Primary Angiitis of the Central Nervous System: Clinical Presentation and Laboratory Findings
Primary CNS vasculitis (PACNS) most commonly presents with headache as the initial symptom, followed by encephalopathy and behavioral changes, with focal neurological deficits occurring in 20-30% of patients 1. This rare disorder affects only 2.4 cases per 1 million person-years 1.
Clinical Presentation
Core Symptoms (in order of frequency)
- Headache - the most common presenting symptom
- Encephalopathy and behavioral changes - including cognitive impairment and altered mental status
- Focal neurological deficits - present in 20-30% of cases
- Seizures - can occur, particularly in tumorous subtypes where 64.7% develop secondary epilepsy 2
- Intracranial hemorrhage - less common but possible 1
Age and Demographics
The mean age of onset is approximately 50 years 3, though the disease can affect both children and adults 2. Males appear more commonly affected, particularly in tumorous PACNS 2.
Clinical Subtypes with Distinct Presentations
Based on recent evidence, PACNS has several subtypes with different clinical profiles 2:
- Tumorous PACNS (most common subtype) - prone to epilepsy, mass-like lesions
- Angiography-positive PACNS - large vessel involvement
- Rapidly progressive PACNS - often presents with infratentorial lesions (pons, medulla) and carries higher mortality
- Hemorrhagic PACNS - rare, multifocal hemorrhagic lesions
- Spinal cord-involved PACNS - thoracic and cervical involvement, poorer prognosis
- Amyloid β-related PACNS - associated with CAA-related inflammation
Laboratory Findings
Cerebrospinal Fluid (CSF)
CSF testing should be performed to exclude alternative diagnoses including autoimmune or infectious diseases 4. While specific findings are not detailed in the guidelines, CSF analysis is essential for ruling out mimics. Recent research identifies elevated interleukin-17 in CSF as a potential biomarker 5.
Serological Markers
Serological markers of inflammation are typically within normal limits 3, which is a critical distinguishing feature. This normal inflammatory profile helps differentiate PACNS from systemic vasculitides.
Emerging Biomarkers
Recent advances have identified potential biomarkers 5:
- Neurofilament light chain
- Circulating endothelial cells
- Soluble triggering receptor expressed on myeloid cells 2 (sTREM2)
- Distinct gene expression profiles (TBC1D3C and TBC1D3L upregulation)
- Increased intrathecal NK-cell and B-cell frequencies
Imaging Findings
MRI Brain Characteristics
All patients exhibit abnormal manifestations on head MRI 2, with the following features 1:
- Multiple infarcts of variable ages - present in up to 50% of patients
- White matter injury - progressive confluent lesions
- Mass lesions - present in 5% of cases
- Meningeal enhancement - occurs in 8% of cases, with 94.1% showing uneven enhancement around lesions or leptomeninges 2
- Hemorrhage - present in 9% of cases
- Asymmetric cortico-subcortical confluent hyperintensities on FLAIR sequences
A normal MRI has nearly 100% sensitivity for excluding CNS vasculitis 1, making it an essential screening tool.
Angiographic Features
Characteristic vessel imaging findings include multifocal stenosis and dilatation of the intracranial vasculature, though these are not always present even in histologically proven cases 1. Magnetic resonance angiography revealed large vessel abnormalities in only a minority of cases 2.
Histopathological Findings
Brain biopsy remains the gold standard for diagnosis 1, with three main subtypes identified 2, 5:
- Lymphocytic vasculitis (24-79% of cases) - most common in one series at 43.7% 2
- Necrotizing vasculitis (14-42% of cases) - 31.2% in recent series, responds well to corticosteroids 2
- Granulomatous vasculitis (32-61% of cases)
Critical Diagnostic Pitfalls
The diagnosis is challenging due to nonspecific findings and numerous mimics 1. Key considerations:
- Low specificity of angiography - significant overlap with atherosclerosis and reversible cerebral vasoconstriction syndrome 1
- Limited sensitivity - small vessel involvement may be below angiographic resolution 1
- Normal inflammatory markers - unlike systemic vasculitis 3
- Heterogeneous presentation - no single finding is pathognomonic 6, 7
For young patients with epilepsy and intracranial tumorous lesions, PACNS should be strongly considered 2. When spinal cord involvement is suspected, comprehensive electromyography is recommended as it commonly reveals neural conduction abnormalities in the anterior horn or roots 2.