A degree of therapeutic success in this formerly fatal disease has been achieved by the use of cyclophosphamide, chlorambucil, rituximab, or azathioprine. Cyclophosphamide in oral doses of 1 to 2 mg/kg per day has ameliorated 90 to 95 percent of the cases. Methotrexate, azathioprine, and rituximab have been used infrequently studied systematically. An exception is the trial conducted by Guillevin and colleagues, in which rituximab was found to be superior to azathioprine in reducing relapses after patients with ANCA positive vasculitis had attained remission with cyclophosphamide and glucocorticoids. Approximately 40 percent of their patients had neurologic features. The literature can be consulted for doses and anecdotal effectiveness as applied to the neurologic aspects. In acute cases, rapidly acting steroids— prednisone, 50 to 75 mg/d—is usually given in conjunction with the immunosuppressant drug(s).
Involvement of the nervous system is an important aspect of this disease but referable syndromes are quite disparate. In the pathologic and clinical series reported by Johnson and Richardson, the central nervous system (CNS) was affected in 75 percent of cases, but our recent experience has suggested a lower frequency of clinical manifestations, especially if minor neurologic aspects such as headache are excluded. Disturbances of mental function—including alteration of consciousness, seizures, and signs referable to cranial nerves—are the usual neurologic manifestations; most often they develop in the late stages of the disease, but they may occur early and may be mild and transient. Hemiparesis, paraparesis, aphasia, homonymous hemianopia, movement disorders (chorea), and derangements of hypothalamic function occur but have been infrequent in our experience. Larger infarcts are usually traceable to emboli from Libman-Sacks (a form of nonbacterial thrombotic) endocarditis.
In some instances, the CNS manifestations resemble multiple sclerosis, especially when there is an optic neuritis or myelopathy. Two manifestations that should be noted are of “longitudinally extensive myelopathy” that simulates Devic disease, and of white matter changes in the cerebral hemispheres with varied clinical manifestations, (“Sjogren sclerosis,” or “lupus sclerosis”). These are discussed in Chap. 35 with multiple sclerosis and diseases that simulate it. The presence of serum antinuclear antibodies is of help in the differentiation of lupus erythematosus but in itself does not establish the diagnosis. Antibodies to double-stranded DNA (anti-dsDNA) are a sensitive indicator of the disease. The CSF is normal or shows only a mild lymphocytic pleocytosis and slight increase in protein content, although in some patients—primarily those with peripheral neuropathy and myelopathy—the protein content may be greatly increased.
Some of the neurologic manifestations can be accounted for by widespread microinfarcts in the cerebral cortex and brainstem; these, in turn, are related to destructive and proliferative changes in arterioles and capillaries. The acute lesion is subtle; it is not a typical fibrinoid necrosis of the vessel wall, like that in hypertensive encephalopathy, and there is no cellular infiltration. Attachment of immune complexes to the endothelium is the postulated mechanism of vascular injury. Thus, the changes do not represent a vasculitis in the strict sense of the word. However, there is also an immune component to some of the white matter and cord lesions that do not require implicating a vasculopathy (see Chap. 35).