What is the recommended management for a patient with central nervous system vasculitis strongly suggested by digital subtraction angiography who presents with new neurological deficits, headache, seizures, or cognitive change?

Management of CNS Vasculitis Suggested by DSA

For patients with CNS vasculitis strongly suggested by DSA presenting with new neurological deficits, headache, seizures, or cognitive changes, initiate combination immunosuppressive therapy with high-dose corticosteroids plus cyclophosphamide, while simultaneously pursuing definitive diagnosis through brain biopsy and comprehensive evaluation to exclude secondary causes. 1, 2, 3

Immediate Diagnostic Priorities

Confirm the Diagnosis and Exclude Mimics

• DSA findings alone are insufficient for definitive diagnosis because angiographic abnormalities (arterial beading, alternating stenosis and dilatation) have low specificity and overlap significantly with intracranial atherosclerosis and reversible cerebral vasoconstriction syndrome 4, 1
• Only 33% of biopsy-confirmed cases show positive DSA findings, and conversely, only 8% of angiogram-confirmed cases have positive biopsies, suggesting these may represent different disease subtypes 5
• Brain and leptomeningeal biopsy remains the most specific diagnostic test and should be performed targeting abnormal areas identified on MRI to maximize yield 1, 2

Complete the Imaging Protocol

• Obtain contrast-enhanced MRI brain with vessel wall imaging (VWI) sequences immediately if not already performed, as this increases diagnostic accuracy from 36% to 89% compared to luminal imaging alone 4, 6
• MRI will be abnormal in >90% of CNS vasculitis cases, showing multiple infarcts of variable ages (50% of patients), mass lesions (5%), meningeal enhancement (8%), or hemorrhage (9%) 1, 7
• Vessel wall enhancement on post-contrast T1 sequences helps differentiate inflammatory vasculitis from non-inflammatory vasculopathies 6

Distinguish Primary from Secondary CNS Vasculitis

Laboratory evaluation must include:

• ANCA testing (both indirect immunofluorescence and ELISA) to identify systemic vasculitis 1
• ESR and CRP (typically normal or minimally elevated in primary CNS vasculitis but elevated in systemic vasculitis) 1, 2, 8
• Cerebrospinal fluid analysis looking for pleocytosis (rarely >250 cells/mm³), elevated protein, or oligoclonal bands 1, 9
• Comprehensive infectious workup if fever is present, as infectious vasculitis shows low CSF glucose and unique oligoclonal bands 9

Critical clinical clues for secondary vasculitis:

• Fever strongly suggests infectious or connective tissue disorder-associated vasculitis rather than primary CNS vasculitis 7, 9
• Known history of connective tissue disease (all CTD-associated vasculitis patients in one cohort had known CTD at presentation) 9
• Systemic symptoms, skin lesions, or glomerulopathy point toward systemic vasculitis 1

Treatment Approach

Induction Therapy

Initiate combination therapy with:

• High-dose intravenous methylprednisolone (most commonly used induction agent, utilized in 63.6% of patients) 9
• Cyclophosphamide as adjunctive therapy for both primary CNS vasculitis and secondary CNS involvement by small-medium vessel systemic vasculitis 2, 3, 8, 9
• Rituximab may be considered as an alternative to cyclophosphamide, particularly if cyclophosphamide is contraindicated 2, 8

Maintenance Therapy

• All patients should receive maintenance immunosuppression after induction therapy 2
• Options include cyclophosphamide, rituximab, azathioprine, or mycophenolate mofetil, often with concurrent prednisone 8, 9
• Methotrexate is recommended as an alternative once remission is achieved 8

Clinical Phenotype Recognition

Medium Vessel Disease (Angiogram-Positive)

• Presents predominantly with focal neurological signs (95% of angiogram-confirmed cases) 5
• Headache occurs in 51% and cognitive impairment in 39% of these patients 5
• Seizures are less common (16%) 5

Small Vessel Disease (Biopsy-Confirmed)

• More commonly presents with cognitive impairment (55%) and seizures (36%) 5
• Focal neurological signs occur in only 56% 5
• Can only be definitively diagnosed with CNS biopsy, as small vessels are below angiographic resolution 2

Critical Pitfalls to Avoid

• Do not delay treatment while awaiting biopsy results in patients with progressive neurological deterioration, as mortality ranges from 8-23% and outcomes worsen with delayed treatment 5, 9
• A negative biopsy does not exclude CNS vasculitis due to the focal, segmental nature of the disease 1, 3
• Do not attribute fever solely to the vascular event itself—it may indicate infectious vasculitis requiring specific antimicrobial therapy in addition to immunosuppression 7
• Relapse rates are high (30-34%), requiring vigilant long-term monitoring and maintenance therapy 5
• Inflammatory cerebral amyloid angiopathy (CAA) mimics primary CNS vasculitis but occurs in older patients with more microhemorrhages and has higher relapse rates 9

Prognosis and Monitoring

• CNS vasculitis carries significant morbidity and mortality with disabling symptoms and frequent relapses 5
• Management should occur at centers of expertise given the rarity and complexity of the condition 1
• Long-term follow-up is essential, with median follow-up periods of 19-57 months reported in major cohorts 5