Consensus recommendations for diagnosis and treatment of Multiple Sclerosis: 2023 revision of the MENACTRIMS guidelines.

With evolving diagnostic criteria and the advent of new oral and parenteral therapies for Multiple Sclerosis (MS), most current diagnostic and treatment algorithms need revision and updating. The diagnosis of MS relies on incorporating clinical and paraclinical findings to prove dissemination in space and time and exclude alternative diseases that can explain the findings at hand. The differential diagnostic workup should be guided by clinical and laboratory red flags to avoid unnecessary tests. Appropriate selection of MS therapies is critical to maximize patient benefit. The current guidelines review the current diagnostic criteria for MS and the scientific evidence supporting treatment of acute relapses, radiologically isolated syndrome, clinically isolated syndrome, relapsing remitting MS, progressive MS, pediatric cases and pregnant women. The purpose of these guidelines is to provide practical recommendations and algorithms for the diagnosis and treatment of MS based on current scientific evidence and clinical experience.

Consensus recommendations for the diagnosis and treatment of multiple sclerosis: 2019 revisions to the MENACTRIMS guidelines.

With evolving diagnostic criteria and the advent of new oral and parenteral therapies for MS, most current diagnostic and treatment algorithms need revision and updating. The diagnosis of MS relies on incorporating clinical and paraclinical findings to prove dissemination in space and in time, and exclude alternative diseases that can explain the findings at hand. The differential diagnostic workup should be guided by clinical and laboratory red flags to avoid unnecessary tests. Appropriate selection of multiple sclerosis (MS) therapies is critical to maximize patient benefit. The current guidelines review the scientific evidence supporting treatment of acute relapses, radiologically isolated syndrome, clinically isolated syndrome, relapsing remitting MS, and progressive MS. The purpose of these guidelines is to provide practical recommendations and algorithms for the diagnosis and treatment of MS based on current scientific evidence and clinical experience.

Alternative diagnoses in patients referred to specialized centers for suspected MS.

OBJECTIVES: The aim of this study is to explore the frequency, type, and predictors of alternative diagnoses among patients referred with a recent diagnosis of multiple sclerosis (MS) to two specialized MS centers in the Middle East. METHODS: This is a retrospective review of a prospectively followed cohort of MS patients at 2 University specialized MS centers. All patients referred for MS were included. The final diagnosis was recorded and demographic, clinical, laboratory, electrophysiological and radiological variables were collected. RESULTS: A total of 554 patients were included in this study of which 431 were referred for diagnostic confirmation. The final diagnosis of MS was confirmed in 300 (70%), while 114 (26%) turned out to have an alternative diagnosis and 15 (3.5%) fulfilled criteria for radiologically isolated syndrome (RIS). The most common alternative diagnoses were psychogenic (16.3%), non-specific MRI white matter lesions (14.7%), NMO (9.5%), migraine (8.6%) and systemic autoimmune disorders (8.6%). The strongest predictors of a final diagnosis of MS were: younger age, presence of oligoclonal bands in the CSF, periventricular, corpus callosum, spinal (P<0.0001), or enhancing lesions (P<0.005) on MRI. CONCLUSIONS: Our study shows that 30% of patients referred for a suspicion of MS end up with a different diagnosis. The most common alternative diagnoses of MS in the Middle East are not different from what has been described in Western countries. Age, MRI and CSF findings can help with the differential diagnosis.

Drinking water system treatment and contamination in Shatila Refugee Camp in Beirut, Lebanon.

Drinking water at Shatila Palestinian Refugee Camp in Beirut, Lebanon is of poor quality and unpredictably intermittent quantity. We aimed to characterize drinking water sources and contamination at Shatila and determine how drinking water can be managed to reduce community health burdens. We interviewed the Popular Committee, well owners, water vendors, water shopkeepers and preschool administrators about drinking water sources, treatment methods and the population served. Water samples from the sources and intermediaries were analysed for thermotolerant faecal coliforms (FCs), Giardia lamblia, Cryptosporidium parvum and microsporidia, using immunofluorescent antibody detection for G. lamblia and C. parvum, and chromotrope-2 stain for microsporidia. All drinking water sources were contaminated with FCs and parasites. FC counts (cfu/mL) were as follows: wells (35-300), water vendors (2-178), shops (30-300) and preschools (230-300). Responsible factors identified included: unskilled operators; improper maintenance of wells and equipment; lack of proper water storage and handling; and misperception of water quality. These factors must be addressed to improve water quality at Shatila and other refugee camps.

Drinking water system treatment and contamination in Shatila refugee camp in Beirut, Lebanon

Drinking water at Shatila Palestinian Refugee Camp in Beirut, Lebanon is of poor quality and unpredictably intermittent quantity. We aimed to characterize drinking water sources and contamination at Shatila and determine how drinking water can be managed to reduce community health burdens. We interviewed the Popular Committee, well owners, water vendors, water shopkeepers and preschool administrators about drinking water sources, treatment methods and the population served. Water samples from the sources and intermediaries were analysed for thermotolerant faecal coliforms [FCs], Giardia lamblia, Cryptosporidium parvum and microsporidia, using immunofluorescent antibody detection for G. lamblia and C. parvum, and chromotrope-2 stain for microsporidia. All drinking water sources were contaminated with FCs and parasites. FC counts [cfu/mL] were as follows: wells [35-300], water vendors [2-178], shops [30-300] and preschools [230-300]. Responsible factors identified included: unskilled operators; improper maintenance of wells and equipment; lack of proper water storage and handling; and misperception of water quality. These factors must be addressed to improve water quality at Shatila and other refugee camps

L'eau potable dans le camp de réfugiés palestiniens de Chatila, au Liban, est de mauvaise qualité et n'est disponible qu'en quantités imprévisibles et irrégulières. La présente étude avait pour objectif d'identifier les sources d'eau potable et de contamination à Chatila, et de déterminer la façon dont l'eau potable peut être gérée pour réduire la charge des problèmes de santé communautaires. Nous avons interrogé le Comité populaire, les propriétaires de puits, les vendeurs d'eau ambulants, les marchands d'eau, les responsables de structures préscolaires sur les sources d'eau potable, les méthodes de traitement et la population desservie. Des échantillons d'eau à la source et au niveau des intermédiaires ont été analysés afin de détecter la présence de coliformes thermotolérants, de Giardia lamblia, de Cryptosporidium parvum et de microsporidies, à l'aide de la recherche des anticorps par immunofluorescence pour G. lamblia and C. parvum, et de la coloration au chromotrope 2R pour les microsporidies. Toutes les sources d'eau potable étaient contaminées par des coliformes thermotolérants et des parasites. Les taux [ufc/ml] de coliformes thermotolérants étaient les suivants : puits [35-300], vendeurs d'eau ambulants [2-178], commerces [30-300] et structures préscolaires [230-300]. Les facteurs responsables identifiés incluaient les points suivants : des opérateurs non formés, une mauvaise maintenance des puits et des équipements, un stockage et une manutention de l'eau inappropriés, et une perception erronée de la qualité de l'eau. Il est nécessaire d'agir sur ces facteurs afin d'améliorer la qualité de l'eau à Chatila et dans les autres camps de réfugiés

Genetic predictors of human chronic pain conditions.

Chronic pain conditions are multifactorial disorders with a high frequency in the population. Their pathophysiology is often unclear, and treatment is inefficient. During the last 20years, genetic linkage analysis and association studies have made considerable strides toward identifying key molecular contributors to the onset and maintenance of chronic pain. Here, we review the genetic variants that have been implicated in chronic pain conditions, divided into the following etiologically-grouped categories: migraine, musculoskeletal pain disorders, neuropathic pain disorders, and visceral pain disorders. In rare familial monogenic pain conditions several strong-effect mutations have been identified. In contrast, the genetic landscape of common chronic pain conditions suggests minor contributions from a large number of single nucleotide polymorphisms representing different functional pathways. A comprehensive survey of up-to-date genetic association results reveals migraine and musculoskeletal pain to be the most investigated chronic pain disorders, in which nearly half of identified genetic variability alters neurotransmission pathways.

The present and future disease burden of hepatitis C virus infections with today's treatment paradigm - volume 3.

The total number, morbidity and mortality attributed to viraemic hepatitis C virus (HCV) infections change over time making it difficult to compare reported estimates from different years. Models were developed for 15 countries to quantify and characterize the viraemic population and forecast the changes in the infected population and the corresponding disease burden from 2014 to 2030. With the exception of Iceland, Iran, Latvia and Pakistan, the total number of viraemic HCV infections is expected to decline from 2014 to 2030, but the associated morbidity and mortality are expected to increase in all countries except for Japan and South Korea. In the latter two countries, mortality due to an ageing population will drive down prevalence, morbidity and mortality. On the other hand, both countries have already experienced a rapid increase in HCV-related mortality and morbidity. HCV-related morbidity and mortality are projected to increase between 2014 and 2030 in all other countries as result of an ageing HCV-infected population. Thus, although the total number of HCV countries is expected to decline in most countries studied, the associated disease burden is expected to increase. The current treatment paradigm is inadequate if large reductions in HCV-related morbidity and mortality are to be achieved.

Strategies to manage hepatitis C virus infection disease burden - volume 3.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries in Europe, the Middle East and Asia, and the relative impact of two scenarios was considered: increased treatment efficacy while holding the annual number of treated patients constant and increased treatment efficacy and an increased annual number of treated patients. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. A 90% reduction in total HCV infections within 15 years is feasible in most countries studied, but it required a coordinated effort to introduce harm reduction programmes to reduce new infections, screening to identify those already infected and treatment with high cure rate therapies. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. Among European countries, the majority of patients were born between 1940 and 1985. A wider range of birth cohorts was seen in the Middle East and Asia (between 1925 and 1995).

Historical epidemiology of hepatitis C virus (HCV) in select countries - volume 3.

Detailed, country-specific epidemiological data are needed to characterize the burden of chronic hepatitis C virus (HCV) infection around the world. With new treatment options available, policy makers and public health officials must reconsider national strategies for infection control. In this study of 15 countries, published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates were gathered from the literature and validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Iran and Lebanon to 4.2% in Pakistan. The largest viraemic populations were in Pakistan (7 001 000 cases) and Indonesia (3 187 000 cases). Injection drug use (IDU) and a historically unsafe blood supply were major risk factors in most countries. Diagnosis, treatment and liver transplant rates varied widely between countries. However, comparison across countries was difficult as the number of cases changes over time. Access to reliable data on measures such as these is critical for the development of future strategies to manage the disease burden.

Consensus recommendations for the diagnosis and treatment of multiple sclerosis: the Middle East North Africa Committee for Treatment and Research In Multiple Sclerosis (MENACTRIMS).

With evolving diagnostic criteria and the advent of new oral and parenteral therapies for MS, most current diagnostic and treatment algorithms need re-evaluation and updating. The diagnosis of MS relies on incorporating clinical and paraclinical findings to prove dissemination in space and in time, and exclude alternative diseases that can explain the findings at hand. The differential diagnostic workup should be guided by clinical and laboratory red flags to avoid unnecessary tests. Appropriate multiple sclerosis (MS) therapy selection is critical to maximize patient benefit. The current guidelines review the scientific evidence supporting treatment of acute relapses, radiologically isolated syndrome, clinically isolated syndrome, relapsing remitting MS, secondary progressive MS, and primary progressive MS. The purpose of these guidelines is to provide practical recommendations and algorithms for the diagnosis and treatment of MS based on current scientific evidence and clinical experience.

EMG-based learning approach for estimating wrist motion.

This paper proposes an EMG based learning approach for estimating the displacement along the 2-axes (abduction/adduction and flexion/extension) of the human wrist in real-time. The algorithm extracts features from the EMG electrodes on the upper and forearm and uses Support Vector Regression to estimate the intended displacement of the wrist. Using data recorded with the arm outstretched in various locations in space, we train the algorithm so as to allow robust prediction even when the subject moves his/her arm across several positions in space. The proposed approach was tested on five healthy subjects and showed that a R(2) index of 63.6% is obtained for generalization across different arm positions and wrist joint angles.

Sleep and wake disturbances following traumatic brain injury.

Traumatic brain injury (TBI) is a major health concern in industrialised countries. Sleep and wake disturbances are among the most persistent and disabling sequelae after TBI. Yet, despite the widespread complaints of post-TBI sleep and wake disturbances, studies on their etiology, pathophysiology, and treatments remain inconclusive. This narrative review aims to summarise the current state of knowledge regarding the nature of sleep and wake disturbances following TBI, both subjective and objective, spanning all levels of severity and phases post-injury. A second goal is to outline the various causes of post-TBI sleep-wake disturbances. Globally, although sleep-wake complaints are reported in all studies and across all levels of severity, consensus regarding the objective nature of these disturbances is not unanimous and varies widely across studies. In order to optimise recovery in TBI survivors, further studies are required to shed light on the complexity and heterogeneity of post-TBI sleep and wake disturbances, and to fully grasp the best timing and approach for intervention.

Consensus guidelines for the diagnosis and treatment of multiple sclerosis.

The diagnosis of multiple sclerosis (MS) is dependent on the presence of clinical and paraclinical evidence demonstrating dissemination of central nervous system lesions in both space and time, as well as the exclusion of other disorders. Diagnostic criteria were originally promulgated in 1965 by the Schumacher committee and modified subsequently by the Poser committee to include paraclinical evidence. The most recent criteria are the 2010 modifications of the 2001 McDonald criteria, which are focused on making an earlier diagnosis of MS. This article provides guidelines, derived from clinical experience as well as evidence-based medicine, for the diagnosis and management of MS with special emphasis on practices in the Middle East.

Evaluation and treatment of lower urinary tract symptoms in older men.

PURPOSE: The 6th International Consultation on New Developments in Prostate Cancer and Prostate Diseases met from June 24-28, 2005 in Paris, France to review new developments in benign prostatic disease. MATERIALS AND METHODS: A series of committees were asked to produce recommendations on the evaluation and treatment of lower urinary tract symptoms in older men. Each committee was asked to base recommendations on a thorough assessment of the available literature according to the International Consultation on Incontinence level of evidence and grading system adapted from the Oxford system. RESULTS: The Consultation endorsed the appropriate use of the current terminology lower urinary tract symptoms/benign prostatic hyperplasia/benign prostate enlargement and benign prostatic obstruction, and recommended that terms such as "clinical benign prostatic hyperplasia" or "the benign prostatic hyperplasia patient" be abandoned, and asked the authorities to endorse the new nomenclature. The diagnostic evaluation describes recommended and optional tests, and in general places the focus on the impact (bother) of lower urinary tract symptoms on the individual patient when determining investigation and treatment. The importance of symptom assessment, impact on quality of life, physical examination and urinalysis is emphasized. The frequency volume chart is recommended when nocturia is a bothersome symptom to exclude nocturnal polyuria. The recommendations are summarized in 2 algorithms, 1 for basic management and 1 for specialized management of persistent bothersome lower urinary tract symptoms. CONCLUSIONS: The use of urodynamics and transrectal ultrasound should be limited to situations in which the results are likely to benefit the patient such as in selection for surgery. It is emphasized that imaging and endoscopy of the urinary tract have specific indications such as dipstick hematuria. Treatment should be holistic, and may include conservative measures, lifestyle interventions and behavioral modifications as well as medication and surgery. Only treatments with a strong evidence base for their clinical effectiveness should be used.

The impact of lesion in-painting and registration methods on voxel-based morphometry in detecting regional cerebral gray matter atrophy in multiple sclerosis.

BACKGROUND AND PURPOSE: VBM has been widely used to study GM atrophy in MS. MS lesions lead to segmentation and registration errors that may affect the reliability of VBM results. Improved segmentation and registration have been demonstrated by WM LI before segmentation. DARTEL appears to improve registration versus the USM. Our aim was to compare the performance of VBM-DARTEL versus VBM-USM and the effect of LI in the regional analysis of GM atrophy in MS. MATERIALS AND METHODS: 3T T1 MR imaging scans were acquired from 26 patients with RRMS and 28 age-matched NC. LI replaced WM lesions with normal-appearing WM intensities before image segmentation. VBM analysis was performed in SPM8 by using DARTEL and USM with and without LI, allowing the comparison of 4 VBM methods (DARTEL + LI, DARTEL - LI, USM + LI, and USM - LI). Accuracy of VBM was assessed by using NMI, CC, and a simulation analysis. RESULTS: Overall, DARTEL + LI yielded the most accurate GM maps among the 4 methods (highest NMI and CC, P < .001). DARTEL + LI showed significant GM loss in the bilateral thalami and caudate nuclei in patients with RRMS versus NC. The other 3 methods overestimated the number of regions of GM loss in RRMS versus NC. LI improved the accuracy of both VBM methods. Simulated data suggested the accuracy of the results provided from patient MR imaging analysis. CONCLUSIONS: We introduce a pipeline that shows promise in limiting segmentation and registration errors in VBM analysis in MS.

HLA (A-B-C and -DRB1) alleles and brain MRI changes in multiple sclerosis: a longitudinal study.

Several major histocompatibility complex (MHC) alleles have been postulated to influence the susceptibility to multiple sclerosis (MS), as well as its clinical/radiological course. In this longitudinal observation, we further explored the impact of human leukocyte antigen (HLA) class I/II alleles on MS outcomes, and we tested the hypothesis that HLA DRB1*1501 might uncover different strata of MS subjects harboring distinct MHC allele associations with magnetic resonance imaging (MRI) measures. Five hundred eighteen MS patients with two-digit HLA typing and at least one brain MRI were recruited for the study. T2-weighted hyperintense lesion volume (T2LV) and brain parenchymal fraction (BPF) were acquired at each time point. The association between allele count and MRI values was determined using linear regression modeling controlling for age, disease duration and gender. Analyses were also stratified by the presence/absence of HLA DRB1*1501. HLA DRB1*04 was associated with higher T2LV (P=0.006); after stratification, its significance remained only in the presence of HLA DRB1*1501 (P=0.012). The negative effect of HLA DRB1*14 on T2LV was exerted in DRB1*1501-negative group (P=0.012). Longitudinal analysis showed that HLA DRB1*10 was significantly protective on T2LV accrual in the presence of HLA DRB1*1501 (P=0.002). Although the majority of our results did not withstand multiple comparison correction, the differential impact of several HLA alleles in the presence/absence of HLA DRB1*1501 suggests that they may interact in determining the different phenotypic expressions of MS.

HLA B*44: protective effects in MS susceptibility and MRI outcome measures.

OBJECTIVE: In addition to the main multiple sclerosis (MS) major histocompatibility complex (MHC) risk allele (HLA DRB1*1501), investigations of the MHC have implicated several class I MHC loci (HLA A, HLA B, and HLA C) as potential independent MS susceptibility loci. Here, we evaluate the role of 3 putative protective alleles in MS: HLA A*02, HLA B*44, and HLA C*05. METHODS: Subjects include a clinic-based patient sample with a diagnosis of either MS or a clinically isolated syndrome (n = 532), compared to subjects in a bone marrow donor registry (n = 776). All subjects have 2-digit HLA data. Logistic regression was used to determine the independence of each allele's effect. We used linear regression and an additive model to test for correlation between an allele and MRI and clinical measures of disease course. RESULTS: After accounting for the effect of HLA DRB1*1501, both HLA A*02 and HLA B*44 are validated as susceptibility alleles (p(A*02) 0.00039 and p(B*44) 0.00092) and remain significantly associated with MS susceptibility in the presence of the other allele. Although A*02 is not associated with MS outcome measures, HLA B*44 demonstrates association with a better radiologic outcome both in terms of brain parenchymal fraction and T2 hyperintense lesion volume (p = 0.03 for each outcome). CONCLUSION: The MHC class I alleles HLA A*02 and HLA B*44 independently reduce susceptibility to MS, but only HLA B*44 appears to influence disease course, preserving brain volume and reducing the burden of T2 hyperintense lesions in subjects with MS.

Prior use of statins and outcome in patients with intracerebral haemorrhage.

BACKGROUND: Pre-treatment with cholesterol lowering drugs of the statin family may exert protective effects in patients with ischaemic stroke and subarachnoid haemorrhage but their effects are not clear in patients with intracerebral haemorrhage (ICH). METHODS: We recruited patients admitted to our University Hospital with an acute ICH and analysed pre-admission demographic variables, pre-morbid therapy, clinical and radiological prognostic markers and outcome variables including 90-day modified Rankin score and NIH stroke scale score (NIHSS). RESULTS: We recruited 399 patients with ICH of which 101 (25%) were using statins. Statin users more often had vascular risk factors, had significantly lower haematoma volumes (P = 0.04) and had lower mortality rates compared with non-users (45.6% vs. 56.1%; P = 0.11). However, statin treatment did not have a statistically significant impact on mortality or functional outcome on multiple logistic regression analysis. CONCLUSIONS: Treatment with statins prior to ICH failed to show a significant impact on outcome in this analysis despite lower haematoma volumes.