Predominantly Focal Brain Disorders
In approaching diagnosis of parenchymal brain disease, it is useful to separate the conditions that cause predominantly focal symptoms and signs from those producing more generalized brain dysfunction. Patients in the former group present with hemiparesis, aphasia, apraxia, hemisensory abnormalities, visual field loss, and the like, as a result of focal macroscopic lesions in cortical or subcortical brain regions. The most important of the focal brain diseases are cerebral toxoplasmosis, primary CNS lymphoma and PML. Although the incidence of each of these has declined with widespread use of HAART, toxoplasmosis, which was once the most common of the three, has decreased disproportionately related to trimethoprim-sulfamethoxazole prophylaxis. Less common are a miscellany of other infections and cerebrovascular disorders.
Although the three major focal disorders all characteristically have a subacute onset and may be clinically indistinguishable, they tend to have somewhat different temporal profiles (Table 411-3) . Thus, cerebral toxoplasmosis typically progresses most rapidly (over a few days) and PML evolves most slowly (over a few weeks), with primary CNS lymphoma somewhere in between. Each may cause similar neurologic deficits, but there are often differences in the associated findings.
Thus, toxoplasmosis commonly presents with a combination of focal deficit and generalized encephalopathy with confusion or clouding of consciousness; fever and headache may also be present. This contrasts with PML in which focal neurologic deficits are unaccompanied by either diffuse brain dysfunction or evidence of a systemic toxic state. CNS lymphoma, when accompanied by significant mass effect or when deep in the frontal or periventricular region, may cause more global mental dysfunction, but, again, these patients are usually afebrile without constitutional symptoms or signs.
Once the focal nature of the patient’s symptoms and signs is recognized, neuroimaging, including computed tomography (CT) or preferably magnetic resonance imaging (MRI), is critical both to confirm the presence of macroscopic focal disease and to determine the nature of the abnormalities (Table 411-3) . Multiple lesions involving the cortex or deep brain nuclei (thalamus, basal ganglia) surrounded by edema strongly favor cerebral toxoplasmosis. In most cases Toxoplasma abscesses exhibit ringlike contrast enhancement. Cerebral lymphoma may produce a similar neuroimaging appearance, although the lesions of lymphoma are usually less numerous (one or two definable lesions), commonly exhibit more diffuse or less clear-cut contrast enhancement, and are more often located in the white matter adjacent to the ventricles. Spread beneath the ependymal lining or across the corpus callosum is also characteristic. PML characteristically involves the white matter, most often adjacent to the cortex, and is without mass effect or contrast enhancement.
The approach to diagnosis of focal brain lesions has evolved in the last few years related to appreciation of their neuroimaging characteristics and the value of toxoplasma serology along with the advent of CSF PCR in diagnosis. The first step in patients with focal neurologic symptoms and signs involves neuroimaging. Where mass lesions are present, the next step usually is distinguishing primary brain lymphoma from toxoplasmosis. If the blood toxoplasma serology is negative and the MRI shows lesions characteristic of lymphoma, then either EBV DNA sequences should be sought in CSF or brain biopsy undertaken without delay so that therapy can begin quickly. If the brain lesions appear more characteristic of toxoplasmosis and the serology is negative, then a trial of antitoxoplasma therapy is undertaken with expectation of clinical improvement within several days and neuroimaging improvement within 1 to 2 weeks. Unless herniation threatens, corticosteroids should be avoided because their effect on lymphoma and brain edema can obscure the more specific influence of antitoxoplasma treatment. Lack of improvement or suspicion of another diagnosis should signal the need for brain biopsy or other diagnostic measures. PML can usually be identified by the combination of steadily progressive focal neurologic dysfunction and the characteristic white matter lesions on MRI. Where further confirmation is needed, either CSF PCR for JC virus or brain biopsy can be used.
Other focal CNS disorders are uncommon but include some treatable lesions. This includes cryptococcal invasion of brain which nearly always develops in the setting of meningitis. Varicella-zoster virus (VZV) can cause both a demyelinating focal disease resembling PML and a cerebral vasculitis and cytomegalovirus (CMV) may rarely cause macroscopic lesions accompanied by focal clinical deficit. Herpes simplex viruses have also been reported to cause focal deficits. All of these evolve subacutely, as do the more common opportunistic problems. Acutely evolving neurologic deficits may follow seizures (Todd’s palsy) or ischemic events.
Revision date: July 6, 2011
Last revised: by Sebastian Scheller, MD, ScD
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