Differential Diagnosis

Differential diagnosis is paramount in evaluating neu-rocognitive symptoms in HIV/AIDS medical inpa-tients, especially when investigating for medical and neuropsychiatric etiological factors related to HIV illness and its treatment. Table 10.2 lists the major differential diagnostic considerations.

Multiple studies have indicated that 60%-70% of patients with HIV infection have one or more psychiatric disorders prior to contracting HIV illness (Perry et al., 1990; Williams et al., 1991; Lyketsos et al., 1995). Patients with Axis I disorders, including depression, bipolar disorder, schizophrenia, and substance abuse, may present with cognitive complaints or impairment. Substance intoxication and/or withdrawal are also common causes of cognitive impairment, particularly delirium. CNS opportunistic illnesses (OIs) and cancers can also present with a wide range of cognitive and neuropsychiatric symptoms, most often in the context of delirium, as a result of both focal and generalized neuropathological processes. Table 10.3 lists the major CNS OIs, their major symptom presentation, and diagnostic workup.

Hepatitis C infection, independent of HIV coin-fection and interferon/ribavirin therapy, is characterized by multiple neuropsychiatric complaints, most frequently fatigue (up to 97% of patients), depression

figure 10.1. Schematic depiction of proposed modified criteria for HIV-associated neurocognitive disorders. NP, neuropsychological; SD, standard deviation. Forstein M et al., 2006.

(up to 25% of patients meet criteria for a current depressive disorder and up to 70% have elevated scores on depression rating scales), and cognitive dysfunction (up to 82% impairment on some measures) (Crone and Gabriel, 2003). Compared to patients with HIV alone, patients with comorbid HIV and hepatitis C are more likely to have disturbances in executive function and dementia (Ryan et al., 2004). The pattern of cognitive impairment associated with hepatitis C is similar to that of HIV. Patients with mild liver disease tend to have impairment in attention and concentration, and patients with more severe liver fibrosis have problems with learning, psychomotor speed, and cognitive flexibility. Patients with end-stage liver disease and cirrhosis experience superimposed delirium ("hepatic encephalopathy"). Combination pegylated interferon alpha 2a and ribavirin treatment for hepatitis C is well known to be a cause ofdysphoria, suicidal ideation, anxiety, sleep disturbance, fatigue, mania, psychosis, confusion, and cognitive dysfunction (Crone and Gabriel, 2003).

Several antiretroviral and other medications used in the context of HIV have been associated with neuropsychiatry side effects. These include zidovudine (Maxwell et al., 1998), didanosine (Brouillett et al., 1994), abacavir (Foster et al., 2004), nevirapine (Mor-lese et al. 2002), efavirenz (Bartlett and Ferrando, 2004), interferon alpha 2a (Crone and Gabriel, 2003), and clarithromycin (Colebunders and Florence, 2002). Most of these effects are infrequent and causal relationships linking them to the medications have been difficult to discern (Johnson et al., 2003). The most widespread clinical concern has been generated by reports of sudden-onset depression and suicidal ideation after treatment with interferon alpha 2a (discussed above) and/or efavirenz. Early reports suggested that efavirenz may be associated with at least transient neuropsychiatric side effects in excess of 50% of patients (Staszewski et al., 1999). Reported effects are protean and include depression, suicidal ideation, vivid nightmares, anxiety, insomnia, psychosis, cognitive dysfunction, and antisocial behavior (Bartlett and Ferrando, 2004). Some, but not all, reports suggest that patients with a prior history of substance use or other psychiatric disorders are at greater risk for the neuropsy-chiatric side effects of efavirenz (Bartlett and Ferrando, table 10.2. Differential Diagnosis of HIV-Associated Neurocognitive Disorders

• Delirium (from multiple possible etiologies, often superimposed on underlying neurocognitive disorder)

• Primary or comorbid psychiatric disorder (e.g., depression)

• Primary or comorbid neurodegenerative disorder (e.g., Alzheimer disease, vascular dementia)

• CNS opportunistic illnesses and cancers (e.g., cytomegalovirus or herpes simplex encephalitis, progressive multifocal leukoencephalopathy)

• Substance intoxication and/or withdrawal

• Neuropsychiatric complications of hepatitis C and its treatments

• Neuropsychiatric side effects of HIV medications

• Metabolic complications of HIV medications (e.g., diabetes, cerebrovascular and cardiovascular disease)

Drug interactions

• Endocrinological abnormalities (e.g., hypogonadism, adrenal insufficiency)

table 10.3. Opportunistic Illnesses of the Central Nervous System in AIDS

Opportunistic Illness

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