Primary Angiitis (Vasculitis ) of the CNS

Learning objectives

Introduction

• Known as Primary central nervous system vasculitis (PCNSV) and Primary Angiitis of the CNS( PACNS)
• The inflammation of blood vessels can lead to changes in blood vessel structure and function as well as stasis and thrombosis.
• Outcomes vary from spontaneous resolution to rapid decline and death
• All ages are vulnerable but seen in middle aged and slightly more so in men
• Very rare with 1-2 cases per 1,000,000 person years

Aetiology

• Unclear but there is an association with amyloid angiopathy
• Possibly triggered by infection CMV/EBV/VZV/HIV mycoplasma and chlamydia have been suggested
• Granulomatous type inflammatory lesions could suggest a Th1-mediated response
• Involves small-medium sized arteries and veins

Differential for "Beading" appearance

Clinical

• Altered cognition, headache, signs may be subtle
• Both haemorrhagic or ischaemic stroke may ensure
• Inflammatory changes lead to seizures, headache, and encephalopathy.
• Coma may develop due to widespread oedema and raised ICP
• There is no identifiable cause and only affects the CNS

Investigations

• FBC: WCC, DWCC, CRP, ESR and abnormal LFTs, U&E, Urinalysis. Coagulation. Complement levels fall in vasculitis associated with immune complexes
• ANA, Anticardiolipin-antibodies, lupus anticoagulant, electrophoresis, CK, LDH, haptoglobulin, ferritin, ACE usually negative
• Cryoglobulins, TSH, thyroid antibodies, RF, ANA, Anti ds-DNA, anti-histone, complement, anti-Ro [SS-A] and anti-La [SS-B-], c- and pANCA/MPO [myeloperoxidase], anti-endothelial antibodies
• Drug screening, blood cultures, Syphilis serology, borreliosis, hepatitis B, and C, HIV all negative
• CSF analysis may be useful and is abnormal in 90%. Usually inflammatory with raised protein and mild elevated white cells and normal glucose but no evidence of organisms or malignant cells or TB which is important especially before considering immunosuppression. For example, in primary angiitis of the central nervous system the CSF may be normal. Also send VZV PCR. Exclude syphilis.
• MRI: Is abnormal in over 90% of cases. It will show the characteristic changes of infarction on DWI and ADC maps and gradient echo sequences will show changes and changes on FLAIR both in cortical and subcortical zones. Some MRI sequences will allow evidence of inflammatory changes. 18-fluorodeoxyglucose positron emission tomography scanning can also be useful in showing increased uptake and inflammatory changes in the vessel walls.
• Angiography: May show narrowing and dilatation that alternates and gives the 'string of beads' name. However, this only signifies a vasculopathy and not necessarily a vasculitis. In pathology proven PACNS the angiography has been shown to be normal. DSA is preferred over MRA.
• Cerebral and meningeal biopsy focused to an area with abnormal radiological appearance with Immunohistochemistry is definitive but often points to alternative diagnoses.

Differentials

• Reversible vasoconstriction syndromes, Secondary cerebral vasculitis, malignancy
• Vasculopathy due to varicella zoster virus, syphilis, polyarteritis nodosa, granulomatosis with polyangiitis or others
• Cortical and subcortical so can mimic large and small vessel stroke
• Demyelination, CADASIL

Management

• The most challenging aspect is making an accurate diagnosis. Normal MRI and CFS is very much against the diagnosis. Angiography is not reliable for accurate diagnosis and a brain biopsy is needed.
• Management requires the use of toxic immunosuppressive therapy so all attempts must be made to establish a reliable diagnosis and assess if the treatment is more harmful than the vasculitis.
• Standard therapies include intravenous methylprednisolone and weekly pulse intravenous cyclophosphamide as induction treatment.

References/Further reading

• Central Nervous System Vasculitis: Still More Questions than Answers. Curr Neuropharmacol. 2011 Sep; 9(3): 437-448.
• Primary angiitis of the central nervous system: avoiding misdiagnosis and missed diagnosis of a rare disease
• Medscape review