HIV and the Brain

[Guest guest]

I wish I could get a show of hands from everyone on this board

concerning the symptoms they mention here. How many of you can

relate to what they are speaking of? Just a thought.

KC

Psychiatric Manifestations of HIV Infection and AIDS

By Ewald Horwath, M.D., and Sara Siris Nash, M.D.

Psychiatric Times November 2005 Vol. XXIII Issue 13

Human immunodeficiency virus (HIV)

HIV and the Brain

Follow the link for full story.

http://www.psychiatrictimes.com/showArticle.jhtml?articleId=174402642

Shortly after the initial HIV infection, the virus enters the

central nervous system and may cause meningitis or encephalitis.

Other serious CNS complications tend to occur late in the course of

disease, when immune function has significantly declined, though

studies have reported conflicting results as to the predictive value

of CD4 counts in assessing cognitive and motor performance

(Bornstein et al., 1991; Goethe et al., 1989; Koralnik et al., 1990;

McArthur et al., 1989; et al., 1990; Saykin et al., 1988).

Viral load is more closely associated with the degree of cognitive

impairment. Patients with serum viral loads ¡Ý30,000 copies/mL are

8.5 times more likely to develop dementia compared to patients with

viral loads <3,000 copies/mL (Childs et al., 1999). In another

study, a cerebrospinal fluid viral load >200 copies/mL was

predictive of progression to neuropsychological impairment (Ellis et

al., 2002).

HIV-Associated Dementia

Patients infected with HIV are at risk of developing dementia as a

direct result of viral infection. This syndrome has been referred to

by various names: HIV-associated dementia complex (HAD) (Working

Group of the American Academy of Neurology AIDS Task Force, 1991),

HIV encephalopathy, subacute encephalitis (Snider et al., 1983),

AIDS encephalopathy and AIDS-dementia complex (Navia et al., 1986b).

HIV-associated dementia is defined as acquired cognitive

abnormalities in two or more domains and is associated with

functional impairment and acquired motor or behavioral

abnormalities, in the absence of another etiology (Table 1).

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.

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 (, 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. (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.

The most common CNS opportunistic infections are cerebral

toxoplasmosis, cryptococcal meningitis and progressive multifocal

leukoencephalopathy. Less common CNS opportunistic infections

include meningitis caused by Mycobacterium tuberculosis and other

fungal CNS infections, such as candidiasis, coccidioidomycosis,

aspergillosis and histoplasmosis. Opportunistic viral infections

involving the CNS include cytomegalovirus, herpes simplex virus and

varicella-zoster virus. Acute mental status changes can also occur

as a result of metabolic disturbances, such as hypoxia, fever,

dehydration, electrolyte disturbances, uremia and hepatic

encephalopathy.

Central nervous system involvement also occurs as a result of

primary CNS lymphoma, which tends to occur late in the course of HIV

infection. Central nervous system manifestations of metastatic

systemic lymphoma and Kaposi's sarcoma have been reported in

patients with AIDS, but are uncommon.

Finally, many antibacterial, antifungal, antineoplastic and

antiviral medications, in addition to the antiretroviral therapies,

have CNS side effects. An awareness of the types of pharmacological

treatments used and their potential side effects is important in the

evaluation of psychiatric symptoms in patients who are HIV positive.

Some of the drugs more commonly used in HIV and their

neuropsychiatric side effects are listed in Table 3.