Differential Diagnosis in Neurology

2.9. Differential Diagnosis of Seizure Disorder vs Syncope

The differential diagnosis of seizure disorder from other conditions with temporary loss of consciousness depends primarily on the history from the patient and any additional information obtainable from bystanders. The neurological and general medical examination may elicit the specific diagnosis. In children a variety of abnormal movements and breath holding spells may be confused with seizures and will not be considered further.

In adults, the differential diagnosis most frequently depends on the differential of true epileptic seizures from the varied causes of syncope, paroxysmal kinesogenic and other forms of abrupt choreoathetosis, myoclonus, and panic and rage attacks. Syncope occurs from an abrupt or gradual reduction of cerebral blood flow. It is characterized by the clinical symptoms of a feeling of lightheadedness or faintness, visual and auditory symptoms, muscle weakness and gastrointestinal symptoms. The specific forms of syncope frequently have historical or physical findings that are very specific and allow for an accurate differential diagnosis.

Vago-vagal syncope refers to an increase of vagal tone initiated from the orbital frontal cortex to the lateral hypothalamus and dorsal vagal nucleus. The patient experiences emotional upset or a visual trigger. There is a premonitory feeling of light headedness, paleness is observed and the patient may fall. The heart rate is slow, the patient often is hyperhidrotic and respiration is labored. The event characteristically lasts for less than 30 seconds. There is no post event confusion and there is amnesia for the event. Rarely sphincter incontinence and myoclonic jerks are noted and complete return of consciousness is greater than two minutes. Vaso depressor syncope is caused by failure of the vasomotor center in the lateral pontine tegmentum to maintain peripheral vascular resistance. Usually, the patient has been in bed for longer than 2–3 weeks or is taking medication for hypertension that blocks sympathetic outflow peripherally or centrally. The patient is able to stand for 30 seconds, blood pressure is maintained for up to one minute and then the patient feels light headed and collapses. The pulse is rapid; consciousness is regained quickly with no residual deficits. No headaches and no post event confusion are noted. The blood pressure may be very low in both vago-vagal and vasodepressor syncope.

Carotid sinus hypersensitivity is a rare cause of syncope in elderly patients. It occurs most frequently in elderly male patients concomitantly with head turning rather than a tight collar. Right carotid sinus massage has been associated more frequently than left with cardiac arrest. Most often the patient is standing when syncope occurs and the patient may be unconscious for longer than two minutes. Vasodepressor syncope from glossopharyngeal neurologia occurs in the context of severe lancinating pain in the tonsillar fossa, throat, deep ear and rarely causes severe bradycardia or asystolic. If prolonged it may cause generalized tonic clonic seizures. There are usually triggers such as chewing, swallowing and speaking and the lancinating pain precedes the cardio depressor syncope. Irritation of the vagus nerve in the neck from esophageal diverticular masses tumors or aneurysms that compress the carotid sinus and carotid body tumors (chromaffin) may present with syncope.

Decreased cardiac out flow from both congenital and acquired causes may decrease cerebral perfusion sufficiently to cause syncope. The tetralogy of Fallot is now rarely seen due to early corrective surgery. Tetrad attacks occurred with exercise which causes right to left shunting and cerebral hypoxia. Patients would characteristically squat, after exercise and occasionally lose consciousness. Pyramidal tract dysfunction with spasticity and bilateral Babinski signs are noted. Severe right to left shunting from large ASD's and VSD's may cause deepening cyanosis with exercise and syncope. Obstructive valvular heart disease, particularly aortic stenosis is, associated with syncope during exercise. The cause may be either poor cerebral perfusion (walking up the second flight of stairs) or associated AV node dysfunctions which may occur concomitantly with calcific aortic stenosis (one of Leriche's Syndromes). Hypertrophic subaortic stenosis usually causes syncope at the end of vigorous exercise. The patient has climbed four flights of stairs, is resting, breathing heavily and then loses consciousness. The infundibulum beneath the aortic valve contracts due to release of norepinephrine and epinephrine released from the adrenal medulla, dilates peripheral resistance vessels in the legs to cause cerebral hypoperfusion. The patient collapses at the top of the stairs. Pulmonic stenosis occurs from a domed valve with a pin-hole orifice. Young patients collapse during vigorous exercise (during track or basketball). This must be differentiated from the long QT syndrome that also occurs with vigorous exercise.

Patients with severe mitral stenosis are too weak to exercise vigorously. They present with syncope due to cardiac cerebral embolus. Cerebral perfusion fails with a cardiac ejection fraction of less than 30%. This situation is also prime for cardiac embolus. Cardiac tumors such as atrial myxomas are a rare cause of valve obstruction and decreased cardiac output. Left atrial myxomas most often cause mitral insufficiency rather than stenosis. Syncope is more often secondary to embolus. Syncope from mitral valve prolapse is most often due to ventricular arrhythmia. Right sided myxomas are characterized by postural obstruction of the tricuspid valve. The patient demonstrates postural shortness of breath (hypopnea), cyanosis and syncope. Once the patient falls, the myxoma block of the tricuspid orifice is relieved and the patient regains consciousness.

Cardiac inflow obstruction with consequent syncope occurs with superior and inferior vena cava obstruction. The former most often occur in the context of lung or other thoracic cancer, X-RT or hypercoagulable states. Swelling and collateral venous channels over the chest wall are evident. Pregnant women may have poor enough venous return from uterine compression of the inferior vena cava to cause syncope. Renal cell cancer may also occlude the inferior vena cava and cause syncope.

Tension pneumothorax, poorly regulated ventilators, neck surgery with superior vena cava obstruction, jugular vein occlusion, and cardiac tamponade may all decrease cardiac filling severely enough to cause syncope. Aortic dissection either alone or below the subclavian artery is associated with syncope at ictus. The former is associated with carotid occlusion and tamponade and the later with spinal cord infarction with consequent vasoconstriction and peripheral vascular resistance.

Cardiac arrhythmias are a major cause of syncope and always need to be differentiated from true seizure activity. In general, atrial arrhythmias cause syncope by increased ventricular rate fast enough to compromise filling. The atrial kick only accounts for approximately 15% of cardiac filling. Ventricular tachycardias are often clearly evident to the patient by a feeling of palpitations and a recognition of a rapid heart rate. As cerebral hypoperfusion supervenes during ventricular tachycardia, patients feel as if they are going to faint, vision closes in from the side, sounds become distant and the patient loses of consciousness. Usually the patient is unconscious for less than 30 seconds if severe cerebral hypoperfusion supervenes but the patient may suffer a major motor convulsion. As a general rule, cardiac syncope can occur in any position, is sudden and may be induced by exercise, and is longer than other benign causes. A heart rate of greater than 140/minutes suggests an ectopic rhythm and a rate of less than 40 minutes suggests heart block.

Stokes Adams attacks refer to loss of consciousness due to complete AV block. The onset is sudden. Rarely there may be visual, sensory, or premonitory auras. The pulse and heart sounds are lost. Patients fall, may have labored respiration, and if greater than 45 seconds, urinary incontinence, clonic jerks and generalized seizures. Focal neurologic signs and symptoms may be evident as there is frequently widespread cerebral vascular disease. The mechanism is distal field ischemia.

Sinoatrial block is most frequent in elderly patients. Patients often note dizziness, light headedness and palpitations. The patients are pale and have a slow or irregular pulse.

The most common supraventricular brady tachycardias are AF, Wolf Parkinson White (WPW) and atrial flutter. The rapid ventricular response with inadequate cardiac filling is the cause of inadequate cerebral perfusion. WPW rarely causes syncope. This is more frequent with the Lown–Ganong–Levine syndrome.

Ventricular arrhythmias cause the most serious loss of consciousness and occur in less than 5 seconds in the context of ventricular fibrillation. There is virtually no reserve cerebral ATP. They usually occur in elderly patients with generalized vascular disease. Long QT syndromes are associated with VIIIth nerve dysfunction and are now known to be due to KCN (potassium channelopathies) and rarely sodium channel dysfunction. Syncope occurs often during vigorous exercise. Episodes usually begin in the first decade of life, but may be seen in the second or third decade.

Hypotension from any cause if severe enough to curtail cerebral perfusion may cause syncope. In general, standing causes an immediate systolic drop of blood pressure (10 mmHg) and a diastolic rise of blood pressure of 5 mmHg. The autonomic neuropathies in which both sympathic and parasympathetic innervations are impaired demonstrate no compensatory increase of heart rate concomitant with the systemic fall in pressure. Patients have the usual visual, auditory and light headed feeling, but also often complains of a "coat hanger headache" (trapezius ridge and posterior cervical areas) prior to loss of consciousness. If the person is suffering from hereditary autonomic neuropathy or multiple system atrophy, the patient's hands are cold, cyanotic, and demonstrate poor capillary reperfusion. Sly–Dräger patients appear parkinsonian, but have no response to dopamine and suffer iris atrophy. Younger patients with Riley–Day Syndrome demonstrate congenital insensitivity to pain, livedo reticularis, and have poor tearing and temperature control. The hereditary autonomic neuropathies may demonstrate distal ulcerations from small fiber pain and temperature dysfunction as well as poor distal circulations.

Orthostatic hypotension is common with tricyclic antidepressants, arterial vasodilators, anti-hypertensive medications, diuretics, calcium channel blockers, alcohol, levodopa, phenothiazine as well as any cause of venous pooling or hypovolemia.

Any central nervous system disease that interrupts descending sympathetic fibers, usually at a spinal cord level, causes hypotension. Most patients with a thoracic level above T6 suffer hypotension. Patients with chronic spinal cord transection may be able to maintain consciousness at blood pressures of 90/60 mmHg.

The autonomic variant of Guillain Barré Syndrome, beriberi, severe, diabetic neuropathy, hepatic porphyrias, alcoholism, and rarely B12 deficiency may have severe orthostatic hypotension.

In general, vertebrobasilar disease causes drop attacks without true loss of consciousness. Patients may appear stunned and respond poorly but are not unconscious. This mental state usually lasts for less than 20 seconds. The subclavian steal syndrome rarely causes loss of consciousness. This is particularly apparent in studies of patients with Takayasu's disease who demonstrate severe arterial disease, but do not lose consciousness. The usual clinical symptomatology is dizziness, dysarthria, and lack of coordination with left arm use. Vasospasm of the vertebrobasilar arterial system in Bickerstaff's migraine often is associated with a brief loss of consciousness of less than 10 seconds. Patients most often suffer paresthesias of the hands, incoordination and basiocciput headache. Turning the head to one side occludes the vertebral artery of that side. If the other vertebral artery is atretic, patients may have momentary loss of consciousness. A few patients lose consciousness with bending their head backwards ("clothes line syndrome"-hanging wash). This is rare and lasts for less than 10 seconds. Sudden carotid occlusion may cause dizziness, a presyncopal feeling, a shaking TIA and loss of consciousness. Patients appear stunned and mute with supplementary motor area stem MCA and thalamic infarction which may last for minutes to hours.

Hypoglycemic symptoms occur in stages. Early as the blood sugar falls, an epinephrine response is elicited. This consists of hunger, piloerection and behavioral change. As the sugar falls to within 30–40 mg%, a parasympathetic response is seen with salivation, smaller pupils, loss of consciousness and seizures. Pulse and blood pressure are minimally decreased. Severe anoxia may produce syncope, but is usually preceded by lethargy or asterixis if associated with hypercarbia. It may also cause vasodepressor syncope. Hyperventilation to syncope is preceded by perioral and extremity paresthesias, light headedness and rarely blurred vision, dry mouth, and chest tightness.

Tussive syncope usually occurs after a severe bout of paroxysmal coughing. It may rarely occur often one cough. Recent transcranial Doppler studies have demonstrated decreased cerebral perfusion. This may occur from a cardiac depressor mechanism or from poor ventricular filling from increased intrathoracic pressure. The patient may have a congested face due to poor venous outflow from the head and then become pale. There may be a feeling of presyncope. The syncopal attack lasts for less than 5–10 seconds with complete recovery.

Micturition syncope occurs most often in young men who have been drinking. The bladder is over stretched and stimulates the posterior hypothalamus that activates the vasomotor center and then sequentially the intermediolateral columns of the spinal cord to effect sympathetic constriction of the peripheral vasculature. Patients strain to initiate micturition, further compromising venous return to the heart. Once the hypothalamic drive (associated with slight shivering and piloerection) is decreased with bladder emptying, the peripheral vascular resistance collapses with consequent hypotension and decreased cerebral perfusion. An epinephrine secreting pheochromocytoma of the bladder has also been associated with micturition syncope. Contributory factors for micturition syncope may be vasodilatory effect of alcohol and its nocturnal occurrence at which time blood pressure is lowest. Defecation syncope is rare and occurs with straining at stool. The same pathophysiology is posited. Charcot's syncope occurs with eating rapidly and swallowing a large bolus. The posterior pharynx is unduly stimulated which activates cardiodepressor nerves from cranial nerve IX. Patients awaken within seconds with no confusion or residual.

Chiari malformations with caudal brainstem compression occasionally are accompanied by episodes of syncope. The patient coughs or exercises a Valsalva maneuver and often suffers a lancinating C2 headache. Rarely, this scenario is followed by a brief loss of consciousness.

Obstruction of cerebral spinal fluid flow, particularly at the foramen of Monroe by a colloid cyst, subependymal giant cell astrocytoma vascular malformation, or aqueductal stenosis may present with a severe postural headache and loss of consciousness. Parasitic masses from cysticercosis or schistosomiasis may also obstruct the ventricles. Patients characteristically lie flat immediately after the obstruction and hold their head. Atonic episodes characterized by weakness may occur suddenly. Some patients report accompanying tinnitus. Syringomyelia of the cervical spine has been associated with precipitate micturition (involvement of the bladder center at C8–T1, ciliary center of Budge) and short repeated syncopal episodes.

Cataplexy, a component of the narcolepsy complex, may be associated with atonia and falling. This phenomenon occurs with sudden stimulation and is not associated with loss of consciousness. A rare dissociated state in which the patient can function, but is not fully alert may be associated with the narcoleptic attack. This may last for minutes to hours.

Systemic conditions that produce hormone or neurotransmitter release such as pheochromocytoma, systemic mastocytosis and the carcinoid syndrome, may cause a momentary loss of consciousness due to alterations in blood pressure. Pheochromocytomas usually are associated with a normal blood pressure. When the tumor is activated, the blood pressure may be dramatically high 250/150 mmHg and is associated with shortness of breath and very loud A2 and P2 heart sounds. Headaches are severe and patients may have short syncopal episodes.

Mastocytosis is a heterogeneous group of disorders in which there is abnormal growth and accumulation of mast cells in different organ systems. Cutaneous mastocytosis is generally benign. Mastocytosis that involves the skin and visceral organs may cause hypotension due to the release of chemical mediators primarily cytokines (IL-6 and other inflammatory mediators) that may open up the systemic circulation with consequent hypotension.

Carcinoids are neuroendocrine tumors of the intestines, pancreatic islets and retroperitoneum. The carcinoid syndrome involves flushing (frequently and inch below the hairline on the forehead is spared), bronchospasm and hypotension.

The major differential points between seizures and syncope are the following: Seizures have no relation to posture and may occur at any time of the day or night. They often have autonomic signs and are associated with incontinence and tongue biting (major motor). They last for 30 seconds, but are associated with postictal confusion, headache and fatigue. They may be associated with Todd's paralysis or other neurological deficits affecting speech or movement. Tachycardia during the seizure is common and thirst is prominent in some complex partial seizures of temporal lobe origin.

Syncopal episodes are frequently posturally related, take longer to develop than seizures and may have specific initiating sights or psychical triggers. They are associated with striking pallor and in general are shorter than seizures. They have no postictal confusion, headache or fatigue. A few convulsive jerks may be noted. There is rare urinary incontinence, no focal neurologic deficits, and prominent cardiovascular signs noted during the ictus. There is no injury from the event.

Cardiac Arrhythmias

• Sinoatrial node (sick sinus syndrome)
• AV node (Stokes Adams)
• Purkinje system disease of the heart (Mobitz Type II)
• Long QT syndrome
• Atrial fibrillation (fast ventricular rate)
• Atrial flutter (fast ventricular rate)
• Right atrial failure
• Wolf Parkinson White
• Lawn–Ganong–Levine

Reflex Brachycardia

• Glosso pharyngeal neuralgia (IX)
• Charcot's syncope (IX, X)
• Hypersensitive carotid sinus syndrome

Decreased Cardiac Output

• Hypertrophic cardiomyopathies (HCM)
  • Idiopathic hypertrophic subaortic stenosis
  • Familial HCM gene encoding Troponin II chrom1q3
  • Familial HCM gene encoding B cardiac myosin chromo 14q 11–12
  • Mitochondrial myopathies
  • Friedreich's ataxia

Restrictive Cardiomyopathies

• Sarcoidosis
• Scleroderma
• PXE
• Storage disease
• Distal myopathy with rimmed vacuoles

Ventricular Filling Defects

• Superior and inferior vena cava obstruction
• Cardiac tumor (myxoma, fibroelastoma)
• Thrombus
• Increased intrathoracic pressure

Cardiomyopathy

• Familial dilated cardiomyopathy; AD chromosome 1p1–q21
• AD Emery–Dreifuss
• Dilated cardiomyopathy without conduction defect; chromosome 1, 9, 10, 15
• Desmin related myopathy
• Duchenne and Becker muscular dystrophies
• Limb Girdle muscular dystrophies

Hypovolemia

• Anemia
• Dehydration
• Acute blood loss

Hypotension

• Small fiber neuropathies
• Hereditary autonomic neuropathies
• Drugs (antihypertensive, diuretics, beta blockers)
• Associations with neurodegenerative disease
  • Sly Drager Syndrome
  • Riley Day Syndrome
  • Multiple system atrophy
  • Parkinson's Disease
• Vagovagal syncope
• Vasodepressor syncope
• Cough/micturition/defecation syncope

Cerebrovascular Disease

• Anterior and posterior circulation ischemia
• Cerebral hemorrhage
• Cerebral embolus (stem MCA; SMA; thalamus)
• Subarachnoid hemorrhage
• Subclavian steal (rare)
• Vasospasm from Bickerstaff's migraine
• Takayasu's disease
• Aortic arch syndrome
• Aortic dissection

Metabolic/Toxic

• Hypoglycemia
• Anemia
• Anoxia
• Cocaine
• Solvent inhalation
  • Glue sniffing
  • Paint
  • Gasoline (Huffer's disease)