm is used repetitively and often overhead
  • Blurred vision
  • Oscillopsia
  • Diplopia
  • Vertigo/spinning
  • Incoordination and imbalance

Clinical signs

• Delayed antecubital and wrist pulse on the stenotic ride
• Smaller pulse volume
• Supraclavicular bruit (rare)
• Inflation of blood pressure cuff on the ipsilateral side:
  • If the bruit is generated from ECVA the bruit increases as more blood flows through the stenosis (less reversal)
  • If the bruit is generated from the subclavian stenosis the bruit decreases (increased pressure of ipsilateral system because there is no arm "run-off")
• Clinical sequelae:
  • Stroke is rare with subclavian steal
  • Clots can form in a subclavian occlusion
    • Embolization to vertebral artery territory
  • Raynaud's phenomenon and autonomic dysregulation of the affected extremity may occur

Innominate Stenosis on the Right Side

• Decrease of carotid flow
• Exacerbated by cigarette smoking
• Women > men
• Associated with other large vessel occlusive disease
• Right subclavian steal < frequent than left
• Clot may spread from the innominate into the carotid arteries
  • Recurrent arm and brain ischemia
  • Floating thrombi within the innominate artery

Differential Diagnosis of Subclavian Artery Disease

• Takayasu's disease
• Severe atherosclerosis
• Aortic arch syndrome
• Syphilis (chronic aortitis)
• Cervical rib
• Giant cell arteritis
• Athletics that utilize a constant throwing motion

In Takayasu's disease, there is major inflammation and occlusion of the aortic arch vessels. Intermittent claudication of the arm is the most common symptom. Loss of vision with head position (precarious arterial supply to optic nerve head from posterior ciliary artery and central retinal artery compromise). Trophic loss of integument of the face and cataracts are common. Most patients with Takayasu's disease are asymptomatic in the face of an arteriographic steal.

Giant cell arteritis may compromise the great vessels at the arch with occlusion and stroke of the carotid artery. A cervical rib most frequently compresses the lower trunk of the brachial plexus with atrophy and weakness of the intrinsic hand muscles.

Vertebrobasilar Infarction

General Features of Lateral Medullary Territory Infarction

Proximal Vertebral Artery Disease

• General Characteristics:
  • Most frequent location of extra axial vertebral artery disease (ECVA) is at the origin from the subclavian artery (accessible to stenting and angioplasty)
  • ICA and ECVA stenosis frequently are affected concomitantly
  • Occurs in Caucasians > Asian and African Americans
• Clinical Features
  • Most common symptom is dizziness
    • Extremely rare for this symptom to be solitary
    • TIAs are not precipitated by arm movement as is the case with subclavian-steal syndrome (on rare occasions)
  • Diplopia
  • Dysphagia
  • Oscillopsia (environment moving)
  • Hemiparesis
  • Bilateral leg weakness
  • Sensory loss on the trunk
• Hypoplastic congenital vertebral and basilar arteries coexist:
  • Patient suffers posterior circulation ischemia
  • L-vertebral artery 80% of the time dominant over right
  • Complete atresia of a vertebral artery is rare

Lateral Medullary Territory (Posterior Inferior Cerebellar Artery)

• Direct penetrators from the distal vertebral supply the lateral medulla and cerebellum
• Posterior inferior cerebellar artery (PICA) supplies the lateral medulla and inferior cerebellum including the floccular nodular lobe
• Posterior inferior cerebellar artery (PICA) frequently overlaps AICA territory or forms an AICA/PICA artery that supplies both territories
• Variable: PICA/AICA supply to the lateral medulla or portions of the pons
• Lateral medullary syndrome: most often occurs from occlusion of the distal perforators of the vertebral artery (VA)
• If coexisting, AICA involved: middle cerebellar peduncle involved (core territory)
• If coexisting, PCIA involved: lower cerebellum infarcted
• Dorsal medulla supplied by branches of PICA (two posterior medullary arteries)

Clinical Signs and Symptoms of Lateral Medullary Infarction

• General:
  • 40% are sudden (ictal)
  • 60% a gradual or stepwise pattern over 24–48 hours
  • 25% of patients have had a preceding TIA in the same arterial territory
• Cranial Nerve Abnormalities:
  • Dysphagia (rostral nucleus ambiguous)
  • Hoarseness (caudal N. ambiguous)
  • Crowing cough (N. ambiguous)
  • Nausea and vomiting:
    • Vestibular nuclei
    • N. tractus solitarius (NTS)
    • Vomiting out of proportion to dizziness
  • Ipsilateral Horner's Syndrome
    • Descending central sympathetic fibers
  • Hiccoughing (singultus; NTS)
  • Ipsilateral VII nerve dysfunction
    • Occurs in 33–50% of patients. This is due to two groups of recurrent VII nerve fibers
    • In the upper medulla an origin that recurs through the lateral medulla
    • Fibers that leave the pyramidal tract (at the decussation in the medial medulla and course rostrally to the contralateral tegmentum
  • Lateral medullary infarction lateral recurrent fibers of VII are infarcted
  • dysarthria caused by faciopalatal-glossal dysfunction and cerebellopetal pathways
• Visual Signs and Symptoms
  • Blurred vision
  • Oscillopsia (with acute infarction)
    • Environment appears to move with patient's nystagmus (usually horizontal)
  • Vertical, horizontal or oblique diplopia
    • Disruption of the ocular tilt reaction (OTR)
  • Incyclotropia
    • Cyclorotation abnormalities (clockwise or counterclockwise eye rotation)
    • Disruption of the vestibulo-ocular response (VOR)
  • Horizontal and rotary nystagmus is most prominent to the ipsilateral side
  • Skew deviation-ipsilateral eye down (otic-oculomotor pathways)
  • Hypermetric saccades to the ipsilateral side (flocculo-nodular lobe of the cerebellum); hypoactive saccades to the contralateral side
  • Deviation of the subjective visual vertical (SVV) to the ipsilateral side (internal concept of the body's vertical position)
• Motor Signs
  • Ipsilateral hemiparesis (Opal ski's Syndrome)
    • If the pyramidal fibers below the decussation at C2 are involved
  • Contralateral hemiplegia occurs with the combined lateral and medial medullary syndrome; no weakness with pure PICA infarction
  • Most often there is ataxia without weakness
• Sensory Signs and Symptoms
  • Ipsilateral facial pain and sensory loss
    • Touch, temperature, pain, cold decreased (ipsilateral V)
    • Loss of ipsilateral corneal reflex (V)
    • "Salt and pepper" facial paresthesia and pain
  • Far lateral medullary infarction of the spinothalamic tract (STT)
    • Crossed hemisensory loss to pinprick and temperature on the contralateral body below the clavicle
  • More medial infarction of the lateral medullary STT
    • Contralateral loss of pinprick and temperature of the face, trunk, and upper limb (the ipsilateral STT from the arm, trunk and leg) and the crossed ventrotegmental ascending fibers that cross medially in the medulla that subserve the contralateral face
  • Medial medullary infarction
    • Bilateral facial hypalgesia with variable contralateral sensory loss (dog's nose pattern)
    • "Onion skin" facial sensory loss
      • Nose involved
      • Preauricular area spared
      • Maybe seen as well with V nerve entry zone lesions
• Headache
  • Occipital
  • Unilateral
  • Non-throbbing
  • Vth nerve origin of trigeminal pain afferents to the dura, proximal blood vessels and sinuses (somatic visceral convergence)
• Brainstem Dysfunction
  • Autonomic dysregulation
    • Cardiac arrhythmia
    • Blood pressure variability
      • Lateral medullary vasomotor center
      • Most often postural hypotension
  • Respiration
    • Sleep apnea
    • Failure of automatic breathing Ondine's curse
      • Disruption of oscillations of lateral and medial respiratory neurons
      • Afferent disruption of IX and X pulmonary afferents (Herring-Breuer reflex) may be carried centrally in STT
• Cerebellar Syndrome
  • Gait and ipsilateral limb ataxia
  • Axial lateropulsion (if restiform body involved from concomitant medial branch infarction); patient is pushed to the side of the lesion

Unilateral Medial Medullary Infarction (Dejerine's Syndrome)

• Less than 1% of posterior circulation strokes
• Branch occlusion from the VA

Motor Signs and Symptoms

• Flaccid hemiparesis
  • Contralateral if above C2
  • Ipsilateral if the infarction spreads to the cervical medullary junction
• Spasticity within days to weeks
  • Flexion of upper extremities
  • Extension of the lower extremities
• Rarely weakness can be minimal or absent
• Rarely upper limb monoparesis
  • Fibers after decussation may be lateral
• Motor deficit is more severe distally in the upper extremity (also typical for pontine infarction)
• Patterns of weakness at the level of the pyramidal decussation
  • Leg fibers may cross anteriorly and then remain lateral to arm fibers
  • Some studies – arm fibers decussate anteriorly to leg fibers
  • Crural paresis:
    • Proximal portion of the limbs affected with finger and toe movements preserved
    • Hemiplegia cruciata
      • Arm involved ipsilaterally with contralateral leg weakness
  • Pontine recurrent pathway may be infarcted with facial weakness

Sensory Signs and Symptoms

• Contralateral lemniscal type sensory loss of the hemibody with or without the face
• More marked distally
• May involve the face only
• Pseudospinal dropped sensory level on the trunk
• Dissociation between vibration and position loss
  • Vibration may be involved with more lateral extension
• Pain sensation
  • Occasionally decreased with preserved temperature, sensation, and mild hypesthesia

Cognitive Dysfunction

• Medial reticular formation involvement:
  • Apathy
  • Somnolence
  • Hallucinations
  • Delirium
• Pathologic laughing and crying with infarction of:
  • Internal capsule
  • Pons
  • Pyramidal tract (usually bilateral)
  • Bilateral temporal lobe (usually trauma)
  • Medial frontal lobe (laughing)

Ophthalmologic Signs

• Upbeat nystagmus:
  • Dorsolateral medulla or pontomedullary junction infarction that spares the medial medulla
  • Ipsilateral MLF or perihypoglossal nuclei are involved in upgaze
  • Horizontal nystagmus (ipsilateral) or multiple directional nystagmus related to vestibular nuclear involvement or their connections to the cerebellum in the lateral medulla
  • Rare – ocular bobbing (usually a pontine lesion)

Lateral Pulsion

• Contralateral lateral pulsion
  • Dorsolateral medulla and cerebellum are not involved
  • Patient feels as if he is pushed to the side
  • Lesion at the level of the restiform body or alivary nuclei

Respiratory Dysfunction

• Ataxic breathing
• Decrease of voluntary control of breathing secondary to corticospinal destruction and lack of intercostal muscle control
• Loss of automatic breathing (Ondine's curse)

Autonomic Dysregulation

• Mild ptosis with hypohidrosis
  • Severe miosis (0.5 mm pupil) with pontine infarction
  • Dissociation of ptosis and pupillary sympathetic fibers is due to a somatotopic arrangement of sympathetic fibers around the N. ambiguus
• Bladder retention or inhibited contractions only occur with bilateral MMI

Cranial Nerve XII

• Isolated contralateral XII nerve
• More common with hemorrhage than infarction

Isolated Drop Attacks

• May progress to stroke over several days
• Ischemia of:
  • Medullary or pontine corticospinal fibers
  • Medial reticular formation involvement (loss of tone)

Differential Diagnosis of Vascular Etiologies of Unilateral Medial Medullary Infarction

• Branch occlusion from VA (upper medulla)
• Dolichoectasia of vertebrobasilar system
• Embolus
• Syphilis
• Branch occlusion from the anterior spinal artery (lower medulla) secondary to atheroma
• of the VA or anterior spinal artery

Underlying Associated Conditions

• Diabetes mellitus
• Birth control pills
• Dissection of VA in 3/4 of patients
• Thrombosis of VA in 3/4 of patients
• Embolus in 1/4

Bilateral MMI Infarction

• Clinical Features:
  • Quadriplegia (flaccid)
  • Associated loss of lemniscal sensation
  • Paralysis of the tongue
  • May have step wise progression
  • Bladder retention or uninhibited contractions
  • Death by cardiorespiratory failure
• Differential diagnosis:
  • Anomalous anterior spinal from one vertebral artery
  • Occlusion of the ASA after it forms a single vessel

Medial and Lateral Syndrome (Babinski–Nageotte)

• Clinical features of combined LMI and MMI:
  • IX, X, XI, XII ipsilaterally
  • Horner's ipsilaterally
  • V ipsilateral (most often STT modalities)
  • Ocular findings (LMI and MMI)
  • Contralateral hemiparesis; may be ipsilateral (depending on infarction below decubation be C2)
  • Lemniscal and STT sensory loss (contralateral)
  • Ipsilateral ataxia

Pontine Infarction

• General Features
  • Isolated pontine infarction occurs in 15% of acute vertebrobasilar strokes
  • The territory supplied by intrinsic pontine vessels is constant
  • In 1/3 of patients TIAs precede stroke onset:
    • Spontaneous laughing and crying spells – "Fourier prodromique"
    • Herald hemiparesis
    • Pseudoseizure – tonic limb spasms with consequent paresis

Ventral Infarction of the Pons

• Most common type; approximately 55% of pontine infarcts
• Occlusion of anteromedial or anterolateral arteries (from the basilar artery)
• Localized to the middle or lower pons
• May involve the medial tegmentum
• Rarely reaches the floor of the IVth ventricle

Ventromedial Pontine Syndrome

• Large infarcts: anteromedial or anteromedial and anterolateral territories
• Facio-brachial crural hemiparesis with dysarthria
• Homolateral (to the motor deficit) brachiocrural ataxia; occasionally contralateral curral ataxia
• Dysarthria with medial infarction at the level of the MCP

Ventrolateral Pontine Syndrome

• Smaller infarction in anterolateral territory
• Pure motor hemiparesis (PMH); leg representation is dorsolateral
• Ataxic hemiparesis (AH)
• Dysarthria clumsy hand (DCH) syndrome
• AH and DCH occur in the middle upper pons; in the ventrolateral pons, or at the ventrotegmental junction
• Dysarthria (posterior 1/3 of ventral pons; medial)

Patterns of Weakness in Pontine Hemiparesis

• Greater in the distal upper extremity than lower extremity
• Less commonly the leg has distal weakness greater than the arm
• Crural or brachiocrural paresis with preservation of finger and toe movement
• Arm fibers – disrupted by more dorsal lateral lesions
• Leg fibers – disrupted by more lateral lesions
• Facial palsy associated with palato-glossal weakness – involvement of pontomedullary bundle
• Dysarthria more common in left pontine infarction
• Isolated dysarthria and facial weakness are rare
• Correlation of severity of motor deficits and contralateral ataxia
• Ataxia – involvement of corticopontocerebellar fibers (Türck's tract); make up the MCP

Ventral Pontine Infarcts and Tegmental Involvement

• 3/4 of patients – associated medial tegmental dysfunction, usually mild and transient
  • Lemniscal sensory deficit
  • Vth nerve weakness
  • Decreased level of consciousness
  • Fascicular VIth nerve palsy
  • Intranuclear ophthalmoplegia
  • One and a half syndrome (abduction alone of the contralateral eye)
• Collateral vascularization of short and long circumferential vessels is the explanation for transient nature of tegmental signs
• isolated dorsal pontine syndrome is rare, suggests nonischemic etiology

Tegmental Pontine Syndrome

• Represent approximately 30% of pontine infarctions
• Small lacunar infarcts
• Mediolateral tegmental area of the middle upper pons; occlusion of short circumferential vessels
• Mild motor deficit
• Eye movement disturbance
• Lemniscal or spinothalamic sensory loss
• Cranial nerve palsy V to VII

Ventrotegmental Pontine Syndrome

• Combination of lateral and medial tegmental signs
• Intranuclear ophthalmoplegia with severe motor deficit

Lateral Pontine Syndrome (Long Circumferential Cerebellar Arteries)

• AICA or superior cerebellar artery infarction
• Lateral pontine syndrome of Marie-Foix is rare
  • Homolateral cranial nerve palsies are rarely seen

Pontine Pure Motor Hemiparesis (PMH)

Clinical features of pontine hemiparesis:

• Dysarthria, vertigo, gait abnormality
• Lacunar process (spares the basal surface); if the basal surface is involved this suggests a branch artery occlusion
• Approximately 60% have transient symptoms
• Midpontine – primarily upper limb involvement
• Mild dysarthria-corticobulbar fibers are affected
• Contralateral cerebellar ataxia (25% of patients)

Pontine Ischemic Rarefaction (MRI Evaluation)

• Hypertensive vascular changes
• Increased perivascular changes
• Perivascular demyelination
• Gait instability
• MRI increased T2 pontine signal

Pontine Signs

• Horner's syndrome (lateral involvement)
• Hypogeusia (ipsilateral taste loss)
• Hemiataxia (MCP)
• Oculopalatal pharyngeal myoclonus
  • Mollaret's triangle
  • Disruption of fibers between the inferior olive, dentate nucleus and the VL nucleus of the thalamus
• Contralateral STT sensory loss

Isolated Tegmental Pontine Infarcts

• Supranuclear eye movement disturbance
• Sensory deficit: one limb; cheiro-oral pattern
  • Abducens palsy (isolated)
  • Facial palsy (isolated)

Bilateral Ventrotegmental Infarcts

• Least common of isolated pontine infarcts (11%)
• Associated with extension or multiple brainstem infarction
• Acute pseudobulbar palsy
• Bilateral motor deficits with tegmental signs
• Para and tetraplegia
• Ataxic tetraparesis
• Locked in syndrome:
  • Awake
  • Unable to move
  • Upgaze and eye closure maintained

Basilar Branch Disease

• Nonlacunar (maximal diameter > 1.5 cm)
• Unilateral ventral infarct extending to pontine surface
• Bilateral infarcts: atheroma of the basilar artery wall occludes one or more perforators
• Motor deficits with fluctuating and progressive course
• Small artery disease: tegmental or small ventral infarcts do not extend to the surface of the pons;
  • Classic lacunar syndrome

Clinical Signs and Symptoms of Basilar Artery TIA Prior to Infarction

• Increasing TIA frequency
• Diplopia, vertigo, blurred vision, ataxia, gait disturbances, hemiparesis
• Confusion and somnolence; to stupor and coma
• Motor abnormalities, pupillary abnormalities, hyperreflexia, bilateral Babinski signs

Clinical Signs and Symptoms of Basilar Artery Thrombosis

• Herald hemiparesis
• Dizziness most frequent early symptom
• Dull, non-throbbing headache (basiocciput)
• Alternating levels of consciousness (confusion to stupor)
• Dysarthria, pseudobulbar symptoms, paralysis of the tongue, emotional lability
• VI and VII cranial nerve palsies with contralateral hemiplegia and paraesthesias
• Bilateral pontine infarction symptomatology
• Ocular bobbing, ocular dipping, <0.5 mm pupils

Midbrain Infarction

• Paramedian arteries
  • Isolated third nerve palsy
  • Nuclear third nerve: bilateral ptosis; bilateral pupillary dysfunction (large): bilateral failure of upgaze (superior rectus palsy)
• IIIrd nerve and contralateral hemiplegia (Weber's Syndrome)
  • Supranuclear gaze palsy; mydriatic or miotic pupil depending on sympathetic involvement; occasional sensory dysfunction: P1 segment of the PCA is infarcted (medial 3/5 of the cerebral peduncle infarcted); patients are awake; hemiparesis may spare the face
  • Concomitant thalamic and occipital lobe involvement may occur
• IIIrd nerve plus cerebellar signs
  • IIIrd nerve palsy and contralateral cerebellar dysfunction is Claude's Syndrome. Basilar paramedian artery (dentatothalamic projections are involved)
  • IIIrd nerve palsy plus contralateral abnormal movements (Benedict's Syndrome). Tremor (rubral, large amplitude at right angle to the line of movement); chorea (paramedian artery; infarction of the red nucleus, dentatothalamic fibers often with third nerve paralysis)
  • The closer the infarction is to the red nucleus, the greater the tremor and failure of extremity postural fixation
• Supranuclear conjugate vertical gaze palsy
  • Median or paramedian infarction of the upper midbrain
  • Superior cerebellar artery: infarction; destruction of:
    • Periaqueductal grey matter
    • Posterior commissure
  • Single trunk (paramedian thalamic mesencephalic artery of Percheron) infarcts involves the medial and subthalamic (STN) areas bilaterally as well as the upper midbrain
  • Upgaze paralysis:
    • Posterior commissure, riMLF (rostral interstitial nucleus of the MLF); PAG
  • Down-gaze palsy:
    • Bilateral upper midbrain infarction; more caudal than upgaze palsy (above the red nucleus; Pasik's syndrome)
  • Combined up and down gaze palsy:
    • Bilateral or unilateral midbrain infarcts
    • Unilateral lesion of the riMLF may decrease conjugate vertical gaze
  • Supranuclear disconjugate vertical gaze palsies:
    • Monocular elevation palsy
    • Vertical one and a half syndrome
    • Infarction of paramedian upper midbrain

Neurophthalmological Deficits

• Skew deviation (lesion is on the side of the down eye)
• Tonic ocular-tilt reaction (incyclotropia or excyclotropia) dysfunction
• Intermittent corectopia (pupillary size changes)
• Upper lid retraction (Collier signs; increased upper lid retraction on down gaze; central caudal nucleus of the IIIrd nerve involved)
• Ptosis with intranuclear ophthalmoplegia
• Convergence retraction nystagmus (PAG; and involvement of the periaqueductal grey area)
• Dissociated vertical gaze palsies

Associated Clinical Midbrain Signs

• Gaze palsies with:
  • Coma and hypersomnia
  • Akinetic mutism
  • Disorientation to time and place
  • Antegrade amnesia
  • Motor and multimodal neglect
  • Faciobrachial hypesthesia
  • Transcortical motor aphasia
  • Delayed athetoid or clonic movements

Specific Stroke Syndromes

• Classic lacunar syndromes from midbrain infarcts (Weber's; Claude's, Benedict's, Masugi's)
• Lateral midbrain involvement of the cerebral peduncle (P1-PCA) pure motor stroke
• Dorsolateral midbrain: hemiparesis, hypesthesia, ataxia

Midbrain Locked-in-Syndrome

• Bilateral lateral midbrain infarction
• Midbrain hematoma-pure sensory stroke (rare)

Hemiplegia with Posterior Cerebral Artery Occlusion

• Proximal P2 infarction
  • Hemiplegia
  • Visual disturbance
  • Neuropsychological abnormalities
  • Mimics MCA occlusion

Rare Stroke Syndromes from Midbrain Infarction

• Subthalamic small deep infarcts
  • Abnormal movements and asterixis
  • Unilateral or bilateral ballistic movements
  • Blepharospasm
• Cerebellar syndromes
  • Rostral and lateral red nucleus infarcts with cerebellar syndromes
  • Unilateral ataxia with superior cerebellar infarct (SCA) with rostral midbrain signs
  • Superior cerebellar decussation syndrome (ataxia of all extremities); infarction of the decussation of the brachium conjunctivum (Windekink's commissure; level of the IVth nerve at the inferior colliculus)
• Masugi's syndrome
  • Ipsilateral IIIrd, IVth nerve
  • Ipsilateral ataxia (SCP)
  • Contralateral hemiparesis
  • Contralateral hemisensory defect
  • Infarction of the superior cerebella artery or branches of lateral and medial posterior choroidal arteries
• Peduncular Hallucinosis
  • Vivid visual hallucinations; objects moving (kaleidoscopic); peculiar dress
  • Rarely auditory hallucinations
  • Often occurs at sundown

Posterior Circulation Major Artery Strokes (Long Circumferential Arteries)

Superior Cerebellar Artery Infarcts

• General Features:
  • Rarely involve the brainstem territory of the SCA; usually partial; good outcome
  • Early and delayed edema (one week); brainstem compression with tonsillar herniation if edema is severe (4–7 days; pseudotumoral presentation)
  • Associated infarction in other territories with complete SCA infarction (usually that of PCA)
    • Rostral territory of the basilar artery
    • Unilateral or bilateral occipitotemporal lobe infarction
    • Thalamic; subthalamic and mesencephalic infarcts
    • Rare upper ventral pontine infarction
    • 1/3 occur with PICA and AICA infarction
    • Partial SCA infarcts most frequently involve the rostral superior cerebellar artery territory
    • Some SCA infarcts occur with MCA infarcts due to emboli

Clinical Features of SCA: 6 Clinical Patterns

• Classic SCA
  • Occur in 3%
  • Involves the brainstem territory of SCA
  • Ipsilateral limb dysmetria
  • Ipsilateral Horner's syndrome
  • Contralateral IV nerve involvement
  • Contralateral loss of pain and temperature
• Unusual signs and symptoms of classic SCA infarction
  • Ipsilateral loss of mimetic facial
  • Unilateral or bilateral hearing loss (nucleus of lateral lemniscus)
  • Sleep disorder (locus ceruleus)
  • Ipsilateral choreiform, athetotic or coarse tremor
  • Head tremor or unsteadiness of the head
  • Palatal myoclonus; may be associated with myoclonus of the tongue, vocal cord, jaw and face
• SCA infarction with top of the basilar artery involvement
  • Vomiting, dizziness, visual field deficits, diplopia, paraesthesia, ataxia, weakness and drowsiness
  • Occipitotemporal lobe concomitant involvement:
    • Cortical blindness and hemianopsia (Anton's syndrome)
    • Balint's syndrome
    • Memory loss or confusion
  • Thalami-mesencephalic infarction
    • Thalamic multimodal sensory loss; latter possibly Dejerine Roussy syndrome (VPL)
    • Contralateral Horner's syndrome
    • Appendicular ataxia (ataxia of stance); involvement of cerebellar thalamic projections
    • Behavioral abnormalities: abulia, contralateral spatial neglect, memory loss, transcortical motor aphasia
  • Midbrain infarction (concomitant)
    • Claude's, Benedict's, Weber's, Nothnagel's Syndromes, Masugi's
    • Parinaud's Syndrome
    • Pseudo VIth nerve, gaze paresis or deviation, Collier's sign, pupillary abnormalities (light near dissociation, inverse Argyll–Robertson pupil, miosis or mydriasis, corectopia)
    • Drowsiness, peduncular hallucinosis, confusion
    • Hemiballismus (subthalamic involvement)
• Coma at initial presentation
  • Tetraplegia and III nerve palsy
  • Embolic occlusion of basilar tip
• SCA involvement with ICA infarction
  • Aphasia
  • Brachiofacial sensorimotor hemiplegia
  • Cardiac embolism; occlusion of innominate artery with embolism to right MCA and vertebral artery with propagation to SCA
• Cerebellar vestibular syndrome
  • Occipital headache and gait ataxia
  • Dizziness and vomiting
  • Nystagmus (most often horizontal to affected side) or contralaterally; rarely vertical
  • Dysarthria-cardinal symptom of SCA infarct
  • Hemiparesis in 25%
• Lateral SCA Syndrome (anterior rostral territory)
  • Arm and leg dysmetria
  • Ipsilateral axial lateropulsion
  • Dysarthria
  • Nystagmus; saccadic overshoot (ipsilaterally)
• Medial SCA syndrome
  • Most medial branch: unsteadiness of gait
  • Lingula, culmen, centralis lobules (anterior cerebellar lobe) appendicular ataxia (legs affected more than arm), head tilt (ipsilateral)
  • Paraverbal involvement: dysarthria; left sided paravermal zone of rostral cerebellum causes consistent dysarthria

Differential Diagnosis of Causes of SCA Infarction

• Cardiac embolic source
• Artery-to-artery embolus
• • Vertebral artery
  • Aortic arch
• Vertebral dissection
• In young patients
  • SCA dissection
  • Fibromuscular dysplasia (FMD)
  • Patent foramen ovale (PFO)

Anterior Inferior Cerebellar Artery Infarction

• Origin: first 1/3 of the basilar artery
• Brainstem signs at presentation
• Involved territory: lateral caudal pons; middle cerebellar peduncle (always involved)
• Supplies the inner ear: internal auditory artery from which derive the anterior vestibular artery; common cochlear artery
• 70% involve the anterior inferior flocculus
• AICA and PICA may arise from a common trunk from the vertebral or basilar artery
• Anastomosis between the AICA and PICA – constant when both arteries have equal dominance
• AICA dominance on one side; then consequent ipsilateral vertebral PICA hypoplasia
• Infarction of the inferolateral pons; may extend up to the middle third of the lateral pons or down to the superior part of the lateral medulla
• AICA infarction: may be associated with PICA and SCA infarction with consequent ventromedial pontine infarction

Clinical Signs and Symptoms

• Prodromal vertigo (minutes); dizziness, dysarthria
  • Ipsilateral peripheral VIInd nerve (small artery to facial nerve in CPA angle)
  • Hearing loss (sudden) ipsilaterally
  • Ipsilateral Vth nerve involvement
  • Horner's syndrome (ipsilaterally)
  • Ipsilateral appendicular dysmetria (arm > leg)
  • Contralateral loss of pain and temperature of the limbs and trunk
  • Delayed facial paralysis

Unusual Signs

• Ipsilateral conjugate or lateral gaze palsy (floccular involvement)
• Dysphagia (superior part of the lateral medulla)
• Ipsilateral motor weakness (involvement of the corticospinal tract in the pons or mesencephalon contralaterally)
• Periodic alternating nystagmus

Coma

• Tetraplegia (massive ventromedial infarction of the basis pontis)
• Cerebellar infarction PICA/AICA/SCA distribution
• Isolated vertigo mimicking labyrinthitis; infarction of the internal auditory artery or its superior vestibular division
• Isolated cerebellar signs

Differential Diagnosis of SCA and AICA Infarction

• Atherosclerotic lower basilar artery occlusion
• Occlusion of the vertebral artery above PICA
• Vascular anomalies of the vertebrobasilar system:
  • Persistent trigeminal artery with embolus from carotid system
  • Dolichoectasia of the basilar artery
  • Hypoplastic vertebral artery
• Pure AICA: a basilar branch occlusion; plaque in the basilar extends to occlude its origin; micro atheromata block the origin of the artery
• Migraine (Bickerstaff variant)
• Extracranial and intracranial vertebrobasilar dissection:
  • Intradural dissection:
    • Subadventitial hematoma of the basilar artery causes:
      • Subarachnoid hemorrhage
      • Brainstem stroke
      • Pseudoaneurysm
      • May occur silently
  • Extracranial dissection
    • Hematoma within the media or intima
    • Emboli at the site rather than a blood flow limiting process cause symptoms
• Post operative cerebellar and brainstem stroke:
  • Signs and symptoms:
    • Altered consciousness; stupor, restless agitation
    • Vestibulocerebellar syndrome
  • Differential diagnosis:
    • Neck positioning during or after surgery
    • Thrombus that embolized from compressed arteries
• Hypercoagulability after surgery
  • Increased thrombin activity
  • Increased fibrinogen
  • Increased factor VIII
  • Decreased fibrinolytic activity
  • altered platelet function

Posterior Cerebral Artery (PCA) Infarction

Vascular Territory Supplied by the PCA

General

• Major blood supply of: midbrain, thalamus, occipital lobes, part of the posterior inferior parietal lobe
• The arterial segment prior to the posterior communicating artery fusion with the basilar artery is the P1 segment
  • 10% of PCAs take origin from the carotid artery (fetal origin). If this occurs, there is a concomitant hypoplastic P1 from the basilar artery
• 29% of patients have large or (24%) unusually small PCA arteries

Vascular Supply

• Vascular supply of the P1 segment (peduncular or pre communal segment; between the tip of the basilar artery and the posterior communicating artery) is:
  • Medial midbrain; posteromedial thalamus
  • Origin of the paramedian mesencephalic arteries (take off is the top of the basilar)
• Tuberothalamic (polar arteries)
  • Origin is the posterior communicating artery
  • Anterior and anterolateral thalamus
  • Tuber thalamic artery may be absent. Its territory is then supplied by the thalamic subthalamic artery (thalamoperforating arteries)
• P2 segment is the origin of the peduncular perforating (PPA); thalamogeniculate arteries (TGA)
  • Thalamoperforate artery supplies:
    • Lateral midbrain
    • VA and VL of the motor thalamus
    • Part of the internal capsule
    • VPL, VPM of the thalamus
  • Thalamogeniculate artery supplies the ventrolateral thalamus: arteries arise from the ambient portion of the PCA
  • Anterior temporal artery arises from the ambient portion of the PCA and supplies the medial temporal lobe
  • Posterior temporal artery (origin between the tentorium and the medial temporal lobe)
  • Parietooccipital artery: originates form the ambient segment; supplies the occipital and medial inferior parietal lobe); this branch is the origin of the posterior pericallosal artery
  • Calcarine artery
    • Usually arises as a single branch of the PCA
    • In 16% of patients the calcarine artery arises from the parietooccipital artery

Clinical Symptoms and Signs of Unilateral PCA Ischemia and Infarction

• PCA stenosis:
  • TIA's precede infarction
  • Usually atherosclerotic narrowing
• General Features of PCA Infarction:
  • Ambient section is affected most frequently which causes a hemispheric branch occlusion
  • P1 segment – 13% of PCA occlusions
  • PCA with thalamic involvement – 37% of infarctions
  • Occipital, parietal and posterior temporal branch arteries are frequently involved concomitantly
  • Anatomic areas involved: medial midbrain, posteromedial thalamus, lateral thalamus, and posterior hemisphere
  • Penetrating arteries from the top of the basilar artery may arise from one PCA (artery of Percheron) and therefore the thalamic infarction may be bilateral and paramedian:
    • Infarctions are usually embolic from the heart, proximal aorta and the proximal vertebral arteries (to the top of the basilar artery)
    • Patients that have suffered rostral paramedian tegmental mesencephalic and posteromedial thalamic infarcts are comatose, hyper somnolent and may demonstrate vertical gaze palsies and an amnestic state

The distinguishing features of proximal PCA infarction (P1 precommissural branch) are:

• Hemiplegia, infarction of the cerebral peduncle (medial 3/5); may spare the face
• Paramedian mesencephalic and PPA arteries are involved
• Partial or complete III nerve palsy
• Nuclear III rd nerve signs include:
  • Bilateral ptosis (central caudal nucleus)
  • Failure of upgaze bilaterally (superior rectus is bilaterally innervated)
  • Dilated pupils
  • Rare
• Midline infarctions: patients are lethargic and abulic

Ambient Segment (P2) Infarction (Thalami Perforating Artery)

Occlusion is proximal to the origin of the thalamogeniculate artery:

• Vascular supple to the motor thalamus
  • Ventroanterior, ventrolateral nuclei
  • VOA, VIM, VOP (stereotactic nomenclature, part of VL)
    • VIM is the target for stereotactic surgery to relieve tremor)
• Motor symptoms:
  • Contralateral 4–6 HZ tremor
  • Usually sudden onset of choreoathetosis:
    • Frequent arterial involvement of diabetic patients
  • Rare contralateral dystonia
  • Thalamic hand
  • More medial lesions in this territory cause thalamic ataxia
    • Interrupt cerebellar projections (dentatorubral loop)
    • "ataxia of stance"

Thalamogeniculate Artery Infarction (TGA)

• Infarction of the lateral thalamus and posterior temporal lobe is known as the syndrome of Foix–Hillman
• Pathogenesis: trunk PCA occlusion (multiple penetrating branches involved) or single atheromatous branch occlusion

Symptoms of Ventrolateral Thalamic Infarction (thalamogeniculate artery, TGA)

• Sensory symptoms
  • Leg may be involved most severely; pattern of face, arm and leg
  • Conscious perception that the symptoms bisect the body (face, trunk, penis)
  • Intraoral involvement (may be bilateral)
  • Quality of sensation: tingling, pricking, crawling, burning (active dysesthesias and paraesthesias)
  • Loss of pinprick, touch, or thermal sensation. May lose vibration sensibility which is rarely lost with cortical infarction. The other location for vibratory loss is the dorsal column nuclei.
  • If medial, ventrolateral or thalamoparietal projections are involved:
    • Proprioceptive, thermal sensory loss, decreased pain
  • Tips of the fingers of the contralateral hand (VPI nucleus)
• Slight hemiparesis
• Clumsiness and ataxia (dentate thalamic projections)
• Choreiform and ataxic limb movements (contralateral)
• Thalamic hand posture
• Clinical symptomatology of thalamic pain:
  • Delayed onset (months after VPM/VPL infraction)
  • Hyperpathic
  • Mechanical and thermal hyperalgesia and allodynia of the affected area
  • Spontaneous
  • If provoked-not stimulus bound
• Associated infarcts in the temporal and occipital lobes if midbrain and thalamus are involved

PCA – Hemispheral Infarction

• Visual field loss:
  • Most common defect – contralateral homonymous dense VF loss
  • Infarction may occur in: lateral geniculate body, optic radiations, or the striate cortex
  • 50% of patients are aware of the deficit
  • If unaware of the deficit there is parietal lobe involvement
• Acute or with resolution of VF defect:
  • Photopsias, colors, and hallucinations in the affected field
• Usual VF deficits: congruent contralateral hemianopia, inferior or superior quadrantanopsia
  • Macular sparing often noted (middle cerebral artery supply)
  • Involvement or sparing of the contralateral visual temporal crescent (anterior most portion of the calcarine fissure subserves the most peripheral temporal field)
  • Homonymous central scotomata (occipital pole infarct)
  • "Checker board" deficit (one inferior quadrant with contralateral superior quadrant)
• Complex visual phenomena
• Visual Perseveration
  • Object seen in sighted field-then noted in the defective hemifield although gaze fixation maintained
  • Object in sighted field appears in the defective hemifield after gaze is shifted to defective field
  • Palinopsia (perseveration of an object)
  • Motion detection in blind field but no ability to discriminate (Riddoch's object phenomena)
  • Defects in distance, depth and localization in the defective hemifield
• Sensory symptoms of PCA hemispheric infarction
  • Paraesthesia, numbness or loss of pain; thermal or positional sense loss

Higher Cortical Deficits from Hemispheric Infarction

• Dominant Hemisphere: parieto-occipital and or temporal branch occlusion:
  • Alexia without agraphia patients; write, speak, and spell normally. They cannot read words or name colors (damage must include left occipital cortex and splenium of the corpus callosum). Can read letters and numbers. Cannot access Wernicke's area
  • Alexia with agraphia
    • Angular gyrus or white matter of the inferior parietal lobule involved
    • Abnormalities of reading, writing, and spelling
• Inferior parietal lobule infarction
  • Decreased ability to read letters and paragraphs
  • Decreased spelling and writing
  • Components of Gerstmann syndrome are noted: dyscalculia, finger agnosia, right left confusion, and dysgraphia and conduction aphasia. The latter may be accompanied by paraphasia
• Paralexia
  • DH: reading errors to the right side of words
  • NDH: reading errors at beginning of words
• Visual agnosia
  • Dominant hemisphere
  • Concomitantly with alexia and agraphia and decreased color naming
• Amnesia
  • Involvement of left hippocampus and adjacent white matter

ND Hemisphere – PCA Infarction

• Neglect of contralateral visual field
• Constructional apraxia (parietal and temporal lesions)
• Right posterior parietal lesion-disorientation for geographical space
• Reduplicative paramnesia (two versions of a geographic location)

Mechanisms of Unilateral PCA Infarction

• Embolism: cardiac, proximal vertebral artery, arch of aorta, fetal origin of PCA
• Emboli arise from the end of atheromatous plaques of recently occluded proximal vertebral artery
• African Americans and Asians patients: infarction is more frequent in context of stenosis with in situ thrombosis
• Migraine
• Coagulopathy
• Transtentorial herniation – temporal and calcarine branches compressed against the tentorium

Bilateral PCA Infarction

• Infarcts often restricted to bilateral inferior or superior calcarine branches

Clinical Syndromes

• Cortical blindness (Anton's syndrome)
  • Bilateral infarction of the striate cortex
    • Anton's syndrome
      • Denial of blindness
      • Maneuver around objects (visual crescent remains, bilateral hemianopsias or scotomata)
      • Visual confabulation
      • Normal pupillary reaction to light
      • Euphoria
• Balint's Syndrome (Superior Parietal and Occipital Lobe)
  • Simultagnosia (patients see objects piecemeal); cannot describe the entire object)
  • Optic ataxia (lack of coordination of hand eye movements; usually under reaching the object)
  • Apraxia of gaze (inability to look at an object on command)
  • Difficulty in breaking fixation of gaze
  • Poor visual scanning of areas of interest
  • May be limited to one visual field
• Amnesia
  • Bilateral infarction of the temporal lobe
  • Amnesia occurs concomitantly with visual sensory loss and acute depression of level of consciousness
• Emboli and infarction (below calcarine fissure)
  • Upper quadrant altitudinal defect
  • Abnormal color perception
  • Difficulty in recognizing faces (prosopagnosia)
  • Inability to re visualize the form of an object; able to re visualize direction and place relationships of objects
  • Agitated delirium (involvement of the lingual and fusiform gyri, inferior temporal lobe)
  • Central achromatopsia (may perform adequately on Ishihara plates) unable to match hues or colors
  • Agitated delirium (left posterior inferior temporal lobe)
  • Emboli to tip of the basilar artery have predilection for inferior calcarine branches
• Bilateral Superior Bank Infarction
  • Severe hypotension (MCA/PCA border zone) is the usual mechanism
  • Less common than lower bank infarcts
  • Disorientation to place, difficulty in revisualization of locations (where people and places are topographically)
• Pathogenesis of Bilateral PCA Infarction
  • Seriatim infarction; stenosis of arteries from atherosclerosis
  • Simultaneous; embolus to top of the basilar artery or from thrombus in the basilar artery
  • Capillary-leak syndrome (primarily white matter) of the occipital lobe
    • Hypertensive encephalopathy
    • Cyclosporine and FK 506 (tacrolimus)
    • Uremia
    • Eclampsia
    • Dissection of distal basilar artery

Infarction of the Lateral Posterior Choroidal Artery (L PchA)

• Lateral geniculate body (LGD)
• Pulvinar and posterior thalamus
• Hippocampus and parahippocampal gyrus

Clinical syndromes of lateral PchA infarction

• Homonymous quadrantanopsia
• With or without hemisensory loss
• Homonymous horizontal sectoranopia (lateral LGD)
• Memory loss
• Delayed movement disorder
• Transcortical aphasia

Specific visual field deficits

• Wedge or tubular homonymous sectoranopia with delayed sectorial optic atrophy
• Lower or upper quadrantanopsia more common but less specific with LGD infarction
• Wedge or tubular sectoranopia also possible with AchA, MCA, PCA infarction
• Visual field deficits with concomitant anatomical lesions of the LGD

Correlative anatomy of the lateral geniculate body

• Anterolateral LGD subserve lower quadrants
• Anteromedial LGD subserve medial quadrants
• Posterior LGD subserve the macula
• Central LGD: supplied by lateral posterior choroidal artery
  • VF defect: homonymous horizontal sectoranopia
  • Supplied by PchA
• AchA also supplies the LGD

Visual field deficits

• Quadruple sectoranopia is characteristic
• Complete homonymous hemianopia
• Superior quadrantanopsia-may have macular sparing
• Homonymous hemianopia
  • Sparing of the horizontal sector
  • Inferior lateral LGD infarction
• Homonymous superior-quadrantanopsia
  • Lateral geniculate infarction
  • Infarction of:
    • Optic tract
    • Origin of the geniculocalcarine tract

Differential Point Between AchA vs PchA Infarction by VF

• PchA
  • Homonymous horizontal sectoranopia
• AchA
  • AchA-middle horizontal sector is spared

Ocular Motility Deficits with PchA Infarction

• Impairment of ipsilateral pursuit
• Poor contralateral saccades

Sensory Symptoms with PchA Infarction

• Involvement of thalamic radiations of the internal capsule or damage to ventroposterior nucleus (caudal part)

Motor Symptoms of PchA Infarction

• Damage to corticospinal or corticobulbar fibers in the internal capsule (PchA)
• AchA more severe hemiparesis than PchA

Aphasia and Higher Cortical Deficits (PchA)

• Transcortical motor aphasia – pulvinar damage
• Transient visual and verbal memory disturbance
• Disorientation for time without confusion or confabulation
  • May also be seen following thalamic stereotactic surgery
• Abulia
• NDH lesion:
  • Visual spatial processing deficit with dorsal lesions

Thalamic Stroke with PchA Infarction

• Neuropsychologic deficits
• Pulvinar infarction on CT/MRI
• Paramedian infarction; tuber thalamic artery involvement (concomitant)

Visual Hallucinations (PchA)

• Paramedian thalamic infarction

Medial Posterior Choroidal Artery (M PchA)

General Features:

• Territory supplied: medial pulvinar; dorsomedial thalamus; anterior thalamic nuclei
• Less common than lateral PchA infarcts

Clinical Signs and Symptoms

Ocular Signs (Midbrain)

• Nystagmus retractorius
• Up gaze or horizontal gaze paralysis
• Meiosis
• Central Horner's syndrome

Sensory Loss (MpchA)

• Lemniscal or spinothalamic

Motor Symptoms

• Mild hemiparesis

Pathogenesis (MpchA)

• HCVD and DM
• Cardiac embolism, large artery disease, migrainous stroke, catheter induced thrombosis

Differential Diagnosis of M PchA vs PchA vs AchA

• M PchA:
  • sensory loss is noted acutely with later onset of pain and abnormal movements
• Movement disorder:
  • Choreoathetotic myoclonic syndrome
  • Pseudobulbar tremor
  • Dystonic posture of the fingers
  • Dystonic thalamic hand worsened by voluntary activity
  • Akathisia
• L PchA infarct
  • Sectoranopia VF deficit
• AchA infarct:
  • Quadruple sectoranopia VF deficit
  • Greater hemiparesis than L PchA stroke

Border Zone Infarction

Border zone infarctions occur between two or three arterial territories during prolonged periods of hypotension or cardiac arrest. The infraction may occur between pial conducting vessels or internally between ascending vessels that are feeding deep nuclear structures and descending penetrating vessels. They tend to be symmetric and occur in characteristic areas. There are internal laminar infarctions between the capillaries that are the functional metabolic columns of the brain. An O₂ molecule diffuses approximately 10μ from the hemoglobin of its 7μ RBC. These 10μ constitute the functional intercapillary metabolic zones of the brain. Patients less than 40 years of age have infarctions in the anterior circulation while older patients tend to infarct the border zones of the posterior circulation. Specific syndromes have been described for many of these infarctions. The "man in the barrel" suggests an anterior cerebral/middle or cerebral artery border zone infarction. The shoulder on upper arm components of the homunculus are involved. These patients have preserved intrinsic hand muscle function. Posterior MCA/PCA infarction may cause Balint's syndrome of infarction of the superior parietal lobule. These patients have a simultagnosia, poor optic scanning, failure to break fixation and optic ataxia. Ascending lenticulostriate and penetrating medullary vessels from pial conducting vessels cause the periventricular vascular stripe. Leg fibers may be preferentially affected. Isolation of the speech area suggests serve cortical hypoxia, carbon monoxide poisoning or hypotension. Ischemia of the optic nerve head from poor perfusion of the central retinal artery and posterior ciliary artery with giant cell arteritis and prolonged hypotension. Border zone infarcts of the brainstem do not demonstrate clear patterns of anatomical localization as those of the anterior circulation.

The following discussion is of the differential diagnosis and characterization of border zone infarcts.

Border Zone Infarcts

• Infarctions at the junction between two or three arterial territories
  • watershed infarcts
    • Between two arterial territories with a reciprocal arteriolar collateral network:
      • In the hemisphere between two pial networks
    • End artery border zone infarcts
      • Terminoterminal infarcts

Differential Diagnosis

• Stenosis or occlusion of extracranial arteries
• Initiating factors: bradycardia, high hematocrit, systemic hypotension, drop in cerebral perfusion pressure
• Systemic hypotension due to:
  • Cardiac surgery
  • Bilateral symmetrical distributions
  • More common in posterior watershed zones (MCA/PCA)
• Systemic disease
  • Artery-to-artery cholesterol microemboli
  • Sickle cell anemia
  • Polycythemia vera
• Clinical features of border zone infarcts
  • Rare headache
  • Syncope at onset
  • Dizziness in brainstem zones

Anterior Border-Zone Infarction (MCA Territory)

• Clinical patterns
  • Motor weakness of the contralateral leg > arm with spared face; shoulder weakness
• DH infarcts:
  • Transcortical motor aphasia
  • No initial mutism (more for stem or SMA occlusion)
• NDH: mood disturbance usually mild or absent
• Proximal arm weakness with preserved distal movement and strength if limited to the cortex "Man in the Barrel" if bilateral:
  • Severe shoulder proximal weakness
  • Preserved strength and fine movement of the hand
  • Preserved movement of the thumb; extremely rare in core MCA territory. Thumb may be spared in posterior motor knuckle syndrome
  • Similar pattern may occur with multiple emboli from MI stenosis

Internal Watershed

• Homolateral carotid stenosis with M1 in situ stenosis:
  • Ischemia of periventricular white matter
  • Sensorimotor stroke
  • Occurs in a setting of severe systemic hypotension
• Patients with ICA occlusion have no border zone infarction in this distribution if there is collateral flow through the posterior communicating artery

Deep Cerebral Infarcts Extending to the Subinsular Region

• Extend between the lateral ventricle and subinsular region
• Paraventricular region extends for 7.5 cm
• Subinsular extent of 1/3 of the anterior posterior extent of the insula
• Clinical features
  • Hemiparesis
  • Aphasia (transcortical conduction type)
  • Dysphasia
  • Dysarthria
• Clinical features overlap with paraventricular infarcts
• Deep cerebral infarcts (DCI) > paraventricular infarcts
  • Risk factors:
    • Cigarette smoking
    • HCVD
    • Large artery occlusion (ICA; MCA)
• Larger size of DCI
  • Poorer collateral blood supply

Posterior Border-Zone Infarction (MCA/PCA Territory)

• Lateral homonymous hemianopsia or lower quadrantanopsia
• Transcortical sensory or Wernicke's aphasia
• No pure alexia
• NDH: hemineglect and anosognosia
• Brachiofacial hemiparesis or no motor deficit
• Hemihypesthesia and cortical sensory loss

Capsular-Thalamic Border Zone Infarction

• Deep border zone between the carotid and vertebrobasilar circulation
• Ischemic area is between the internal capsule and lateral thalamus
  • Also territory between the ascending lenticulostriate arteries from the MI segment of the MCA and the descending pial MCA arteries (medullary arteries)
• Clinical signs and symptoms
  • Brachiofacial paresis
  • Corresponding sensory loss (cortical type)
  • DH: subcortical aphasia
• Vascular stripe on MRI
  • T2 weighted signals periventricularly

Bilateral Hemispheric Border Zone Infarction

• Transient loss of consciousness (global hypoperfusion)
• Bilateral motor and sensory loss
• No dysconjugate eye movements (I & O or 1 1/2 syndrome)
• Bilateral cortical anterior border zone: "man in the barrel" syndrome (proximal arm muscles weakness)
• Deep subcortical white matter: paraparesis or plegia (spinal stroke pattern); motor cortical fibers to lower extremities (infarction of the centrum semiovale)
• Bilateral posterior border zone infarction
  • Balint's syndrome (optic ataxia)
  • Anton's syndrome (cortical blindness)
  • Visual disorientation and hallucinations

Border-Zone Cerebellar Infarction

• General Features:
  • Less than 2 cm in diameter
  • Between SCA and PICA boundary zones
  • Between left and right SCAs on the cortex
  • Between SCA and PICA branches in the deep cerebellar white matter
• Involved Territories
  • Cortical border zone infarcts
    • Perpendicular to the cortex
    • At boundary zones between
      • SCA and PICA territories
      • AICA-PICA
      • Medial PICA–lateral PICA
      • Medial PICA-SCA
      • Medial SCA–lateral SCA
    • Between the medial rostral territories of the right and left SCA territories
  • Deep watershed territory:
    • Caudal cerebellum
    • Deep boundary zones of AICA–lateral PICA, medial PICA–lateral SCA and medial SCA territories
    • Appear as round holes above the dentate nucleus;
    • Rare cortical dorsal border zone infarcts between PICA and SCA territories
• Clinical Features
  • Similar to territorial infarcts
  • Rarely: transient loss of consciousness; pitching sensation; dysequilibrium
  • May represent low flow state of the posterior circulation
• Differential Diagnosis of Pathogenesis (BZI)
  • Focal hypoperfusion from severe occlusive disease of the vertebral or basilar artery secondary to atherosclerosis
  • Rarely generalized hypotension

Border-Zone Brainstem Infarction

• Hypotensive setting
• Symmetrical necrosis of the tegmentum
  • Between pontine penetrating vessels and short and long circumflex arteries
• Clinical picture
  • Cranial nerve/brainstem dysfunction
  • Coma

Granular Cortical Atrophy

• Multiple small foci of cortical infarction in all border-zones

Lacunar Stroke

Lacunes are small ovoid lesions 1–2 mm in size noted in deep nuclear grey matter of the basal ganglia and thalamus as well as the internal capsules, centrum semiovale and pons. They are found in the setting of poorly controlled diabetes and hypertension. They are caused by fibrinoid necrosis of the endothelium and adventia of the single perforating arterioles. The infarct is limited to the territory of deep perforators and is caused by in situ infarction. The process may also be caused by atheromatous occlusion of the mouth of these blood vessels. If a series or group of perforators are involved simultaneously emboli are suspected as causal (thus most often occurs in the lenticulostriate territory).

Discrete clinical syndrome are noted with infarctions of these perforators which outline their territory and allow anatomic localization.

Involvement of arm, face, and leg suggests lacunar infarction of the middle 1/3 of the posterior limb of the intend capsule. Genu involvement is suggested by more face than arm involvement and severe dysarthria. The posterior 1/3 of the capsule may be selectively involved with hemisensory numbness. Occasionally, a single extremity may become weak from involvement of the medullary strica arteries is then perfuse the centrum semiovale. The motor and sensory fibers are separated in the fiber deep into the brain. The dysarthria clumsy hand syndrome occurs from posterior ventral 1/3 pontine infarction in which the corticobulbar fibers, speech and arm fibers are closely opposed. Ataxic hemiparesis suggests pontine lacunar involvement at the midpontine level.

Lacunar infarctions rarely ever are associated with headache VF cut or aphasia. Pine motor, pure sensory and mixed deficits are common. There is no cortical sensory, behavior manifestations which differentiates this from pial artery stroke. Puremotor hemiparesis with III nerve pattern (Weber, Benedict; Claude's and Nothnagel's) places the lesion in the midbrain. Rarely hemiballisms occurs from lacunar infarction of the subthalamic nucleus due to paramedian thalamic involvement. Lacunes of basilar artery territories are suggested by dizziness, diplopia, and intranuclear ophthalmoplegic without weakness.

Lacunar Disease

• General Features:
  • Involvement of the territory of one single perforating arteriole
  • <1.5 cm lesion on CT or MRI; (ovoid in shape)
  • Infarct is limited to the territory of the deep perforators
  • Caused by in situ small vessel disease
• Infarcts limited to the territory of deep perforators may occur with:
  • Cardiac emboli
  • Ipsilateral internal carotid artery stenosis or occlusion
• Diabetes is a major risk factor for lacunes
• The most suggestive clinical syndrome for lacunar infarction:
  • Pure motor hemiparesis with face, arm and leg involvement
• Arterial networks that supply subcortical territories:
  • Deep perforating branches form the ACA
    • Recurrent artery of Huebner (A2)
    • Direct anterior lenticulostriate branches
  • Deep perforating branches from the anterior choroidal artery
  • Thalamic arteries from P1 and P2 segments
    • Interpeduncular (top of the basilar)
    • Thalamoperforate
    • Thalamogeniculate
    • Posterior choroidal artery
    • Tuberothalamic artery (from the posterior communicating artery) These arteries are perforators, but have collateral branches and are not terminal branches
  • White matter medullary arteries
    • Originate from the superficial (pial) branches of the MCA > ACA > PCA
    • 2–5 cm long
    • Selective territories
    • No collaterals
    • Subserves the centrum semiovale
    • Do not anastomose with the deep perforators (lenticulostriate arteries)
  • Cortical arteries with subcortical territories that supply:
    • U fibers
    • Extreme capsule
    • External capsule
    • Claustrum
  • Most commonly found:
    • Centrum semiovale
    • Basal ganglia
    • Thalamus
    • Midbrain
    • Pons
    • Medulla

Infarction in these territories are often not lacunar (i.e., from one perforator) but may be secondary to distal field ischemia (carotid stenosis) or cardiac thromboembolism.

Epidemiology of Lacunar Stroke

• Lacunes – 20–30% of ischemic strokes
• Blacks and Hispanics 2× incidence of whites
• No increase in HCVD, DM, cigarette smoking, hypercholesterolemia or TIA compared to other ischemic strokes
• Some series a 40–50% incidence of ischemic heart disease
• If a specific lacunar syndrome is present: there is an 87% chance the patient has suffered a lacunar stroke
• Predictive value for lacunar stroke
  • Pure sensory stroke 100%
  • Highly correlated
    • Ataxia, hemiparesis
    • Sensorimotor stroke
• Ataxic hemiparesis can occur from: corona radiata, pons, basal ganglia or thalamus infarction
  • Pontine site is the most frequent
• 25% of lacunes are due to a non-lacunar mechanism
  • Atherosclerosis
  • Cardiac source of emboli
    • 10–15 perforators are affected simultaneously
    • Larger size

Clinical Presentation of Lacunar Infarction

General Features

• Occur more commonly during sleep
• Arm, face, leg may be affected separately (corona radiata and pons most common areas of infarction)
• Pure motor, pure sensory or mixed clinical patterns
• Rare aphasia (a differential point against lacunar stroke)
• No headache
• No visual field deficit
• May have stuttering course over 2–3 days
• No cortical sensory or behavioral manifestations (strong differential point for lacunar stroke)
• Cause of multi-infarct dementia (état spongiosis)

Clinical Patterns of Lacunar Stroke

• Pure sensory stroke (PSS) (primarily thalamus)
• Pure motor hemiparesis
  • Corona radiata
  • Middle internal capsule
  • Cerebral peduncle (medial 3/5)
  • Ventral pons
  • Medullary pyramidal
    • At decussation with cruciate pattern (ipsilateral arm; contralateral leg)
• Ataxic hemiparesis (AH) (pontine grey – MCP and descending CST)
• Dysarthria clumsy hand syndrome (pons)
• Pure motor hemiparesis sparing the face (farther posterior in the middle 1/3 of the posterior limb of the internal capsule)
• Mesencephalic; decreased upgaze (Nothnagel's syndrome)
• Thalamic dementia (DM, AV nuclei)
• PMH with horizontal gaze palsy – lower 1/3 of pons, PPRF (para pontine reticular formation)
• PMH with III nerve (Weber's syndrome)
• PMH with III nerve and ataxia – Claude's syndrome (midbrain)
• PMH with III and movement disorder (Benedict's) (midbrain)
• PMH with VI nerve palsy (Ramon's syndrome); pons
• PMH with confusion (brainstem RF; thalamus AV/DM)
• Sensorimotor stroke (thalami-capsular)
• Hemiballism – (STN; paramedian mesencephalic vessels)
• Lacune of basilar territory (dizzy, diplopia, gaze dysfunction)
• Lateral medullary partial infarction (penetrators from the vertebral artery)
• Lateral pontomedullary territory (partial AICA)
• Loss of memory (DM nuclei of thalamus); paramedian perforator
• Locked in syndrome (infarction of ventral pons; bilateral cerebral peduncles)
• Unusual lacunar syndromes
  • Weakness in one leg with falling (corona radiata; ventral portion of ventral pons)
  • Pure dysarthria – posterior 1/3 of ventral pons
  • Acute dystonia (thalamoperforate to basal ganglia)

Differential Diagnosis by Arterial Territory and Anatomical Structure of Pontine Stroke with Lacunar Infarction

• Paramedian arteries
  • Medial basis pontis
  • Ventral tegmentum
    • Corticospinal tract
    • VIth cranial nerve fibers as they exit
    • Facial nerve fibers as they exit
    • Rare PPRF (para pontine reticular formation by extension)
• Short circumferential arteries
  • Lateral 3/5 of the pons involved
• Long circumferential arteries
  • Lateral tegmentum
  • Tectum
    • Cerebellar projections
    • Vth and VIIIth cranial nerves
    • Part of sensory lemniscus infarcted
• Large bilateral pontine infarcts
  • Basilar artery lesions
    • PPRF, 1 1/2 syndrome
    • Ocular bobbing and dipping
    • < 0.5 mm pupils
    • Decreased consciousness
    • Decerebration
    • Hyperactive reflexes
    • Babinski signs

Differential Diagnosis Between Pontine Hemorrhages vs. Infarction

• Ischemic:
  • Prior TIA
  • Stuttering clinical course

• Hemorrhage:
  • Abrupt headache
  • Nausea and vomiting
  • Meningeal imitation
  • Rapid decrease of consciousness
• Lacunar syndrome may be due to hemorrhage or infarction; isolated small hemorrhage may be associated with:
  • Dysarthria clumsy hand syndrome
  • Pure sensory stroke
  • Ataxic hemiparesis

Clinical Presentation and Patterns of Pure Motor Hemiparesis

• Motor Cortex
  • Hand and arm representation is in the precentral gyrus "motor knuckle"
    • C5–C6 roots are represented medially
    • C8–T1 are more lateral
  • Infarction frequently appears as a pseudo radial palsy (wrist drop)
  • Embolic pathogenesis from the internal carotid artery
  • Rare that face is involved in isolation
  • Cranial nerve III or VI involved with pure hemiparesis, ataxia or movement disorder
  • Medullary pyramid-flaccid hemiparesis that spares the face
• Ataxic Hemiparesis or Corticobulbar Dysfunction
  • Ataxic hemiparesis
    • Infarction of the descending corticospinal tracts and pontine crossing fibers (comprises the middle cerebellar peduncle)
    • Leg more severely affected than the arm
  • dysarthria – clumsy hand syndrome
    • Corticobulbar fibers to the X and XII nerve with contralateral ataxia of the hand and arm
    • III nerve palsy with contralateral ataxia (Claude's syndrome); contralateral movement disorder (Benedict's); failure on up gaze Nothnagel's)
• Pure Sensory Stroke
  • Lacune in the centrum semiovale (deep penetrating medullary arteres)
    • Usual feeling of numbness or heaviness.
  • Infarction of ventrobasilar thalamic complex (VPM or VPL):
    • Patients may describe numbness, paraesthesias, formication or pain
    • Bilateral intraoral loss of sensation (VPM). This is to be differentiated from a vascular brainstem stroke in which patients may feel numbness on one side of the tongue. VPL involvement may present as numbness of the trunk and extremities in 20% of patients. Dysesthetic, paraesthetic and burning occurs more often in the involved territory. Later this territory may be associated with the hyperpathia of Dejerine-Roussy syndrome (thalamic pain). Associated thermal and mechanical allodynia and hyperalgesia are frequently present concomitantly with this syndrome. Thalamic lesions respect the midline and may involve vibration sensibility. Exception is bilateral decreased periumbilical sensation
  • Thalamic-capsular lacunar infarction most often causes sensorimotor stroke. Feeling loss is perceived as numbness and heaviness
  • Involvement of the ventral medial spinothalamic tract (quintothalamic tract) by lacunar infarction at medullary levels causes unilateral or bilateral facial pain or numbness (onion skin distribution)
• Hemiballism – infarction of at least 2/3 of the corpus Luysi (subthalamic nucleus. Usually thalamoperforate or paramedian thalamic penetrating artery is occluded.)
• Tetraplegia (locked in syndrome)
  • Patients are fully awake
  • Quadriplegic
  • Able to blink and look up and down on command
  • Unable to perform lateral eye movements
  • Involvement of the basis pontis (basilar artery) or the cerebral peduncles (bilaterally)
    • P1 segment of the PCA's
• Patterns of lacunar weakness
  • Weakness in one leg with falling
    • Basis pontis (ventral portion of ventral pons)
    • Posterior corona radiata fibers
  • Pure dysarthria: corona radiata, internal capsule, cerebral peduncle; basis pontis
    • No difference in dysarthria
    • Imprecise articulation of labials and glottals
    • Monotonous voice
    • Slowed rate
    • Pontine or medullary areas more severe
    • Left paraverbal cerebellar lesions
      • Coordination of articulation and respiration is disrupted
  • Acute dystonia
  • • Thalamus (VA, VL, or VIM)
    • Putamen

Rarer Lacunar States

• Loss of memory
  • Anterior thalamic nuclei
  • Anterior limb of internal capsule that involves anterior thalamic efferent fibers
• Thalamic dementia (dorsal medial nucleus from paramedian infarction)
• Pure motor hemiparesis sparing the face
• Multiple lacunar infarctions:
  • Primarily in the basal ganglia
  • "État" Lacunaire
• Dysarthria, facial, lingual paresis
  • Genu capsular syndrome
• Cerebellar lacunes
  • Unusual small round lesions in the watershed between SCA, PICA, AICA
  • One case of giant lacune in the cerebellum
  • SCA greater deep territory supply from AICA or PICA
  • Large artery occlusion, cardiac embolic, end artery lesion

Multiple Infarctions

The differential diagnosis of multiple infarctions is usually suggested by the clinical setting. Not surprisingly many patients in the course of their evaluation for their first clinical stroke are found to have had either asymptomatic prior strokes or concomitant strokes in territories other than that suspected by their clinical presentation. The major categories of illness that cause multiple infarctions are:

• Atherosclerosis
• Cardiac emboli
• Angiopathies
• Hematologic disorders
• Hypoperfusion and venous infarction

Patients with poorly controlled diabetes, hypertension and similar history have an overwhelming probability of suffering both large and small vessel disease. Lacunes are expected in the basal ganglia, pons, internal capsule, thalamus and centrum semiovale. Accelerated and disseminated large vessel atheroma will be seen at the carotid bifurcation, siphon, and at M1 and M2. Calcified and thick, vertebral carotid and basilar arteries are expected on CT. Severe hypertension will produce dolicoectasia. In situ thrombosis, flow limiting ischemic stenosis greater than 70% and cholesterol laden plaques will be seen asymmetrically in both anterior and posterior circulations. Accelerated atherosclerosis will be seen beyond bifurcations of the great vessels and intracranially in the fields of X-ray therapy.

Cardiac emboli from clots formed from an ischemic myocardium, arrhythmias, dilated myocardial failure or valve disease embolize primarily to the MCA circulation that receives the most CBF. Emboli tend to go to the same territory due to flow and viscosity characteristics. They often occur in showers in which two circulations are involved simultaneously. Emboli from atrial fibrillating often occlude the temporoparietal occipital branch of the inferior division of the MCA. Carotid distribution and superior cerebellar artery concomitant stroke suggest an embolic cardiac origin. Occlusion of the top of the basilar artery is most often embolic often from a cardiac source is which the midbrain, thalamus and posterior cerebral arteries are involved. An embolic event in younger patients in two distinct circulations over a long time course suggest a patent ovale with or without an atrial septal aneurysm. Peripheral aneurysms in two distal circulations suggest atrial myxoma. Rhabdomyosarcoma is to be expected with tuberous sclerosis. A shower of emboli in a cancer patient suggests non-bacterial thrombolic emboli. Severe migraine with visual aura and stroke in two circulations is strong evidence for the anticardiolipin syndrome.

Small strokes in pial conducting vessels of all territories of the cerebral cortex occur with active and severe collagen vascular disease. SLE is the most prominent of these illnesses.

Hematologic illness such as leukemia and lymphoma, particularly when the white cell could approach 250,000/mm³ is attended by strokes in multiple territories. Polycythemia most frequently occlude the posterior circulation. Disseminated intravascular coagulation may strike large extracranial vessels as well as conducting intracranial vessels. Sickle cell disease affects large and small vessels of both anterior and posterior inculpations.

Hypoperfusion causes strokes by distal perfusion failure in affected arteries as well as by circulatory compromise between vascular territories. This complication is to be expected and is routine with cardiac pump surgery and following cardiac arrest.

Venous infarction is immediately suggested in the setting of pregnancy and delivery, dehydration and a hypercoagulable state. Bilateral thalamic infarction easily seen on CT or MRI is characteristic as is superficial vascular cortical infarction.

Multiple infarctions other than that from atherosclerosis suggest internal medical and cardiac disease as the source. The younger the patient the more this is true.

Concomitant Infarction

• 33% of patients when diagnosed with first stroke have multiple infarcts in the carotid territory
• 2% of multiple infarcts are in vertebrobasilar territory
• 2% of patients at first infarct have had prior strokes in both territories (carotid and vertebrobasilar territories)

Asymptomatic Infarction

• Occurs in 10–38% of stroke patients
• Often occurs in non-critical areas and are small
• Right sided deep hemisphere and basal ganglia lesions more common than left sided if nonlacunar
• Risk the same in multiple and single lesions

Differential Diagnosis of Multiple Infarctions

Atherosclerosis

• Atherosclerosis: large and medium sized arteries
• Small vessel disease
  • Lipohyalinosis (penetrating vessels); HCVD
  • Spread of atheromatous plaque to occlude adjacent origins of major vessels
  • Atheroma at origin of penetrating vessels
  • Emboli: artery to artery; cardiac or arch of aorta are sources
  • recurrent stroke in patients with first lacunar infarct is 1.8%

Cardiac Embolism

• Nonrheumatic atrial fibrillation (AF) most common source of cardiac embolism
• AF with emboli 10% per year:
  • Multiple pial territory infarction suggests a cardioemboli source
  • Bilateral anterior circulation infarcts are more common in patients with emboligenic heart disease

Angiopathies

• Isolated angiitis of the CNS (cerebrum, cerebellum)
• Granulomatous vasculitis
• Herpes Zoster
  • Affects small and medium sized vessels
  • Infarction more common than hemorrhage
  • Localized lesions: cerebrum, cerebellum, brainstem in more than 75% of patients
  • May occur in carotid MCA territory if V1 involved. Occurs 2 weeks after onset of skin lesions or may be delayed
• SLE
  • Vasculitis (inflammation of blood vessels) less common than vasculopathy (abnormalities of blood vessel intima and media)
  • Embolic infarcts most common cause of infarction:
    • Libman Sachs endocarditis
    • Chronic valvulitis
    • Mural thrombus
  • Antiphospholipid antibodies
  • Lupus anticoagulant
  • Seizures
  • Psychosis
  • Recurrent and multiple small strokes
• Differential diagnosis of noninflammatory angiopathies with multiple strokes:
  • Eales Disease (arterioles and venules involved)
  • Sneddon's syndrome (livedo reticularis)
  • Moyamoya syndrome (carotid occlusion at siphon with collaterals)
  • MELAS (mt DNA) mitochondrial encephalopathy with lactic acidosis and stroke
  • Cerebral amyloid angiopathy (associated dementia)
  • Intravascular lymphoma (angiotrophic endovascular lymphomatosis); dural involvement
  • Arterial dissection of intracranial and cervical arteries (diseases of collagen)

Hematological Disorders

• Thrombotic thrombocytopenic purpura (TTP)
  • Multiple occlusions of small vessels
  • Large artery occlusion
  • Hallucinations
  • Renal failure
  • Focal cortical deficits
  • Seizures
• Polycythemia vera
  • Posterior > anterior circulation stroke
  • Megakaryocyte proliferation greater than one million has a high incidence of stroke
  • Hemoglobins of 18–22 g/dl
  • Rheological abnormalities (dysfunction of laminar flow)
• Sickle Cell Disease (HbSS)
  • Stroke occurs in 3–17% of patients
  • Ischemic stroke 15%
  • Large and small vessels involved
  • Strokes <15 years of age; border zone, and subcortical areas
  • Hemoglobin C: strokes in pregnancy; aseptic necrosis of the hip
  • Severe abdominal and joint pain
• Disseminated intravascular coagulations (DIC)
  • Small and large vessel strokes (often concomitantly)
  • Encephalopathy
  • Nonbacterial thrombotic emboli (NBTE) frequently associated
  • SAH
• Systemic lupus erythematosus
  • Vasculopathy affecting:
    • Small arteries
    • Arterioles
    • Capillaries
    • Pathology is fibrinoid neurosis
  • Vasculitis
    • Pathologically similar to hypersensitivity
    • Approximately 10% of patients
  • Microangiopathy:
    • 50% of SLE patients
    • Circulating antiphospholipid antibodies (APA's)
    • 2 mm to 3 cm infarction size
  • Clinical manifestation of stroke:
    • May occur at any time during course of the disease
    • Caused by APA's (antiphospholipid)
      • Titer may fluctuate and is not tightly correlated with systemic disease activity
      • Circulating IgG and IgM antibodies associated with the thrombotic events
      • APA's that bind to the phospholipid on factor V and X
        • Inhibits conversion of prothrombin to thrombin:
          • Anticoagulant properties in vitro (lupus anticoagulant) LAC
          • Some LAC are procoagulant
    • High titers of anticardiolipin antibodies (ACL)
      • Greater specificity for thrombotic events
      • IgG > association with thrombosis than IgM
      • Stroke risk with secondary APA's in SLE is increased with:
        • Oral contraceptives
        • Smoking
        • Hypertension
    • Stroke types
      • Branch occlusion most common
      • Multiple infarcts
      • Centrum semiovale strokes
      • Cardioembolic from Libman–Sachs endocarditis
    • Vasculitis in SLE
      • Ischemic and hemorrhagic stroke
      • Intracranial hemorrhage
        • Parenchymal
        • SAH
        • Most associated with vasculitis
      • Most likely cause of stroke if:
        • Active systemic disease
        • Normal TEE
    • Associated collagen vascular disease
    • Hyperviscosity syndromes
      • Bing–Neel syndrome (poor cerebral perfusion from high viscosity)
      • Bleeding gums
      • Myeloproliferative and dysglobulinemia states (IgM particularly severe)
      • Multiple occlusions of small blood vessels
      • Petechial hemorrhage
      • Waldenström's macroglobulinemia
        • Petechia below the knee
        • Acrocyanosis

• Hypoperfusion
  • Severe hypotension (cerebral perfusion pressure of less than 70 mm systolic)
  • Prolonged hypoxemia
  • Cardiac circulatory failure (no reflow phenomena of specific microcirculations)
  • Symmetrical and asymmetrical watershed infarcts
  • Infarcts in deep and superficial MCA territories
  • Cerebellar watershed infarcts
  • Multiple clinical syndromes depending on involved circulations
• Venous infarction
  • Hemorrhagic
  • Specific circumstance: pregnancy, prothrombotic state, cancer, Behçet's disease
  • Grey matter (basal/thalamus); subcortical white matter

Differential Diagnosis of Stroke in Young Patients

Approximately forty percent of cerebral thrombosis in young patients will be caused by HCVD 23%, diabetes mellitus 11%, and migraine in 6%. Dissection certainly must be considered in patient with neck or face pain. Carotid dissection will often be announced by oculosympathetic paresis. Posterior neck pain, occasionally accompanied by lateral eye brow pain occurs with vertebral obstruction and dissection. Migraine headaches are characteristic of mitochondrial disease, collagen vascular disease and CADASIL. Sporadic hemiplegic migraine has a greater chance of permanent stroke than familial migraine. Migraine with multiple visual auras is suggestive of anticardiolipin antibody syndrome. Prothrombotic states should always be sought in the context of a family history of thrombophlebitis or venous clotting in the upper extremity or chest wall. Vasospastic occlusion as well as hemorrhage from underlying vascular malformation or aneurysms are characteristics of strokes from cocaine or other sympathomimetic drugs. Oral contraceptives, hypertension and diabetes cause strokes of PICA and the thalamoperforate and thalamogeniculate arteries. Cigarette smoking in this context exacerbates this risk in young patients.

Sickle cell disease, leukemia and lymphoma cause approximately 5–10% of thrombotic strokes in young patients. Sickle cell disease is particularly dangerous during pregnancy. Stroke is frequent during chemotherapy for leukemia and lymphoma possibly due to the release of thromboplastin from lysed neoplastic cells.

Cardiac causes of stroke in young patients are similar to those in adults except that congenital anomalies, infective endocarditis (drug use), mitral valve prolapse and PFO are more common.

Stroke in Young Patients

• Approximately 3% of cerebral infarctions occur in patients < 40 years of age
• Specific age related vascular disease:
  • 70% of subarachnoid hemorrhage <40 years of age
  • 97% of cerebral infarction >40 years of age
  • 60% of cerebral infarctions occur between 65 to 84 years of age
• Differential diagnosis of cerebral thrombosis in young patients:
  • HCVD (23%)
  • Diabetes mellitus (11%)
  • Migraine (6%)
  • Collagen vascular disease (5%)
  • Cryptogenic (10–30%)
  • Dissection of carotid or vertebral artery (10%)
  • Prothrombic states (5%)
  • Hematologic diseases (5%)
• Stroke in women (15–45 years old)
  • Aneurysm or AVM without hemorrhage in 3.4%
  • Hemorrhage – 42%
  • SAH – berry aneurysm > AVM
  • Intracranial hemorrhage
    • Leukemia
    • Thrombotic thrombocytopenia
    • Aplastic anemia
  • Infarction – 18%
  • Embolism – 56% cardiac (33% from cardiovascular surgery)
  • Thrombosis
  • • Carotid 30%
    • Vertebrobasilar 7%
• Early onset atherosclerosis with or without HCVD associated with:
  • Evidence of: coronary artery disease, peripheral vascular disease or arterial occlusive disease
• Oral contraceptive risk (general)
• • 1/10,000 women
  • Death from stroke

Migraine

• 5% of stroke in young women
• No relation to specific attack
• Vasospasms, vessel occlusion, platelet hyper agreeability (subset of migrainous)

Pregnancy

• Pregnancy and the puerperium
  • 3% of cerebral thrombosis in young women
  • 4% within 30 days

Differential Diagnosis of Stroke from Cross Section of Community or Referral Hospitals

• Stroke in patients (15 to 44); heterogeneous population
  • 50% probable cause
  • 20% possible cause
  • 30% (cryptogenic); arch of aorta source, PFO and atrial septal aneurysm discovery are decreasing this percentage
• First Stroke
  • 50% women
  • 60% black patients (38% of population studies); 35% Caucasian patients (60% of population studied)
• Patients with recurrent stroke:
  • 60%women
  • 70% black patients
  • 16% <30 years old
  • <2% more than one probable cause
• Probable cause (approximately percentage)
  • Cardiac embolism – 16%
  • Lacunar stroke – 10%
  • Hematologic – 10%
  • Non atherosclerotic vasculopathy – 6%
  • Illicit drug use 5% (probably much higher)
  • Oral contraceptive 5%
  • Large artery atherosclerosis <2%
  • Migrainous <1% (probably higher)

Cardiac Causes of Stroke in Young Patients

High risk cardiac source:

• Ischemic heart disease and dyskinetic left ventricular segment
• Atrial Fibrillation (AF)
• AF with dilated left atrium
• Mechanical prostatic valve with AF
• Rheumatic mitral stenosis, atrial fibrillation, dilated left atrium
• Left ventricular thrombus
• Dilated cardiomyopathy with left ventricular clot
• Atrial myxoma
• Infective endocarditis
• Congenital heart disease – atrial septal defect perioperative
• Congenital heart disease – Ebstein's anomaly
• Congenital heart disease – Tetralogy of Fallot

Medium risk cardiac source:

• Patient foramen ovale (PFO)
• Atrial septal aneurysm and PFO
• Mitral valve prolapse (MVP)
• Hypertensive heart disease and hypokinetic left ventricular segment

Cardiac Valve Tumors

• Have risk of cardiac emboli:
  • Aortic > mitral > pulmonary > tricuspid
  • Mean age 52 (2–88 years)
  • Male patients more than female
  • Less aggressive than non-valve tumors
  • Less than 10% of cardiac tumors are on the valve
• Clinical presentation
  • Most are asymptomatic
  • Cardiopulmonary symptoms
    • Coronary artery occlusion
    • Congestive heart failure
  • Embolic stroke (usually pial vessels)
  • Rare occurrence of sudden death
  • Left sided more symptomatic than right sided lesions
  • A few patients have multiple tumors

Valvular Cardiac Tumors

• Papillary fibroelastoma (most common)
• Myxoma (medium stroke risk)
• Fibroma
• Sarcoma (rhabdomyosarcoma; tuberous sclerosis)
• Hemangioma
• Histiocytoma
• Undifferentiated

Differential Diagnosis of Stroke in the Young

Determined Causes of Stroke (ages 15–40)

• Hematologic disorder
• Arterial dissection
• Vasculitides
• SLE
• Primary antiphospholipid antibody syndrome
• Migraine
• Neurocysticercosis (specific populations)
• Eclampsia
• Oral contraceptives
• Extracranial carotid aneurysm
• Central venous thrombosis
• Vasospasm after subarachnoid hemorrhage
• Complication of angiography
• Moyamoya disease

Cerebral Embolism (ages 15–40 Order of Frequency)

Ischemic Stroke Due to Deficiency of Coagulation Inhibitors (young patients)

• Thromboses secondary to hematologic or clotting disorders occurs in approximately 4% of young patients
• Hematologic disturbances young stroke patients
  • Abnormalities of platelet function
  • Coagulation inhibitors
  • Fibrinolysis defects
• Free protein S enhances inhibition of V and VIII by activated Protein C; oral contraceptives and inflammatory conditions may decrease its concentration
• Antithrombin III; inhibits thrombin (factor Xa, IXa, XIa, XIIa – minor effect) deficits may be AD; acquired deficits
  • Inhibits thrombin
  • Minor effect inhibits clotting factors
  • AD form
  • Acquired deficits
    • Failure to synthesize due to cirrhosis
    • Diabetes
    • Age
    • Protein malnutrition
    • Low serum albumin
• Acquired deficiencies of coagulation inhibitory proteins occur with:
  • Malignancies
  • Plasmapheresis
  • Hemolysis
  • Nephrotic syndrome
  • Hepatic failure
  • Oral contraceptives
• Factor V Leiden defect (effects on protein C)
• Prothrombin gene defect
• Increased fibrinogen and factor VIII levels and acquired hyperfibrinolysis occur in young adults with ischemic stroke
• Strong predictors of myocardial infarction and stroke
  • Plasma levels of fibrinogen (increased)
  • Tissue plasminogen activator concentration (decreased)
  • Plasminogen activator inhibitor type I (PAI-1) concentrations (decreased)
• Decreased fibrinolytic factors:
  • Obesity
  • Hyperlipidemia
• Young stroke patients (subgroup) have:
  • Generalized defect in fibrinolytic system
  • Diurnal circadian rhythm of tPA and PA1-1 tPA
    • PA I-1 activity doubles from early morning until afternoon
  • Genetic control of circulating PAI-1 (plasminogen activator inhibitor type I)