Primary angiitis of the central nervous system (PACNS) is a rare, subacute vasculitis restricted to the vasculature of the CNS.30 Vessels of any size may be affected, but small-vessel vasculitis is always present.31 Other than constitutional symptoms, such as fever, malaise, and anorexia, there is no consistent evidence for systemic disease related to this disorder.

The most common clinical features of the disease include seizure, stroke, headache, intellectual deterioration, or spinal cord syndromes.31 Seizures occur in up to 44% of patients.32,33

The pathophysiology of PACNS is not known. It is presumed to have an immune-mediated basis, based on its response to immune-modulating drugs. The similarities in histopathologic findings in the brain between this disorder and others such as sarcoidosis and disseminated herpes zoster suggest the possibility of an underlying process that is yet to be identified.30

Neurologic manifestations

The most common presenting symptoms of PACNS are cognitive changes, present at disease onset in 45% of patients, and headache, present in 42%.30 Headaches may be diffuse or focal, but they are typically severe and throbbing.31 Focal neurologic signs may be present at onset in up to 16% of patients.

Seizures are the presenting sign in about 10% of cases,30 but can occur in up to 44% at some time during the illness.32,33 Seizures are more frequent than can be explained on the basis of focal strokes, which occur in about 15% of patients. Seizures may be focal or generalized.

The course of PACNS is consistent with a progressive encephalopathy, with both focal and generalized manifestations becoming more common as the disease progresses. Up to one-half of the cases develop coma during some part of the illness.

Diagnosis

The diagnosis of PACNS is based on clinical suspicion and the absence of other diseases. Serologic studies to rule out systemic disorders, as well as antibody titers for some of the other immune-mediated diseases, are necessary. Unlike other disorders associated with a peripheral vasculitis, erythrocyte sedimentation rates are usually normal.31

MRI of the brain might demonstrate strokes with extensive signal abnormalities in the white matter. These findings are nonspecific and do not aid in finalizing a diagnosis.

Examination of the spinal fluid usually reveals elevated protein and a normal to moderately elevated lymphocytosis.30 Red cells may be present, with up to 200-400 cells per mm.31

EEG is also nonspecific, with findings varying from generalized slowing to focal sharp waves.

Cerebral angiography has been reported to be normal in up to 40% of cases.30 When angiography is positive, typical findings include segmental and nonsegmental narrowing or beading of small and medium-size vessels.30,31

Biopsy may be diagnostic, but the vasculitis may be missed, given its scattered, segmental nature. A diagnostic biopsy reveals evidence of small-vessel vasculitis.

Treatment

Treatment is based on immunosuppressant therapy. High-dose corticosteroids or cytotoxic agents, such as cyclophosphamide, are commonly used. There is little evidence that these drugs are effective in altering the outcome of the disease, however.

Control of seizures may be difficult. It relies on aggressive treatment of the underlying disorder.

Prognosis

Based on a review of 78 patients, mortality was close to 80%,30 with a mean survival of 6 months from onset of symptoms to death. The accuracy of these numbers is not clear, however, given the difficulty in unequivocally establishing the diagnosis.

Adapted from: Seiden L and Krumholz A. Inflammatory noninfectious disorders. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;135-154.
With permission from Elsevier (www.elsevier.com).
Reviewed and revised March 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.

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