M Grassi

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.

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.

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

ObjectivesTo evaluate the correlation between immunohistochemical positive patterns (globular and filamentous structures) of β-amyloid precursor protein (β-APP), used as a marker of axonal damage, and the different distribution of HIV p24 antigens, in three different brain areas of AIDS patients. MethodsEighteen 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-β-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. ResultsHIV 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. β-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 β-APP globules and HIV p24 antigens. ConclusionsThe data obtained confirm the coexpression of β-APP and viral antigens in particular areas of the brain with HIV-related lesions; there is a strict correlation between β-APP globules (indicating chronic cerebral damage) and the interstitial pattern of HIV p24 immunohistochemistry.

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.

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/μl 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.

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.

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.SommarioUn uomo di 65 anni affetto da mieloma multiplo IgG lambda ha sviluppato una forma severa di polineuropatia con prevalente coinvolgimento della sensibilità termo-dolorifica e del sistema autonomico. Sebbene la presentazione clinica suggerisse una neuropatia da amiloidosi, la biopsia del nervo ha messo in evidenza le caratteristiche immunoistochimiche ed ultrastrutturali della malattia da depositi di catene leggere (LCDD). Vengono riportate, per la prima volta, le caratteristiche morfologiche e cliniche della neuropatia da depositi di catene leggere.

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.

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.

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.