The clinical manifestations of HAD are predominantly those of subcortical dementia, with some similarity to those found in dementia associated with Huntington's disease and Parkinson's disease. Neuropathological evidence demonstrates that HIV-related diseases in the CNS are preferentially located in certain subcortical structures of the brain (e.g., white matter, basal ganglia and hippocampus) as well as in the spinal cord (Cummings, 1990; Navia et al., 1986a). Consistent with the subcortical nature of the dementing process, patients with HAD typically have disturbances in three neuropsychiatric spheres of functioning: cognitive, motor and behavioral.
The cognitive disturbance usually has a subtle onset and involves slowed thinking, memory impairment, forgetfulness and difficulty concentrating. Patients often complain that normal activities take longer or that they have to repeatedly reread paragraphs of text in order to understand them. As the dementia progresses, gross cognitive disturbances often occur, and patients begin to experience greater difficulty managing their financial affairs or shopping and caring for themselves.
Frank disorientation, confusion and muteness are observed late in the illness. Psychiatric symptoms, such as agitation, mania, hallucinations and paranoid delusions, are also not unusual in advanced disease stages. The management of these psychiatric disturbances needs to take into account the greater sensitivity to the extrapyramidal side effects of antipsychotic medications seen in patients with HIV infection (Perry, 1990). For this reason atypical antipsychotics with a low risk of EPS, such as quetiapine (Seroquel) and aripiprazole (Abilify), may be preferable in this population.
The motor disturbance begins with subtle signs such as slowed movements or hand tremor. Other common symptoms include decreased balance, lack of coordination, difficulty with rapid alternating movements, abnormal eye movements (including saccades and pursuit) and a sense of general clumsiness. For patients afflicted with vacuolar myelopathy or spinal cord involvement from HIV, motor signs include gait difficulty or bumping into things. When sitting, they may find themselves unexpectedly leaning or falling to one side in the absence of adequate postural support.
As the impairment progresses, patients experience weakness in their upper and lower extremities. In late stages of disease, paraplegia and urinary and bowel incontinence occur. When motor signs and symptoms occur in the absence of HIV dementia, the syndrome is known as HIV-associated myelopathy.
Behavioral symptoms include social withdrawal, apathy, sleep disturbances, fatigue, headaches and decreased libido. These features may be difficult to distinguish from depressive symptoms, though the patient often lacks the dysphoria experienced in a clinical major depression. Perry (1990) has commented that the apathy, withdrawal and mental slowing found in HAD can be differentiated clinically from low self-esteem, irrational guilt and other features characteristic of depression. Nonetheless, these symptoms are important to recognize and should not be dismissed simply as emotional responses to the diagnosis of HIV infection. A less severe form of CNS disease associated with HIV infection is HIV-associated minor cognitive-motor disturbance, which is differentiated from HAD based upon the presence of fewer symptoms and little or no functional impairment (Table 1).
Opportunistic Infections
Infection with HIV may indirectly lead to neuropsychiatric disturbances due to CNS opportunistic infections, neoplasms and metabolic disorders (Table 2). These infections are unusual in the absence of HIV and tend to occur late in the course of illness, when immune function is waning, CD4+ cell counts fall to very low levels and viral load is rising. With the widespread use of highly active antiretroviral therapy (HAART), the incidence of opportunistic infections and other complications of HIV infection have fallen dramatically. The identification of the underlying cause of neuropsychiatric disturbance in an individual infected with HIV is very important because some of these conditions are responsive to treatment, and delayed diagnosis and treatment may result in permanent CNS damage.
