Objective: To determine the relationship between cerebrospinal fluid (CSF) beta-2-Microglobulin (beta-2M) and severity of AIDS dementia complex (ADC), and between CSF beta-2M and response of ADC to zidovudine.Design: A prospective study.Setting. Tertiary referral hospital.Patients, participants: Seventy-eight patients with varying stages of ADC were selected from a subgroup of a cohort of HIV-seropositive patients who are being studied prospectively for the neurological complications of HIV-1 infection. To enter our study, patients had to have an ADC stage of at least 0.5 (equivocal symptoms or abnormal neurological signs in the absence of functional impairment). A control group of 11 HIV-1-seropositive, neurologically normal patients was chosen randomly from the patients followed in the Multicenter AIDS Cohort Study.Interventions: Patients were assessed neurologically and neuropsychologically and computed tomography of the brain and CSF studies were performed.Main outcome measures: Patients were staged according to severity of ADC on clinical criteria. Neuropsychological test scores were converted to an impairment score. CSF beta-2M was quantified in both serum and CSF of all patients and in 10 patients with pre- and post-zidovudine assessments.Results: There was a high correlation between CSF beta-2M concentration and severity of ADC (P < 0.0001); treatment with zidovudine significantly reduced these concentrations (P = 0.013). CSF beta-2M concentration was independent of CSF white-cell count and blood-brain barrier impairment. Other CSF changes in the same patients (including blood-brain barrier permeability to albumin, intrathecal synthesis of immunoglobulin G and HIV-1-p24-antigen levels) were less useful as objective correlates of ADC severity and response to zidovudine therapy.Conclusions: CSF beta-2M may be a valuable marker of ADC severity and response to antiviral therapy.

We assessed dichotic speech and complex-pitch discrimination in nine young patients with unilateral left-hemisphere injury and eight young patients with unilateral right-hemisphere injury incurred in the pre-peri-natal (congenital) period. As in adults with acquired unilateral lesions, both congenital lesion groups demonstrated poor performance on stimuli presented to the ear contralateral to the lesion. In overall performance on speech discrimination, however, the left-hemisphere congenital lesion group performed significantly better than the acquired-lesion group did. On complex-pitch discrimination, the right-hemisphere congenital lesion group performed significantly better than did the acquired-lesion group, but both left- and right-hemisphere congenital lesion groups were significantly worse at complex-pitch discrimination than were their age and gender-matched normal controls. These results indicate that although congenital damage produces a "lesion effect" in dichotic listening similar to that after damage acquired in adulthood, overall function is relatively spared. To the extent that complex-pitch discrimination is affected by congenital damage to either hemisphere but speech discrimination is not, the present results are consistent with an asymmetric form of crowding during reorganization after congenital unilateral brain damage.

Quinolinic acid is an "excitotoxic" metabolite and an agonist of N-methyl-D-aspartate receptors. Of patients infected with human immunodeficiency virus type 1 (HIV-1) who were neurologically normal or exhibited only equivocal and subclinical signs of the acquired immunodeficiency syndrome (AIDS) dementia complex, concentrations of quinolinic acid in cerebrospinal fluid (CSF) were increased twofold in patients in the early stages of disease (Walter Reed stages 1 and 2) and averaged 3.8 times above normal in later-stage patients (Walter Reed stages 4 through 6). However, in patients with either clinically overt AIDS dementia complex, aseptic meningitis, opportunistic infections, or neoplasms, CSF levels were elevated over 20-fold and generally paralleled the severity of cognitive and motor dysfunction. CSF concentrations of quinolinic acid were significantly correlated to the severity of the neuropsychological deficits. After treatment of AIDS dementia complex with zidovudine and treatment of the opportunistic infections with specific antimicrobial therapies, CSF levels of quinolinic acid decreased in parallel with clinical neurological improvement. By analysis of the relationship between levels of quinolinic acid in the CSF and serum and integrity of the blood-brain barrier, as measured by the CSF:serum albumin ratio, it appears that CSF levels of quinolinic acid may be derived predominantly from intracerebral sources and perhaps from the serum. While quinolinic acid may be another "marker" of host- and virus-mediated events in the brain, the established excitotoxic effects of quinolinic acid and the magnitude of the increases in CSF levels of the acid raise the possibility that quinolinic acid plays a direct role in the pathogenesis of brain dysfunction associated with HIV-1 infection.

Cognitive skills were assessed in 13 females with a history of precocious adrenarche (PA). They were of average intelligence. In terms of lateralized cognitive skills, PA had no effect on verbal fluency. The spatial abilities of females with a history of PA, who had reached gonarche (were fully pubertal), were inferior to those of females tested in the midst of PA and to population controls. The physiologic/hormonal changes associated with normal adrenarche may curtail further specialization of the right hemisphere, resulting in a relative spatial deficit among females in general, who as a group reach adrenarche earlier than males. This spatial performance deficit is exaggerated in females with PA.

Patients with left hemisphere lesions deep in parietal or parietal-occipital regions close to the lateral ventricles have been reported to have impaired performance on left ear speech stimuli in dichotic listening tests. This loss has been termed "paradoxical" because it presents at the ear ipsilateral to the lesion. Two patients with infiltrating tumors which involved the corpus callosum demonstrated that effect, but also demonstrated right ear extinction on a complex-pitch discrimination test that required right hemisphere processing. Since the side at which the impairment will be demonstrated depends upon the type of test used, the term "paradoxical extinction" does not clearly describe this phenomena. It is suggested that the so-called paradoxical loss is better referred to as callosal extinction.

Forty‐three normal 7 to 12‐year‐olds were tested on dichotic complex‐pitch and speech discrimination tests. For each age group (7 to 8 years, 9 to 10 years, and 11 to 12 years), the adult patterns of perceptual asymmetries were observed: a right‐ear advantage for speech and a left‐ear advantage for complex‐pitch, without significant changes either in the magnitude of perceptual asymmetries or in the frequency of occurrence of particular patterns of asymmetry as a function of age. For overall accuracy, however, a significant increase with age was found for speech but not for pitch discrimination, suggesting that despite the absences of significant age‐related changes in perceptual asymmetries in these two tasks, they may nevertheless undergo different developmental courses.