NeuroQuiz Section Editor: Lawrence S. Honig, MD, PhD, Columbia University, New York, New York.
A 32-year-old right-handed man with a history of AIDS presented with a series of 3 generalized epileptic seizures, associated with lip laceration, incontinence, postictal sonorous breathing, and postictal lethargy. Two months earlier, when his CD4 lymphocyte count was 7/μL, he had headaches and was diagnosed as having cryptococcal meningitis. The cerebrospinal fluid antigen titer was 1:1024, and he was treated with intrathecal amphotericin B and flucytosine. His medical history included syphilis (serum rapid plasma reagin titer of 1:256) treated with penicillin, renal insufficiency, and macrocytic anemia. Treatment included maintenance fluconazole and high-intensity antiretroviral therapy. There was a history of marijuana and alcohol use. Neurological examination findings, after resolution of the postictal state, were normal except for mild papilledema. Laboratory studies revealed low-level human immunodeficiency viremia (600 human immunodeficiency virus RNA copies/mL), a low CD4 lymphocyte count (75/μL), and abnormal cerebrospinal fluid findings, with a white blood cell count of 53/μL (to convert to ×109/L, multiply by 0.001), a protein level of 0.154 g/dL (to convert to grams per liter, multiply by 10.0) , a glucose level of 34 mg/dL (to convert to millimoles per liter, multiply by 0.0555), and a cryptococcal antigen titer of 1:32. Magnetic resonance imaging of the brain revealed signal abnormalities on T2-weighted fluid-attenuated inversion recovery sequence images, including cortical sulcal and basal ganglionic hyperintensities (Figure). Contrast administration was deemed inadvisable owing to renal insufficiency.
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Correct Answer: Immune Reconstitution Inflammatory Syndrome.
What is your diagnosis?
Magnetic resonance images show fluid-attenuated inversion recovery T2-weighted signal abnormalities in the basal ganglia bilaterally as well as extensive subtle signal hyperintensity in the meninges. The basal ganglia changes are consistent with the history of cryptococcal meningitis and are not necessarily indicative of active disease. The magnetic resonance imaging abnormalities in the meninges are characteristic of an active cellular inflammatory meningeal infiltrate. Cerebrospinal fluid abnormalities of mild to moderate pleiocytosis, an elevated protein level, and hypoglycorrhachia are consistent with an inflammatory or infectious process. While cortical magnetic resonance imaging abnormalities after seizures can be seen on diffusion-weighted magnetic resonance imaging, the meningeal fluid-attenuated inversion recovery abnormalities seen here are not consistent with seizure-related signaling abnormalities. The differential diagnosis includes infections or inflammation. The diffuse pattern of convexity changes is not characteristic of syphilis. Meningitis due to bacteria or atypical bacteria would likely be reflected in a febrile encephalitic syndrome with greater neurological impairment. This sort of meningeal involvement would be unusual for lymphoma, as would the cerebrospinal fluid findings. Therefore, the differential diagnosis is between active cryptococcal meningitis and immune reconstitution inflammatory syndrome. The cerebrospinal fluid data with a reduced fungal antigen titer together with increasing CD4 lymphocyte counts suggestive of immune reconstitution point to a diagnosis of immune reconstitution inflammatory syndrome. This syndrome appears to relate to acute inflammation due to reconstitution of the immune system. Typically, more successful antiretroviral therapy (perhaps compared with prior medical noncompliance) results in improved immune system function, with immune recognition of remnant organismal antigens, and ensuing inflammation. Supporting this diagnosis, cultures for fungi were negative and seizures abated with glucocorticosteroid and anticonvulsant treatment without additionally instituted antifungal treatment.