Clinical Findings

The mode of onset is acute or subacute. Although the classic picture is one of progressive, cumulative, and multifocal neurological dysfunction, there are abundant exceptions, including patients whose presentation suggests cerebral tumor, chronic meningitis, demyelinating disease, acute encephalitis, myelopathy, simple dementia, and even degenerative disorders. Although often mentioned in the differential diagnosis, especially in patients without risk factors, isolated CNS vasculitis rarely causes stroke (Wiszniewska et al., 2003). When isolated CNS vasculitis presents as a stroke, it is usually due to intracerebral hemorrhage, which occurs in approximately 15% of patients at some time in the illness. The disease rarely causes single cerebral infarcts or transient ischemic attacks in the absence of clinical or laboratory evidence of widespread CNS inflammation, verified by cerebrospinal fluid (CSF) pleocytosis.

Nonfocal symptoms such as headache and confusion are the most common presenting complaints. Aside from confusion, the most common sign at presentation is hemiparesis. Ataxia of limbs or gait, focal cortical dysfunction including aphasia, and seizures are also frequent. Virtually every neurological sign or symptom has been reported at least once (Schmidley, 2000). Nonspecific visual complaints occur in approximately 15% of patients, but disorders of specific ocular motor nerves, optic nerve, or visual fields are much less common. Systemic symptoms are generally absent. Fully developed cases almost invariably show signs and symptoms of progressive, widespread neurological dysfunction; however, occasional patients present with a multiple sclerosis–like course of early relapses and partial remissions or clinical manifestations largely restricted to one part of the nervous system, such as the spinal cord or cerebellum.

Pathology

The vascular inflammation is usually of a chronic granulomatous nature, with monocytes and histiocytes, lymphocytes, and plasma cells infiltrating the walls of small (200 µm) arteries and veins, particularly in the leptomeninges. Larger vessels may be involved but never to an extent exceeding that of smaller ones. Although present in most autopsy cases, giant cells are not required to make a diagnosis. There is no predilection for bifurcations, as in polyarteritis nodosa, although fibrinoid necrosis can occur; eosinophils are not present in large numbers. Small, clinically silent foci of vasculitis are occasionally discovered in one or more viscera but by definition produce neither laboratory nor symptomatic evidence of organ dysfunction.

Cause and pathogenesis are unknown. Many vasculitis syndromes are a result of deposition of immune complexes, but there is little support for this mechanism in isolated CNS vasculitis. There is no convincing evidence of infection with Mycoplasma or any other microorganism in isolated CNS vasculitis, although Mycoplasma does cause a CNS vasculitis in animals. A secondary cerebral vasculitis frequently complicates acute or chronic meningeal infections and may be responsible for cerebral infarction or hemorrhage in these conditions.

Laboratory Findings

General medical laboratory investigations are usually unremarkable. Some patients have an elevated sedimentation rate but usually not to the degree seen in temporal arteritis. The laboratory is of use only in eliminating systemic vasculitis, neoplasm, infection, or other alternative diagnoses. Electroencephalography and computed tomography are not specific but are usually abnormal. Magnetic resonance imaging (MRI) is equally nonspecific. Although some literature has claimed the contrary, the CSF has been abnormal (in some way) in almost all autopsy-documented cases. Unfortunately, the CSF abnormalities are totally nonspecific, namely a mild lymphocytic pleocytosis and a mild to moderate elevation in protein. Oligoclonal bands and elevated immunoglobulin (Ig) G index are occasionally encountered, as are low glucose values and leukocyte counts of several hundred per microliter. The major value of CSF examination in investigating suspected CNS vasculitis is to rule out infection, including syphilis, and neoplastic infiltration of the meninges.

Although some publications emphasize the value of angiography in making the diagnosis, cerebral angiography has been entirely normal in many pathologically documented cases, and the arteriographic changes of vasculitis, when seen, are not specific (Schmidley, 2000). Given its lower spatial resolution, magnetic resonance angiography is unlikely to be useful either.

The “typical” findings of vasculitis in cerebral angiography are widespread segmental changes in the contour and caliber of vessels. Small aneurysms, usually on vessels more distal than those bearing congenital saccular aneurysms, are occasionally present but cannot be distinguished from aneurysms complicating atrial myxoma or infective endocarditis. Occlusion of large cerebral vessels is rare.

It is our opinion that many published cases of angiographically diagnosed CNS vasculitis, including the so-called benign variant, represent misinterpretation or overinterpretation of nonspecific angiographic changes, unconfirmed by a tissue diagnosis. Until the pathological processes underlying these cases are established, the use of more circumspect terms such as cerebral angiopathy or reversible segmental cerebral vasoconstriction (RSCV), also known as Call-Fleming syndrome, is appropriate. The latter is a poorly defined syndrome that appears to be induced by several different stimuli (Calabrese et al., 2007). The typical patient with RSCV is a woman between the ages of 20 and 50, with acute onset of headache and focal neurologic deficits. Often, the headache can be so severe (“thunderclap”) as to suggest aneurysmal subarachnoid hemorrhage. By definition, angiographic changes “typical” for vasculitis are seen, but these invariably improve, usually in a timeframe incompatible with resolution of vasculitis. The improvement often takes place concurrent with the administration of prednisone, other immunosuppressive agents, calcium channel blockers, or magnesium but cannot be confidently attributed to any therapy, since an identical degree of resolution has occurred in the absence of any specific therapy. Brain biopsy has been negative in the few cases where it was done; CSF, although not invariably normal, is much more likely to be normal than in true CNS vasculitis. A variety of drugs have been implicated in RSCV, most commonly the ergots, other antimigraine therapies, over-the-counter sympathomimetics, cocaine, and most recently the selective serotonin reuptake inhibitors. The syndrome is not progressive and seldom recurs. Optimal therapy is unknown; often a brief course of prednisone or calcium channel blockers is given. It is prudent to discontinue any implicated drugs.