Correlations between cerebrospinal fluid biomarkers, neurocognitive tests, and resting-state electroencephalography (rsEEG) in patients with HIV-associated neurocognitive disorders.

HIV-associated neurocognitive disorders (HAND) are highly prevalent in people living with HIV (PLWH) despite successful treatment with combination antiretroviral therapy (cART). HAND pathogenesis is complex and definitive surrogate biomarkers are not clearly defined. Brain function has been assessed through the evaluation of cortical source rhythms with delta waves associated with neurological impairment. The aim of this study was to assess the correlation between EEG cortical sources, cerebrospinal fluid (CSF) biomarkers, and neurocognitive tests in PLWH with HAND. PLWH with HAND without significant comorbidities were enrolled. Baseline rsEEG-LORETA waves, CSF biomarkers (t-tau, p-tau, ß-amiloid42, neopterin, S100ß), and neurocognitive tests were correlated and compared through non-parametric tests (Spearman's rho and Mann-Whitney); data are presented as medians (interquartile ranges). Fifty-four patients were enrolled. Median time of suppressed HIV-RNA and CD4+ T-lymphocyte were 10 years (5.5-15) and 691/uL (477-929). Thirty-nine participants (72%) underwent CSF collection: abnormal biomarkers were found in a small percentage. Only neopterin showed a statistically significant correlation with delta activity [parietal (rho 0.579; p < 0.001), occipital (rho 0.493; p = 0.007), and global sources (rho 0.464 p = 0.011)]. Seven patients (12.9%) showed an abnormal neopterin level (> 1.5 ng/mL) with significantly higher delta source activity compared to the ones with in-range concentrations. We observed a statistically significant correlation between working memory test Trail Making B with both CSF neopterin levels and delta waves (p values < 0.05). In a small sample of PLWH with HAND, we observed that higher CSF neopterin levels were associated with higher EEG delta waves and worse working memory tests.

Nocturnal anomalous movement reduction and sleep microstructure analysis in parkinsonian patients during 1-night transdermal apomorphine treatment.

This study analyzed the macrostructure and microstructure of sleep in 12 parkinsonian patients under basal conditions (T0) and during 1-night treatment (T1) with a new formulation of apomorphine. This new formulation consisted in a microemulsion of apomorphine administered by the transdermal route, able to provide a constant release of the drug over several hours (APO-TD). Sleep analysis at T1 compared with T0 revealed a 16% increment of total sleep time, a 12% increment of sleep efficiency, a 16% increment of stage 3 and 4 non-REM sleep, a 15% reduction of periodic limb movements index, a 22% reduction of arousal index, and a 23% reduction of cycling alternating patterns/non-REM. We conclude that APO-TD may be able to reduce nocturnal anomalous movements, akinesia, and rigidity in Parkinson's disease, and may reduce the disturbed sleep typical of Parkinson's disease.

Are the neurophysiological techniques useful for the diagnosis of diaphragmatic impairment in multiple sclerosis (MS)?

OBJECTIVE: To characterize cortico-diaphragmatic pathway involvement in multiple sclerosis (MS) by means of transcranial magnetic stimulation (TMS), and verify its clinical impact. METHODS: TMS from diaphragm (Dia), and abductor digiti minimi (AbdV degrees ) was performed in 26 MS patients. Phrenic nerve (PN) conduction study was also performed. Expanded disability status scale (EDSS) and fatigue descriptive scale (FDS) were measured. Forced vital capacity (FVC), forced expiratory volume at the first second (FEV1), peak expiratory flow (PEF) were tested: the predicted percentage value (% pred) was considered. RESULTS: Cortical motor evoked potential (Cx-MEP) latency and central motor conduction time (CMCT) were prolonged, respectively, in 31 and 23% of patients from Dia, in 76 and 79% from AbdV degrees. PN-compound motor action potential (CMAP) was normal. EDSS correlated to Cx-MEP from AbdV degrees (P<0.01), and PN-CMAP amplitude (P<0.05), FEV1 % pred (P<0.01), PEF % pred (P<0.01). PN-CMAP amplitude correlated to FVC % pred P=0.05, FEV1 % pred P<0.01, PEF % pred P<0.01. Fatigue was related to AbdV degrees Cx-MEP and CMCT (P<0.05 and P<0.01). CONCLUSIONS: Cortico-diaphragmatic pathway is impaired only in a minority of MS patients. Lack of correlation between TMS findings from Dia and respiratory tests argues against its routinary use to detect subclinical respiratory alterations. Fatigue seems to be related to the motor impairment rather than to respiratory distress.

Quantitative PCR reveals increased levels of tumor necrosis factor-alpha mRNA in peripheral blood mononuclear cells of multiple sclerosis patients during relapses.

Quantification of tumor necrosis factor-alpha (TNF-alpha) mRNA in peripheral blood mononuclear cells (PBMC) could provide information about disease activity in multiple sclerosis (MS); however, specific competitive methods must be utilized. A competitor cDNA, having the same sequence of the target TNF-alpha cDNA, a part from an internal 49-bp deletion, was generated and used to set-up a quantitative polymerase chain reaction (PCR) to quantify mRNA of TNF-alpha. Competitor and target were co-amplified using the same primers. The rates of generation of competitor and target TNF-alpha conformed closely to the prediction of the mathematical model, and a high level of accuracy and reproducibility was achieved. The method was applied to quantify TNF-alpha mRNA in PBMC of normal subjects and multiple sclerosis (MS) patients both during clinical relapses and remissions. A statistically significant higher level of TNF-alpha mRNA was detected during relapses than during remissions. High levels of TNF-alpha mRNA were found in 44% of relapses and 12% of samples during remissions, suggesting that TNF-alpha mRNA synthesis is abnormal in MS.