What is the initial evaluation and treatment approach for a patient with suspected brain vasculitis?

Initial Evaluation of Suspected Brain Vasculitis

For suspected CNS vasculitis, begin with MRI brain with and without contrast (including vessel wall imaging sequences) plus MRA head without contrast, as this combination provides the highest diagnostic accuracy and should guide decisions about further invasive testing or biopsy. 1, 2, 3

Clinical Presentation to Recognize

Key clinical features that should trigger suspicion:

• Headache followed by encephalopathy and behavioral changes are the most common presenting symptoms 1, 2
• Focal neurological deficits occur in 20-30% of patients 1, 2
• Ischemic or hemorrhagic stroke, particularly recurrent stroke or stroke with encephalopathic changes 2
• Stroke accompanied by fever, multifocal neurological events, unexplained skin lesions, glomerulopathy, or elevated sedimentation rate 2
• Seizures and intracranial hemorrhage may also be presenting features 1, 2
• Small-vessel strokes developing over weeks to many months 2

Initial Laboratory Workup

Essential first-line laboratory tests:

• ANCA testing using both indirect immunofluorescence and ELISA (Level of evidence 1A, Grade A recommendation) 2, 4
• Complete blood count with differential to assess for anemia, leukocytosis, or cytopenias 4
• Comprehensive metabolic panel including serum creatinine to evaluate renal function 4
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), though these are characteristically normal or only minimally elevated in primary CNS vasculitis 2, 4
• Urinalysis at every visit to detect hematuria, proteinuria, and red cell casts 2, 4
• Cerebrospinal fluid analysis may reveal increased opening pressure, elevated protein, or lymphocytic pleocytosis (rarely exceeding 250 cells/mm³) 2

Critical caveat: Approximately 10% of patients with ANCA-associated vasculitis may be ANCA-negative, requiring tissue biopsy for definitive diagnosis 4. Additionally, ESR and CRP cannot distinguish between vasculitis activity and concomitant infection 4.

Neuroimaging Protocol

Primary imaging approach:

MRI brain with and without contrast is the cornerstone of initial evaluation:

• Abnormal in >90% of CNS vasculitis cases, with sensitivity approaching 100% when normal 1, 2, 3
• Multiple infarcts of variable ages are present in up to 50% of patients 1, 2
• Other findings include mass lesions (5%), meningeal enhancement (8%), and hemorrhage (9%) 1, 2
• Progressive confluent white matter lesions, cortical and subcortical T2 lesions, multiple microhemorrhages, and enhancing small vessels/perivascular spaces 1, 3

Vessel wall imaging (VWI) with contrast enhancement:

• Adding contrast-enhanced MRI vessel wall imaging to luminal imaging increases diagnostic accuracy to 89% compared to 36% with luminal imaging alone 1, 3
• Helps differentiate CNS vasculitis from other cerebrovascular diseases as inflammatory changes of the vessel wall differ between conditions 1, 3

MRA head without contrast:

• Time-of-flight MRA is abnormal in 81% of patients with angiographic findings of vasculitis 1, 3
• Can detect multifocal stenosis and dilatation of intracranial vessels 3
• However, specificity is limited by overlap with atherosclerosis and reversible cerebral vasoconstriction syndrome 1, 3
• Sensitivity is limited to resolution as vasculitis can involve small distal arteries below native MRA resolution 1

Imaging modalities NOT recommended for initial evaluation:

• CT head, CT head perfusion, CTA neck, CTV head, MRA neck, and MRI head perfusion have no supporting literature for initial CNS vasculitis evaluation 1

Role of Conventional Angiography

Digital subtraction angiography (DSA):

• Has been the historical standard due to submillimeter resolution 1, 3
• However, has low specificity for vasculitis given significant overlap with atherosclerosis and reversible cerebral vasoconstriction syndrome 1, 3
• Limited sensitivity as vascular involvement can be below angiography resolution 1
• Recent evidence suggests DSA may be of limited benefit when considered in context of clinical findings and MRA/CTA results 5

Important pitfall: In one study, 59% of patients who underwent both noninvasive imaging and DSA showed no evidence of vasculitis on either study, yet some were still treated empirically based on clinical symptoms 5. This highlights the risk of overdiagnosis and unnecessary immunosuppression.

When to Proceed to Brain Biopsy

Brain biopsy indications:

• Strongly supportive of vasculitis when positive and recommended to assist diagnosis (Level of evidence 3, Grade C recommendation) 2
• Cortical-leptomeningeal biopsy is the most specific diagnostic test for diffuse or multifocal CNS vasculitis 2
• Should be performed when diagnosis remains uncertain after comprehensive imaging and laboratory evaluation 2
• Yield increases significantly if performed in an area demonstrably abnormal on MRI or cerebral angiography 2

Critical limitation: Due to the focal nature of primary cerebral arteritis, a negative biopsy result does not preclude the diagnosis 2.

Diagnostic Criteria and Pitfalls

Formal diagnostic criteria:

• Original Calabrese and Mallek criteria (1988) required diagnosis via histopathology or characteristic findings on DSA 1, 2
• More recent criteria proposed by some experts require histology from biopsy or autopsy rather than relying solely on angiography 1, 2

Major pitfalls to avoid:

• "Blind" immunosuppressive therapy should be strictly avoided in unrecognized non-inflammatory differential diagnoses 6, 7
• Only 17% of patients referred for suspected CNS vasculitis actually have inflammatory vascular disease 7
• Main differential diagnoses include noninflammary vasculopathies (42%), coagulopathies (18%), cardiogenic embolism, and multiple sclerosis 7
• Not all individuals with cerebral vasculitis have clinical or laboratory signs of inflammation 2

Recommended Diagnostic Algorithm

1. Obtain detailed history focusing on headache, encephalopathy, stroke characteristics, systemic symptoms, and risk factors 2, 6

2. Perform initial laboratory panel: ANCA (both methods), CBC, CMP, ESR, CRP, urinalysis 2, 4

3. Obtain CSF analysis for opening pressure, protein, cell count, and differential 2

4. Perform MRI brain with and without contrast (including vessel wall imaging sequences) plus MRA head without contrast 1, 2, 3

5. If MRI/MRA findings are suggestive but not definitive, consider conventional cerebral angiography (DSA) 2, 5

6. If diagnosis remains uncertain despite imaging, proceed to brain biopsy targeting abnormal areas identified on imaging 2

7. Integrate all clinical, laboratory, imaging, and histopathological findings before initiating immunosuppressive therapy 2, 8, 7

Management Considerations

Once diagnosis is established:

• Patients should be managed in collaboration with or at centers of expertise (Level of evidence 3, Grade D recommendation) 2
• Treatment typically involves corticosteroids and cytotoxic agents, particularly cyclophosphamide 2, 9
• Distinguish between transient/nonprogressive and progressive arteriopathies, as some patients stabilize or improve without specific treatment 2