In the latest Case Record of the Massachusetts General Hospital, a 39-year-old man with a recent diagnosis of HIV infection was admitted to this hospital with fever and bizarre, nihilistic delusions, including statements that he had died. A diagnostic procedure was performed.
Psychosis is a symptom, not a diagnosis, and can be organized into primary and secondary (organic) psychoses. Unfortunately, there is no easy way to reliably differentiate primary from secondary psychoses on the basis of the characteristics of the psychosis itself, and assessment of the overall clinical situation is very important in narrowing the differential diagnosis and determining the degree of urgency.
• How is the diagnosis of delirium made?
The clinical diagnosis of delirium hinges on the presence of two cardinal features: disruption of attention and disruption of the sleep-wake cycle, which leads to fluctuation in symptoms over the course of a day. A delirium can be easily missed if ancillary features such as psychosis overshadow the core problem of inattention. A routine electroencephalogram (EEG) showing abnormal slowing is useful if positive, but a normal EEG is not sensitive enough to reliably rule out a delirium. The sudden onset of psychosis in a patient with fluctuating mental status is a delirium until proven otherwise.
• What are the typical clinical features of HIV-associated psychosis and how is it treated?
The common clinical features of HIV-associated psychosis include sudden onset without prodrome, delusions (87% of patients), hallucinations (61%), and mood symptoms (81%). In HIV-associated psychosis, neurologic findings are typically limited and CT findings are nonspecific; however, EEGs are abnormal in 50% of cases. Cognitive impairment has consistently been described as a feature of HIV-associated psychosis, although it cannot be distinguished from a first episode of schizophrenia. Since substance abuse is a common coexisting disorder in HIV-infected patients and can further impair cognition, it is important to rule out the use of alcohol or other drugs as a contributing cause. When psychosis occurs in patients with HIV-associated dementia, it is characterized by prominent agitation, irritability, and delusions and is often part of a manic syndrome that has been called “AIDS mania.” Olanzapine is an antipsychotic agent often chosen for treatment because of its proven efficacy and relatively low risk of causing extrapyramidal symptoms and tardive dyskinesia, which are highly prevalent among patients with HIV.
Morning Report Questions
Q: What is the differential diagnosis of sudden change of mental status in a patient with advanced HIV-1 infection?
A: The differential diagnosis includes processes that cause central nervous system disease in immunosuppressed hosts. Cerebral toxoplasmosis should be considered, particularly in the setting of serologic evidence of past infection. Magnetic resonance imaging (MRI) typically demonstrates ring-enhancing lesions. Cryptococcal meningitis is another possibility. Results of cerebrospinal fluid (CSF) analysis are often bland in cryptococcal meningitis, since the organism may not elicit a robust inflammatory response. Detection of cryptococcal antigen in the CSF helps to establish this diagnosis. Infection with Mycobacterium tuberculosis may cause chronic central nervous system disease, which may manifest as tuberculous meningitis or a tuberculoma. Although MRI may reveal gross disease, it is not particularly sensitive for the detection of invasion of the central nervous system; therefore, tuberculosis affecting the central nervous system cannot be ruled out. Cytomegalovirus (CMV) infection should also be considered, especially if abnormalities are seen on retinal examination. Testing for CMV in the blood and CSF is used to make this diagnosis; negative results make CMV encephalitis unlikely although not impossible. These patients are also at risk for progressive multifocal leukoencephalopathy or lymphoma associated with Epstein-Barr virus.
Q: What is the immune reconstitution inflammatory syndrome (IRIS)?
A: Immune reconstitution inflammatory syndrome (IRIS) is a paradoxical worsening of inflammation caused by the reconstitution of immune function while on antiretroviral therapy. As immune function starts to recover, patients often mount an exuberant inflammatory response to an underlying infectious agent. IRIS is typically treated with prednisone, in addition to treatment of the underlying infection.