In this week’s Case Record of the Massachusetts General Hospital, a 45-year-old man with a history of alcoholism was admitted to the hospital because of cognitive decline and jaundice. He had a 3-month history of cough, blood-tinged sputum, and vomiting. Imaging showed a peripherally enhancing brain lesion. A diagnostic procedure was performed.
Somnolence may result from abnormalities in either cerebral cortex, the reticular activating system (rostral brain stem), or both sides of the medial thalamus. The findings of somnolence (in the absence of signs of aphasia or amnesia), slow speech, difficulty putting words together, conversational repetition, and slurred speech suggest global hemispheric dysfunction.
• What neoplastic processes are part of the differential diagnosis of a peripherally enhancing brain lesion?
The differential diagnosis of a peripherally enhancing brain lesion should always include the following neoplastic processes: metastatic tumors, primary glial tumors, and primary lymphoma of the central nervous system. Although tumor metastases may cause a solitary peripherally enhancing lesion, such lesions are more commonly multifocal. High-grade glioma may cause a solitary, rim-enhancing lesion as the relatively rapid tumor growth outstrips the blood supply, leading to central necrosis. However, both anaplastic astrocytoma and glioblastoma are more typically heterogeneously enhancing and often cross the midline. Primary lymphoma of the central nervous system, usually diffuse large B-cell lymphoma, may occur in otherwise healthy persons. Alternatively, it may occur as part of advanced infection with human immunodeficiency virus (HIV), in which case it is characteristically associated with detectable Epstein-Barr virus (EBV) DNA in the cerebrospinal fluid. It is usually homogeneously enhancing, although cases involving patients who are HIV positive may be heterogeneous or peripherally enhancing.
• What is the differential diagnosis of a subacute confusional state in a patient with liver disease?
The differential diagnosis includes five major syndromes: hepatic encephalopathy, Wernicke’s encephalopathy, alcohol withdrawal, occult seizures, and infection. Hepatic encephalopathy refers to an alternation in cognitive function that is secondary to a metabolic process caused by liver failure. Wernicke’s encephalopathy refers to the triad of gait ataxia, opthalmoplegia and confusion caused by thiamine deficiency, commonly seen in chronic alcoholics. Alcohol withdrawal, occult seizures, and underlying infection may also cause a subacute confusional state in a patient with chronic liver disease.
Morning Report Questions
Q: What is the typical presentation of CNS toxoplasmosis?
A: Toxoplasma is a protozoon that rarely causes serious illness in normal hosts. In patients with advanced HIV infection, however, it is the most common cause of focal brain mass lesions. Patients with toxoplasma infection typically present subacutely with headache, fever, changes in mental status, and focal neurologic deficits. Imaging studies of the brain reveal characteristic rim-enhancing lesions that are usually multifocal but may be solitary in up to 30% of cases. Lesions are typically less than 4 cm in diameter. Serologic testing for toxoplasma IgG would be helpful, since this test has high sensitivity for toxoplasma exposure. However, antibodies may be lost in patients with profound immunosuppression, and seroprevalence is higher in Europe than in the United States. These lesions characteristically improve rapidly with appropriate treatment. Therefore, if the clinical scenario allows observation, a trial of specific antimicrobial agents may be both therapeutic and diagnostic.
Q: What is the appropriate treatment for CNS toxoplasmosis?
A: First-line treatment for cerebral toxoplasmosis includes pyrimethamine and sulfadiazine, with folinic acid (leucovorin) to reduce the hematologic adverse effects from the antimicrobial agents. Second-line therapy, in patients who cannot take sulfadiazine or in whom it is not tolerated, is clindamycin, pyrimethamine, and folinic acid.