Clinical aspects of the AIDS dementia complex in relation to histopathological and immunohistochemical variables.

To correlate cerebral histopathological and immunohistochemical changes in the neuroclinical features of the AIDS dementia complex (ADC), autopsy results of 28 ADC patients were related, in a retrospective analysis, to scores on a standardised neurological examination performed at neurologic onset. From a histopathological point of view, the cases were classified as follows: 9 cases of HIV leucoencephalopathy (HIVL; diffuse myelin damage and rare microglial nodules), 7 cases of HIV encephalitis (HIVE; several microglial nodules and no myelin damage) and 12 cases of mixed HIVL and HIVE (HIVL-E). The groups differed significantly with respect to symptoms and CD4 count at neurologic onset, survival and neurological impairment. Immunohistochemically, the interstitial component (p24-positive cells scattered singly within the white matter) was significantly more prevalent in HIVL, and the micronodular component (p24-positive cells confined within microglial nodules) in HIVE. Neurological damage was worse in cases with a high prevalence of interstitial component or a low prevalence of micronodular component. HIVE, HIVL and HIVL-E are distinct clinical forms of ADC. Neurological impairment is related to white matter damage.

Rantes distribution and cellular localization in the brain of HIV-infected patients.

OBJECTIVE: To study the immunochemical distribution ofRantes chemokine and its correlation with HIV-p24 expression, in brains with HIV-related lesions. MATERIAL AND METHODS: 17 HIV-positive cases of HIV-related brain lesions, 7 HIV-positive cases without cerebral HIV-related lesions (5 with opportunistic brain diseases), and 7 HIV-negative cases as controls (4 with brain lesion) were selected. RESULTS: High expression of Rantes was observed in the cases with inflammatory brain lesions (22/24 HIV-positive and 2/7 HIV-negative patients). Positivity was observed in the diffuse and nodular microglial cells and lymphocytes. In the patients with HIV-related lesions, the presence of Rantes-stained microglia did not correlate with that of HIV-p24-positive cells. Positive astrocytes were only found in the HIV-positive patients. Multinucleated giant cells were always Rantes-negative. CONCLUSIONS: Our results seem to demonstrate the role of Rantes chemokine in inducing inflammatory brain perivascular and microglial reactions both in HIV-positive and -negative patients.

Beta amyloid precursor protein and patterns of HIV p24 immunohistochemistry in different brain areas of AIDS patients.

OBJECTIVES: To evaluate the correlation between immunohistochemical positive patterns (globular and filamentous structures) of beta-amyloid precursor protein (beta-APP), used as a marker of axonal damage, and the different distribution of HIV p24 antigens, in three different brain areas of AIDS patients. METHODS: Eighteen AIDS patients with HIV-related brain lesions were included in the study. Forty-nine sections from basal ganglia, frontal cortex and hippocampus were selected. After microwave oven pre-treatment, the sections were incubated with anti-HIV p24 and anti-beta-APP monoclonal antibodies; the reactions were developed with peroxidase/3,3'diaminobenzidine. The positivity was graded by semi-quantitative scores. Double immunohistochemical staining was used to evaluate the co-localization of the antigens. RESULTS: HIV p24 immunohistochemistry was positive in 44 of 49 sections (89%), with a prevalence of interstitial positive cells and positive microglial nodules in 27 and 13 sections respectively. beta-APP-positive structures were demonstrated in 23 of 44 sections (52%) with HIV-related lesions, and were absent from the five sections without viral expression. Globular and filamentous lesions were observed in 21 of 23 sections and 10 of 23 lesions respectively. Moreover, a high grade of globular type lesion was related to an elevated presence of diffuse interstitial HIV p24-positive cells in basal ganglia; double immunohistochemical reactions demonstrated the co-localization of beta-APP globules and HIV p24 antigens. CONCLUSIONS: The data obtained confirm the coexpression of beta-APP and viral antigens in particular areas of the brain with HIV-related lesions; there is a strict correlation between beta-APP globules (indicating chronic cerebral damage) and the interstitial pattern of HIV p24 immunohistochemistry.

Decreasing incidence of CNS AIDS-defining events associated with antiretroviral therapy.

The authors enrolled 1,029 patients with CD4 counts

Assessment of cognitive function in asymptomatic HIV-positive subjects.

This retrospective study aims to assess cognitive involvement in pre-AIDS, not drug abuser subjects and to determine whether CD4 status or disease stage best correlates with cognitive changes that may portend development of ADC. 328 cases were analyzed. No differences in psychometric performance in relation to CDC stage were found. Instead, patients with CD4 < 200/microl performed worse overall, with a statistically significant difference for Digit Symbol, Corsi Test, Block Design and HIVDA Scale. Even if cognitive decline is not evident in the early phase of HIV infection, CD4 count seems the more sensitive early indicator of cognitive changes adequately pointed out by the HIVDA Scale, which could be considered a useful screening tool for cognitive deficit.

Microglial nodular encephalitis and ventriculoencephalitis due to cytomegalovirus infection in patients with AIDS: two distinct clinical patterns.

In patients with AIDS, cerebral infection due to cytomegalovirus (CMV) results in two distinct neuropathological patterns: microglial nodular encephalitis (MGNE) and ventriculoencephalitis (VE). In order to identify clinical features to facilitate the differential diagnosis of these two forms of CMV encephalopathy in living patients, we retrospectively reviewed the clinical records of 18 patients with MGNE or VE diagnosed at autopsy. We identified the following clinical features as distinguishing the two encephalopathies: (1) MGNE manifests earlier than VE; (2) the onset of MGNE is acute, whereas the onset of VE is insidious; (3) the onset of MGNE is marked by confusion and delirium, which do not occur in VE; (4) VE is frequently associated with radiculopathy, which is absent in MGNE; and (5) VE is associated with more marked alterations in cerebrospinal fluid (high protein levels and pleocytosis). The early neurological manifestations of MGNE should prompt a search for systemic CMV infection, which may lead to earlier treatment.

Light chain deposition disease neuropathy resembling amyloid neuropathy in a multiple myeloma patient.

A 65-year-old man with IgG lambda multiple myeloma developed severe polyneuropathy with prominent thermal-pain sensory impairment and autonomic failure. Although the clinical presentation suggested amyloid neuropathy, nerve biopsy showed the immunohistochemical and ultrastructural features typical of light chain deposition disease (LCDD). A precise morphologic and clinical description of LCDD neuropathy is given for the first time in the present report.

Effects of HIV seropositivity and drug abuse on cognitive function.

Fifty-eight HIV-positive drug abusers and 22 HIV-positive nondrug abusers at stages II-III and IV of the Centers for Disease Control classification were evaluated neuropsychologically. The study confirmed previous findings that drug abuse has a negative influence on cognitive function. It also emerges that seropositivity affects cognitive function, although the poor performance of group II-III patients compared to group IV may be explained by factors related to seropositivity (anxiety and panic) rather than the disease itself. It is concluded that disease-related factors probably determine cognitive performance in the earlier stages of HIV infection.

HIV infection and drug use: influence on cognitive function.

OBJECTIVE: To examine the involvement of cognitive function in HIV-seropositive drug users (DU) in a pre-AIDS state. DESIGN: Fifty-six HIV-positive DU were prospectively evaluated. They belonged to groups II, III and IV (subgroups A, C2 and E) of the 1987 Centers for Disease Control and Prevention classification, with anamnesis negative for neurological pathology. HIV-negative DU (n = 19) and non-DU (n = 27) were used as controls. Infection with HIV and use of toxic drugs were considered variables of influence on cognitive function. METHOD: Subjects underwent neuropsychological evaluation by tests designed to explore cortical and subcortical function. RESULTS: HIV-positive DU showed worse performance scores at the psychometric tests than HIV-negative non-DU, but there was no difference when compared with HIV-negative DU. Ex-DU showed better performance than active DU. No difference with regard to degree of disease evolution was observed among HIV-positive individuals (i.e., groups II and III versus group IV). CONCLUSIONS: There was no evidence of cognitive deficits in HIV-positive individuals in non-AIDS phases to indicate early involvement by HIV at the cerebral level. Progression of the disease, prior to the AIDS phase, did not determine a worsening of intellectual performance. Instead, cognitive function was affected by the chronic and current use of toxic substances. In HIV-positive DU, a decline in cognitive function was found to be attributable to the chronic use of toxic substances rather than HIV infection.

Reversible bilateral opercular syndrome secondary to AIDS-associated cerebral toxoplasmosis.

A case of reversible anterior bilateral opercular syndrome (Foix-Chavany-Marie syndrome) secondary to cerebral toxoplasma abscesses is described in a patient with AIDS. The symptoms regressed following antitoxoplasma and antiedema drug therapy. Although this is the first reported AIDS-related case, the syndrome is likely to recur in AIDS sufferers in whom multifocal cerebral lesions are common.

Neuropsychological performance in HIV-1-infected drug abusers.

Twenty-five HIV-seropositive drug abusers (DA+HIV+) (groups II-III and IV [A, C2 and E] of the CDC classification) were evaluated by use of the WAIS scale to determine any possible involvement of cognitive functions in the not yet overt phases of AIDS. The results were compared with those obtained in two control populations composed of 19 seronegative drug abusers (DA+HIV-) and 24 healthy subjects (DA-HIV-) to evaluate, in addition to the disease, the possible effect of the use of alcohol and toxic substances on cognitive performance. In spite of the small number of subjects, the study indicated that drug abuse is the main factor, among those analyzed, in determining a decline in cognitive functions.

Guillain-Barré syndrome associated with high titers of anti-GM1 antibodies.

We found high titers of anti-GM1 antibodies (1/1280 or more) in 3 of 14 consecutive patients (21%) with Guillain-Barré syndrome (GBS) and in 2 additional patients who developed GBS, 10-11 days after starting parenteral treatment with gangliosides. Antibodies were IgG in 4 patients and IgM in one, and they all bound to asialo-GM1, and, in 3, to GD1b as well. Although the clinical features in all the patients with high anti-GM1 titers fulfilled the criteria for the diagnosis of GBS and in 4 of them, proteins but not cells were elevated in cerebrospinal fluid, electrodiagnostic studies in 3 patients showed prominent signs of axonal degeneration, that in one case were confirmed by morphological studies on sural nerve biopsy. No recent antecedent infection was reported by these patients, but in 3, including patients treated with gangliosides, anti-Campylobacter jejuni antibodies were elevated. In 3 patients a consistent decrease in anti-GM1 levels was observed after the acute phase of the disease suggesting that the frequent occurrence of these antibodies in patients with GBS and their frequent association with a prominent axonal impairment may have pathogenetic relevance.

Effects of a MAO-B inhibitor in the treatment of Alzheimer disease.

119 patients were enrolled in a double-blind randomized parallel study versus placebo carried out to assess both the efficacy and tolerability of L-deprenyl (10 mg/day) for treatment of patients with organic mental disorders of the Alzheimer type (DAT). The treatments were given for 3 months, starting after a run-in period of 15 days to evaluate efficacy. A complete neuropsychological battery was administered monthly after the start of treatment whereas tolerability was assessed by checking, recording and classifying all the unfavorable experiences occurring. According to the results, L-deprenyl would seem to be a useful and reliable tool for the treatment of DAT patients in an attempt to improve their cognitive functions and reduce behavioral alterations, without frequent or severe side effects.

Aphasia in left-handers. Comparison of aphasia profiles and language recovery in non-right-handed and matched right-handed patients.

The present retrospective analysis reports two studies. In Study 1, clinical aspects of aphasia are compared in right-handed (RH) and non-right-handed (NRH) patients; in Study 2, recovery from aphasia is compared in RH and NRH aphasic patients with a minimum of 5 months of daily language rehabilitation. From a continuous series of 1200 brain-damaged subjects, 24 NRH patients with a vascular lesion documented by computerized tomography were selected. In 19 cases the lesion was in the left hemisphere and in 5 cases in the right hemisphere. For 14 NRH patients, a RH subject with similar lesion, matched for age, education, length of illness, etiology (ischemic vs. hemorrhagic), and, when possible, sex was found. Presence and type of aphasia were compared in the two patients of the same pair and were found similar except for Pair 14; the RH subject had global aphasia and the NRH had conduction-like aphasia. Fifteen NRH patients were rehabilitated and reexamined at least 5 months after the first examination. Recovery of the 12 patients with a left-hemisphere lesion was compared with recovery of a group of RH subjects and no significant differences were found. Recovery of the three patients with right-hemisphere lesions is described. It is concluded that differences in type of aphasia and recovery between RHs and NRHs have been overemphasized in the past and must be reconsidered.

The role of the right hemisphere in recovery from aphasia. Two case studies.

We report two female patients who became global aphasic following a large left hemisphere lesion. With passage of time they recovered to a considerable extent, but three years and six months, respectively, after the former CVA, a new stroke lateralized to the right hemisphere occurred and they showed a definite worsening of language disturbances. Possibilities and limits of the right hemisphere in "taking over" language functions are discussed.

Dystonic-Parkinsonian syndrome after cyanide poisoning: clinical and MRI findings.

Progressive Parkinsonism, dystonia and apraxia of eye opening were seen after cyanide poisoning. CT scan and MRI showed lesions in the basal ganglia, cerebellum and cerebral cortex consistent with reported pathological findings.

Alterations in vasopressin regulation in Alzheimer's disease.

A decreased concentration of vasopressin (AVP) in the plasma of patients with Alzheimer's disease has been shown recently and suggests damage to hypothalamic neurosecretory cells. To verify this, osmolar and hypotension (sodium nitroprusside) stimulations on AVP release were applied. The effect of metoclopramide, a powerful stimulator of AVP, was also assessed. Patients with Alzheimer's disease released AVP normally after hypotension. However, AVP response to osmotic stimulation was altered in eight out of 10 patients, owing to low osmoreceptor sensitivity and/or high threshold. Metoclopramide increased AVP in controls but not in patients. Normal AVP response to hypotension in patients with Alzheimer's disease makes it unlikely that there is a significant anatomical loss or damage of hypothalamic neurosecretory cells. Alterations in osmoreceptor function and AVP unresponsiveness to metoclopramide point to damage in the control of AVP release in Alzheimer's disease.