The objective assessment of sleep in cluster headache: State of the art and future directions.

Several lines of evidence suggest that cluster headache is related to chronobiology and sleep. Nevertheless, the nature of such a relationship is unclear. In this view, the objective evaluation of sleep in cluster headache has strong theoretical and clinical relevance. Here, we provide an in-depth narrative review of the literature on objective sleep assessment in cluster headache. We found that only a small number of studies (N = 12) focused on this topic. The key research aims were directed to assess: (a) the relationship between cluster headache and sleep breathing disorders; (b) the temporal relationship between sleep stages/events and cluster headache attacks; (c) sleep macrostructure in patients with cluster headache. No studies considered sleep microstructure. The reviewed studies are heterogeneous, conducted by a few research groups, and often characterised by relevant methodological flaws. Results are substantially inconclusive considering the main hypothesis. We outline several methodological points that should be considered for future research, and suggest that evaluating sleep microstructure, local sleep electrophysiology and actigraphic measures may strongly increase knowledge on the relationship between sleep and cluster headache.

Relapsing-remitting and secondary-progressive multiple sclerosis patients differ in decoding others' emotions by their eyes.

BACKGROUND AND PURPOSE: Difficulties in emotion processing and social cognition identified in multiple sclerosis (MS) patients have a potential impact on their adaptation to the social environment. We aimed to explore the neural correlates of emotion recognition in MS and possible differences between relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) patients by the Reading the Mind in the Eyes test (RMEt). METHODS: A total of 43 MS patients (27 RRMS, 16 SPMS) and 25 matched healthy controls (HC) underwent clinical assessments, RMEt, and a high-resolution T1-weighted 3-T magnetic resonance imaging (MRI) scan. The number of correct answers on the RMEt was compared between groups. T1-weighted volumes were processed according to an optimized voxel-based morphometry (VBM) protocol to obtain gray matter (GM) maps. Voxelwise analyses were run to assess potential associations between RMEt performance and regional GM volumes. RESULTS: Taken altogether, MS patients reported significantly lower performance on the RMEt compared to HC. When dividing the patients into those with RRMS and those with SPMS, only the latter group was found to perform significantly worse than HC on the RMEt. VBM analysis revealed significant association between RMEt scores and GM volumes in several cortical (temporoparieto-occipital cortex) and subcortical (hippocampus, parahippocampus, and basal ganglia) brain regions, and in the cerebellum in SPMS patients only. CONCLUSIONS: Results suggest that, in addition to other clinical differences between RRMS and SPMS, the ability to recognize others' emotional states may be affected in SPMS more significantly than RRMS patients. This is supported by both behavioral and MRI data.

Cognitive Performance in Relapsing-Remitting Multiple Sclerosis: At Risk or Impaired?

INTRODUCTION: Since cognitive impairment (CI) occurs on average in 45% of multiple sclerosis (MS) patients, the early detection of patients "at risk" of CI is important in order to promptly apply preventive strategies. The aim of the present study was to investigate the prevalence and risk factors for CI in MS patients using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) as a screening test. METHODS: During the 1-year period, CI was evaluated in 82 consecutives mild relapsing-remitting MS (EDSS ≤ 3.5) patients. Patients with 1 altered BICAMS test were defined "at risk." Both "at risk" and CI patients underwent an extensive neuropsychological battery. RESULTS: We found that: (i) 23% had CI, (ii), 25% were "at risk" of CI, and (iii) 76% of the "at risk" patients were already impaired at the NP assessment. In particular, the Symbol Digit Modalities Test was the most compromised (70% of "at risk" and 79% of CI patients). Patients with CI had more frequently an EDSS ≥ 2.5 (p = 0.05), lower education (p = 0.05), and relapses in the last 12 months (p = 0.03). CONCLUSIONS: CI is a significant issue in MS and integration of a screening test, such as the SDMT, into routine clinical practice could be of worth to identify "at risk" patients and to promote an early therapeutic intervention.

Depression, anxiety and alexithymia symptoms are major determinants of health related quality of life (HRQoL) in cirrhotic patients.

HRQoL is impaired in cirrhosis. Establishing the relevance of depression, anxiety, alexithymia and cirrhosis stage on the patients' HRQoL. Sixty cirrhotics underwent a neuropsychological assessment, including ZUNG-SDS, STAI Y1-Y2 and TAS-20. Minimal hepatic encephalopathy (MHE) was detected by PHES, HRQoL by Short-Form-36 (SF-36). Depression was detected in 34 patients (57 %, 95%CI = 44-70 %), state-anxiety in 16 (27 %, 95%CI = 15-38 %), trait-anxiety in 17 (28 %, 95%CI = 17-40 %), alexithymia in 14 (31 % 95%CI = 16-46 %) and MHE in 22 (37 %, 95%CI = 24-49 %). Neuropsychological symptoms were unrelated to cirrhosis stage, hepatocellular carcinoma or MHE. A significant correlation was observed among psychological test scores and summary components of SF-36. At multiple linear regression analysis including Child-Pugh and MELD scores, previous-HE and the psychological test scores as possible covariates, alexithymia and depression as well as to the Child-Pugh score were significantly related to the SF-36 mental component; while trait-anxiety was the only variable significantly and independently related to the SF-36 physical component. Depression, state and trait-anxiety and alexithymia symptoms are frequent in cirrhotics and are among the major determinants of the altered HRQoL.

Assessing 'no evidence of disease activity' status in patients with relapsing-remitting multiple sclerosis: a long-term follow-up.

Introduction: Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the CNS with an autoimmune pathogenesis. Over the years, numerous disease-modifying therapies (DMTs) have proven effective in disease control; to date, there is a need to identify a personalized treatment effective in ensuring disease-free status or no evidence of disease activity (NEDA). Objective: identify clinical, demographic and treatment approach characteristics that affect the maintenance of NEDA-3 and the occurrence of clinical relapses during a 6-years follow-up. Materials and method: a retrospective study was conducted on a cohort of MS patients followed up with six-year period. All participants were treated with first- or second-line MS drugs.Clinical relapse, NEDA-3 at 6 years and sustained EDSS were assessed as disease activity outcomes. Patients with follow-up of less than 6 years and insufficient clinical and radiological data were excluded from the study. Results: Two-hundred-eighty naive patients (mean age was 49.8 years, SD ± 11.35 years, 23-76, F/M 182/98), with MS were followed up for 6 years.The mean age at diagnosis was 34.3 years (SD ±11.5, 14-62 years), the mean EDSS score at the onset was 1.9 (±1.3), 76.8% of patients had an EDSS below or equal to 2.5 at diagnosis.In the cohort 37 (13.2%) directly received second-line treatment, 243 (86.8%) received first-line drugs.The analysis showed that second-line treatment from beginning had a protective effect for the achievement of NEDA-3 (p = 0.029), on the prevention of clinical relapse (p = 0.018) and on number of relapses (p = 0.010); this finding was confirmed by logistic regression analysis (p = 0.04) and Kaplan-Meier analysis (p = 0.034). Conclusion: The results of this study demonstrate the efficacy of targeted and early intervention so as to act in the right time window, ensuring a favorable outcome in both clinical and radiological terms; this could be decisive in reducing clinical relapse, disease progression and related disability. Therefore, prescribing highly effective drug in the early stages of the disease represents a leading strategy with the most favorable cost-benefit ratio.

Recognition and naming of famous buildings: Italian normative data.

Semantically unique items are concrete entities characterized by a unique cluster of semantic information. In this field, neuropsychology has always given more attention to faces than to other kind of stimuli. An important category that has been largely neglected so far is famous buildings. A total of 200 healthy Italian adults with age, sex and education homogenously distributed across subgroups were administered a famous buildings naming and recognition test, which assessed both visual and verbal modalities. The test was divided in seven sections; norms were calculated taking into account demographic variables such as age, sex and education. Multiple regression analyses showed that education influenced significantly the performance on all subtests; age had a significant effect for five subtests; sex for three subtests. Adjusted scores were used to determine inferential cutoff scores and to compute equivalent scores.

Modulation of Phenylalanine and Tyrosine Metabolism in HIV-1 Infected Patients with Neurocognitive Impairment: Results from a Clinical Trial.

To investigate the effects of oral bacteriotherapy on intestinal phenylalanine and tyrosine metabolism, in this longitudinal, double-arm trial, 15 virally suppressed HIV+ individuals underwent blood and fecal sample collection at baseline and after 6 months of oral bacteriotherapy. A baseline fecal sample was collected from 15 healthy individuals and served as control group for the baseline levels of fecal phenylalanine and tyrosine. CD4 and CD8 immune activation (CD38+) was evaluated by flow cytometry. Amino acid evaluation on fecal samples was conducted by Proton Nuclear Magnetic Resonance. Results showed that HIV+ participants displayed higher baseline phenylalanine/tyrosine ratio values than healthy volunteers. A significand reduction in phenylalanine/tyrosine ratio and peripheral CD4+ CD38+ activation was observed at the end of oral bacteriotherapy. In conclusion, probiotics beneficially affect the immune activation of HIV+ individuals. Therefore, the restoration of intestinal amino acid metabolism could represent the mechanisms through which probiotics exert these desirable effects.

A pilot study on the effects of probiotic supplementation on neuropsychological performance and microRNA-29a-c levels in antiretroviral-treated HIV-1-infected patients.

INTRODUCTION: The gut microbiota is involved in the regulation of cognition, mood, anxiety, and pain, and can impact cognitive functions by producing neuroactive substances or releasing bacterial by-products and metabolites. No information is available on the effects of a probiotic supplementation on brain function of HIV+ subjects. In light of the above considerations, we performed a pilot study in cART-treated HIV-1-positive patients with long-term virologic suppression. The aims were to analyze the effect of high-concentration multistrain probiotic supplementation (Vivomixx®; Visbiome®) on several neurocognitive abilities and to evaluate the safety of this supplementation. METHODS: To address those issues, neurocognitive performances were explored by administering neuropsychological tests; moreover, miRNA-29a-c levels were measured in cerebrospinal fluid (CSF) to confirm the persistent undetectable levels of HIV-RNA in the central nervous system after probiotic supplementation. RESULTS: Our results show that the Rey auditory verbal learning test (RAVLT) (immediate and delayed recall), Rey-Osterrieth complex figure test (ROCF) (copy immediate and delayed recall), phonological verbal fluency (PVF) test, Toronto alexithymia scale-20 (Tas-20), State-trait anxiety inventory Y-2 (STAY Y-2), and time and weight estimation test (STEP) scores improved significantly during the study. Moreover, we found unchanged levels, associated to high degree of individual variability, in miRNA-29 levels in CSF collected before and after probiotic supplementation. CONCLUSIONS: In conclusion, we observed that HIV patients treated with 6 months of this probiotic supplementation appear to have an improvement in some neurocognitive functions; moreover, this approach is safe and did not modify significantly the levels of miRNA in CSF. Further studies are needed to better understand the contribution of the probiotics in modulating gut-brain-axis in HIV patients.

Impact of High-Dose Multi-Strain Probiotic Supplementation on Neurocognitive Performance and Central Nervous System Immune Activation of HIV-1 Infected Individuals.

BACKGROUND: Gut microbiota has metabolic activity which influences mucosal homeostasis, local and systemic immune responses, and other anatomical systems (i.e., brain). The effects of dysbiosis are still poorly studied in Human Immunodeficiency Virus-1 (HIV-1) positive subjects and insufficient data are available on the impairment of the gut-brain axis, despite neurocognitive disorders being commonly diagnosed in these patients. This study evaluated the impact of a probiotic supplementation strategy on intrathecal immune activation and cognitive performance in combined antiretroviral therapy (cART) treated HIV-1 infected subjects. METHODS: Thirty-five HIV-1 infected individuals were included in this study. At baseline (T0) a battery of tests was administered, to evaluate neurocognitive function and a lumbar puncture was performed to determine neopterin concentration in cerebrospinal fluid (CSF), as a marker of Central Nervous System (CNS) immune activation. Subsequently, a subgroup of participants underwent a 6-month course of multi-strain probiotics supplementation; this intervention group was evaluated, after probiotic treatment, with a second lumbar puncture and with repeated neurocognitive tests. RESULTS: At T0, all participants showed impaired results in at least one neurocognitive test and elevated neopterin concentrations in CSF. After supplementation with probiotics (T6), the interventional group presented a significant decrease in neopterin concentration and a significant improvement in several neurocognitive tests. In contrast, no significant modifications were observed in the neurocognitive performance of controls between T0 and T6. The CNS Penetration Effectiveness Score of antiretroviral therapy did not show an influence from any of the investigated variables. CONCLUSIONS: Multi-strain probiotic supplementation seems to exert a positive effect on neuroinflammation and neurocognitive impairment in HIV-1 infected subjects, but large trials are needed to support the concept that modulation of the gut microbiota can provide specific neurological benefits in these patients.