What are the forms of Central Nervous System (CNS) vasculitis?

Forms of Central Nervous System (CNS) Vasculitis

CNS vasculitis can be broadly categorized into primary CNS vasculitis and secondary CNS vasculitis, with further classification based on vessel size (large, medium, and small vessel) involvement. 1, 2

Primary CNS Vasculitis

Primary CNS vasculitis, also known as Primary Angiitis of the Central Nervous System (PACNS), is a rare idiopathic disorder affecting blood vessels exclusively in the brain, spinal cord, and meninges 3. It can be subcategorized into:

1. Large-to-medium vessel vasculitis (angiography positive)

   • Detectable on conventional angiography, MRA, or CTA
   • Typically presents with focal neurological deficits, stroke episodes, and transient ischemic attacks 2
   • More likely to cause ischemic or hemorrhagic stroke

2. Small vessel vasculitis (angiography negative)

   • Too small to be demonstrated on conventional imaging techniques 1
   • Best diagnosed by brain biopsy 1, 3
   • Typically presents with headaches, altered consciousness, and cognitive deficits 2
   • May present as a mass lesion or multifocal encephalopathy 1

3. Histopathological patterns of PACNS 4:

   • Granulomatous vasculitis (most common, ~60%)
   • Lymphocytic vasculitis (~25%)
   • Necrotizing vasculitis (least common, ~12%)

Secondary CNS Vasculitis

Secondary CNS vasculitis occurs as part of systemic conditions 1, 5:

1. ANCA-Associated Vasculitis:

   • Granulomatosis with polyangiitis (GPA) - formerly Wegener's granulomatosis
   • Eosinophilic granulomatosis with polyangiitis (EGPA) - formerly Churg-Strauss syndrome
   • Microscopic polyangiitis (MPA)

2. Large Vessel Vasculitis:

   • Giant cell arteritis - affects proximal portions of intracranial arteries 6
   • Takayasu's arteritis - typically involves extracranial arteries 6

3. Medium Vessel Vasculitis:

   • Polyarteritis nodosa
   • Kawasaki disease

4. Other Causes of Secondary CNS Vasculitis:

   • Systemic autoimmune diseases: Systemic lupus erythematosus, Sjögren's syndrome
   • Infectious causes: Varicella-zoster virus, HIV, hepatitis C virus, syphilis, tuberculosis
   • Malignancy-associated
   • Drug-induced
   • Post-varicella angiopathy 1
   • Transient cerebral arteriopathy 1

Special Considerations in Pediatric Patients

In children, CNS vasculitis presents as:

1. Childhood primary angiitis of the CNS 1

   • Similar subcategorization as adult PACNS
   • Diagnosis requires:
     • Acquired neurologic deficit
     • Angiographic or histologic features of CNS vasculitis
     • No evidence of systemic condition

2. Post-infectious cerebral arteriopathy

   • Including post-varicella angiopathy 1

Diagnostic Approach

The diagnosis of CNS vasculitis is challenging and requires:

1. Laboratory studies:

   • Erythrocyte sedimentation rate (ESR) - often normal or minimally elevated in primary CNS vasculitis 1
   • CSF analysis - may show increased opening pressure, elevated protein, lymphocytic pleocytosis 1, 2

2. Neuroimaging:

   • MRI - abnormal in >90% of cases, showing multifocal parenchymal lesions 1
   • Conventional angiography - most sensitive for medium-large vessel disease 1
   • CT - typically negative in CNS vasculitis 1

3. Definitive diagnosis:

   • Cortical-leptomeningeal biopsy - most specific diagnostic test 1, 3
   • Yield increases when performed in areas abnormal on imaging 1

Treatment Considerations

For primary CNS vasculitis, treatment typically involves:

1. Induction therapy: Glucocorticoids plus cyclophosphamide with an 80% response rate 2
2. Maintenance therapy: Azathioprine, mycophenolate mofetil, or methotrexate 3, 7
3. Refractory cases: Biological agents such as rituximab or TNF-alpha inhibitors 3, 7

For secondary CNS vasculitis, treatment should target the underlying cause along with appropriate immunosuppression 2.

Prognostic Factors

Poor prognostic factors include:

• Increasing age at diagnosis
• Large vessel involvement
• Cerebral infarcts at presentation
• Diagnosis by angiography alone without biopsy confirmation 2

Better outcomes are associated with gadolinium-enhanced cerebral lesions and prompt diagnosis with early treatment initiation 2.