In this exploratory study, we examined the long-term neuropsychological outcomes in individuals with a history of AIDS-related CNS-OI, including TE, CM, and PML. To our knowledge, this is the first systematic group study of residual CNS-OI effects on neurocognitive function in HIV+ individuals. Our observations suggest that these conditions leave most individuals with a poor prognosis regarding recovery of cognitive functioning. Characterizing the deficits in these individuals could lead to targeted rehabilitation and possibly improve prognosis and return to independence.
Upon study entry, all three CNS-OI groups had poorer neuropsychological functioning than did HIV+ individuals who did not have a history of AIDS-related CNS-OI, despite the fact that the latter group had been infected with HIV for an equal or longer duration. Those with past TE appeared to have the poorest neuropsychological functioning across all but the memory domain, and this was not attributable to the large number of primary Spanish speakers in that group. The CM group differed from the comparison group on the verbal fluency and motor domains, while the PML group differed on the information processing and motor domains. More so than the other domains, these consisted of measures given under the pressure of time, in which scores were time dependent. Thus, it may be that the AIDS-related CNS-OIs examined here result in persistent deficits of cognitive and psychomotor processing speed. Notably, such deficits have historically been among the most commonly observed in HIV+ individuals, even those considered asymptomatic (Arendt & von Giesen, 2002
; Davis, Skolasky, Selnes, Burgess, & McArthur, 2002
; Dunlop et al., 2002
; von Giesen, Haslinger, Rohe, Köller, & Arendt, 2005
). Thus, these AIDS-related CNS-OIs may serve to potentiate HIV-related deficits in psychomotor and cognitive processing speed. Conversely, the deficits may exist as a consequence particular to these conditions.
Aside from these deficits, which were consistent across AIDS-related CNS-OIs in our cohort, it is unlikely that these conditions are associated with a distinct neuropsychological profile, as they can affect the entire brain or large portions within. For example, toxoplasmic tachyzooites, the cause of TE, multiply rapidly in the brain cells that they parasitize and give rise to a strong inflammatory reaction and diffuse brain lesions in grey and white matter (Falangola, Reichler, & Petito, 1994
). TE thus results in a variety of focal neurological deficits, brain edema, and increased intracranial pressure. Survivors of TE may be afflicted with any number of problems, including hydrocephalus, permanent focal motor and sensory deficits, or seizures (Arendt et al., 1999
). PML causes severe demyelination associated with lysis of oligodendrocytes, as well as axonal loss, and focal neurological deficits such as hemiparesis (Roberts, 2005
). And while most cases of CM preferentially involve the meninges, AIDS patients may develop focal abscesses (cryptococcomas) within the brain parenchyma (Lee, Dickson, & Casadevall, 1996
), and CM can result in increased intracranial pressure, strokes, brain abscess, and parenchymal loss (Bicanic & Harrison, 2004
; Woodworth, McGirt, Williams, & Rigamonti, 2005
). The effects of the lesions caused by these CNS-OIs on neurobehavioral functioning varies widely. CM has been associated with mania (Johannessen & Wilson, 1988
), TE has been found to mimic HIV-associated dementia (Arendt et al., 1991
) and to be associated with alexia (Luscher & Horber, 1992
), and PML has been associated with integrative agnosia (Butter & Trobe, 1994
). Thus, these conditions can result in focal or generalized neuropsychological abnormalities, as well as alterations in psychiatric functioning. This is supported by the case studies described earlier (Gasnault et al., 1999
; Paul et al., 2007
; Wyen et al., 2005
), in which there were vastly differing long-term outcomes in individuals with PML. In sum, it appears from our results, as well as previous findings, that aside from decreased cognitive and psychomotor processing speed, these infections may not be associated with distinct neuropsychological profiles, but instead with a wide range of neurologic and psychiatric impairments. In those with HIV, it may also be increased severity of deficits rather than a distinct profile.
To our knowledge, these findings are drawn from the largest cohort of individuals with a history of AIDS-related CNS-OI to date. However, the conclusions are tentative due to a number of limitations. First, information regarding the dates of AIDS-related CNS-OI was not available. As a result, it is not known how much time had passed since the acute phase of the illnesses. Such information will be valuable in the future, as it will allow trajectory of recovery to be ascertained. The recent findings reported by Paul et al. (2007)
provide a promising methodology (i.e., diffusion tensor imaging) for such studies; however, larger sample sizes will be required. A second limitation is the limited power due to small sample sizes. Fortunately, the small CNS-OI group sizes likely reflect the efficacy of antiretroviral treatment. However, they are also the result of rather stringent inclusion criteria used for the present study. Individuals were excluded who had current substance use disorders and history of a wide variety of neurologic disorders and complications. Substance use is quite common in our cohort and typical of the HIV+ population in the greater Los Angeles area. Finally, it can be argued that our decision to exclude individuals with HIV-associated neurocognitive disorders resulted in an inflated difference of neuropsychological scores between the comparison and CNS-OI groups. However, in this exploratory study we wished to characterize the deficits in the CNS-OI groups, which was possible only by comparing them to a similar group of individuals that differed only on the presence or history of an AIDS-related CNS-OI. For future studies, in which the long term functional and real-world outcomes of CNS-OIs are examined, the inclusion of individuals with HIV-related cognitive deficits will be important.
To conclude, we have presented data indicating that HIV+ individuals with a history of CNS-OI continue to have severe and lasting neuropsychological impairments as compared to HIV+ individuals with no history. Studies employing more participants, as well as functional measures of day-to-day functioning, are required to further advance our understanding of the long-term consequences of AIDS-related CNS-OI.