Publications by authors named "Raed Alroughani"

112 Publications

Primary Headache Disorder Among School Students in Kuwait.

Front Neurol 2021 2;12:621017. Epub 2021 Feb 2.

Neurology Department, Ibn Sina Hospital, Safat, Kuwait.

Primary headaches are remarkably prevalent worldwide and are increasingly reported among children. However, the exact trend in this age group, particularly in the Gulf region, remains largely unknown. To examine the prevalence of primary headache disorders among primary and middle school students in Kuwait. We conducted a cross-sectional study that included Kuwaiti primary and middle school children and adolescents of both genders in randomly selected schools located in two governorates in Kuwait in the 2018/2019 academic year. Prevalence and attributable burden of headaches, definite and probable migraines, definite and probable tension-type headaches, chronic headaches (≥15 days/month), and probable medication-overuse headaches were assessed using the Headache-Attributed Restriction, Disability, Social Handicap, and Impaired Participation (HARDSHIP) questionnaire for children and adolescents. Of 1,485 questionnaires that were distributed, 1,089 students completed the questionnaire with a respondent rate of 73.4%. The study population consisted of 420 boys (38.56%) and 669 girls (61.43%) students with a mean age of 11.5 ± 2.11 years. The 1-year prevalence of primary headache disorders was 42.78%, with more middle schoolers reporting headaches than primary schoolers (50.37 vs. 30.48%; < 0.02). The mean age of students with primary headaches was 11.98 ± 2.03 years in both genders. When stratified according to diagnostic criteria, migraine headaches were the most frequently reported (20.75%), followed by tension type headaches (18.8%), chronic headaches (2.75%), and probable medication-overuse headaches (0.46%). Primary headaches were significantly higher in girls compared to boys among middle schoolers (66.46 vs. 38.49%; < 0.001); however, no significant difference between genders was noted among primary school students (33.12 vs. 22.33%; < 0.118). Primary headaches are remarkably common in Kuwaiti school students, with migraine headaches being the most frequently reported type. Age and female gender may play a role in the development of primary headaches. These findings necessitate the direction of health services and research efforts toward this age group and warrant the need for further epidemiological studies.
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http://dx.doi.org/10.3389/fneur.2021.621017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884619PMC
February 2021

Onabotulinumtoxin A Improves Psychological Aspects in Chronic Migraine Patients.

Front Neurol 2020 27;11:633355. Epub 2021 Jan 27.

Neurology Department, Ibn Sina Hospital, Kuwait, Kuwait.

Chronic migraine (CM) affects 5.4% of the Kuwaiti population. It is associated with significant headache-related disability, psychiatric comorbidity and reduced quality of life. The aim of this study is to assess the efficacy of Onabotulinumtoxin A on psychological aspects of chronic migraine patients. This prospective study over 36 months included chronic migraine patients in a tertiary headache center. Eligible patients met International Classification of Headache Disorders disorders-third edition, beta version (ICHD-III) revision criteria for chronic migraine. Patients with history of psychiatric or medical problems other than migraine disorders were excluded. Patients who received less than 4 injections cycles of Onabotulinumtoxin A were excluded. Identified patients received 155 units of Onabotulinumtoxin A quarterly according to the Phase III Research Evaluating Migraine Prophylaxis Therapy Trail (PREEMPT) protocol. Quality of life, the seven-item Generalized Anxiety Disorder (GAD-7) scores, the nine-item Patient Health Questionnaire (PHQ9), and the Pittsburgh Sleep Quality Index (PSQI) were collected before injection and at the end of the study. Mean comparison tests were performed using the independent sample test to assess the effects of Onabotulinumtoxin A on quality of life and comorbid symptoms of anxiety, depression, and quality of sleep. The study identified 131 chronic migraine patients with a mean age of 44.92 years, mean disease duration of 12.20 years and a mean treatment sessions of 7.58. In their last visit, most of our sample showed improvement in quality of life (81%), GAD-7 (81%), PHQ9 (79%), and PSQ1 (76%). The mean score of patient satisfaction was 7.21. Onabotulinumtoxin A treatment for CM improved quality of life significantly (72.92 vs. 103.62 < 0.0001). It was also associated with significant reduction in anxiety [GAD-7 (12.00 vs. 6.61 < 0.0001)] and depression [PHQ-9 (17.91 vs. 12.52; < 0.0001)] scores, as well as reduced difficulty in sleeping [PSQI (12.60 vs. 6.66; < 0.0001)] at the last visit. Prophylactic Onabotulinumtoxin A treatment for CM was associated with significant improvement of quality of life, reduction in symptoms of anxiety and depression, as well as improved symptoms of poor sleep.
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http://dx.doi.org/10.3389/fneur.2020.633355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873558PMC
January 2021

Delayed-Release Dimethyl Fumarate Safety and Efficacy in Pediatric Patients With Relapsing-Remitting Multiple Sclerosis.

Front Neurol 2020 4;11:606418. Epub 2021 Jan 4.

Biogen, Cambridge, MA, United States.

Pediatric multiple sclerosis (MS) is rare: only 1.5-5% of MS cases are diagnosed before 18 years of age, and data on disease-modifying therapies (DMTs) for pediatric MS are limited. The CONNECTED study assessed the long-term safety and efficacy of treatment with delayed-release dimethyl fumarate (DMF), an oral MS DMT, in pediatric patients with MS. CONNECTED is the 96-week extension to FOCUS, a 24-week phase 2 study of patients aged 13-17 years; participants received DMF 240 mg twice daily. Endpoints included (primary) incidence of adverse events (AEs), serious AEs, and DMF discontinuations due to an AE, and (secondary) T2 hyperintense lesion incidence by magnetic resonance imaging and annualized relapse rate (ARR). Twenty participants [median (range) age, 17 (14-18) years; 65% female] who completed FOCUS enrolled into CONNECTED; 17 (85%) completed CONNECTED. Eighteen participants (90%) experienced AEs: the most frequent was flushing (25%). None experienced infections or fever related to low lymphocyte counts. Three participants experienced four serious AEs; none led to DMF discontinuation. Twelve of 17 participants (71%) had no new/newly enlarged T2 lesions from weeks 16-24, two (12%) had one, and one each (6%) had two, three, or five or more lesions [median (range), 0 (0-6)]. Over the full 120-week treatment period, ARR was 0.2, an 84.5% relative reduction ( = 20; 95% confidence interval: 66.8-92.8; < 0.0001) vs. the year before DMF initiation. The long-term safety and efficacy observed in CONNECTED was consistent with adults, suggesting pediatric and adolescent patients with MS might benefit from DMF treatment.
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http://dx.doi.org/10.3389/fneur.2020.606418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812971PMC
January 2021

Determinants of therapeutic lag in multiple sclerosis.

Mult Scler 2021 Jan 11:1352458520981300. Epub 2021 Jan 11.

CORe, Department of Medicine, University of Melbourne, Melbourne, VIC, Australia/Melbourne MS Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia.

Background: A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups.

Objectives: The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation.

Methods: Data from MSBase, a multinational multiple sclerosis (MS) registry, and OFSEP, the French MS registry, were used. Patients diagnosed with MS, minimum 1 year of exposure to MS treatment and 3 years of pre-treatment follow-up, were included in the analysis. Studied outcomes were incidence of relapses and disability accumulation. Therapeutic lag was calculated using an objective, validated method in subgroups stratified by patient and disease characteristics. Therapeutic lag under specific circumstances was then estimated in subgroups defined by combinations of clinical and demographic determinants.

Results: High baseline disability scores, annualised relapse rate (ARR) ⩾ 1 and male sex were associated with longer therapeutic lag on disability progression in sufficiently populated groups: females with expanded disability status scale (EDSS) < 6 and ARR < 1 had mean lag of 26.6 weeks (95% CI = 18.2-34.9), males with EDSS < 6 and ARR < 1 31.0 weeks (95% CI = 25.3-36.8), females with EDSS < 6 and ARR ⩾ 1 44.8 weeks (95% CI = 24.5-65.1), and females with EDSS ⩾ 6 and ARR < 1 54.3 weeks (95% CI = 47.2-61.5).

Conclusions: Pre-treatment EDSS and ARR are the most important determinants of therapeutic lag.
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http://dx.doi.org/10.1177/1352458520981300DOI Listing
January 2021

Effect of Disease-Modifying Therapy on Disability in Relapsing-Remitting Multiple Sclerosis Over 15 Years.

Neurology 2021 02 28;96(5):e783-e797. Epub 2020 Dec 28.

From CORe (T.K., I.D., S.S., C.M.), Department of Medicine, University of Melbourne; MS Centre (T.K., I.D., S.S., C.M.), Department of Neurology, Royal Melbourne Hospital, Australia; Karolinska Institute (T.S.), Stockholm, Sweden; Department of Neuroscience (T.S., V.J., A.v.d.W., O.S., H.B.), Central Clinical School, Monash University, Melbourne; Burnet Institute (T.S.), Melbourne, Australia; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), General University Hospital and Charles University in Prague, Czech Republic; Department of Basic Medical Sciences, Neuroscience and Sense Organs (M. Trojano), University of Bari, Italy; Hospital Universitario Virgen Macarena (G.I.), Sevilla, Spain; Department of Neuroscience, Imaging and Clinical Sciences (A.L.), University "G. d'Annunzio," Chieti; Department of Biomedical and Neuromotor Sciences (A.L.), University of Bologna, IRCCS Istituto delle Scienze Neurologiche di Bologna, Italy; Hopital Notre Dame (A.P., M.G., P.D.), Montreal; CHUM and Universite de Montreal (A.P., M.G., P.D.); CISSS Chaudière-Appalache (P.G.), Levis, Canada; Department of Neurology (V.J., A.v.d.W., O.S., H.B.), Alfred Hospital, Melbourne, Australia; Neuro Rive-Sud (F. Grand'Maison), Quebec, Canada; Department of Neuroscience (P.S., D.F.), Azienda Ospedaliera Universitaria, Modena, Italy; Isfahan University of Medical Sciences (V.S.), Isfahan, Iran; Amiri Hospital (R. Alroughani), Kuwait City, Kuwait; Zuyderland Ziekenhuis (R.H.), Sittard, the Netherlands; Medical Faculty (M. Terzi), 19 Mayis University, Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Karadeniz Technical University, Trabzon, Turkey; School of Medicine and Public Health (J.L.-S.), University Newcastle; Department of Neurology (J.L.-S.), John Hunter Hospital, Newcastle, Australia; UOC Neurologia (E.P.), Azienda Sanitaria Unica Regionale Marche-AV3, Macerata, Italy; Cliniques Universitaires Saint-Luc (V.V.P.), Brussels, Belgium; University of Parma (F. Granella); C. Mondino National Neurological Institute (R.B.), Pavia; Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino (D.S.), Italy; Flinders University (M. Slee), Adelaide; Westmead Hospital (S.V.), Sydney, Australia; Nemocnice Jihlava (R. Ampapa), Czech Republic; University of Queensland (P.M.), Brisbane; Royal Brisbane and Women's Hospital (P.M.), Brisbane, Australia; Hospital Germans Trias i Pujol (C.R.-T.), Badalona, Spain; CSSS Saint-Jérôme (J.P.), Canada; Hospital Universitario Donostia (J.O.), Paseo de Begiristain, San Sebastián, Spain; Hospital Italiano (E.C.), Buenos Aires, Argentina; Brain and Mind Centre (M.B.), University of Sydney, Australia; INEBA-Institute of Neuroscience Buenos Aires (M.L.S.), Argentina; Hospital de Galdakao-Usansolo (J.L.S.-M.), Galdakao, Spain; Liverpool Hospital (S. Hodgkinson), Sydney, Australia; Jahn Ferenc Teaching Hospital (C.R.), Budapest, Hungary; Craigavon Area Hospital (S. Hughes), UK; Jewish General Hospital (F.M.), Montreal, Canada; Deakin University (C.S.), Geelong; Monash Medical Centre (E.B.), Melbourne, Australia; South East Trust (O.G.), Belfast, UK; Perron Institute (A.K.), University of Western Australia, Nedlands; Institute of Immunology and Infectious Diseases (A.K.), Murdoch University; Sir Charles Gairdner Hospital (A.K.), Perth, Australia; Department of Neurology (T.C.), Faculty of Medicine, University of Debrecen, Hungary; Bombay Hospital Institute of Medical Sciences (B.S.), Mumbai, India; St Vincents Hospital (N.S.), Fitzroy, Melbourne, Australia; Veszprém Megyei Csolnoky Ferenc Kórház zrt (I.P.), Veszprem, Hungary; Royal Hobart Hospital (B.T.), Australia; Semmelweis University Budapest (M. Simo), Hungary; Central Military Emergency University Hospital (C.-A.S.), Bucharest; Titu Maiorescu University (C.-A.S.), Bucharest, Romania; BAZ County Hospital (A.S.), Miskolc, Hungary; and Box Hill Hospital (H.B.), Melbourne, Australia.

Objective: To test the hypothesis that immunotherapy prevents long-term disability in relapsing-remitting multiple sclerosis (MS), we modeled disability outcomes in 14,717 patients.

Methods: We studied patients from MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year, and exposed to MS therapy, and a subset of patients with ≥15-year follow-up. Marginal structural models were used to compare the cumulative hazards of 12-month confirmed increase and decrease in disability, Expanded Disability Status Scale (EDSS) step 6, and the incidence of relapses between treated and untreated periods. Marginal structural models were continuously readjusted for patient age, sex, pregnancy, date, disease course, time from first symptom, prior relapse history, disability, and MRI activity.

Results: A total of 14,717 patients were studied. During the treated periods, patients were less likely to experience relapses (hazard ratio 0.60, 95% confidence interval [CI] 0.43-0.82, = 0.0016), worsening of disability (0.56, 0.38-0.82, = 0.0026), and progress to EDSS step 6 (0.33, 0.19-0.59, = 0.00019). Among 1,085 patients with ≥15-year follow-up, the treated patients were less likely to experience relapses (0.59, 0.50-0.70, = 10) and worsening of disability (0.81, 0.67-0.99, = 0.043).

Conclusion: Continued treatment with MS immunotherapies reduces disability accrual by 19%-44% (95% CI 1%-62%), the risk of need of a walking aid by 67% (95% CI 41%-81%), and the frequency of relapses by 40-41% (95% CI 18%-57%) over 15 years. This study provides evidence that disease-modifying therapies are effective in improving disability outcomes in relapsing-remitting MS over the long term.

Classification Of Evidence: This study provides Class IV evidence that, for patients with relapsing-remitting MS, long-term exposure to immunotherapy prevents neurologic disability.
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http://dx.doi.org/10.1212/WNL.0000000000011242DOI Listing
February 2021

Evaluation of disparities in multiple sclerosis risk by age, sex, and nativity in Kuwait:1980-2019.

Mult Scler Relat Disord 2021 Jan 6;47:102676. Epub 2020 Dec 6.

Department of Medicine, Division of Neurology, Amiri Hospital, Arabian Gulf Street, Sharq 11013, Kuwait.

Objective: This cross-sectional cohort study quantified the disparities in MS risk by age, sex, nativity from 1980 to 2019 in Kuwait.

Methods: Age-standardized MS incidence rate (ASIR) (per 100,000 person-years) overall and by subcohorts defined by cross-classification of the period (5-year groups) of diagnosis, age at onset, sex (female or male) and nativity (Kuwaiti or non-Kuwaiti) were computed and analyzed using multivariable negative binomial model.

Results: Overall MS ASIR (per 100,000 person-years) was 3.41 (95% CI: 1.61, 5.21), which exponentially increased from 1980 to 2014 before drifting downward in 2015-2019 period. Compared with adults (age ≥ 40 years), males, non-Kuwaiti residents respectively, young adults (20-39 years), females and Kuwaiti nationals were significantly (p < 0.05) more likely to develop MS after adjusting for the period effect.

Conclusions: A high overall MS ASIR (per 100,000 person-years) was recorded with substantial temporal variation between 1980 and 2019. Young adults (20-39 years), females and Kuwaiti nationals constituted MS high-risk groups. The knowledge of underlying interface pathways between genetic and environmental factors may provide insights into MS pathogenesis and leads for future research.
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http://dx.doi.org/10.1016/j.msard.2020.102676DOI Listing
January 2021

Predictors of Multiple Sclerosis Severity Score in Patients with Multiple Sclerosis.

Int J MS Care 2020 Sep-Oct;22(5):233-238. Epub 2020 Jan 13.

Background: Multiple sclerosis (MS) is a demyelinating autoimmune disorder. Several factors have been shown to associate with MS clinical severity. The influence of different lifestyle factors on MS clinical severity as assessed by the Multiple Sclerosis Severity Score (MSSS) was investigated.

Methods: A questionnaire was administered to 128 Kuwaiti MS patients to assess the association of smoking, nutritional supplement use, food allergy, physical activity (PA), and educational level with MSSS. A multiple linear regression model was used to test for associations. Regression model results were adjusted for sex, history of blood transfusion, age at MS onset, and marital status.

Results: Smoking status, passive smoking, and food allergy are not associated with MSSS. Patients with MS with a college education and graduate/professional degrees score, on average, 2.56 lower on the MSSS compared with those with less than a high school education (β= -2.22, = .045; and β = -2.90, = .048, respectively). Patients who perform PA score, on average, 2.32 lower on the MSSS compared with those with no PA (moderate exercise, = .003; rigorous exercise, = .001), and PA correlated significantly with MSSS outcomes ( = 0.452, < .001).

Conclusions: Educational level and PA are significantly associated with reduced MSSS, and both contribute to a less severe MS clinical course. Current MS management protocols should consider lifestyle changes to improve the quality of life of patients with MS.
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http://dx.doi.org/10.7224/1537-2073.2019-054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643849PMC
January 2020

Joinpoint Regression Analysis of Trends in Multiple Sclerosis Incidence in Kuwait: 1980-2019.

Neuroepidemiology 2020 11;54(6):472-481. Epub 2020 Nov 11.

Division of Neurology, Department of Medicine, Amiri Hospital, Kuwait City, Kuwait.

Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system with unknown precise etiology. Temporally, a tendency for increasing MS incidence has been recorded worldwide. This cross-sectional cohort study sought to quantify trends in the age-standardized incidence rates (ASIRs) (per million person-years) of MS in Kuwait from 1980 to 2019, overall and by subcohorts defined by age at MS onset, sex, and nationality.

Methods: MS incidence data from 1980 to 2019 were obtained from the Kuwait National MS Registry (KNMSR). Using midyear relevant Kuwait population as denominator and the World Standard Population as a reference, MS ASIRs overall and by subcohorts defined by age at onset (0-19, 20-39, and 40+ years), sex (male and female), and nationality (Kuwaiti and non-Kuwaiti) were computed. Joinpoint regression analysis was conducted to estimate average annual percent change (AAPC) and its 95% confidence interval (CI) overall and by subcohorts.

Results: During 1980-2019, a total of 1,764 MS incident cases of 95.6 million person-years at-risk were diagnosed and registered in KNMSR. The overall MS ASIR (per million person-years) during the study period was 34.1 (95% CI: 16.1, 52.1). Between 1980 and 2010, in the total cohort, ASIRs of MS significantly increased by 13% (AAPC = 13.0; 95% CI: 10.8, 15.3; p < 0.001), followed by statistically nonsignificant declining trend during the ensuing period (AAPC = -3.8; 95% CI: -14.8, 8.8; p = 0.522). Joinpoint regression analysis revealed that 2 subcohorts of Kuwaiti females each with one joinpoint had significant increasing trends in MS ASIRs (0- to 19-year-old Kuwaiti females, AAPC: 1980-2009, 81.0; 95% CI: 58.2, 107.0; p = 0.001; 20- to 39-year-old Kuwaiti females, AAPC: 1980-1999, 131.7; 95% CI: 26.9, 322.8; p = 0.021). Additionally, of remaining 10, 6 subcohorts had significantly (p < 0.05) increasing trends in MS ASIRs from 1980 to 2019.

Conclusions: From 1980 to 2010, Kuwait has an overall significantly increasing trend in MS ASIRs followed by a nonsignificant declining drift in the ensuing period. The increasing trend in MS risk appeared to be driven by increased risk among Kuwaiti females younger than 40 years. The underlying factors modulating MS risk in Kuwait need further studies.
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http://dx.doi.org/10.1159/000511205DOI Listing
November 2020

The use of alemtuzumab in patients with relapsing-remitting multiple sclerosis: the Gulf perspective.

Ther Adv Neurol Disord 2020 16;13:1756286420954119. Epub 2020 Sep 16.

Sanofi Genzyme, Dubai, United Arab Emirates.

Over the past decade, the development of high-efficacy disease-modifying therapies (DMTs) has been responsible for more effective management of relapsing-remitting multiple sclerosis (RRMS). However, the gaps in optimal care for this complex disease remain. Alemtuzumab (Lemtrada®) is a highly efficacious DMT that shows better patient outcomes and therapeutic benefits, but its use is under-recognized in the Gulf region. Experts in the care of multiple sclerosis shared their opinions based on study data and daily clinical experience in identifying the appropriate patient profile suitable for alemtuzumab's therapeutic benefits. Age, disease activity and severity, disability status, physician experience, and economic condition are some of the key indicators for alemtuzumab use.
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http://dx.doi.org/10.1177/1756286420954119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498833PMC
September 2020

Correction to: A matched case-control study of risk factors associated with multiple sclerosis in Kuwait.

BMC Neurol 2020 Aug 19;20(1):306. Epub 2020 Aug 19.

Division of Neurology, Department of Medicine, Amiri Hospital, Arabian Gulf Street, 13041, Sharq, Kuwait.

An amendment to this paper has been published and can be accessed via the original article.
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http://dx.doi.org/10.1186/s12883-020-01886-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550772PMC
August 2020

Impact of coronavirus disease (COVID-19) pandemic on multiple sclerosis care.

Clin Neurol Neurosurg 2020 10 2;197:106203. Epub 2020 Sep 2.

Division of Neurology, Department of Medicine, Amiri Hospital, Sharq, Kuwait.

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http://dx.doi.org/10.1016/j.clineuro.2020.106203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467025PMC
October 2020

Impact of Puberty in Girls on Prevalence of Primary Headache Disorder Among Female Schoolchildren in Kuwait.

Front Neurol 2020 17;11:594. Epub 2020 Jul 17.

Neurology Department, Ibn Sina Hospital, Safat, Kuwait.

The prevalence of primary headaches in the pediatric population is shaped by many factors, of which pubertal status may possibly play a substantial role. Epidemiological studies in the pediatric population in the gulf region remain scarce. To examine the impact of puberty on the prevalence of primary headache disorders among female schoolchildren in Kuwait. We conducted a cross-sectional study that included Kuwaiti primary and middle schoolgirls in randomly selected schools located in two governorates in Kuwait during the academic year 2018/2019. Prevalence of headache was assessed using the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire for children and adolescents. Female students were asked about their menarchal status and whether they attained menarche before or after experiencing headaches. The questionnaire was completed by 669 girls with a mean age of 11.44 ± 2.14 years. The 1-year prevalence of migraine headache disorder among girls was 23.62%, and the lifetime prevalence of any headache was 84.9%, whereas the 1-year prevalence of primary headache disorders was 47.98%. The mean age of girls with headaches was 11.44 ± 2.14 years. With respect to diagnostic criteria, migraine headache was the most frequently reported (23.62%), followed by tension-type headaches (20.93%), chronic headaches (2.99%), and probable medication-overuse headaches (0.45%). Postpubertal females were at significantly higher risk of having primary headaches compared to their prepubertal counterparts (64.26 vs. 34%; < 0.0001). All types of primary headaches were more significantly prevalent among postpubertal girls compared to those who are prepubertal. Migraine headache is commonly reported among Kuwaiti schoolgirls. Postpubertal females are at higher risk of developing primary headaches compared to prepubertal females. Pubertal transition and female sex hormones may play a significant role in the pathophysiology of headaches, migraines in particular, and further research is therefore needed to investigate the underlying mechanisms.
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http://dx.doi.org/10.3389/fneur.2020.00594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379333PMC
July 2020

Prediction of on-treatment disability worsening in RRMS with the MAGNIMS score.

Mult Scler 2020 Jul 8:1352458520936823. Epub 2020 Jul 8.

CORe, Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, Australia/ Melbourne MS Centre, Department of Neurology, The Royal Melbourne Hospital, Melbourne, VIC, Australia.

Background: The magnetic resonance imaging in multiple sclerosis (MAGNIMS) score combines relapses and magnetic resonance imaging (MRI) lesions to predict disability outcomes in relapsing-remitting multiple sclerosis (RRMS) treated with interferon-β.

Objective: To validate the MAGNIMS score and extend to other disease-modifying therapies (DMTs). To examine the prognostic value of gadolinium contrast-enhancing (Gd+) lesions.

Methods: This RRMS MSBase cohort study ( = 2293) used a Cox model to examine the prognostic value of relapses, MRI activity and the MAGNIMS score for disability worsening during treatment with interferon-β and three other DMTs.

Results: Three new T2 lesions (hazard ratio (HR) = 1.60,  = 0.028) or two relapses (HR = 2.24,  = 0.002) on interferon-β (for 12 months) were predictive of disability worsening over 4 years. MAGNIMS score = 2 (1 relapse and ⩾3 T2 lesions or ⩾2 relapses) was associated with a greater risk of disability worsening on interferon-β (HR = 2.0,  = 0.001). In pooled cohort of four DMTs, similar associations were seen (MAGNIMS score = 2: HR = 1.72,  = 0.001). Secondary analyses demonstrated that the addition of Gd+ to the MAGNIMS did not materially improve its prediction of disability worsening.

Conclusion: We have validated the MAGNIMS score in RRMS and extended its application to three other DMTs: 1 relapse and ⩾3 T2 lesions or ⩾2 relapses predicted worsening of disability. Contrast-enhancing lesions did not substantially improve the prognostic score.
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http://dx.doi.org/10.1177/1352458520936823DOI Listing
July 2020

Radiological characteristics of neuromyelitis optica spectrum disorder in Kuwait.

Clin Neurol Neurosurg 2020 Sep 24;196:106047. Epub 2020 Jun 24.

Division of Neurology, Department of Medicine, Amiri Hospital, Sharq, Kuwait. Electronic address:

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disorder of the central nervous system that predominantly targets optic nerves and spinal cord. Studies of NMOSD are scarce in the Middle East.

Objective: To evaluate the MRI characteristics of NMOSD patients in Kuwait.

Patient And Methods: This is an observational, retrospective study on NMOSD patients who attended the MS clinic. Patients who fulfilled the 2015 diagnostic criteria of NMOSD were included. Patients` clinical, radiological and serological data were extracted from the medical records. The radiological variables were compared according to gender and AQP4 serostatus.

Results: Forty-two patients fulfilling the NMOSD diagnostic criteria. The mean age and mean age of onset were 32.6 ± 11.4 and 28.9 ± 9.8 years respectively. Females represented 83.3 % of the cohort with female-to-male ratio of 5:1. Thirty-one patients (73.8 %) tested positive for AQP4 antibody. Nineteen patients (45.2 %) had bilateral optic nerve involvement, while chiasmal involvement was seen in 8 (19.0 %) patients. Spinal cord was involved in 36 (85.7 %) patients; of whom 27 (64.3 %) had LETM. The most common spinal segment involved was the cervical (72.2 %) followed by the dorsal (25.0 %) regions. The brain was involved in 39 (92.8 %) patients and the periventricular region around fourth and lateral ventricles was the most commonly involved site (n = 35; 83.3 %), along with periaqueductal (n = 25; 61.9 %) and corpus callosal (n = 24; 57.1 %) regions. Isolated area postrema involvement was observed in 9 (21.4 %) patients.

Conclusion: This is the first study describing the radiological characteristics of NMOSD in Kuwait. Although our data is comparable with the previous international studies, a higher percentage of bilateral optic nerve, brain, and callosal involvement was observed. Further multicenter studies with a larger cohort are needed to confirm our results.
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http://dx.doi.org/10.1016/j.clineuro.2020.106047DOI Listing
September 2020

Disease-Modifying Drugs and Family Planning in People with Multiple Sclerosis: A Consensus Narrative Review from the Gulf Region.

Neurol Ther 2020 Dec 20;9(2):265-280. Epub 2020 Jun 20.

Neurology Department, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates.

Most disease-modifying drugs (DMDs) are contraindicated in pregnancy. Management of MS is especially challenging for pregnant patients, as withdrawal of DMDs leave the patient at risk of increased disease activity. We, a group of experts in MS care from countries in the Arab Gulf, present our consensus recommendations on the management of MS in these patients. Where possible, a patient planning pregnancy can be switched to a DMD considered safe in this setting. Interferon β now can be used during pregnancy, where there is a clinical need to maintain treatment, in addition to glatiramer acetate. Natalizumab (usually to 30 weeks' gestation for patients with high disease activity at high risk of relapse and disability progression) may also be continued into pregnancy. Cladribine tablets and alemtuzumab have been hypothesised to act as immune reconstitution therapies (IRTs). These drugs provide a period of prolonged freedom from relapses for many patients, but the patient must be prepared to wait for up to 20 months from initiation of therapy before becoming pregnant. If a patient becomes pregnant while taking fingolimod, and requires continued DMD treatment, a switch to interferon β or natalizumab after a variable washout period may be prescribed, depending on the level of disease activity. Women who wish to breastfeed should be encouraged to do so, and interferon β may also be used during breastfeeding. There is a lack of data regarding the safety of using other DMDs during breastfeeding.
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http://dx.doi.org/10.1007/s40120-020-00201-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606397PMC
December 2020

Disability outcomes of early cerebellar and brainstem symptoms in multiple sclerosis.

Mult Scler 2020 Jun 15:1352458520926955. Epub 2020 Jun 15.

CORe, Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia; Department of Neurology, The Royal Melbourne Hospital, Melbourne, VIC, Australia.

Background: Cerebellar and brainstem symptoms are common in early stages of multiple sclerosis (MS) yet their prognostic values remain unclear.

Objective: The aim of this study was to investigate long-term disability outcomes in patients with early cerebellar and brainstem symptoms.

Methods: This study used data from MSBase registry. Patients with early cerebellar/brainstem presentations were identified as those with cerebellar/brainstem relapse(s) or functional system score ⩾ 2 in the initial 2 years. Early pyramidal presentation was chosen as a comparator. Andersen-Gill models were used to compare cumulative hazards of (1) disability progression events and (2) relapses between patients with and without early cerebellar/brainstem symptoms. Mixed effect models were used to estimate the associations between early cerebellar/brainstem presentations and expanded disability status scale (EDSS) scores.

Results: The study cohort consisted of 10,513 eligible patients, including 2723 and 3915 patients with early cerebellar and brainstem symptoms, respectively. Early cerebellar presentation was associated with greater hazard of progression events (HR = 1.37,  < 0.001) and EDSS (β = 0.16,  < 0.001). Patients with early brainstem symptoms had lower hazard of progression events (HR = 0.89,  = 0.01) and EDSS (β = -0.06,  < 0.001). Neither presentation was associated with changes in relapse risk.

Conclusion: Early cerebellar presentation is associated with unfavourable outcomes, while early brainstem presentation is associated with favourable prognosis. These presentations may be used as MS prognostic markers and guide therapeutic approach.
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http://dx.doi.org/10.1177/1352458520926955DOI Listing
June 2020

Replication analysis of variants associated with multiple sclerosis risk.

Sci Rep 2020 04 30;10(1):7327. Epub 2020 Apr 30.

Human Genetics Unit, Department of Pathology, Faculty of Medicine, Kuwait University, Jabriya, Kuwait.

Multiple Sclerosis (MS) is a complex chronic neurodegenerative disorder resulting from an autoimmune reaction against myelin. So far, many genetic variants have been reported to associate with MS risk however their association is inconsistent across different populations. Here we investigated the association of the most consistently reported genetic MS risk variants in the Kuwaiti MS population in a case-control study designs. Of the 94 reported MS risk variants four variants showed MS risk association in Arabs exome analysis (EVI5 rs11808092 p = 0.0002; TNFRSF1A rs1800693 p = 0.00003; MTHFR rs1801131 p = 0.038; and CD58 rs1414273 p = 0.00007). Replication analysis in Kuwaiti MS cases and healthy controls confirmed EVI5 rs11808092A (OR: 1.6, 95%CI: 1.19-2.16, p = 0.002) and MTHFR rs1801131G (OR: 1.79, 95%CI: 1.3-2.36, p = 0.001) as MS risk genetic factors, while TNFRSF1A rs1800693C had a marginal MS risk association (OR: 1.36, 95%CI: 1.04-1.78, p = 0.025) in the Kuwaiti population. CD58 rs1414273 did not sustain risk association (p = 0.37). In conclusion, EVI5 rs11808092A, TNFRSF1A rs1800693C and MTHFR rs1801131G are MS risk factors in the Kuwaiti population. Further investigations into their roles in MS pathogenesis and progression are merited.
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http://dx.doi.org/10.1038/s41598-020-64432-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193640PMC
April 2020

Neuromyelitis optica spectrum disorders in Arabian Gulf (NMOAG); establishment and initial characterization of a patient registry.

Mult Scler Relat Disord 2020 Feb 19;38:101448. Epub 2019 Oct 19.

Division of Neurology, Department of Medicine, Amiri Hospital, Kuwait.

Objective: To describe the clinical and radiological characteristics of neuromyelitis optica spectrum disorders (NMOSD) patients from the Arabian Gulf relative to anti-aquaporin 4 antibody serostatus.

Methods: Retrospective multicentre study of hospital records of patients diagnosed with NMOSD based on 2015 International Panel on NMOSD Diagnosis (IPND) consensus criteria.

Results: One hundred forty four patients were evaluated, 64.3% were anti-AQP4 antibody positive. Mean age at onset and disease duration were 31±12 and 7 ± 6 years respectively. Patients were predominantly female (4.7:1). Overall; relapsing course (80%) was more common than monophasic (20%). Optic neuritis was the most frequent presentation (48.6%), regardless of serostatus. The proportion of patients (54.3%) with visual acuity of ≤ 0.1 was higher in the seropositive group (p = 0.018). Primary presenting symptoms of transverse myelitis (TM) were observed in 29% of patients, and were the most significant correlate of hospitalization (p<0.001). Relative to anti-APQ4 serostatus, there were no significant differences in terms of age of onset, course, relapse rates or efficacy outcomes except for oligoclonal bands (OCB), which were more often present in seronegative patients (40% vs.22.5%; p = 0.054). Irrespective of serostatus, several disease modifying therapies were instituted including steroids or immunosuppressives, mostly, rituximab and azathioprine in the cohort irrespective of serostatus. The use of rituximab resulted in reduction in disease activity.

Conclusion: This is the first descriptive NMOSD cohort in the Arabian Gulf region. Seropositive patients were more prevalent with female predominance. Relapsing course was more common than monophasic. However, anti-AQP4 serostatus did not impact disease duration, relapse rate or therapeutic effectiveness. These findings offer new insights into natural history of NMOSD in patients of the Arabian Gulf and allow comparison with patient populations in different World regions.
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http://dx.doi.org/10.1016/j.msard.2019.101448DOI Listing
February 2020

Expert consensus from the Arabian Gulf on selecting disease-modifying treatment for people with multiple sclerosis according to disease activity.

Postgrad Med 2020 May 28;132(4):368-376. Epub 2020 Feb 28.

Department of Neurology, The Royal Hospital , Muscat, Oman.

Recent research has expanded our understanding of the natural history and clinical course of multiple sclerosis (MS) in the Arabian Gulf region. In addition, the number of available therapies for MS has increased greatly in recent years, which complicates considerably the design of therapeutic regimens. We, an expert group of physicians practising in Arabian Gulf countries, present pragmatic consensus recommendations for the use of disease-modifying therapy, according to the level of MS disease activity, according to objective criteria, and prior treatment (if any) received by a given patient.
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http://dx.doi.org/10.1080/00325481.2020.1734394DOI Listing
May 2020

A matched case-control study of risk factors associated with multiple sclerosis in Kuwait.

BMC Neurol 2020 Feb 21;20(1):64. Epub 2020 Feb 21.

Division of Neurology, Department of Medicine, Amiri Hospital, Arabian Gulf Street, 13041, Sharq, Kuwait.

Background: Genetic and environmental factors seem to have etiologic roles in multiple sclerosis (MS). Kuwait is regarded as medium to high risk country for MS. However, there is a paucity of published data on the risk factors for MS in Kuwait. Therefore, this matched case-control study examined the association between various factors including family history, stressful life events, exposure to tobacco smoke, vaccination history, comorbidities and MS risk in Kuwait.

Methods: Confirmed 110 MS cases and age (± 5 years), gender and nationality matched controls (1:1) were enrolled. A pre-tested structured questionnaire was used to collect the data through face-to-face interviews both from cases and controls. Conditional logistic regression was used to analyze the data.

Results: Among both cases and controls, majority were Kuwaiti (82.7%), and female (76.4%). Multivariable model showed that cases compared to controls were significantly more likely to have had a family history of MS (adjusted matched odds ratio (mOR) = 5.1; 95% CI: 2.1-12.4; p < 0.001) or less likely to have been vaccinated against influenza A and B viruses before MS onset (mOR = 0.4; 95% CI: 0.2-0.8; p = 0.010). None of the other variables considered were significantly related to MS status in this study.

Conclusions: Family history of MS had significantly direct, whereas, vaccination against influenza A and B viruses had inverse associations with MS status. Future studies may contemplate to verify the observed results.
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http://dx.doi.org/10.1186/s12883-020-01635-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033919PMC
February 2020

Family planning is the second most relevant factor for treatment decisions after disease activity - Yes.

Authors:
Raed Alroughani

Mult Scler 2020 05 21;26(6):640-641. Epub 2020 Feb 21.

Division of Neurology, Department of Medicine, Amiri Hospital, Sharq, Kuwait.

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http://dx.doi.org/10.1177/1352458519877689DOI Listing
May 2020

Neuromyelitis optica spectrum disorders in the Arabian Gulf: challenges and growing experience.

Mult Scler J Exp Transl Clin 2020 Jan-Mar;6(1):2055217319850195. Epub 2020 Jan 10.

Department of Neurology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.

Neuromyelitis optica spectrum disorders (NMOSD) have been studied in different ethnic groups, including Asians, African-Americans, and Caucasians. Demonstrating the clinical features among diverse communities is important to understand the variable disease phenotypes, which will lead to further classification and better clinical management. Testing for antibody against aquaporin-4 (AQP4), the most common target antigen in NMOSD, is not available in many countries and tests use different methods, with variable sensitivity. With negative antibody results, the diagnosis of NMOSD becomes challenging and may affect the outcomes of patients with NMOSD. There are no adequate studies that assess NMOSD cohorts in the Arabian Gulf region, despite the increasing number of diagnosed cases. It is worth assessing NMOSD cohorts in the Arabian Gulf population to study the natural history of disease and to establish an epidemiological background for future perspectives. Various challenges to implement such a mission are outlined, including disease rarity, overlapping presenting symptoms and signs, which posed the issue of mimickers in the differential diagnosis, lack of specialized clinics, absence of highly sensitive testing methods for diagnosis, and the indefinite agreement on the negative AQP4 NMOSD criteria. Collaborative efforts started to take a place among many experts in the region to establish a registry of NMOSD patients for better perception of the disease pattern.
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http://dx.doi.org/10.1177/2055217319850195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956599PMC
January 2020

Clinical and therapeutic predictors of disease outcomes in AQP4-IgG+ neuromyelitis optica spectrum disorder.

Mult Scler Relat Disord 2020 Feb 25;38:101868. Epub 2019 Nov 25.

CORe, Department of Medicine, University of Melbourne, Melbourne, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia. Electronic address:

Background: Aquaporin-4-IgG positive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD) is an uncommon central nervous system autoimmune disorder. Disease outcomes in AQP4-IgG+NMOSD are typically measured by relapse rate and disability. Using the MSBase, a multi-centre international registry, we aimed to examine the impact immunosuppressive therapies and patient characteristics as predictors of disease outcome measures in AQP4-IgG+NMOSD.

Method: This MSBase cohort study of AQP4-IgG+NMOSD patients examined modifiers of relapse in a multivariable proportional hazards model and expanded disability status score (EDSS) using a mixed effects model.

Results: 206 AQP4-IgG+ patients were included (median follow-up 3.7 years). Age (hazard ratio [HR] = 0.82 per decade, p = 0.001), brainstem onset (HR = 0.45, p = 0.009), azathioprine (HR = 0.46, p<0.001) and mycophenolate mofetil (HR = 0.09, p = 0.012) were associated with a reduced risk of relapse. A greater EDSS was associated with age (β = 0.45 (per decade), p<0.001) and disease duration (β = 0.07 per year, p<0.001). A slower increase in EDSS was associated with azathioprine (β = -0.48, p<0.001), mycophenolate mofetil (β = -0.69, p = 0.04) and rituximab (β = -0.35, p = 0.024).

Interpretation: This study has demonstrated that azathioprine and mycophenolate mofetil reduce the risk of relapses and disability progression is modified by azathioprine, mycophenolate mofetil and rituximab. Age and disease duration were the only patient characteristics that modified the risk of relapse and disability in our cohort.
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http://dx.doi.org/10.1016/j.msard.2019.101868DOI Listing
February 2020

The FTO gene polymorphism rs9939609 is associated with obesity and disability in multiple sclerosis patients.

Sci Rep 2019 12 13;9(1):19071. Epub 2019 Dec 13.

Human Genetics Unit, Department of Pathology, Faculty of Medicine, Kuwait University, Kuwait, PO Box 24923, Safat, 13110, Kuwait.

Obesity is a well-known risk factor for multiple diseases including multiple sclerosis (MS). Polymorphisms in the fat-mass obesity (FTO) gene have been consistently found to be associated with obesity, and recently found to increase the risk of developing MS. We therefore assessed the common FTO gene polymorphism (rs9939609) in relation to obesity, risk of developing MS and its disability in a cohort of MS patients. A cohort of 200 MS patients (135 females and 65 males) were genotyped for the FTO rs9939609 polymorphism. Using both logistic and linear regression we assessed the relationship between the variant and the selected phenotypes under both an additive and recessive genetic models. The A-allele was found to be associated with being overweight/obese in MS patients (OR = 2.48 (95% CI 1.17-5.29); p = 0.01). In addition, The A-allele was also found to be associated with increased MS disability (β = 0.48 (95% CI 0.03-0.92); p = 0.03). However, no association was found with risk of developing MS (p > 0.05). Moreover, our association with obesity is consistent with previous reports, whereas the association with disability is novel and warrants further investigation on the role of FTO in disease progression.
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http://dx.doi.org/10.1038/s41598-019-55742-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6911041PMC
December 2019

Efficacy of alemtuzumab in relapsing-remitting MS patients who received additional courses after the initial two courses: Pooled analysis of the CARE-MS, extension, and TOPAZ studies.

Mult Scler 2020 12 25;26(14):1866-1876. Epub 2019 Nov 25.

Division of Neurology, Department of Medicine, The University of British Columbia, Vancouver, BC, Canada.

Background: Alemtuzumab is given as two annual courses. Patients with continued disease activity may receive as-needed additional courses.

Objective: To evaluate efficacy and safety of additional alemtuzumab courses in the CARE-MS (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis) studies and their extensions.

Methods: Subgroups were based on the number of additional alemtuzumab courses received. Exclusion criteria: other disease-modifying therapy (DMT); <12-month follow-up after last alemtuzumab course.

Results: In the additional-courses groups, Courses 3 and 4 reduced annualized relapse rate (12 months before: 0.73 and 0.74, respectively; 12 months after: 0.07 and 0.08). For 36 months after Courses 3 and 4, 89% and 92% of patients were free of 6-month confirmed disability worsening, respectively, with 20% and 26% achieving 6-month confirmed disability improvement. Freedom from magnetic resonance imaging (MRI) disease activity increased after Courses 3 and 4 (12 months before: 43% and 53%, respectively; 12 months after: 73% and 74%). Safety was similar across groups; serious events occurred irrespective of the number of courses.

Conclusion: Additional alemtuzumab courses significantly improved outcomes, without increased safety risks, in CARE-MS patients with continued disease activity after Course 2. How this compares to outcomes if treatment is switched to another DMT instead remains unknown.
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http://dx.doi.org/10.1177/1352458519888610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720359PMC
December 2020

Redefining the Multiple Sclerosis Severity Score (MSSS): The effect of sex and onset phenotype.

Mult Scler 2020 11 31;26(13):1765-1774. Epub 2019 Oct 31.

Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.

Background: The Multiple Sclerosis Severity Score (MSSS) is a widely used measure of the disability progression rate. However, the global MSSS may not be the best basis for comparison between all patient groups.

Objective: We evaluated sex-specific and onset phenotype-specific MSSS matrices to determine if they were more effective than the global MSSS as a basis for comparison within these subsets.

Methods: Using a large international dataset of multiple sclerosis (MS) patient records and the original MSSS algorithm, we constructed global, sex-specific and onset phenotype-specific MSSS matrices. We compared matrices using permutation analysis.

Results: Our final dataset included 30,203 MS cases, with 28.9% males and 6.5% progressive-onset cases. Our global MSSS matrix did not differ from previously published data ( > 0.05). The progressive-onset-specific matrix differed significantly from the relapsing-onset-specific matrix ( < 0.001), with lower MSSS attributed to cases with the same Expanded Disability Status Score (EDSS) and disease duration. When evaluated with a simulation, using an onset-specific MSSS improved statistical power in mixed cohorts. There were no significant differences by sex.

Conclusion: The differences in the disability accrual rate between progressive- and relapsing-onset MS have a significant effect on MSSS. An onset-specific MSSS should be used when comparing the rate of disability progression among progressive-onset cases and for mixed cohorts.
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http://dx.doi.org/10.1177/1352458519881994DOI Listing
November 2020

Leptin rs7799039 polymorphism is associated with multiple sclerosis risk in Kuwait.

Mult Scler Relat Disord 2019 Nov 24;36:101409. Epub 2019 Sep 24.

Human Genetics Unit, Department of Pathology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait. Electronic address:

Background: Leptin association with Multiple sclerosis (MS) pathogenesis and MS related clinical characteristics is inconsistent. Here, we investigated whether two common variants in leptin (LEP) and leptin receptor (LEPR) genes influence MS risk and leptin levels in MS patients.

Methods: In a case-control study including 169 MS patients and 100 controls we examined the association of leptin in MS. Blood samples were used for DNA extraction and plasma retrieval. Taqman genotyping assays were used for LEP rs7799039 and LEPR rs1137101 genotyping, and enzyme-linked immunosorbent assay for plasma leptin level.

Results: Leptin levels were significantly lower in MS patients compared to controls (β = 0.157, 95%CI: 0.033-0.26, p = 0.012). LEP rs7799039AA associated with MS risk (OR: 2.52; 95%CI: 1.35-4.67, p = 0.003). None of the assessed markers associated with MS disability, severity or response to treatment.

Conclusion: LEP rs7799039AA is a risk factor for MS in our Kuwaiti population, and leptin levels are lower in MS patients compared to healthy controls. Our findings suggest future studies must consider all factors influencing leptin levels to resolve its controversial involvement in MS pathogenesis or progression.
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http://dx.doi.org/10.1016/j.msard.2019.101409DOI Listing
November 2019

Retinal inner nuclear layer volume reflects inflammatory disease activity in multiple sclerosis; a longitudinal OCT study.

Mult Scler J Exp Transl Clin 2019 Jul-Sep;5(3):2055217319871582. Epub 2019 Sep 5.

Department of Neurology, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands.

Background: The association of peripapillary retinal nerve fibre layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness with neurodegeneration in multiple sclerosis (MS) is well established. The relationship of the adjoining inner nuclear layer (INL) with inflammatory disease activity is less well understood.

Objective: The objective of this paper is to investigate the relationship of INL volume changes with inflammatory disease activity in MS. In this longitudinal, multi-centre study, optical coherence tomography (OCT) and clinical data (disability status, relapses and MS optic neuritis (MSON)) were collected in 785 patients with MS (68.3% female) and 92 healthy controls (63.4% female) from 11 MS centres between 2010 and 2017 and pooled retrospectively. Data on pRNFL, GCIPL and INL were obtained at each centre.

Results: There was a significant increase in INL volume in eyes with new MSON during the study ( = 61/1562, β = 0.01 mm,  < .001). Clinical relapses (other than MSON) were significantly associated with increased INL volume (β = 0.005,  = .025). INL volume was independent of disease progression (β = 0.002 mm,  = .474).

Conclusion: Our data demonstrate that an increase in INL volume is associated with MSON and the occurrence of clinical relapses. Therefore, INL volume changes may be useful as an outcome marker for inflammatory disease activity in MSON and MS treatment trials.
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http://dx.doi.org/10.1177/2055217319871582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728683PMC
September 2019

Prevalence and Burden of Primary Headache Disorders in Kuwaiti Children and Adolescents: A Community Based Study.

Front Neurol 2019 30;10:793. Epub 2019 Jul 30.

Department of Neuropsychiatry, Minia University, Minia, Egypt.

Primary headaches are common in the pediatric and adolescent population and can be disabling for them and their families. We aimed to assess the prevalence and burden of primary headache disorders among children and adolescents in Kuwait. A cross-sectional community-based study included Kuwaiti population aged 6-17 years. They were randomly recruited from all six governorates of Kuwait using stratified multistage cluster sampling. The Headache-Attributed Restriction, Disability, and Social Handicap and Impaired Participation (HARDSHIP) questionnaire for children and adolescents was used to collect the data. Data were collected from 3,423 subjects; 664 subjects were diagnosed as having primary headache disorders. The mean age was 12.61 ± 2.51 years and 64.2% were females. One year prevalence of headache was 19.4%. It was significantly prevalent in females compared to males (25.2% vs. 13.8%; < 0.001). Primary headache disorder significantly increased in age group 12-17 when compared to age group 6-11 years (25.8% vs. 10.4 %; < 0.001). One year primary headache prevalence showed non-significant differences in both males and females in age group 6-11 years (10.1% in males vs. 10.6% in females; < 0.79), while it was significantly higher in female vs. males (38.1% vs. 15.8%; < 0.001) in age group 12-17 years. Migraine prevalence was 10.9% followed by tension type headache (TTH) 6.2% and chronic headache 0.9%. Medical care utilization was reported in 67% of our cohort. The majority (95%) of the patients received symptomatic drugs for headache attacks and only 7.5% used preventive medication. The students with headache lost a mean of 1.29 ± 1.23 days of school, reported mean of 1.16 ± 1.50 days they could not do activities they had wanted to. Their parents lost a mean of 1.01 ± 1.02 days of work because of headaches of their children during the preceding 4 weeks of the study. The estimated 1 year prevalence of headache was 19.4% overall. Primary headache prevalence increased with age and it was more prevalent in female adolescents compared to males of the same age. Headache disorders in children/adolescents affect school and social activities as well as their parents work. The awareness for early diagnosis and preventive medications for headache in this age group may reduce the headache burden.
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http://dx.doi.org/10.3389/fneur.2019.00793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682654PMC
July 2019

Risk of secondary progressive multiple sclerosis: A longitudinal study.

Mult Scler 2020 01 9;26(1):79-90. Epub 2019 Aug 9.

CORe, Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia/Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia/L4 Centre, Melbourne Brain Centre at Royal Melbourne Hospital, Parkville, VIC, Australia.

Background: The risk factors for conversion from relapsing-remitting to secondary progressive multiple sclerosis remain highly contested.

Objective: The aim of this study was to determine the demographic, clinical and paraclinical features that influence the risk of conversion to secondary progressive multiple sclerosis.

Methods: Patients with adult-onset relapsing-remitting multiple sclerosis and at least four recorded disability scores were selected from MSBase, a global observational cohort. The risk of conversion to objectively defined secondary progressive multiple sclerosis was evaluated at multiple time points per patient using multivariable marginal Cox regression models. Sensitivity analyses were performed.

Results: A total of 15,717 patients were included in the primary analysis. Older age (hazard ratio (HR) = 1.02,  < 0.001), longer disease duration (HR = 1.01,  = 0.038), a higher Expanded Disability Status Scale score (HR = 1.30,  < 0.001), more rapid disability trajectory (HR = 2.82,  < 0.001) and greater number of relapses in the previous year (HR = 1.07,  = 0.010) were independently associated with an increased risk of secondary progressive multiple sclerosis. Improving disability (HR = 0.62,  = 0.039) and disease-modifying therapy exposure (HR = 0.71,  = 0.007) were associated with a lower risk. Recent cerebral magnetic resonance imaging activity, evidence of spinal cord lesions and oligoclonal bands in the cerebrospinal fluid were not associated with the risk of conversion.

Conclusion: Risk of secondary progressive multiple sclerosis increases with age, duration of illness and worsening disability and decreases with improving disability. Therapy may delay the onset of secondary progression.
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http://dx.doi.org/10.1177/1352458519868990DOI Listing
January 2020