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Multiple sclerosis (MS) is a neurodegenerative inflammatory condition mediated by autoreactive immune processes. Due to its potential to influence host immunity and gut-brain communication, the gut microbiota has been suggested to be involved in the onset and progression of MS. To date, there is no definitive cure for MS, and rehabilitation programs are of the utmost importance, especially in the later stages. However, only a few people generally participate due to poor support, knowledge, and motivation, and no information is available on gut microbiota changes. Herein we evaluated the potential of a brief high-impact multidimensional rehabilitation program (B-HIPE) in a leisure environment to affect the gut microbiota, mitigate MS symptoms and improve quality of life. B-HIPE resulted in modulation of the MS-typical dysbiosis, with reduced levels of pathobionts and the replenishment of beneficial short-chain fatty acid producers. This partial recovery of a eubiotic profile could help counteract the inflammatory tone typically observed in MS, as supported by reduced circulating lipopolysaccharide levels and decreased populations of pro-inflammatory lymphocytes. Improved physical performance and fatigue relief were also found. Our findings pave the way for integrating clinical practice with holistic approaches to mitigate MS symptoms and improve patients’ quality of life.

BACKGROUND Grey Matter (GM) atrophy has been extensively described in Multiple Sclerosis (MS) patients, while cerebral hypoperfusion has been less consistently reported. Since hypoperfusion might be related to atrophy, we evaluated the presence of both damages. OBJECTIVE We aimed to assess if the regions of altered perfusion and atrophy overlapped with one another and if the two parameters were locally related. METHOD 3D-T1 weighted and arterial spin labelling sequences were acquired using a 1.5T Magnetic Resonance Imaging scanner from 26 relapsing remitting MS patients and 26 Healthy Controls (HC). GM volume and Cerebral Blood Flow (CBF) differences and their correlation were tested with a voxel-wise approach. RESULTS MS patients (41.4±12.5 years; 14 females) had a median [25th-75th percentile range] Expanded Disability Status Scale of 1.0[1.0-2.4] and a median [25th-75th percentile range] disease duration of 8.0 [4.0-16.5] years. HC were age- and sex-matched (43.9±17.4 years; 11 females). GM atrophy was detected for MS group in the right parahippocampal gyrus, thalami and left caudate (pFWE≤0.05). Areas of significant (after family-wise error -FWE- correction for multiple comparisons) (pFWE≤0.05) hypoperfusion were found for MS in the anterior cingulate and paracingulate gyri, supplementary motor cortex, precentral and superior frontal gyrus. GM volume and CBF showed a significant correlation (pFWE≤0.05) in the right lateral occipital cortex and precuneus in the MS group. CONCLUSIONS GM atrophy and hypoperfusion in MS were located in different areas. Perfusion estimate might be used as a further marker of tissue damage, in addition to GM volume.

Background: Multiple sclerosis (MS) has a relevant impact on quality of life (QOL) and is associated with increased risks of psychological morbidity. Mindfulness-based interventions (MBIs) are among the most studied interventions, although few well-conducted studies have tested them in this field. Furthermore, the participation in typical MBIs may be impaired by time and logistics. Objective: We aimed to test the efficacy of an online MBI to improve QOL, psychological well-being, sleep, and fatigue. Methods: We conducted a randomized controlled trial, in which 139 participants were randomly assigned to an MS-specific online mindfulness meditation intervention or to a psychoeducational (active control) group. Participants were assessed for QOL, depression, anxiety, sleep problems, and fatigue, at three different times: at recruitment, after 2 months, and after 6 months. Results: In comparison to the control group, the experimental subjects reported higher QOL and lower depression, anxiety, and sleep problems at the end of intervention. However, after 6 months these group differences were no longer significant. Conclusion: An online MBI could be an effective psychological treatment for the promotion of well-being in MS in short-term. However, the lack of lasting effects requires the development of new strategies to support long-term changes.

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Brain functional connectivity is a widely investigated topic in neuroscience. In recent years, the study of brain connectivity has been largely aided by graph theory. The link between time series recorded at multiple locations in the brain and the construction of a graph is usually an adjacency matrix. The latter converts a measure of the connectivity between two time series, typically a correlation coefficient, into a binary choice on whether the two brain locations are functionally connected or not. As a result, the choice of a threshold τ over the correlation coefficient is key. In the present work, we propose a multiple testing approach to the choice of τ that uses the Bayes false discovery rate and a new estimator of the statistical power called average power function to balance the two types of statistical error. We show that the proposed average power function estimator behaves well both in case of independence and weak dependence of the tests and it is reliable under several simulated dependence conditions. Moreover, we propose a robust method for the choice of τ using the 5% and 95% percentiles of the average power function and False Discovery Rate bootstrap distributions, respectively, to improve stability. We applied our approach to functional magnetic resonance imaging and high density electroencephalogram data.

We assessed cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) within gray matter (GM), normal appearing white matter (NAWM) and white matter (WM) lesions in a group of multiple sclerosis (MS) patients. Furthermore, correlations between CBF, CVR and age were investigated. 31 MS patients and 25 healthy controls (HC) were examined on a 1.5 T MRI scanner, using pseudo-continuous arterial spin labeling MRI. MS vs HC CBF and CVR differences were assessed in GM regions of interest (i.e. resting state networks and vascular territories), and within WM. Correlations between CBF/CVR and age were then computed for MS and HC groups. Whereas no significant CBF and CVR differences were observed between MS and HC in any of the considered brain areas, significantly lower CBF was found in WM lesions with respect to NAWM (p

Objective: Only a limited percentage of persons with MS (pwMS) participate to multidisciplinary rehabilitation (MDR) because of poor support, knowledge and motivation. We reasoned that pwMS should be more effectively prepared to increase their adherence. We implemented an innovative collaborative approach, called “brief highimpact preparatory experience” (b-HIPE), inspired by an overarching model based on the interplay between competence, motivation and opportunity to increase in a short time awareness and motivation of pwMS. Methods: B-HIPE integrates physiotherapy, mindfulness, sailing, healthy diet, and cultural activities to be experienced in a convivial form at a beautiful seaside location in Sardinia. Sixteen pwMS participated to 3 successive one-week editions of the b-HIPE, co-sponsored by the Rotary Club of Milan and supported by researchers of our Institute and of partner associations. The feasibility was assessed with structured questionnaires and free reports concerning accommodation, logistics, coordination, social climate and the specific activities proposed. For this pilot study we used a single-group design with repeated measurements at baseline and post-intervention. The SF-36 QoL scale was the main outcome measure, the Fatigue Severity Scale (FSS), the Berg Balance scale (BBS) and the 9 hole peg test (9HPT) were the secondary outcomes. Results: The approach was feasible. Scores on several FS-36 scales and secondary outcomes were significantly improved. Participants’ satisfaction with all aspects of the experience was above expectations. PwMS became more motivated and aware of physical and mental resources, all learned to sail adapted monohulls, strategies to master stress and to modify their diet according to specific recommendations. Conclusion: B-HIPE is safe and feasible. The interplay of multiple factors produced in a very short time the expected changes in participants’ attitude toward a healthier lifestyle. A monitoring program is ongoing to assess long-term effects including adherence to hospital-based MDR. Publisher PDF

The aim of this retrospective study was to preliminarily assess whether the EP-score, a summary score derived from multimodal evoked potentials tests, might be used as a measure of treatment efficacy in multiple sclerosis (MS).A sample of 56 relapsing remitting MS (RRMS) patients who at diagnosis started treatment with interferon β (INFβ, n = 19), glatiramer acetate (GA, n = 15) or refused any chronic treatment were assessed at baseline (before treatment) and at a median of 1.7 and 3.6 years thereafter. Outcome variables were Expanded Disability Status Scale (EDSS), EP-Score, visual evoked potentials (VEP) and somatosensory evoked potentials (SEP) scores measured as differences between baseline and follow-ups. Statistical differences between groups and follow-ups were assessed using non-parametric analyses.Treatment effects were not significant for EDSS both at the first and at the second follow-up, while a trend toward significance was observed in the EP-score only in the first follow-up (p = 0.07). Post-hoc analysis showed a greater decrease in median VEP-score for the IFNβ group compared to the GA and DF groups at both the first and second follow-ups.We found no evidence that either INFβ or GA significantly improved disability in RRMS patients. Using the EP-score as an outcome measure, we found that it was improved at both follow-ups in the INFβ group mainly due to a decrease in the VEP-score. This finding supports the proposal to include the EP-score as an additional outcome variable in future studies of treatment efficacy in MS.

Previous research using stepwise regression analyses found self-reported hypnotic depth (srHD) to be a function of suggestibility, trance state effects, and expectancy. This study sought to replicate and expand that research using a general state measure of hypnotic responsivity, the Phenomenology of Consciousness Inventory: Hypnotic Assessment Procedure (PCI-HAP). Ninety-five participants completed an Italian translation of the PCI-HAP, with srHD scores predicted from the PCI-HAP assessment items. The regression analysis replicated the previous research results. Additionally, stepwise regression analyses were able to predict the srHD score equally well using only the PCI dimension scores. These results not only replicated prior research but suggest how this methodology to assess hypnotic responsivity, when combined with more traditional neurophysiological and cognitive-behavioral methodologies, may allow for a more comprehensive understanding of that enigma called hypnosis.

The concurrent usage of actigraphy and heart rate variability (HRV) for sleep efficiency quantification is still matter of investigation. This study compared chest (CACT) and wrist (WACT) actigraphy (actigraphs positioned on chest and wrist, respectively) in combination with HRV for automatic sleep vs wake classification. Accelerometer and ECG signals were collected during polysomnographic studies (PSGs) including 18 individuals (25-53 years old) with no previous history of sleep disorders. Then, an experienced neurologist performed sleep staging on PSG data. Eleven features from HRV and accelerometry were extracted from series of different lengths. A support vector machine (SVM) was used to automatically distinguish sleep and wake. We found 7 min as the optimal signal length for classification, while maximizing specificity (wake detection). CACT and WACT provided similar accuracies (78% chest vs 77% wrist), larger than what yielded by HRV alone (66%). The addition of HRV to CACT reduced slightly the accuracy, while improving specificity (from 33% to 51%, p 0.05). On the contrary, the concurrent usage of HRV and WACT did not provide statistically significant improvements over WACT. Then, a subset of features (3 from HRV + 1 from actigraphy) was selected by reducing redundancy using a strategy based on Spearman's correlation and area under the ROC curve. The usage of the reduced set of features and SVM classifier gave only slightly reduced classification performances, which did not differ from the full sets of features. The study opens interesting possibilities in the design of wearable devices for long-term monitoring of sleep at home.

The usefulness of sympathetic skin responses (SSR) in multiple sclerosis (MS) has been advocated by several studies in the last 20 years; however, due to a great heterogeneity of findings, a comprehensive meta-analysis of case-control studies is in order to pinpoint consistencies and investigate the causes of discrepancies. We searched MEDLINE, EMBASE and Cochrane databases for case-control studies comparing SSR absence frequency and latency between patients with MS and healthy controls. Thirteen eligible studies including 415 MS patients and 331 healthy controls were identified. The pooled analysis showed that SSR can be always obtained in healthy controls while 34% of patients had absent SSRs in at least one limb (95% CI 22–47%; p

The color-word Stroop paradigm is a neuropsychological test often employed for the evaluation of the cognitive processing when a conflict between different attributes of the same visual stimulus is present. In clinical environments, the standard practice for the Stroop test administration is still based on paper supports and stopwatches. Thus, the aim of the present pilot study was to investigate the usability in clinical practice of a completely computerized system for the Stroop test administration. The computerized system developed for this study was made up of the following modules: i) a PC for stimuli administration and data acquisition connected to two monitors (one for the user, the other for the experimenter); ii) a response system composed of three colored electronic buttons; iii) a wireless electroencephalography (EEG) acquisition module (i.e. headset and dedicated software). The system was installed in the IRCCS Don Carlo Gnocchi Foundation and tested on 7 subjects hospitalized in the neurorehabilitation Unit. The developed system was able to provide information about the subjects' reaction time to stimuli in addition to the traditional behavioral scores. Moreover, the integrated EEG acquisition module allowed monitoring the user's engagement during the test through the computation of a simple EEG-based evaluation index. We believe that this pilot study could set a further step towards the clinical use of computerized systems to monitor cognitive functions.

Ménière disease (MD) is a chronic illness of the inner ear that affects a substantial number of patients every year worldwide. Because of a dearth of well-controlled studies, the medical and surgical management of MD remains quite empirical. The main reason is that it is very difficult to investigate patients affected with Certain MD due to the post-mortem criterion necessary for this diagnostic grade. Although Endolymphatic Hydrops (EH) is the worldwide accepted mechanism of MD, the causes that induce it are still not clear. In fact MD has been correlated mostly to a wide and different disturbances ranging from trauma to sleep disorders. It is nowadays sufficiently demonstrated that Chronic Cerebro Spinal Venous Insufficiency (CCSVI) is very frequent in MD. Even if CCSVI may potentially induce EH through a pure hydraulic mechanism CCSVI, per se does not explain how the various disorders correlated with MD may interact with CCSVI and provoke EH. The aim of this review is an attempt to approach MD into the context of the more recent findings about the global brain waste clearance system, to which inner ear is anatomically and functionally connected, in order to build a reasonable model of MD pathogenesis. The major part of the diseases correlated to MD may act on the inner ear disturbing the Glymphatic (GS) and/or Brain Lymphatic System (BLS) activity. The venous system interplays with GS and BLS. In this model CCSVI is considered more than a direct cause of MD rather the anatomical predisposition to develop the disease. In this model EH, and then MD, is the consequence of a failure of the compensation of the congenital venous abnormalities, anatomical compensation as collateral pathways and/or functional compensation as GS and BLS. In this model the major part of the disturbances correlated to MD and the various treatment proposed find their appropriate placement.

Background Mindfulness-based interventions, modified and shortened versions of meditation teachings, have proved to be effective in the improvement of quality of life in many clinical conditions, including chronic diseases. Preliminary results available in the literature and in clinical experience indicate a high potential for this treatment for the reduction of psychological suffering in people with chronic diseases. Methods/Design This randomized controlled trial will investigate the impact of a multiple sclerosis (MS) specific telemedicine meditation intervention on the quality of life of people with multiple sclerosis and their caregivers. This trial will recruit 120 patients, men and women, with a diagnosis of relapsing-remitting or secondary progressive MS and their caregivers to participate in a 2-month intervention. Patients will undergo assessments of quality of life, anxiety, depression, quality of sleep, mindfulness and fatigue levels conducted at baseline, at week 8 (conclusion of the intervention) and at week 27 (6 months follow-up). Caregivers will complete assessments conducted at the same time for the same areas, plus caregiver burden. The intervention condition will consist of 2 hours/week of online meditation in a group setting led by a trainer, plus 1 hour/week of individual exercises. The control condition will incorporate a psycho-education online program and will require the same contact time commitment as the intervention condition. Discussion Primary outcome measures will consist of assessments of quality of life, anxiety, and depression level. Assessments of mindfulness level, quality of sleep and fatigue level will be considered secondary outcome measures. This investigation will increase understanding of the role of meditation as part of a treatment plan for people with MS and their caregivers. Overall, this study design has the potential to lead to effective meditation intervention strategies for this population and improve their quality of life. Trial registration Clinical Trials Register NCT02364505. https://clinicaltrials.gov/ct2/show/NCT02364505

Patients with multiple sclerosis (MS) frequently report symptoms related to vestibular disorders in the course of their disease. At present, the fundamental tests assessing vestibulospinal involvement are posturography and vestibular evoked myogenic potentials (VEMPs). While posturography cannot be performed in every subject requiring minimal stance control, VEMPs do not require any specific skill on the part of the subjects and they may be investigated in all patients able to sit. VEMPs were recorded for 40 patients (17 men, 23 women; mean age 38 years, range 17-71 years) fulfilling diagnostic criteria of clinically defined MS, by means of rarefaction clicks, recording modulation of sterno-cleido-mastoideus tonic contraction saccule-mediated modulation. VEMPs were found to be abnormal in 28 of 40 patients. In 18 of the cases the VEMPs were asymmetric, i.e., had a prolonged latency on one side. In six cases latency was increased on both sides (mean delay 4.1 ms). In four subjects VEMPs were absent on one side. C oncordance with clinical findings of presence/absence of brainstem involvement was found in 55% and with MRI findings in 65% of the cases. A bnormal VEMPs indicated brainstem dysfunction in four patients (10%) with normal MRI and no specific clinical signs.

This study investigated whether exploration of computer-generated environments can selectively enhance spatial memory in patients with multiple sclerosis (MS). Fifteen patients and 15 healthy subjects who controlled their movements in a virtual house using a joystick recalled the spatial layout of the environments better than 15 patients and 15 controls who merely watched the active participants' progress. Among passive subjects, only healthy controls did significantly better than active participants in the recall of virtual objects. There were no significant differences between active and passive participants' recall of correct object locations in the virtual environments. MS patients' recall of the spatial layout and of the virtual objects was significantly worse than that of healthy subjects, but patients' data did not correlate with traditional neuropsychological measures of spatial memory. It is suggested that virtual reality can be used in MS patients to assess aspects of spatial memory that are not measured by traditional tests.

Paroxysmal positioning vertigo (PPV) is a major cause of vertigo accounting for 14 % of all equilibrium disorders with an annual incidence of about 100 per 100,000 of population [1]. It starts suddenly and is usually first noticed in bed, when waking from sleep. Any turn of the head seems to bring on violent but brief bursts of dizziness. Patients often describe the occurrence of vertigo with tilting of the head, looking up or down, or rolling over in bed. It is not unusual for nausea and vomiting to accompany the vertigo. Even if a spell is brief, a feeling of queasiness may last several minutes or even hours, and those who suffer from this kind of vertigo are distressed and incapacitated for several days severely impacting on social costs due to lost working days. PPV is a common vestibular disorder leading to significant morbidity, psychosocial impact, and medical costs. PPV accounted for 8 % of individuals with moderate or severe dizziness/vertigo. Is commonly accepted that PPV is due to displacement of otoconia and/or to vestibular macula/maculae lesion.

Immersive virtual reality (IVR) is a technology already developed to assist cognitive psychologists and therapists in their clinical work with brain-damaged patients. The rationale, the software and the hardware of the first application (ARCANA 1) based on affordable technology are discussed here, in order to provide a concrete example of what the authors think may be the role of IVR as a clinical tool. Although prospects are exciting, extensive research is needed to validate this new approach and reveal its limitations and advantages.

To devise a multivariate parametric model for short-term prediction of disability using the Expanded Disability Status Scale (EDSS) and multimodal sensory EP (mEP). A total of 221 multiple sclerosis (MS) patients who underwent repeated mEP and EDSS assessments at variable time intervals over a 20-year period were retrospectively analyzed. Published criteria were used to compute a cumulative score (mEPS) of abnormalities for each of 908 individual tests. Data of a statistically balanced sample of 58 patients were fed to a parametrical regression analysis using time-lagged EDSS and mEPS along with other clinical variables to estimate future EDSS scores at 1 year. Whole sample cross-sectional mEPS were moderately correlated with EDSS, whereas longitudinal mEPS were not. Using the regression model, lagged mEPS and lagged EDSS along with clinical variables provided better future EDSS estimates. The R 2 measure of fit was significant and 72% of EDSS estimates showed an error value of ±0.5. A parametrical regression model combining EDSS and mEPS accurately predicts short-term disability in MS patients and could be used to optimize decisions concerning treatment.

We investigated frontal cognitive function in a group of 153 patients with multiple sclerosis and 100 healthy controls using a global scale composed by a set of items from the Luria-Nebraska Neuropsychological Battery (LNNB) which has been validated by Malloy and colleagues on frontally damaged patients. A second scale was built with LNNB items tapping parietal lobes function. Patients who were specifically impaired on the frontal scale (12%) had a shorter disease duration and were less physically disabled than those failing on the parietal tasks (8.5%) or those showing combined deficits (21.5%). Sixty-four patients were also tested on the Wisconsin Card Sorting Test (WCST). Twenty-seven (37.5%) patients were found to be impaired on the WCST, but the latter could not predict reliably their performance on the LNNB frontal scale. We also examined whether age of onset and disease duration could have had any effect on the cognitive performance of selected groups of patients. We found that relative to normals, deficits on the frontal scale were more severe in patients with a clinical onset around age 20 than in patients with a later onset (i.e., around 35), the two groups being comparable for duration and degree of disability. Furthermore, patients with a longstanding illness (> 10 years) were more affected on visuospatial processing and frontal control of language than those with a short duration (1.5 yrs). We propose that a greater disease activity interacting with contingent (developmental?) factors is responsible for the appearance of transient frontal deficits in several young MS patients. A differential involvement of long associative and connecting bundles is also proposed as a basis for understanding the pattern of cognitive deficits encountered in selected patient groups.

Electroencephalogram (EEG) reactivity to eyes opening and 12-Hz photic stimulation was investigated in 14 healthy elderly subjects, 21 parkinsonian patients (PD), 7 demented parkinsonian patients (PDD), and 10 patients with Lewy body dementia (LBD) using global field synchronization (GFS). During eyes closed Theta GFS was increased in Parkinson's disease and patients and alpha1 GFS was decreased in LBD subjects. During 12-Hz intermittent photic stimulation (IPS), reactivity of posterior electrodes was decreased in PD and LBD patients. No reactivity was observed in PDD. Results are consistent with a graded posterior cortical disconnection in parkinsonian syndromes and with a model of dopamine-modulated thalamocortical interplay in visual processing.

Background: poor sleep is common in MS and it contributes to fatigue. The β interferons produce systemic effects which may not adapt and may induce fatigue. Objective: to verify whether subjective poor sleep and fatigue during chronic therapy correspond to reduced sleep efficiency obtained by actigraphy at home. Methods: 42 ambulatory relapsing remitting MS patients with mild disability were monitored for at least 7 nights. Habitual sleep quality and fatigue were assessed with the MOS sleep measure and the Fatigue Severity Scale. Sleep logs provided daily sleep quality assessments during actigraphy at home. Patients were grouped according to their current treatment: no therapy, glatiramer acetate, IFNβ 3 times a week, and IFNβ once a week. Results and Conclusion: sleep efficiency was reduced by an average of 5% in 2/3 of the nights following IFNβ injections compared to the other nights, and daily sleep ratings correlated with actigraphy. Patients on glatiramer acetate also showed a lower sleep efficiency than patients without therapy. Actigraphy data were only modestly correlated with MOSsm scores, not with fatigue. Long term adaptation of sleep effects of immunomodulant agents is incomplete and needs to be considered in treatment planning and assessment of sleep in MS.

Peripheral blood lymphocyte subsets and serum immunoglobulin levels were assessed in 42 patients and 37 healthy controls. 24 patients were free from neuroleptic medication and 15 had never been treated with neuroleptics. 31 patients had a diagnosis of schizophrenia (DSM-III criteria) and 11 a diagnosis of a disorder of the schizophrenic spectrum. As compared to healthy subjects, the drug naive schizophrenic patient group showed an increase of T suppressor lymphocytes, while the drug-treated schizophrenic group showed an increase of T helper lymphocytes. The drug-treated schizophrenic group differed from the drug naive one relative to a decrease of T suppressor lymphocytes. As compared to healthy subjects, the drug naive spectrum disorder patients showed an increase of absolute number of lymphocytes, while the drug treated spectrum group showed an increase of B lymphocytes. These findings did not correlate with any clinical or neuromorphological variables taken into account.

Corticobasal degeneration (CBD) presents with symptoms that often overlap with other neurological conditions. In many cases, diagnosis, prognosis and consequent clinical management remain uncertain. Structural and functional asymmetric brain changes represent the most consistent imaging findings that may assist in CBD diagnosis. Diffusion Tensor MRI (DT-MRI) is a quantitative technique that allows microscopic tissue abnormalities to be non-invasively assessed in vivo. A single case of clinically suspected CBD with symmetric diffuse brain atrophy on conventional-MRI scans was studied using DT-MRI by voxel-wise comparison with eight healthy subjects. The lateralized distribution of DT-MRI abnormalities was consistent with clinical features providing a substantial support to the diagnosis. (C) 2008 Elsevier Ltd. All rights reserved.

Patients affected with multiple sclerosis (MS) frequently suffer from vestibular disorders due to vestibulospinal involvement. The vestibulospinal reflexes in these subjects can be well investigated through vestibular evoked myogenic potentials (VEMPs). Evoked by the acoustic stimulation of the saccular macula and mediated by the vestibulocollic reflex pathway, they are recorded using surface electromyographic electrodes from the ipsilateral sternocleidomastoid muscle tonically contracted. Abnormal findings (e.g., absence of response, prolonged latencies) disclose a lesion anywhere in the pathway. We examined VEMPs in 19 patients with definite MS (5 men, 14 women; age range, 31-59 years; mean age, 45 years) and compared them to VEMPs in 10 subjects with onset MS (2 men, 8 women; age range, 24-35 years; mean age, 29 years). VEMPs in definite MS subjects were abnormal in 14, absent (on the left side only) in 1, and normal in the remaining 4. In patients with onset MS, VEMPs were abnormal in 6. These results suggest that latencies of vestibulospinal reflexes can be remarkably delayed in MS at different stages of disease, whereas vestibulospinal involvement is more frequent in definite cases. To date, no study has yet investigated different VEMPs involvement at different stages of MS.

Equilibrium disorders caused by involvement of brainstem and cerebellar structures are common in patients with multiple sclerosis (MS), but peripheral conditions such as benign paroxysmal positional vertigo (BPPV) can be sometimes confused with those of a central origin. Therefore, an accurate otoneurologic investigation paying attention to differential diagnosis aspects should be performed in these subjects. Among available diagnostic tools, electro-oculography, posturography and vestibular evoked myogenic potentials (VEMPs) are especially suited to assess vestibulo-oculomotor and vestibulospinal systems. This paper briefly describes the most recent otoneurologic diagnostic strategies for MS patients and the results of initial clinical experiences, and finally provides suggestions for differentiating MS-related vestibular disorders from other common otoneurological conditions.

This study aimed to assess the efficacy and specificity of direct computer-assisted memory retraining (CR) in MS patients, in comparison to non-specific retraining, while controlling for severity of impairment, psychiatric symptoms and retest effects. Sixty patients with definite MS and a stable clinical condition were selected. All were assessed neuropsychologically and divided into three matched groups. One group received an 8-week specific CR programme (SCRP) and another received a non-specific 8-week CR programme (NCRP) to retrain attention; a third (control) group received no treatment. After the programmes were completed, all patients were reexamined with the same test battery. Patients were impaired on all 11 memory and attention tests at baseline. Those who received SCRP improved on 7 memory outcome measures, compared to only 1 in the NCRP group and none in the control group. Attention training had no significant effect on relevant outcome measures. Some non-retrained patients showed deterioration of cognitive performance at retest. These results indicate that direct memory training in MS patients is effective in the short-term and is specific. In selected cases, benefits extended to everyday life activities.

We report on a study of the autocorrelation times of the local version of the Hybrid Monte Carlo (LHMC) algorithm for pure gauge $SU(3)$. We compare LHMC to standard multi-hit Metropolis and to the global version of the same HMC. For every algorithm we measure the autocorrelation time for a variety of observables and the string tension as a function of beta. The measurements performed on 8^4 and 16^4 lattices indicate that the autocorrelation time of LHMC is significantly shorter than for the other two algorithms., 11 pages Latex, UPRF June 93 preprint /370/

We studied the relationships between magnetic resonance imaging (MRI) and the Luria-Nebraska Neuropsychological Battery (LNNB) in 64 patients with relapsing-remitting multiple sclerosis (MS). MRI films were scored according to arbitrary descriptive criteria designed to emphasize patterns of alterations. Five groups were created: group 1 and 2 had typical discrete white matter lesions, group 3 had confluent lesions, group 4 had large discrete lesions and group 5 had only few small lesions. In addition, groups 2 and 3 had evidence of parenchymal atrophy. Groups 2 and 3 were the most impaired on the LNNB, but none of these patients was actually demented. Groups 1 and 5 were globally intact in spite of very different mean age and MRI pattern. Group 4 was composed of younger subjects with a shorter disease duration; they showed mild loss of attentive and abstracting abilities. We suggest that since their MRI was showing greater signs of local biological activity their mental deficits may be a transitory condition capable of two distinct outcomes: a favorable one as in groups 1 and 5, and a slowly progressive one associated with loss of brain tissue as in groups 2 and 3.

A clinical study has been conducted on a selected group of 9 children and 12 adults with attention deficit disorder, evaluating the response to the therapy with magnesium pemoline by means of EEG power spectra. Pemoline was given orally in increasing doses ranging from 20 to 80 mg/day. EEG was recorded during baseline and at three fixed intervals during the treatment. Clinical response was assessed by objective and subjective ratings. In the adult sample, the drug produced two opposite patterns of EEG response which allowed us to discriminate by the 1st day of treatment responders who reported a paradoxical calming and non-responders who reported a worsening in anxiety. Inconsistent EEG power changes produced by the drug in children did not allow the discrimination of responders and non-responders. Children did not show paradoxical signs of sedation. EEG and clinical data suggest that adults and children show different drug response and that the paradoxical sedation is present only in adults.

Abnormal anterior pituitary responsiveness to acute administration of thyrotropin-releasing hormone was investigated in 8 patients, 6 women and 2 men, with primary affective disorders in a depressive

Ten chronic schizophrenic patients were given bromocriptine in doses increasing from 1.25 to 5 mg over 6 days (the low-dose therapy) and then up to 40 mg over 15 days (the high-dose therapy). Psychopathological status was assessed using the Brief Psychiatric Rating Scale, twice daily the first 6 days, and every 2 days thereafter. The prolactin (PRL) response to haloperidol stimulation (1 mg i.v.) was measured in five cases before and 3 days after the end of high-dose therapy, and in one patient before and 3 days after the end of low-dose therapy. Electroencephalographic sleep studies were carried out before therapy and every 2 nights during low-dose therapy in five patients, and in two cases during high-dose therapy. Bromocriptine therapy modified neither clinical symptomatology nor sleep patterns. The PRL response to haloperidol after therapy was markedly lower than that before therapy in the five patients treated with high doses, and markedly higher in the single patient tested who was treated only with low-dose therapy.

The electroencephalographic sleep patterns of 10 primary depressives were recorded during baseline nights and two morning nap sessions using a fixed time schedule. Averaged sleep measures for baseline nights replicated previous findings of altered rapid eye movement (REM) sleep patterns and sleep continuity. REM sleep during morning naps occurred only in patients with elevated REM indexes on baseline and prenap nights; it failed to appear in morning sleep of patients who exhibited contrasting REM characteristics. An analysis of hourly REM sleep distribution and averaged deviations from group means revealed significant differences between the two groups which could account for the uneven daytime REM propensity.

Background The prognostic value of evoked potentials (EPs) in multiple sclerosis (MS) has not been fully established. The correlations between the Expanded Disability Status Scale (EDSS) at First Neurological Evaluation (FNE) and the duration of the disease, as well as between EDSS and EPs, have influenced the outcome of most previous studies. To overcome this confounding relations, we propose to test the prognostic value of EPs within an appropriate patient population which should be based on patients with low EDSS at FNE and short disease duration. Methods We retrospectively selected a sample of 143 early relapsing remitting MS (RRMS) patients with an EDSS < 3.5 from a larger database spanning 20 years. By means of bivariate logistic regressions, the best predictors of worsening were selected among several demographic and clinical variables. The best multivariate logistic model was statistically validated and prospectively applied to 50 patients examined during 2009–2011. Results The Evoked Potentials score (EP score) and the Time to EDSS 2.0 (TT2) were the best predictors of worsening in our sample (Odds Ratio 1.10 and 0.82 respectively, p=0.001). Low EP score (below 15–20 points), short TT2 (lower than 3–5 years) and their interaction resulted to be the most useful for the identification of worsening patterns. Moreover, in patients with an EP score at FNE below 6 points and a TT2 greater than 3 years the probability of worsening was 10% after 4–5 years and rapidly decreased thereafter. Conclusions In an appropriate population of early RRMS patients, the EP score at FNE is a good predictor of disability at low values as well as in combination with a rapid buildup of disability. Interestingly, an EP score at FNE under the median together with a clinical stability lasting more than 3 years turned out to be a protective pattern. This finding may contribute to an early identification of benign patients, well before the term required to diagnose Benign MS (BMS).

A group of 27 patients with definite (n = 20) or probable (n = 7) RDC major depressive disorder underwent 2 sleep EEGs and 1 TRH test while in a drug-free depressive phase. A short mean REM latency (less than 60 min) identified 55.5% of major depressives while added use of blunted TSH responses (delta max. less than 5 microU/ml) increased that percentage by 11%. When patients were subdivided into RDC endogenous and nonendogenous, mean REM latency and global depression scores distinguished the 2 groups, while delta TSH did not. A short mean REM latency identified endogenous depression with 80% specificity and 76% sensitivity. The combination of REM latency and delta TSH reduced the specificity to 60%, and therefore cannot be recommended for differentiating endogenous from nonendogenous depression.