Infections in the Immunocompromised Host: Progressive Multifocal Leukoencephalopathy and Nocardiosis

Progressive Multifocal Leukoencephalopathy. Progressive multifocal leukoencephalopathy (PML) is a disease caused by the JC virus, a polyoma virus that is acquired in childhood, establishes latent infection in the kidneys and lymphoid organs, and reactivates in the setting of cellular immunosuppression. Because PML is a viral infection of oligodendrocytes causing focal areas of demyelination, the clinical presentation is that of focal or multifocal neurologic deficits, including hemianopsia, hemiparesis, or aphasia. On neuroimaging, the lesions are located in the subcortical hemispheric white matter, sparing the U fibers, and are typically not contrast enhancing and not surrounded by edema. The spinal fluid is similarly noninflammatory. There may be a slight increase in the white blood cell count and a mild elevation in the protein concentration. The diagnosis is made by demonstration of JC virus deoxyribonucleic acid (DNA) by polymerase chain reaction (PCR) of cerebrospinal fluid (CSF) or by brain biopsy. There is no specific antiviral therapy, and treatment is directed at reversing the immunosuppression.

Nocardiosis. Nocardia asteroides is a gram-positive bacterium that is found in soil and decaying vegetables. This bacterium is a causative organism of a brain abscess in individuals with impaired cell-mediated immunity. Risk factors include organ transplantation, immunosuppressive therapy, pulmonary alveolar proteinosis, sarcoidosis, and pregnancy. Unlike the primary management of the majority of bacterial brain abscesses by stereotactic aspiration guided by computed tomography (CT) or magnetic resonance imaging (MRI), a brain abscess due to Nocardia asteroides requires surgical excision through a craniotomy. These are thick-walled multiloculated brain abscesses. The infection is treated with trimethoprim-sulfamethoxazole or sulfonamide. Nocardial brain abscesses are relatively rare in human immunodeficiency virus (HIV)-positive individuals, because many HIV-positive individuals take trimethoprim-sulfamethoxazole to prevent Pneumocystis carinii.

Listeriosis. Listeria monocytogenes is a gram-positive bacterium that causes meningitis in immunocompromised individuals from organ transplantation, malignancies, chronic corticosteroid therapy, immunosuppressive therapy, diabetes mellitus, and pregnancy. Increasing age is also a risk factor for Listeria monocytogenes meningitis due to the natural decrease in cell-mediated immunity. Infection is acquired from soft cheeses, unpasteurized milk, hot dogs, deli meats, and cole slaw. In addition to meningitis, Listeria monocytogenes is one of the causative organisms of a brainstem encephalitis (rhomboencephalitis). Patients typically have headache, nausea, vomiting, and fever, followed by brainstem symptoms and signs, the most common of which is a unilateral facial nerve palsy. This is followed by dysarthria, vertigo, dysphagia, and hemiataxia. Spinal fluid analysis demonstrates a CSF pleocytosis with a predominance of neutrophils but also a mixture of lymphocytes and monocytes. The spinal fluid may also show a predominance of lymphocytes or monocytes. The glucose concentration may be decreased or normal. The organism can be grown in culture of CSF. In rhomboencephalitis, a lesion of increased signal intensity on T2-weighted and fluid attenuated inversion recovery (FLAIR) imaging can be seen in the pons and medulla. Therapy of meningitis due to Listeria monocytogenes is with ampicillin. In patients who are obtunded, gentamicin is added. Rhomboencephalitis is treated with a combination of ampicillin and gentamicin.

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