Differential Diagnosis in Neurology

4.10. Vascular Disease of the Spinal Cord

• General considerations:
  • Vascular anatomy
    • A single artery spinal originates from vertebral arteries, merges and courses from the foramen magnum to the filamen terminale in the ventral midline. It supplies the ventral horns and white matter of the lower 2/3 of the spinal cord.
    • The sulcal arteries arise in turn such that a small segment of the major artery may supply alternate halves of the cord. If occluded over a long enough segment both sides of the cord will be infarcted. X-RT therapy frequently causes a proliferative endarteritis which may occlude only one sulcal artery that causes a consequent Brown–Sequard syndrome. Compression of the ventral cord may infarct both sides of the spinal cord.
    • The ventral pattern of vascular supply to the spinal cord is similar to that of the basilar artery with midline perforators and short and long circumferential arteries. The lateral circumferential arteries give rise to perforating arteries that supply the corticospinal pathways, the ventral white matter and tips of the anterior horn.
    • The sulcal arteries supply the ventral gray.
    • A posterior spinal artery arises from each vertebral artery to supply the dorsal 1/3 of the spinal cord. This consists of the dorsal columns and most of the dorsal horn (to Rexed layer V).
    • The spinal cord is perfused at a very low pressure 90/50 mmHg. Many spinal cord vascular events are obscured by major deficits induced by infarction of the cerebral vasculature at equivalent perfusion pressures.
    • The major watershed infarction of the spinal cord often occurs through the pyramidal tract.
    • Thyrocervical and costocervical branches of the subclavian artery perfuse the cervical enlargement
    • The thoracic spinal cord is perfused primarily by intercostal arteries from the aorta and radicular deep cervical arteries. The watershed of the thoracic cord is usually at T2–T4 or T2–T6. The lumbosacral cord is fed by the great radicular artery of Adamkiewicz. It enters the cord from the left side and originates from the ilioinguinal artery derived from the aorta. It usually is found from T9–T12, but may enter the cord at L2. On arteriography it is easily recognized by its hair pin appearance. The sacral cord and cauda equina are nourished by vasovasorum from the hypogastric and obturator arteries whose origin is the aorta. These anatomical considerations of aortic origin are important as younger patients suffer infarction of the cord from various arterial procedures.
    • The posterior cord vascular plexus whose origin is the paired posterior spinal arteries from the vertebral arteries are fed by radicular arteries at each level.
    • Segmental arteries that supply paraspinous processes may anastomose with vasovasorum of the nerve roots and are often the source of spinal arteriovenous malformations.

Venous Drainage of the Spinal Cord

• General considerations:
  • This drainage is most important as compression of the spinal cord by facet and ligament hypertrophy as well as traction (spondylolisthesis) may compromise venous drainage and raise cord pressure. This mechanism has been posited for the common myelopathy associated with severe cervical spondylosis. Once initiated, surgical decompression does not reverse any deficits, but may halt neurological deterioration.
  • Radicular veins at reach level drain into paravertebral and the intravertebral plexus and ultimately the pelvic veins. Thus severe pelvic thrombophlebitis may give rise to venous infarction. The posterior venous drainage is into a large midline vein.

Rare Features of Spinal Cord Vascular Disease

• Transient ischemic attacks
  • Posterior columns are spared; vibration is intact
  • Putative source is aortic plaque emboli
• Vertebral body ischemia may occur concomitantly with spinal cord infarction from aortic emboli
• Pseudomotor neuron disease:
  • Selective ischemia of the sulcal arteries that perfuse the ventral horns with pyramidal tract involvement
  • Process may be subacute and progressive

Division A: Arterial Syndromes

• General considerations:
  • Origin of the anterior spinal is from the vertebral artery
    • Atherosclerosis of the vertebral artery and orifice of ASA
• Clinical features:
  • Medial medullary syndrome:
    • Ipsilateral XII nerve paralysis
    • Contralateral proprioceptive and vibratory deficit
    • Contralateral weakness of arm and leg (above the decussation of the pyramidal tract at C2)
    • Crural plegia (arm ipsilateral and leg contralateral) may occur
  • Low anterior spinal artery infarction:
    • Involvement of the ventral 2/3 of the spinal cord
    • Weakness of extremities below the lesion
    • Loss of temperature and pain below the lesion
    • Bladder involved in 50% of patients (often recovers)
    • Intact dorsal column sensory function
• Differential Diagnosis of Anterior Spinal Artery Syndrome
  • Atherosclerosis of the artery or its feeding vessels
  • Vertebral artery dissection
  • Syphilis (Erb's spastic paraparesis) and tuberculosis (proliferative endarteritis)
  • Compression from extruded disc or bone fragment
  • Sarcoid (meningeal involvement or vasculitis)
  • Vasculitis (SLE, Wegener's granulomatosis, collagen vascular disease)
  • Emboli: (from the heart, atrial myxoma; atrial fibrillation); cholesterol emboli, SBE
  • Idiopathic pachymeningitis
  • Aortic dissection
  • Giant cell arteritis
  • Takayasu's disease
  • Bends (nitrogen bubbles)
  • Hypoperfusion
    • Lumbosacral > cervical > cervicothoracic areas affected

Fibrocartilaginous emboli

• General considerations:
  • Women > men
  • Mid to low thoracic levels
  • Cartilaginous material from intervertebral discs blocks spinal arteries and veins
  • Primarily in cervical levels in young women
  • Risk factors appear to be pregnancy, the puerperium, oral contraceptives, neck movement of minor trauma
• Clinical features:
  • First symptom is neck, upper back or radicular pain
  • Asymmetric weakness that may evolve to quadriparesis
  • Dissociated sensory loss in a cape distribution
  • May occur in the conus medullaris
  • Usually is an ischemic infarct, but maybe hemorrhagic
  • Imaging studies usually do not show herniated discs that compress the cord or nerve roots
  • Ischemic rather than a hemorrhagic infarction

Ischemia of the Lower Thoracic Cord and the Lumbar Enlargement

• General considerations:
  • The spinal cord is perfused at a much lower pressure 60–70 mm Hg than the brain
  • Infarction of the spinal cord is frequently overshadowed by cerebral signs and symptoms that occurred during an incident of anoxia and hypotension
  • Dropped sensory levels to T4–T6 frequently occur from cervical cord disease (lamination of the spinothalamic tract)
  • Internal watershed zones in the spinal cord are:
    • Corticospinal pathways
    • Rexed layers V–VI
  • Selective grey matter necrosis does occur
  • Most susceptible region to low flow states is T4
• Clinical settings in which spinal cord ischemia occurs:
  • Renal arteriogram
  • Surgical procedures (cross clamping the aorta)
  • Aortic dissection
  • Atherosclerosis
  • Emboli: heart; cholesterol; air; nitrogen bubbles, fibrocartilaginous
  • Aortic dissection

Differential Diagnosis of Causes of Thoracic Watershed Infarction:

• Systemic hypotension
• Prolonged surgical procedures
• Cardiac arrest
• Anoxia
• Vertebral artery occlusion (primary involvement may be C8–T1)
• Aortic dissection
• Carbon monoxide poisoning

Ischemia of the Lower Cervical Cord

• General considerations:
  • Extremely rare
  • Atherosclerosis
  • Dissection or occlusion of the vertebral arteries
• Clinical features:
  • Severe sensory ataxia (particularly without vision)
  • Loss of vibration and position sense
  • Rarely severely gyrating arms
  • Lateral drift with "finger playing hands"

Aortic Disease as a Cause of Spinal Cord Ischemia

• General considerations:
  • Surgical procedures of the aorta are a common cause of spinal cord ischemia
  • Most dangerous procedures are repair of thoracic and abdominal aneurysms
    • 3–5 hour procedures
    • Concomitant spondylosis that may compromise radicular arteries and the vasovasorum of the nerve roots
  • Compromised radicular artery supply to the anterior spinal artery
  • Emboli occur during cross clamping of the aorta
  • Dissections of the aorta occlude radicular arteries
• Clinical features:
  • Thoracic cord infarction following surgery:
    • Spinal shock occurs with paralysis, hypotonia and loss of bowel and bladder function with the demarcation of a thoracic sensory level
    • One month to six weeks later the lower extremities become spastic and wasted

Lumbar Cord Infarction Following Aneurysm Surgery

• Hypotonia
• Loss of bowel, bladder and sexual function (conus medullaris)
• Leg flexion may occur
• Paralysis may occur from ischemia to the nerve roots
• Primarily "saddle" or perineal sensory loss; variable sensory loss to all modalities may occur up to the T11–T12 dermatomes.

Differential Diagnosis of Aortic Artery Disease with Spinal Cord Infarction

• Unruptured aneurysms
• Dissection
• Embolic occlusion of the aorta (usually the artery of Adamkiewicz is involved)
• Takayasu's arteritis (may present with isolated pulmonary or aortic vasculitic segments)
• Cholesterol emboli syndrome:
  • Isolated digital toe artery occlusion ("purple toe" syndrome)
• Atrial myxoma
• Fat emboli
• During severe hyperglycemia (fat)
• Coarctation of the aorta

Medical Causes of Ischemic Spinal Cord Disease

• Atherosclerosis
• Systemic hypotension
• Collagen vascular disease (PAN, SLE)
• Thromboangiitis obliterans (Buerger's Disease)
• Aortic arch syndrome (gradual occlusion of both carotid and vertebral arteries)
• Dissection of the aorta (infarction of grey matter; superficial white matter)
• Neoplastic endarteritis (malignant angioendotheliosis)
• Infective endarteritis:
  • Syphilis
  • Cryptococcus
  • HIV
  • TBC
  • Lyme borreliosis
• Fungal invasion of blood vessels
  • Mucormycosis
  • Nocardia
  • Aspergillosis
• Illicit drugs:
  • Cocaine
  • Propalolamine
  • Amphetamine
• Disseminated intravascular coagulation
• Prothrombotic states
• Aortic atherosclerosis (supplying vessels; emboli)
• Aortic aneurysm
• Aortic surgery (particularly cross clamping > 18 minutes)
  • Abdominal aortic aneurysms; cord and cauda equina may be infracted
• Ligation of lower thoracic intercostal vessels
• Nonpenetrating abdominal trauma (torsional occlusion of vessels supplying the cord)
• X-RT (intraspinal vessels are occluded from peripheral endarteritis)
• Adhesive arachnoiditis

Embolic Disease of the Spinal Cord

• Atheromatous aortic plaque
  • Blue toe syndrome (cholesterol emboli)
• Cardiac source:
  • Atrial fibrillation
  • Red clot
  • Infective endocarditis (bacteria; fungi)
  • Mitral valve prolapse
  • Valvular clots
  • Atrial myxoma
• Fibrocartilaginous debris (disc)
• Angiography
  • Catheterization for dural AVM
• Fat:
  • Broken bones (long bones) in young people
  • Hip replacement (older patients)
  • Diabetic ketoacidosis
• Tumor cells
• Nitrogen bubble (Caisson's disease)
• Air bubbles:
  • Diving accidents
  • Cardiac surgery
  • Surgical procedures in a sitting position (ENT and neurosurgery)
• Therapeutic renal artery embolization

Division B: Venous Infarction of the Spinal Cord

• General considerations:
  • Venous infarctions without hemorrhage are hard to diagnose; the underlying medical condition is most helpful
  • Extension of Thrombophlebitis of pelvic veins:
    • Usually occurs in long standing bed ridden patients
    • Associated leg vein thrombosis
    • Propagates into the cord through the venous plexus
  • Associated with chronic obstructive pulmonary disease
  • Polycythemia vera
  • Subacute necrotizing myelitis:
    • Associated with spinal cord thrombophlebitis
    • No systemic foci
    • Association with chronic obstructive pulmonary disease
  • Associated with epidural abscess
  • Endoscopic sclerotherapy (reported for esophageal varices)
    • Cervical spinal cord
  • Coagulopathy:
    • Factor V Leiden with protein C resistance
    • Anti-thrombin III
    • Factor C deficiency
    • Factor S deficiency
    • Anti-phospholipid syndrome
    • Lupus anticoagulant
  • Cancer (prothrombotic states); breast and pancreas are the most common
  • Subacute necrotizing myelopathy (paraneoplastic); small cell lung carcinoma
  • Birth control pills
  • Pregnancy
  • DIC
  • Dehydration
  • Possible mechanism of progressive cervical myelopathy

Division C: Hemorrhagic Spinal Cord Disease

• General considerations:
  • Hemorrhages of the spinal cord occur in specific locations:
    • Epidural space
    • Intradural and extramedullary space
    • Intraparenchymally
  • Hematomyelia
    • Hematomyelia is bleeding into the spinal cord parenchyma
    • Area of involvement is often the central gray of the cervical cord
    • Vascular malformations may present with ischemia rather than hemorrhage; may have both ischemic and hemorrhagic symptomatology
  • Specific categories of spinal malformations that may bleed:
    • Angioma
      • Tortuous groups of dilated arteries and veins
    • Venous angioma
      • Veins predominant in the malformation
    • Arterial predominance
      • Arteriovenous malformation
    • Telangiectasia
      • Composed of capillaries

Functional Division of Malformations

Type I Dural Malformations

• General considerations:
  • The blood supply is derived from arteries located in the dural sleeves of nerve roots
  • The nidus of these arteriovenous malformations is from dural branches of radicular arteries
  • Drainage of the malformation is through enlarged dorsal spinal cord veins
  • The dural arteries do not supply the spinal cord; there may be more than one arterial feeder
  • Low-flow lesion by angiography that has no concomitant arterial or venous aneurysms
  • Cervical fistulas:
    • Often are located at the cervicomedullary junction
    • May cause SAH
• Clinical features:
  • Progressive paraparesis or worsening radiculopathy
  • Acute exacerbations with bladder involvement
  • Back pain occurs often in the mid back or in a radicular pattern
  • Symptoms and signs may worsen with exercise. Prior to MRI these patients were often thought to suffer MS
  • Paralysis may occur from prolonged venous hypertension or venous thrombosis
• Imaging evaluation:
  • Increased T2 weighted signal with edema is noted in the cord by MRI
  • Dorsal myelography is being supplanted by radicular artery selective angiography; dorsal serpiginous veins are often seen by magnetic resonance angiography

Spinal and Paraspinal Dural Fistula

• General considerations:
  • Primary locations are the spine or paraspinal structures
  • Drainage is into the epidural venous system
• Clinical features:
  • Compressive myelopathy from enlarged veins
  • Venous hypertension with progressive myelopathy
• Imaging evaluation:
  • MRI demonstrates a positive T2 weighted signal with an intramedullary lesion, tortuous epidural veins, and dilatation of perimedullary veins

Intradural Type II Arteriovenous Malformations

• General considerations:
  • Intramedullary or parenchymal in most instances; some may have an intradural extramedullary component
  • Categories of intradural malformation:
    • Glomus malformation:
      • Well localized nidus of abnormal arteries and veins intramedullary
    • Juvenile malformation:
      • May involve the entire cord
      • Fed by segmental arteries
    • Arteriovenous fistulas:
      • Derived from blood vessels that supply the cord
    • Cavernous angiomas:
      • Similar to cavernous hemangiomas of the brain
      • Associated syrinx may be present
• Clinical features:
  • Present in young patients, < 25 years of age in 65%
  • Male > female
  • High flow lesions that may hemorrhage occur in a significant percentage of patients
  • Distributed throughout the spinal cord with a cervical predominance
  • Associated with spinal and extraspinal aneurysms and AVMs of the neuraxis
• Imaging evaluation:
  • MRI demonstrates a nidus of juvenile, glomus and intradural AVM on T2 weighted images
  • Enlarged cord with dilated serpiginous veins
  • Hemosiderin ring around the lesion represents a prior bleed. Increased T2 weighted image within the malformation represents a 4–7 day old bleed and methemoglobin (a "popcorn" lesion)

Subarachnoid Hemorrhage in the Spinal Cord

• General considerations:
  • Spinal SAH < 1% of all SAH
  • Most common cause is rupture of a spinal AVM; other causes are:
    • Coarctation of the aorta
    • Rupture of a spinal artery
    • Aneurysm of a spinal artery
    • Polyarteritis nodosa
    • Lumbar puncture
    • Spinal tumors
    • Blood dyscrasias
    • Anticoagulation
• Clinical features:
  • Acute onset
  • Severe back pain at the level of the hemorrhage
  • Pain quickly becomes diffuse with signs of meningeal irritation
  • Radiculopathy at the site of the lesion or down the legs
  • If blood diffuses above the foramen magnum:
    • Headache
    • Cranial neuropathy
    • Depressed level of consciousness
    • Decreased ankle jerks with increased knee and upper extremity reflexes
    • Increased intracranial pressure with papilledema (rare)
• Laboratory evaluation:
  • CSF:
    • Hemorrhage greater than 1,000,000 RBCs/mm³)
    • Within days may have hypoglycorrhachia (severely depressed glucose < 20 mg /dL)

Hematomyelia

• General considerations:
  • Trauma
    • Direct injury to the spine (penetrating and non-penetrating)
    • Hyperextension of the cervical spine
  • Bleeding of a vascular malformation
  • Hemorrhage into a tumor
  • Hemorrhage into a syrinx
  • Coagulopathy
  • Anticoagulation (particularly coumadin)
  • Venous infarction
  • Syphilis
• Clinical features:
  • Presents as spinal shock, back pain, sensory loss, paralysis and areflexia
  • Autonomic instability
  • Gray matter more affected than white matter; weakness of the arms
  • Spasticity develops below the level of the lesion
  • Atrophy and fasciculations of affected segments occur with time
  • Babinski's sign is prominent
  • Sensory level:
    • Two segments lower than the lesion (if thoracic)
    • Higher in the back than front (follows patterns of intercostal nerves)
    • Dropped sensory level (T4–T6) following cervical lesions is common (lamination of the spinothalamic tract)
    • Rare suspended sensory loss (interruption of segmental dorsal horn at the level of injury with preserved long tract sensory function)
  • Mass reflex late in the course of the illness

Spinal Epidural and Subdural Hemorrhage

• General considerations:
  • Epidural hemorrhage > frequency than subdural hemorrhage, 4:1
  • Spinal epidural hemorrhage:
    • Peak occurrence during childhood and the fifth to sixth decade
    • Cervical lesions more common in childhood; thoracic and lumbar lesions in adults
    • Frequently occur with trivial trauma or exertion
• Clinical features:
  • Similar for both subdural and epidural hematoma
  • Severe back pain at the level of the bleed
  • Myelopathy (compressive)
  • Cauda equina syndrome
  • Radicular pain (involved segment)
  • Progresses over hours to days
  • Acute transverse myelitis (presentation of epidural hematoma)
  • Bowel, bladder and sexual dysfunction
  • Rare Brown–Sequard pattern
• Imaging evaluation:
  • MRI:
    • T1 weighted images:
      • Signal intensity of the epidural hematoma is primarily isointense to the spinal cord
      • T2 weighted images of epidural hemorrhage:
        • Heterogenous hyperintensity as compared to the cord
        • Focal hypointensity (acute blood; deoxyhemoglobin)
      • Capping of epidural fat
      • Direct continuity with adjacent osseous structures
      • Compression of epidural fat, subarachnoid space and spinal cord
      • Posterolateral location
      • Spontaneous spinal epidural hematomas located in the ventral space:
        • Premembranous hematoma
        • Posterior longitudinal ligament hematoma
• Differential diagnosis of spinal epidural hemorrhage:
  • Epidural anesthesia
  • Lumbar puncture (particularly in anticoagulated patient
  • Blood dyscrasias
  • Anticoagulation
  • Neoplasm
  • Vascular malformations
  • Thrombocytopenia
  • Following heparinization after lumbar surgery
  • Portal hypertension
  • Following exercise and valsalva maneuvers

Specific Spinal Cord Malformations

Differential Diagnosis of Specific Spinal Cord Malformations

• Hemangioblastoma (Von Hippel–Lindau syndrome)
• Arteriovenous malformation (glomus, juvenile, paravertebral)
• Dural arteriovenous fistula (Type I)
• Intramedullary spinal cord cavernous malformations and type II lesions
• Bannayan–Zonana syndrome
• Occult vascular malformations
• Foix Alajouanine syndrome
• Cobb's syndrome

Hemangioblastoma

• General considerations:
  • May arise in isolation
  • Major manifestation of Von Hipple–Lindau disease (VHL)
    • Prevalence 1/36,000 population

Von Hippel Lindau Disease (VHL)

• General considerations:
  • AD: chromosome 3p25–3p26 deletions or mutations
  • Associated central nervous system hemangioblastomas:
    • Cerebellum
    • Retinal
  • Associated systemic manifestations:
    • Renal cysts
    • Renal carcinoma
    • Pheochromocytoma (specific alleles of VHL disease)
    • Increased levels of vascular endothelial neurotrophic factor
• Clinical features:
  • 80% in cerebellum
  • 20% in spinal cord
  • 35% of patients with hemangiomas have VHL disease; 60% of those patients who are symptomatic are less than 30 years of age
  • Spinal hemangioblastoma:
    • Related to VHL more often than those found in infratentorial locations
  • VHL at diagnosis are younger than sporadic cases
  • VHL patients develop endolymphatic sac tumors (tinnitus or deafness as clinical manifestations)
  • Spinal hemangioblastoma:
    • Often associated with cerebellar hemangioblastoma
    • May be multiple
    • May be extramedullary and on spinal roots in location
    • Renal cell carcinoma may metastasize to the hemangioblastoma

Arteriovenous Malformations (Type I and Type II)

• General considerations:
  • Males > females
  • Thoracolumbar location (dorsal)
  • Associated with:
    • Cobb's syndrome
    • Wyburn Mason syndrome
    • Kartagener's syndrome

Spinal Dural Arteriovenous Malformations (Type I)

• General considerations:
  • Most frequent spinal arteriovenous malformation
  • Posterior and posterolateral dorsal cord most common location
• Clinical features:
  • Diagnosis established after months of intermittent symptoms
  • Progressive myelopathy
  • Cauda equina and conus medullaris dysfunction
  • Low back pain (pseudo radicular pain)
  • Lower extremity weakness
  • Sphincter disturbance
    • Early involvement of micturition
    • Late involvement with disc disease
  • Combined upper and lower motor neuron signs
  • Symptoms may vary with posture, menses and exercise
• Imaging evaluation of dural arteriovenous fistula (DAVF) Type I
  • MRI:
    • Enlarged spinal perimedullary veins; occasionally also seen with intracranial fistulas
    • Intramedullary high intensity signal changes on T2 weighted images; high intensity lesions decrease within 1–4 months after treatment
    • Angiographic evaluation:
      • Anterior spinal vein draining a SDAVF
      • Distortion of the hairpin turn of the artery of Adamkiewicz
      • Some angiographic evidence for vascular steal phenomenon as a cause of symptoms
• Laboratory evaluation:
  • CSF is abnormal in >75–90% of patients

Dural Arteriovenous Fistula at the Craniocervical Junction

• Clinical presentation of craniocervical junction AVM:
  • Present with SAH
  • Progressive myelopathy that may interfere with respiration

Cavernous Angioma

• General considerations:
  • Incidence is not known
    • Occur with 3–11% of spinal cord tumors
    • Women slightly greater incidence than men
    • Clinical presentation between 30–70 years of age
    • Cervical > lower thoracic > conus medullaris are the most frequent location
    • Posterior or posterior lateral intraspinal location
    • Cervical lesions produce symptoms earlier
    • May develop tethering of the cord following surgery
    • Approximately 50% may have multiple cavernous malformations in the neuraxis
    • Associated with cryptic venous malformations
• Clinical features:
  • Onset with pain, weakness and sensory symptoms
  • Later bowel and bladder dysfunction
  • Onset associated with:
    • Exercise
    • Trauma
    • Pregnancy
    • Menstruation
    • May bleed during sleep
    • Cavernous angiomas may cause:
      • Increased local venous pressure
      • Decreased arterial flow by pressure on the anterior spinal artery of the ventral fissure
      • Ischemia of the cord
    • Onset of symptoms to diagnosis may be delayed
    • Severe weakness in 20% of patients by six months after presentation; 50% by three years
    • After onset of leg weakness further disability is rapidly progressive
    • Pain may be local or radicular
    • Spinal bruit (extremely rare)
    • Upper and lower motor neuron weakness
    • Conus medullaris syndrome (rare)
• Imaging evaluation (MRI):
  • Heterogenous well circumscribed lesion
  • Hemosiderin external ring (prior bleed)
  • Central area of increased T2-weighted image (7–10 day old blood)

Differential Diagnosis of Cavernous Angioma

• Multiple sclerosis
• Neoplasm
• Herniated disc
• Spondylolisthesis
• Intracranial SAH (5% present with neck and back pain)
• Subacute combined degeneration
• Longitudinal myelitis; inflammatory; collagen vascular disease
• Meningovascular syphilis