Central nervous system vasculitis

Central nervous system (CNS) vasculitides represent a heterogeneous group of inflammatory diseases affecting the walls of blood vessels in the brain, spinal cord, and the meninges.

Please refer to the article on vasculitis for a general discussion of that entity. 

The aim of this article will be to discuss the primary angiitis of the CNS (PACNS) since the other vasculitides wereare already discussed in specific articles. 

Terminology

CNS vasculitides are classified as ^1-2,2:

• primary: confined to the CNS with no involvement of other systems - referred as PACNS
• secondary: occurs in the context of a systemic inflammatory or infectious process

Please, note that this classification is different from that one used when discussing systemic vasculitides.

Epidemiology

PACNS remains a rare disorder: an estimated average annual incidence rate of 2.4 cases per million. It affects patients of all ages, but peaks at around 50 years of age, with males affected more commonly than females ¹.

Secondary causes of CNS vasculitis far exceed in number PACNS ². Please refer to each specific vasculitis for further details.  

Clinical presentation

Clinical features of PACNS are non-specific. The diagnosis is made based on Calabrese’s criteria ⁴, including:

• the presence of an acquired otherwise unexplained neurological or psychiatric deficit
• the presence of either classic angiographic or histopathological features of angiitis within the CNS (biopsy remains the standard of reference for diagnosis ³)
• no evidence of systemic vasculitis or any disorder that could cause or mimic the angiographic or pathological features of the disease

When part of a systemic disorder, the diagnosis may be easier, unless the cerebral symptoms are the first to manifest. Please refer to a specific vasculitis for further details on clinical manifestation. 

Pathology

For almost all forms of vasculitis, including PACNS, the triggering factor is unknown ³. 

CNS secondary vasculitides:

• affecting large blood vessels
  • Takayasu arteritis: uncommon to have CNS involvement
  • giant cell arteritis
• affecting medium blood vessels
  • polyarteritis nodosa (PAN)
  • Kawasaki disease
• affecting small blood vessels
  • IgA arteritis
  • microscopic polyangiitis (microscopic polyarteritis)
  • granulomatosis with polyangiitis
  • eosinophilic granulomatosis with polyangiitis
• variable vessels sizes
  • Cogan syndrome
  • Behçet disease
• associated with systemic disease
  • SLE
  • rheumatoid arthritis
  • Sjogren syndrome
  • APLA syndrome
  • scleroderma
• associated with a known aetiology 
  • infection-induced vasculitis
  • drug-induced
  • malignant-induced
  • radiation-induced

Radiographic features

Imaging findings for PACNS are usually variable and nonspecific, with ischemic infarctions the most common lesions, occurring in 53% of cases ⁵. 

CT

May show areas of hypoattenuation.

Angiography (DSA)

ShowsDigital subtraction angiography shows focal or multifocal segmental narrowing of both small and medium-sized blood vessels, occlusions are also present. The same findings could be demonstrated in both CTA and MRA.

MRI 

More specific to show multiple infarctions: usually bilateral, affecting different vascular territories of variable size, and in various stages of healing. 

T2 and FLAIR high-intensity lesions in the white matter are also very common in PACNS, but completely nonspecific. 

Meningeal enhancement and intracranial haemorrhage can also be seen.

Vessel wall MRI (VW-MRI) may be a useful adjunct to conventional MRI, allowing differentiation between vasculitis, where there is contrast enhancement of the affected arterial wall, and other causes of vascular narrowing, such as intracranial atherosclerotic plaque, reversible cerebral vasoconstriction syndrome, dissection, and moyamoya disease⁷. 

Treatment and prognosis

PACNS is managed with high dose steroids and cytotoxic agents ³. 

History and etymology

PACNS was initially reported in 1959 by Humberto Cravioto and Irwin Feigin ⁶.

Differential diagnosis

• reversible cerebral vasoconstriction syndromes (RCVS)
• Moyamoyamoyamoya disease

Practical points

Remember that despite being composed by nonspecific findings, MRI is almost 100% sensitive for PACNS and a normal exam practically excludes this diagnosis ¹.