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.

Radiologically isolated syndrome and multiple sclerosis.

BACKGROUND: Incidental white matter lesions (WML) are increasingly seen on brain magnetic resonance imaging (MRI) in clinical practice. Demyelination consistent with MS is seen in 0.1-0.7% of the population as evident by autopsy and MRI studies. The term radiologically isolated syndrome (RIS) was coined to define a subgroup of patients with demyelinating lesions highly suggestive of multiple sclerosis (MS). The Okuda criteria for diagnosing RIS help in stratifying the risk of conversion to MS but RIS is still not considered a distinct MS phenotype. METHODS: The authors reviewed the current literature on diagnostic criteria, natural history and treatment indications in RIS, to assess the challenges faced in diagnosing and treating such patients in clinical practice. RESULTS: Typically, one-third of patients convert to clinically definite MS within 5 years, with some progressing directly into primary progressive MS (PPMS). The main risk factors for conversion are: age < 37 years, male gender and presence of spinal cord lesions. Patients with RIS have evidence of early axonal loss, brain atrophy, cognitive deficits, increased anxiety and depression, and subclinical inflammatory disease. CONCLUSION: Patients with RIS at high risk of clinical conversion might be considered for treatment, although this is still a controversial issue. Prospective follow-up of RIS patients by an MS specialist is recommended.

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.

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.

Predictors of quality of life among multiple sclerosis patients: a comprehensive analysis.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a debilitating neurological disease of young people with substantial consequences on patients' quality of life (QOL). A variety of QOL instruments have been used to evaluate the efficacy of treatments. However, no study assessed the role of the different demographic, clinical, physical, social, economic and psychological parameters in the perception of patients with MS of their QOL. METHODS: Two-hundred and one consecutive patients attending outpatient clinics were prospectively studied and objectively assessed using Expanded Disability Status Scale (EDSS), 8-m walk test, and Symbol Digit Modality Test. Patients completed the following questionnaires: MS QOL-54, Hamilton Depression Rating Scale, Fatigue Severity Scale, Brief Pain Inventory Average Pain Score, Drug Side-Effects Severity Scale, Social Support, Religiosity, Physiotherapy and Exercise, and Socioeconomic Profile. Overall, QOL, physical (PHCS) and mental (MHCS) health composite scores were computed as outcome measures from MSQOL-54. RESULTS: Depression, social support, religiosity, education years and living area predicted overall QOL by linear regression (R(2) = 0.43). Unemployment and absence of fatigue correlated with poor and good QOL, respectively. Fatigue, pain, depression, EDSS, social support, MS type and anti-cholinergic treatment predicted PHCS (R(2) = 0.81). Fatigue, pain, depression, education years and social support predicted MHCS (R(2) = 0.70). CONCLUSION: The QOL in patients with MS is not solely determined by physical disability, but rather by the level of social support, living area, depression, level of education, employment, fatigue and religiosity. Accordingly, we suggest that these should be evaluated in every patient with MS as they may be modified by targeted interventions.

MR imaging findings in autosomal recessive hereditary spastic paraplegia.

BACKGROUND AND PURPOSE: Hereditary spastic paraplegia (HSP) is a disorder characterized by degeneration of the corticospinal tracts and posterior column of the spinal cord. Previously described radiologic findings included nonspecific brain abnormalities such as brain atrophy and white matter lesions, as well as atrophy of the spinal cord. In our study, we aimed to better characterize brain and spine MR imaging findings in a series of patients with HSP. MATERIALS AND METHODS: Nine patients from 4 different Lebanese families with the autosomal recessive form of HSP were included in the study. All patients underwent brain and whole-spine MR imaging. We assessed the presence of white matter abnormalities mainly along the corticospinal tracts, brain atrophy, thinning of the corpus callosum, and the presence of spinal cord atrophy or abnormal signal intensity. RESULTS: Imaging revealed mild brain atrophy (44%), atrophy of the corpus callosum (55%), white matter lesions (67%), abnormal T2 high signal intensity in the posterior limb of the internal capsule (55%), and mild spinal cord atrophy (33%). CONCLUSIONS: The MR imaging findings of HSP are nonspecific and variable; however, the most prominent features include atrophy of the corpus callosum, T2 signal intensity in the posterior limb of the internal capsule, and spinal cord atrophy.

Biosimilars: opinion of an expert panel in the Middle East.

BACKGROUND: Several biotechnology-derived drugs are reaching the end of their patent lives. As a result, so-called biosimilar products are in development, and a few have already gained approval in Europe and other countries such as the USA. Biosimilars, unlike generic versions of conventional drugs, are not identical to their reference product, and their production is complex and sensitive to even slight changes in the manufacturing and storage process. Therefore, the registration of these products requires more stringent evaluation than that for conventional generics. METHODS AND SCOPE: A consensus group of experts from the Near and Middle East discussed the currently available guidelines for registration of biosimilars--including those produced by the European Medicines Agency (EMEA)--and their application in this region. To inform this report, a literature search was also conducted on PubMed in January 2008, using the search terms 'biosimilar' and 'follow-on biologic'. This paper provides an overview of the issues in the development and registration of biosimilars, a description of the EMEA guidelines and the recommendations of the consensus group for the registration of biosimilars in the Middle East. FINDINGS: Because of the complex nature of biosimilars and their potential immunogenicity, these products cannot undergo the abbreviated approval process used for generic agents. Instead demonstration of their quality, safety and efficacy, in comparison with their reference biological product, is required. CONCLUSIONS: The consensus group recommended the implementation of the EMEA guidelines as the basis of Regional guidelines for the registration of biosimilars in the Near and Middle East. Registration would, therefore, require demonstration of the robustness of the manufacturing process and quality-control methods, the comparability of pharmacokinetics, pharmacodynamics, efficacy and safety between the biosimilar and reference product and plans for post-marketing surveillance of the long-term risks and immunogenicity of new biosimilars.

Clinical characteristics of multiple sclerosis in Lebanon.

The epidemiologic, clinical, radiological and laboratory characterization of multiple sclerosis (MS) is very well documented in Caucasian and Japanese populations, but very little is known about MS in the Arab world. Such knowledge is becoming of paramount importance, with the recent advances in therapies, MRI techniques and other diagnostic procedures. We report a cohort of Lebanese MS patients, including details of their clinical and laboratory characteristics. The medical records of 202 patients fulfilling the Mc Donald's diagnostic criteria, and followed in our tertiary care center were reviewed. This cohort is highly representative of the disease in Lebanon where the number of MS patients is estimated to be between 1200 and 1700. The peak age of onset of MS in our cohort was in the third decade with 62.4% of patients developing their first symptoms between 20 and 39 years. The female/male ratio was 1.8/1.0. A positive family history for MS was present in 5% of patients. The most frequent presenting symptoms were brainstem-cerebellar (46.2%) followed by sensory (42.5%), motor (33.9%) and visual (29.6%). Of the total number of patients, 85.1% had relapsing remitting MS at onset, and 7.9% primary progressive MS. Benign MS defined as EDSS<=2.0 after 10 years from onset was present in 20% of patients. The mean time from onset to secondary progressive MS was around 9 years. Visual, brainstem, and somatosensory evoked potentials were abnormal in 65.6%, 27.8%, and 50.7% of patients tested respectively. Cerebrospinal fluid showed pleocytosis in 32.6%, increased IgG synthesis in 45.2%, positive oligoclonal bands in 40%, and elevated protein in 34% of patients tested. Although some of the clinical characteristics of our MS population were different compared to western series, the natural history of the disease was similar.

Successful treatment of refractory neuroSjogren with Rituximab.

We report a 47-year-old female with Sjogren's syndrome (SS) and severe weakness in her lower extremities refractory to cyclophosphamide therapy, who was treated with the monoclonal anti CD-20 antibody rituximab at a weekly dose of 375 mg/m2 for four consecutive weeks. Patient responded within few days of the first dose and her motor power in the lower extremities started to improve gradually along with progressive resolution of the paresthesias and dysesthesias. The improvement was sustained and progressive and eight months after the last dose, she was able to walk for 60 meters without aid or rest. Rituximab may be considered as an effective and promising novel therapy in SS patients with neurological involvement.

Two randomized vitamin D trials in ambulatory patients on anticonvulsants: impact on bone.

OBJECTIVE: To investigate the effects of two doses of vitamin D given over 1 year on bone density in ambulatory patients on long-term antiepileptic drug (AED) therapy. METHODS: We conducted two parallel, randomized, controlled trials in 72 adults (18 to 54 years old) and 78 children and adolescents (10 to 18 years) on long-term AED therapy. They received either low-dose vitamin D 400 IU/day or high-dose vitamin D 4,000 IU/day (adults) and 2,000 IU/day (children/adolescents). Bone mineral density (BMD) was measured using dual-energy x-ray absorptiometry. RESULTS: In adults, baseline BMD was lower than that of age- and gender-matched controls vs either a Western or an ethnically identical population. After 1 year, there were significant increases in BMD at all skeletal sites compared to baseline in the high-, but not in the low-dose treatment group. However, BMD at 1 year remained below normal. In children, baseline BMD was normal vs age- and gender-matched controls and showed significant and comparable increases in both treatment groups. CONCLUSIONS: In ambulatory adults on antiepileptic drugs, high-dose vitamin D therapy substantially increased bone mineral density at several skeletal sites. In children, both doses resulted in comparable increases in bone mass.

Effect of antiepileptic drugs on bone density in ambulatory patients.

BACKGROUND: Long-term antiepileptic drug (AED) use causes multiple abnormalities in calcium and bone metabolism that have been most extensively described in institutionalized patients. The objective is to determine the effect of AED on vitamin D levels and bone density in ambulatory patients and to compare the effects of enzyme-inducing and -noninducing AED and of single vs multiple therapy on bone density. METHODS: A cross-sectional evaluation was conducted of 71 patients (42 adults and 29 children/adolescents) on anticonvulsant therapy for at least 6 months who presented to neurologists at a tertiary referral center. Bone mineral density (BMD) as well as serum 25 hydroxy-vitamin D (25-OHD) levels were measured. A detailed questionnaire assessing calcium intake as well as previous and current intake of antiepileptic medications was administered to all patients. RESULTS: Over 50% of adults and children/adolescents had low 25-OHD levels, but this finding did not correlate with BMD. Antiepileptic therapy decreased BMD in adults. Generalized seizures, duration of epilepsy, and polypharmacy were significant determinants of BMD, more so at skeletal sites enriched in cortical bone. Subjects on enzyme-inducing drugs such as phenytoin, phenobarbital, carbamazepine, and primidone tended to have lower BMD than those on noninducers such as valproic acid, lamotrigine, clonazepam, gabapentin, topamirate, and ethosuximide. CONCLUSION: Epilepsy and its therapy, including the newer drugs, are risk factors for low bone density, irrespective of vitamin D levels. Skeletal monitoring with the institution of appropriate therapy is indicated in patients on chronic antiepileptic therapy.

Prolactin secretion is increased in patients with multiple sclerosis.

Before the onset and during experimental allergic encephalomyelitis (EAE), the animal counterpart of multiple sclerosis (MS), prolactin levels were found to be elevated and bromocriptine was found to attenuate the attacks. This study was designed to determine whether patients with MS show evidence of hyperprolactinemia. Twelve patients with MS and twelve healthy controls were studied at baseline and with TRH stimulation, a provocative test for prolactin secretion. Compared to matched controls, patients with MS had slightly but significantly higher prolactin levels at baseline (10.2+/-1.6 vs 6.4 4+/-0.57 ng/ml, P=0.042), however, values were within the normal range. The prolactin levels post TRH were significantly higher in patients with MS: peak prolactin level was higher in patients than controls (57.08+/-6.144 vs 32.94+/-4.92 ng/ml, P=0.006). The area under the curve of prolactin was also higher in patients than in controls (3421.87+/-394.53 vs 2317.62+/-257.22 ng/ml, P=0.030). These findings are compatible with data from studies of experimental animals with MS and suggest that prolactin may play a role in the immunology of MS.

Narghile (hubble-bubble) smoking, low birth weight, and other pregnancy outcomes.

Narghile smoking, a common habit among women in many non-Western societies, is assumed by the public to be minimally harmful. This study aims at identifying the effect of smoking narghiles during pregnancy on the weight of the newborn and other pregnancy outcomes. Three groups of pregnant women were interviewed in several hospitals in Lebanon between 1993 and 1995: 106 who smoked narghiles during their pregnancy, 277 who smoked cigarettes, and 512 who did not smoke. The adjusted mean birth weight of babies born to women who smoked one or more narghiles a day during pregnancy and to women who started smoking in the first trimester was more than 100 g less than that of babies born to nonsmokers (p < 0.1). The adjusted odds ratio of having babies with low birth weight (<2,500 g) among the narghile smokers was 1.89 (95% confidence interval (CI) 0.67-5.38). The risk increased to 2.62 (95% CI 0.90-7.66) among those who started smoking narghiles in the first trimester. A stronger association and a dose-response relation were found among cigarette smokers. The association between narghile smoking and other pregnancy outcomes, especially Apgar score and respiratory distress, was also noticeable. Further research and a policy action to fight the misperception that narghile smoking is safe are both recommended.

Meningeal carcinomatosis as the presenting manifestation of gastric adenocarcinoma.

Leptomeningeal involvement is usually reported as a secondary event in advanced, already diagnosed, gastric adenocarcinoma. We report a case of leptomeningeal carcinomatosis in which identification of mucus-secreting "signet-ring" carcinoma cells in the cerebrospinal fluid allowed the diagnosis of an otherwise asymptomatic gastric cancer. This is one of the very few reported cases manifesting as such in the medical literature.

Alpha-interferon in the treatment of subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis is an inexorably progressive disease with no effective therapy. Recent trials of intrathecal and intraventricular alpha-interferon yielded controversial results. We tried intrathecal or intraventricular alpha-interferon in four patients with subacute sclerosing panencephalitis. None of them had evidence of improvement. We reviewed the previously published studies on the use of alpha-interferon in subacute sclerosing panencephalitis. Further international collaborative studies are needed to determine the role of alpha-interferon in the treatment of subacute sclerosing panencephalitis.