Autoimmune Encephalopathy

Eoin P. Flanagan, M.B.B.Ch.; Richard J. Caselli, M.D.


Semin Neurol. 2011;31(2):144-157. 

In This Article

Encephalopathy in Cerebral Vasculitis

Primary CNS Vasculitis

Primary CNS vasculitis (PCNSV) is an immune-mediated attack on the small and medium blood vessels in the brain that most frequently presents as an autoimmune encephalopathy with or without multiple cerebral infarctions.[24] An important initial step in the diagnosis of PCNSV is undertaking an evaluation to exclude mimics, especially those causing secondary CNS vasculitis including infection, systemic autoimmune disorders, and malignancy (see below).

Infarcts or hemorrhages are often seen on MRI. Magnetic resonance angiography (MRA) is frequently performed but is usually normal as it has poor resolution for small and medium vessels. CSF examination may demonstrate evidence of inflammation, including lymphocytic pleocytosis and increased protein concentration in the majority of patients with PCNSV.[25] Conventional cerebral angiography may reveal the classic finding of alternating segments of ectasia and stenosis in the small arteries known as "beading."[26] The sensitivity of angiography is poor due to the small size of vessels involved, and brain biopsy may be needed to confirm the diagnosis. Furthermore, this beading pattern can be seen with other diseases, and the gold standard for diagnosis is histopathology. A brain biopsy should involve the leptomeninges and parenchyma, preferably in an affected region. Pathologic findings classically demonstrate granulomatous segmental vasculitis of the small and medium leptomeningeal or cortical arteries with Langerhans or foreign body giant cells.[26] A necrotizing vasculitis or lymphocytic vasculitis may also be seen.[27]

Treatment of PCNSV involves the use of corticosteroids and cyclophosphamide. Early recognition of the diagnosis and early initiation of treatment appears to improve outcomes.[25] Initial treatment is with high-dose oral prednisolone 1 mg/kg for 4 to 6 weeks followed by a slow taper over 6 months. Cyclophosphamide in daily oral dose of 1.5–2 mg per day or 750 mg/m2 monthly infusions are used for 3 to 6 months. Cyclophosphamide may be replaced, if needed, by a less-toxic immunosuppressant, such as mycophenolate or azathioprine, for a further 6 to 12 months of treatment. Close monitoring of blood counts and renal function every 2 weeks and urinalysis monthly should be undertaken to detect early complications. Patients undergoing intermittent infusions of cyclophosphamide require mercaptoethane sulfonate (MESNA) to minimize hemorrhagic cystitis. Patients should be counseled regarding the risks of infertility with cyclophosphamide (that may require harvesting of eggs or sperm).

Secondary CNS Vasculitis

Central nervous system vasculitis may occur as a secondary phenomenon in systemic vasculitic diseases or in connective tissue disorders. Infections may also cause secondary CNS vasculitis, and therefore prompt examination of serum and CSF should be undertaken to exclude infectious causes, such as varicella zoster associated vasculitis. The clinical features and appropriate diagnostic tests for connective tissue disorders and systemic vasculitides are outlined in Table 5. Treatment of these disorders is similar to that outlined in the section on autoimmune encephalopathies; however, specific proven treatments for the underlying systemic autoimmune disease often guide treatment of the encephalopathy.

Large Vessel Vasculitis

The two major causes of large vessel vasculitis include giant cell (temporal) arteritis, which almost always affects those over age 60, and Takayasu's arteritis, which typically affects children and young women and is most common in Japan. Giant cell arteritis usually presents with new-onset headache in a middle-aged to elderly patient with an elevated ESR. Bilateral temporal artery biopsies are often recommended to obtain diagnosis. Acute encephalopathy is a rare complication of giant cell arteritis and is most often due to extracranial vasculitis[28] causing stroke, but intracranial involvement has also been reported.[29] Patients may also have a vascular dementia-like disorder. The overall prognosis of giant cell arteritis associated encephalopathy is poor.[29] Takayasu's arteritis is a granulomatous disease of the aortic arch and its proximal branches and may affect the carotid arteries. Claudication symptoms in the upper limbs and differences in blood pressure between both arms are commonly found.[30] Encephalopathy may arise secondary to stroke. Diagnosis is made by the appropriate clinical features occurring in a patient less than 40 years of age with angiographic findings of proximal aortic involvement.[31] Treatment of both giant cell arteritis and Takayasu's arteritis involves high-dose oral prednisolone followed by a prolonged taper.


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