Approach Considerations

When initially abnormal, brain MRI and CSF examination can be used with clinical findings to evaluate patient response to treatment.

Patients taking cyclophosphamide should be evaluated periodically for signs of drug toxicity. CBC should be performed every 2 weeks. The dose should be reduced or the drug should be temporarily held in case of leucopenia (WBC < 4000) or absolute neutropenia (neutrophils < 2000).

Patients, especially elderly patients, taking steroids should be given vitamin D and calcium supplements for bone mineral loss, and H2 blockers or proton-pump inhibitors for peptic ulcer disease. Blood glucose should also be monitored closely to detect iatrogenic diabetes.

Medical Care

Combined immunosuppressive therapy is the treatment of choice for primary angiitis of the central nervous system (PACNS). This therapy was initially proposed after its success in patients with systemic vasculitis such as Wegner granulomatosis and polyarteritis nodosa but is not supported by evidence from controlled trials in PACNS.

Current recommendation is oral prednisone, 1 mg/kg/d, and cyclophosphamide, 2 mg/kg/d. Treatment consists of 2 phases: Induction of remission and maintenance of remission. Duration of each phase is debatable, but most centers use prednisone and cyclophosphamide for 4-6 months to induce clinical remission, and then taper prednisone off to continue cyclophosphamide for 1 year.

Joseph and Scolding suggest a the following relatively different plan:^[6]

An induction regimen for 9-12 weeks: Cyclophosphamide 2.5 mg/kg/d coupled with intravenous methylprednisolone, 1 g/d for 3 days, then oral prednisolone, 60 mg/d, to be decreased by 10 mg at weekly intervals to reach a dose of 10 mg/d, if possible.
A maintenance regimen for further 10 months: Alternate day steroids (10-20 mg prednisolone) along with azathioprine, 2 mg/kg/d, substituted for cyclophosphamide.

Methotrexate, 10–25 mg weekly, might be used in case of cyclophosphamide or azathioprine toxicity. Although no prospective controlled studies have been performed on this treatment, retrospective reviews showed good outcomes of prednisone with cyclophosphamide therapy in PACNS and provide support for the use of this regimen in pathologically confirmed cases.

Intravenous immunoglobulin (IVIG), plasmapheresis, and monoclonal antibodies have not been used extensively in PACNS. Their use in systemic vasculitis has produced variable results.^[6]

Rituximab has recently been used in combination with steroids in two patients, with reported neurologic improvement.^[27]

Benign angiopathy of CNS (BACNS) is probably not a true vasculitis, but rather reversible vasoconstriction, and should be treated differently. Several case series showed good outcomes of prednisone, 1 mg/kg/d, for a short course (< 6 mo), along with calcium channel blockers such as verapamil, amlodipine, or nimodipine.^[17]However, many authors now recommend only nimodipine, 60 mg every 4-8 hours for 4-12 weeks, without steroids.^[24]Some patients have resolved on no treatment.

In patients with presumed BACNS, a brain biopsy should be obtained in cases of questionable diagnosis, failure of medical management, and persistence of symptoms.

Surgical Care

Insertion of external ventricular drain might be indicated as usual in cases of primary angiitis of the central nervous system (PACNS) with intraparenchymal or intraventricular hemorrhage and associated hydrocephalus.

Consultations

Rheumatology, infectious diseases, or other medical specialties should be consulted as indicated in individual cases of primary angiitis of the central nervous system (PACNS). Neurologists not familiar with the use of cyclophosphamide should seek the aid of a rheumatologist or oncologist.

Diet

A calorie-controlled and sodium-controlled diet should be advised for patients with primary angiitis of the central nervous system (PACNS) who take steroids. These patients should also be taking adequate vitamin D and calcium supplements.

Medication

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Media Gallery

Lateral right internal carotid angiogram shows beading of anterior cerebral arteries (arrowheads) and beading (straight arrows), segmental dilatation (curved arrow), and narrowing of middle cerebral arteries (open arrow).
Low power view of inflamed vessel in the subarachnoid space shows fibrinoid necrosis (pink areas) superiorly.
Higher power view of small inflamed vessel in the medulla, with fibrinoid necrosis in the wall and chronic transmural inflammation.
(a) T1-weighted left parasagittal MRI showing hypointense lesions in the cortical and subcortical white matter of the left superior temporal gyrus and frontal and frontoparietal operculum with sulcal obliteration. (b) The postgadolinium MRI at this level showing nodular parenchymal and linear pial enhancement.
(a) T2-weighted axial MRI showing hyperintense lesions in the lentiform nuclei, head of the caudate nuclei and frontoparietal subcortical white matter. (b) On T1-weighted (postgadolinium) axial image, the lentiform nuclei and head of caudate nuclei are heterogeneously hypointense, while subcortical white matter lesions are isointense. Linear areas of pial enhancement are seen bilaterally.
(a) T2-weighted axial MRI showing large, well-defined hyperintense lesions in the left frontal and parietal lobes. (b) Postgadolinium T1-weighted axial MRI showing nodular parenchymal and cortical-pial enhancement of the lesion. A follow up (after 3 mo) T2-weighted axial (c) and postgadolinium (d) T1-weighted axial MRIs showing significant reduction of the lesion size and nodular enhancing areas.