What are the diagnostic criteria and treatment options for central nervous system (CNS) vasculitis?

CNS Vasculitis: Diagnosis and Presentation

CNS vasculitis diagnosis requires a combination of clinical presentation, laboratory findings, neuroimaging, and often brain biopsy, with histopathology remaining the gold standard for definitive diagnosis. 1

Clinical Presentation

CNS vasculitis presents with highly variable symptoms depending on the vessels involved:

• Medium vessel vasculitis typically presents with:

  • Focal neurological deficits
  • Stroke episodes
  • Transient ischemic attacks
  • Progressive reversible ischemic neurological deficits
  • Lacunar infarctions 1

• Small vessel vasculitis more commonly presents with:

  • Headaches (often the initial symptom)
  • Altered consciousness/encephalopathy
  • Cognitive deficits
  • Seizures
  • Behavioral changes 1, 2

Additional symptoms may include:

• Fatigue
• Depression
• Sleep disturbances
• Multifocal neurological events
• Unexplained skin lesions (in systemic vasculitis) 1

Diagnostic Criteria

The diagnostic criteria for CNS vasculitis proposed by Calabrese and Mallek (1988) require either:

1. Histopathological confirmation via brain biopsy, OR
2. Characteristic findings on digital subtraction angiography (DSA) 1

However, more recent criteria emphasize the importance of histopathology, as angiographic findings alone have limited specificity 1, 2.

Diagnostic Approach

Laboratory Tests

• Cerebrospinal fluid analysis:
  • Elevated protein levels
  • Lymphocytic pleocytosis (rarely exceeding 250 cells/mm³)
  • Opening pressure may be increased 1, 2
• Inflammatory markers:
  • Erythrocyte sedimentation rate (may be normal or only minimally elevated)
  • Serum cryoglobulins (particularly in HCV-associated CNS vasculitis) 1

Neuroimaging

1. MRI Brain (first-line imaging):

   • Multiple infarcts of variable ages (in up to 50% of cases)
   • White matter lesions
   • Mass lesions (5%)
   • Meningeal enhancement (8%)
   • Hemorrhage (9%) 1, 3

2. MRA Head:

   • Multifocal stenosis and dilatation of intracranial vasculature
   • Sensitivity approximately 81% compared to DSA
   • Limited resolution for small vessel disease 1

3. Digital Subtraction Angiography (DSA):

   • Long considered the standard for imaging diagnosis
   • Shows arterial beading and alternating areas of constriction/dilatation
   • Submillimeter resolution but limited specificity
   • Findings overlap with atherosclerosis and reversible cerebral vasoconstriction syndrome 1

4. CTA Head:

   • Shows multifocal vessel wall narrowing and dilatation
   • Circumferential mural thickening (>2-3mm)
   • Wall enhancement patterns
   • Limited resolution for small vessel disease 1, 4

Brain Biopsy

• Cortical-leptomeningeal biopsy is the most specific diagnostic test
• Yield increases when performed in areas abnormal on imaging
• False negatives can occur due to the focal nature of the disease 1

Differential Diagnosis

Critical differential diagnoses include:

• Reversible cerebral vasoconstriction syndrome (most common mimicker)
• Intracranial atherosclerosis
• Migraine with aura
• Infections (particularly HCV-associated vasculitis)
• Malignancy
• Drug-induced vasculopathy 2, 5, 6

Treatment Approach

For primary CNS vasculitis:

• Induction therapy: Glucocorticoids plus cyclophosphamide (80% response rate)
• Alternative: Rituximab may be considered in selected cases
• Maintenance therapy: All patients should receive maintenance immunosuppression 2, 3

For secondary CNS vasculitis:

• Treat the underlying cause (e.g., HCV infection)
• Immunosuppression based on the specific etiology 1

Prognostic Factors

Poor prognostic factors include:

• Increasing age at diagnosis
• Large vessel involvement
• Cerebral infarcts at presentation
• Diagnosis by angiography alone 3

Better outcomes are associated with:

• Gadolinium-enhanced cerebral lesions
• Prompt diagnosis and early treatment initiation 5, 3

Pitfalls and Caveats

• Persistent wall thickening may be seen in up to 49% of patients despite clinical response to treatment
• Angiographic findings alone have limited specificity
• Small vessel vasculitis may be below the resolution threshold of conventional angiography
• A negative biopsy does not exclude the diagnosis due to the focal nature of the disease 1, 4, 5