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Abstract Cladribine tablets (CladT), like alemtuzumab, acts as an immune reconstitution therapy. However, CladT is administered orally (alemtuzumab is given by infusion) and without the potential for serious side effects that limit the therapeutic use of alemtuzumab in multiple sclerosis (MS). Treatment with CladT, given initially as short courses of treatment 1 year apart, provides years of freedom from MS disease activity in responders to treatment. The appearance of mild or moderate MS disease activity after the initial 2 years of treatment may prompt careful follow-up or a further course of CladT, depending on the nature of the activity and individual circumstances. The appearance of severe MS disease activity requires a switch to an alternative high-efficacy disease-modifying treatment (DMT). The accumulating data from CladT-treated people with MS in real-world studies, including those with follow-up durations extending for years beyond the initial treatment, have demonstrated long-term freedom from MS disease activity in a good proportion of patients. This clinical experience has also confirmed that treatment with CladT is generally safe and well tolerated. The best time to prescribe a high-efficacy DMT is the subject of debate, with evidence that earlier versus later use of such agents may provide more effective long-term protection from disability progression. High-efficacy DMTs have traditionally been reserved for use in people with MS and high disease activity on presentation or breakthrough disease on one or more DMTs, as per the current product labels. The latest evidence from real-world studies suggests that CladT is effective and safe in DMT-naïve patients, including those with shorter disease duration.

BackgroundOnabotulinumtoxinA (BoNT-A) is approved as a prophylactic treatment of chronic migraine (CM) only. We aimed to assess the efficacy and safety of BoNT-A in the treatment of episodic migraine (EM).MethodsThis is a prospective study included migraine patients, aged 18–65 years, and completed 1 year treatment with BoNT-A. Patients received 4 courses of BoNT-A treatment. Patient’s headache was assessed by headache diary at baseline, and before every injection. Migraine Specific Quality of Life Questionnaire (MSQ) and work productivity were collected at baseline and in their last visit. Adverse events (AEs) were reported.ResultsThe study recruited 210 patients. Between baseline and the final visit, there were a significant reduction in migraine days, analgesic consumption days, and headache severity (9.54 ± 1.70 versus 4.58 ± 2.77, p

Background: The relationship between coronavirus disease 2019 (COVID-19) infection and multiple sclerosis (MS) relapse and disease progression remains unclear. Previous studies are limited by small sample sizes and most lack a propensity-matched control cohort. Objective: To evaluate the effect of COVID-19 infection on MS disease course with a large propensity-matched cohort. Design: This multi-centre cohort study analysed relapse and disability outcomes post-COVID-19 infection after balancing covariates using a propensity score matching method. The study period was from the 11th of September 2019 to the 16th of February 2023. The mean follow-up period was 1.7 years. Methods: Data were retrieved from the MSBase Registry. Propensity scores were obtained based on age, sex, disease duration, baseline Expanded Disability Status Scale (EDSS), MS course, relapses pre-baseline, disease-modifying therapy (DMT) class and country. Primary outcomes were time to first relapse, annualised relapse rate (ARR) and time to confirm EDSS progression. Secondary outcomes were time to EDSS of 3, 4 or 6. Sensitivity analyses with baseline DMT classes were performed. Results: The study included 2253 cases and 6441 controls. After matching, there were 2161 cases and an equal number of matched controls. Cases had a significantly higher ARR (ARR = 0.10 [95% CI 0.09–0.11]) compared to controls (ARR = 0.07 [95% CI 0.06–0.08]). Cases had a significantly greater hazard of time to first relapse compared to controls (hazard ratio (HR) = 1.54 [95% CI 1.29–1.84]). There was no association between COVID-19 infection and 24-week EDSS progression (HR = 1.18 [95% CI 0.92–1.52]), or time to EDSS of 3, 4 or 6. For patients on interferons and glatiramer acetate (BRACE), COVID-19 infection was associated with a greater hazard of time to first relapse (HR = 1.83 [95% CI 1.25–2.68]) and greater hazard of time to EDSS of 3 (HR = 2.04 [95% CI 1.06–3.90]) compared to patients on BRACE therapy without COVID-19 infection. Conclusion: COVID-19 infection was associated with a significantly increased MS relapse rate and a shorter time to first relapse. There was no effect on confirmed EDSS progression over the short term. These results support ongoing COVID-19 risk minimisation strategies to protect patients with MS.

Background: Optic neuritis is an inflammatory disorder of the optic nerve and is often the initial manifestation of systemic demyelinating diseases such as multiple sclerosis (MS), neuromyelitis optic spectrum disorder (NMOSD), and myelin-oligodendrocyte glycoprotein (MOG) antibody-mediated disease. There are ethnic variations in the etiology of optic neuritis across the world. While multiple sclerosis is common in the West, NMOSD and MOG are more common causes in Asian patients. There is a paucity of reports on the clinical profile of optic neuritis in the Middle East. Objectives: To study the demographic and clinical features of patients with new onset optic neuritis in a main tertiary care center. Methods: A retrospective study of cases with new-onset optic neuritis at a tertiary care center between 2012 and 2022. The clinical and demographic characteristics were obtained from medical records and were summarized using descriptive statistics. Univariate analysis and multivariate analysis to assess the short-term visual outcome. Results: Seventy-one patients with new-onset optic neuritis (70 unilateral and one bilateral) were included in the study. The mean age was 33.3 years, they were predominantly females (73 %), and most of the cases were MS (53 %) followed by idiopathic optic neuritis (42.3 %). Final visual acuity of at least 20/40 was seen in at least 91.5 %. Conclusion: While the clinical profile of patients in this study closely resembles the Optic Neuritis Treatment Trial with a high incidence of MS and a good visual outcome in most patients and a good response to intravenous steroids, there is a significant proportion of idiopathic optic neuritis cases that may need to be better characterized with longer follow up and repeated serum biomarker testing.

BackgroundDisability progression is a key milestone in the disease evolution of people with multiple sclerosis (PwMS). Prediction models of the probability of disability progression have not yet reached the level of trust needed to be adopted in the clinic. A common benchmark to assess model development in multiple sclerosis is also currently lacking.MethodsData of adult PwMS with a follow-up of at least three years from 146 MS centers, spread over 40 countries and collected by the MSBase consortium was used. With basic inclusion criteria for quality requirements, it represents a total of 15, 240 PwMS. External validation was performed and repeated five times to assess the significance of the results. Transparent Reporting for Individual Prognosis Or Diagnosis (TRIPOD) guidelines were followed. Confirmed disability progression after two years was predicted, with a confirmation window of six months. Only routinely collected variables were used such as the expanded disability status scale, treatment, relapse information, and MS course. To learn the probability of disability progression, state-of-the-art machine learning models were investigated. The discrimination performance of the models is evaluated with the area under the receiver operator curve (ROC-AUC) and under the precision recall curve (AUC-PR), and their calibration via the Brier score and the expected calibration error. All our preprocessing and model code are available at https://gitlab.com/edebrouwer/ms_benchmark, making this task an ideal benchmark for predicting disability progression in MS.FindingsMachine learning models achieved a ROC-AUC of 0⋅71 ± 0⋅01, an AUC-PR of 0⋅26 ± 0⋅02, a Brier score of 0⋅1 ± 0⋅01 and an expected calibration error of 0⋅07 ± 0⋅04. The history of disability progression was identified as being more predictive for future disability progression than the treatment or relapses history.ConclusionsGood discrimination and calibration performance on an external validation set is achieved, using only routinely collected variables. This suggests machine-learning models can reliably inform clinicians about the future occurrence of progression and are mature for a clinical impact study.

Multiple sclerosis (MS) is a complex, neurodegenerative chronic disorder. Circulating diagnostic biomarkers for MS have remained elusive, and those proposed so far have limited sensitivity and specificity to MS. Plasma-circulating microRNAs (miRNAs) have advantageous biochemical and physiological attributes that can be utilized in clinical testing and disease monitoring. MS miRNA expression microarray datasets analysis resulted in four candidate miRNAs that were assessed for their expression in a separate MS case-control study. Only miR-24-3p was downregulated in all MS patients compared to healthy controls. MiR-484 was significantly upregulated in relapsing-remitting MS (RRMS) patients compared to healthy controls. Mir-146-5p and miR-484 were significantly downregulated in secondary-progressive MS (SPMS) compared to RRMS. MiR-484 downregulation was associated with worsening disability and increased lipocalin-2 levels. Mir-342-3p and miR-24-3p downregulation were associated with increased semaphorin-3A levels in MS and RRMS patients. In conclusion, mir-24-3p downregulation is diagnostic of MS, and mir-484 upregulation and downregulation are potential biomarkers for RRMS and SPMS conversion, respectively. The differential expression of miR-146a-3p in MS subtypes suggests its potential as an SPMS transition biomarker. The association of downregulated mir-24-3p and mir-484 with increased neurodegeneration biomarkers suggests they play a role in MS pathogenesis and neurodegeneration.

Abstract Objective It has been reasoned that stressful life events tend to alter immune function thereby increasing the susceptibility to autoimmune diseases including multiple sclerosis (MS). Using the database of Kuwait National MS Registry, this quasi-experimental study assessed the impact of the first Gulf War (Iraqi invasion of Kuwait in 1990) on MS risk in Kuwait. Methods MS incidence data from 1980 to 2019 were obtained from the Kuwait National MS Registry. Annual age-standardized incidence rates (ASIRs) (per 105 person-years) were computed using the World Standard Population as a reference. Interrupted time series analysis with the option of autoregressive order (1) was used to evaluate the impact of the first Gulf War on MS risk by treating 1990 as an intervention year. Results Estimated baseline annual ASIR (per 105 person-years) was 0.38 (95% CI: -1.02, 1.78; p = 0.587). MS ASIRs (per 105 person-years) tended to increase significantly every year prior to 1990 by 0.45 (ASIR per 105 person-years = 0.45; 95% CI: 0.15, 0.76; p = 0.005). During the first year of the first Gulf War, there seemed to be a non-significant increase (step change) in ASIRs (per 105 person-years) of MS (ASIR per 105 person-years = 0.85; 95% CI: − 5.16, 6.86; p = 0.775) followed by a non-significant increase in the annual trend in MS ASIRs per 105 person-years (relative to the preintervention trend i.e., the difference between the pre-first Gulf War versus the post-first Gulf War trends) by 0.65 (ASIR per 105 person-years = 0.65; 95% CI: − 0.22, 1.52; p = 0.138). However, a postestimation measure of the post-first Gulf War trend was statistically significant (ASIR per 105 person-years = 1.10; 95% CI: 0.40, 1.80; p = 0.003), which implies that the post-first Gulf War trend in the annual ASIRs (per 105 person-years) inclined to be the same as was the pre-first Gulf War (i.e., counterfactual of the pre-first Gulf War trend in annual ASIRs (per 105 person-years) as if no first Gulf War took place).The Durbin-Watson test statistic (d = 1.89) showed almost non-significant autocorrelations across the time series observations on ASIRs (per 105 person-years). Conclusions This study suggests that the first Gulf War was not significantly associated with the increasing trend in MS risk at population level in Kuwait neither with any short-term change nor with secular trend. Future studies may consider confirming the role of conflict-related stress or other stressful life events in potential exacerbation of MS risk along with unraveling biologically plausible mechanistic pathways.

Abstract Introduction Inconvenient administration and side effects of some disease-modifying therapies (DMTs) for relapsing multiple sclerosis (RMS) can deter adherence. We evaluated treatment satisfaction with cladribine tablets (CladT) for RMS in the Arabian Gulf. Methods This was a non-interventional, multicentre, prospective observational study in non-pregnant/lactating adults (aged ≥ 18 years) with RMS eligible for 1st treatment with CladT (EU labelling). The primary outcome was overall treatment satisfaction at 6 months (Treatment Satisfaction Questionnaire for Medication [TSQM]-14, v. 1.4), Global Satisfaction subscale. Secondary endpoints were TSQM-14 scores for convenience, satisfaction with side effects and satisfaction with effectiveness. Patients provided written informed consent. Results Of 63 patients screened, 58 received CladT and 55 completed the study. Mean age was 33 ± 9 years; mean weight 73 ± 17 kg; 31% male/69% female; mostly from the United Arab Emirates (52%) or Kuwait (30%). All had RMS (mean 0.9 ± 1.1 relapses in the past year), mean Expanded Disability Status Scale (EDSS) 1.4 ± 1.2; 36% were DMT-naïve. Mean [95% CI] score was high for overall treatment satisfaction (77.8 [73.0–82.6]), ease of use (87.4 [83.7–91.0]), tolerability (94.2 [91.0–97.3]) and effectiveness (76.2 [71.6–80.7]). Scores were similar irrespective of DMT history, age, gender, relapse history or EDSS. No relapses or serious treatment-emergent adverse events (TEAE) occurred. Two severe TEAE occurred (fatigue, headache) and 16% reported lymphopenia (two cases of grade 3 lymphopenia). Absolute lymphocyte counts at baseline and 6 months were 2.2 ± 0.8 × 109/L and 1.3 ± 0.3 × 109/L, respectively. Conclusions Treatment satisfaction, ease of use, tolerability and patient-perceived effectiveness for CladT were high, irrespective of baseline demographics, disease characteristics and prior treatment.

Background: Aggressive disease control soon after multiple sclerosis (MS) diagnosis may prevent irreversible neurological damage, and therefore early initiation of a high-efficacy disease-modifying therapy (DMT) is of clinical relevance. Objectives: Evaluate long-term clinical outcomes in patients with MS who initiated treatment with either natalizumab or a BRACETD therapy (interferon beta, glatiramer acetate, teriflunomide, or dimethyl fumarate). Design: This retrospective analysis utilized data from MSBase to create a matched population allowing comparison of first-line natalizumab to first-line BRACETD. Methods: This study included patients who initiated treatment either with natalizumab or a BRACETD DMT within 1 year of MS diagnosis and continued treatment for ⩾6 months, after which patients could switch DMTs or discontinue treatment. Patients had a minimum follow-up time of ⩾60 months from initiation. A subgroup analysis compared the natalizumab group to patients in the BRACETD group who escalated therapy after 6 months. Outcomes included unadjusted annualized relapse rates (ARRs), time-to-first relapse, time-to-first confirmed disability improvement (CDI), and time-to-first confirmed disability worsening (CDW). Results: After 1:1 propensity score matching, 355 BRACETD patients were matched to 355 natalizumab patients. Patients initiating natalizumab were less likely to experience a relapse over the duration of follow-up, with ARRs [95% confidence interval (CI)] of 0.080 (0.070–0.092) for natalizumab patients and 0.191 (0.178–0.205) for BRACETD patients ( p

BackgroundTreatment switching is a common challenge and opportunity in real-world clinical practice. Increasing diversity in disease-modifying treatments (DMTs) has generated interest in the identification of reliable and robust predictors of treatment switching across different countries, DMTs, and time periods.ObjectiveThe objective of this retrospective, observational study was to identify independent predictors of treatment switching in a population of relapsing-remitting MS (RRMS) patients in the Big Multiple Sclerosis Data Network of national clinical registries, including the Italian MS registry, the OFSEP of France, the Danish MS registry, the Swedish national MS registry, and the international MSBase Registry.MethodsIn this cohort study, we merged information on 269,822 treatment episodes in 110,326 patients from 1997 to 2018 from five clinical registries. Patients were included in the final pooled analysis set if they had initiated at least one DMT during the relapsing-remitting MS (RRMS) stage. Patients not diagnosed with RRMS or RRMS patients not initiating DMT therapy during the RRMS phase were excluded from the analysis. The primary study outcome was treatment switching. A multilevel mixed-effects shared frailty time-to-event model was used to identify independent predictors of treatment switching. The contributing MS registry was included in the pooled analysis as a random effect.ResultsEvery one-point increase in the Expanded Disability Status Scale (EDSS) score at treatment start was associated with 1.08 times the rate of subsequent switching, adjusting for age, sex, and calendar year (adjusted hazard ratio [aHR] 1.08; 95% CI 1.07–1.08). Women were associated with 1.11 times the rate of switching relative to men (95% CI 1.08–1.14), whilst older age was also associated with an increased rate of treatment switching. DMTs started between 2007 and 2012 were associated with 2.48 times the rate of switching relative to DMTs that began between 1996 and 2006 (aHR 2.48; 95% CI 2.48–2.56). DMTs started from 2013 onwards were more likely to switch relative to the earlier treatment epoch (aHR 8.09; 95% CI 7.79–8.41; reference = 1996–2006).ConclusionSwitching between DMTs is associated with female sex, age, and disability at baseline and has increased in frequency considerably in recent years as more treatment options have become available. Consideration of a patient's individual risk and tolerance profile needs to be taken into account when selecting the most appropriate switch therapy from an expanding array of treatment choices.

Abstract Background Migraine frequently is associated with White Matter Hyperintensities (WMHs). We aimed to assess the frequency of WMHs in migraine and to assess their risk factors. Methods This is cross-sectional study included 60 migraine patients of both genders, aged between 18 and 55 years. Patients with vascular risk factors were excluded. We also included a matched healthy control group with no migraine. Demographic, clinical data, and serum level of homocysteine were recorded. All subjects underwent brain MRI (3 Tesla). Results The mean age was 38.65 years and most of our cohort were female (83.3). A total of 24 migraine patients (40%) had WMHs versus (10%) in the control group, (P

Abstract Background Coronavirus disease-19 is caused by the severe acute respiratory syndrome coronavirus 2 Headache is a common symptom during and after Coronavirus disease-19. We aimed to study headache character in relation to COVID-19. Methods This was a cross-sectional study. Patients who had Coronavirus disease-19, confirmed by reverse transcription polymerase chain reaction technique and presented to the headache clinic within 3 months after the onset of infections were identified to the study. Study included patients diagnosed as primary headache disorders according to The International Classification of Headache Disorders, 3rd edition. Participants were grouped into categories according to having previous or de novo headache. Descriptive data, paired sample t-test and the chi-squared test (X 2) were used for statistical analyses of the data. Results A total of 121 patients were included in this study. Their mean age was 35.29 + 9.54 and most of them were females (83.5%). Prior to Coronavirus disease-19 infections, 78 (64.5%) had migraine and 11(9.1%) experienced a tension-type headache while 32 (26.4) reported de novo headache post Coronavirus disease-19. Patient had significant increase in headache days 11.09 ± 8.45 post Coronavirus disease-19 compared with 8.66 ± 7.49 headache days before Coronavirus disease-19 infection (p

Abstract 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.

Abstract 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 (mORadj) = 5.1; 95% CI: 2.1–12.4; p

Abstract This article discusses the opinions of the multiple sclerosis (MS) experts in the Gulf region on the use of high-efficacy disease-modifying drugs (DMDs; natalizumab, fingolimod, alemtuzumab, cladribine tablets, and ocrelizumab) in clinical practice. The experts reviewed the current literature including pivotal clinical trials and meta-analyses for high-efficacy DMDs, supplemented by the expert opinions on the usage of these DMDs in clinical practice. Several criteria were discussed by the panel based on different efficacy, safety, and convenience attributes. The panel concluded that all the DMDs available for the treatment of MS have benefits and risks, which should be considered while discussing the treatment plan with the patient. It is important to have a personalized approach based on the risk-benefit assessment for each case. Common considerations while choosing treatments include effectiveness, side effects/safety, and convenience/route of administration. Funding: Merck Serono Middle East FZ LTD.

Background: Family planning and pregnancy decisions are key considerations in the management of women with multiple sclerosis (MS), who are typically diagnosed between the ages of 20–40 years. Despite a strong evidence base that pregnancy is not harmful for women with MS, many knowledge gaps remain. These include: best management strategies through pregnancy in the era of highly effective disease-modifying therapies (DMT); foetal risks associated with DMT exposure in utero or in relation to breastfeeding; knowledge base around the use of assisted reproductive technologies; the long-term impact of pregnancy on disease outcomes, as well as the impact of long-term DMT use on women’s health and cancer risk. Methods: Here, we describe the new MSBase pregnancy, neonatal outcomes and women’s health registry. We provide the rationale for, and detailed description of, the variables collected within the registry, together with data acquisition details. Conclusion: The present paper will act as a reference document for future studies.

Background: 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.Aims and Objectives: To examine the prevalence of primary headache disorders among primary and middle school students in Kuwait.Methods: 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.Results: 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%; p < 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%; p < 0.001); however, no significant difference between genders was noted among primary school students (33.12 vs. 22.33%; p < 0.118).Conclusion: 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.

Background: 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.Methods: 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 t-test to assess the effects of Onabotulinumtoxin A on quality of life and comorbid symptoms of anxiety, depression, and quality of sleep.Results: 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; P < 0.0001). It was also associated with significant reduction in anxiety [GAD-7 (12.00 vs. 6.61; P < 0.0001)] and depression [PHQ-9 (17.91 vs. 12.52; P < 0.0001)] scores, as well as reduced difficulty in sleeping [PSQI (12.60 vs. 6.66; P < 0.0001)] at the last visit.Conclusion: 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.

Background: 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.Methods: 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).Results: 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 (n = 20; 95% confidence interval: 66.8–92.8; p < 0.0001) vs. the year before DMF initiation.Conclusions: 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.

Few studies examine health-related quality of life (HRQoL) in Arabic-speaking multiple sclerosis (MS) patients. However, HRQoL tools such as the Short Form-36 QoL instrument (SF-36) and the Multiple Sclerosis International QoL (MusiQoL) questionnaire have been validated in other languages. The primary objective of this study was to prospectively assess HRQoL using the MusiQoL questionnaire among Arabic-speaking MS patients treated with subcutaneous interferon (sc IFN β-1a) over 12 months, as part of a prospective, multinational, multicenter cohort study. Patients’ clinical parameters and HRQoL were assessed at baseline, 6 months, and 12 months. Changes in MusiQoL total and subdomain scores were compared using a Friedman test. Correlation between MusiQoL total score and Expanded Disability Status Score (EDSS) was also evaluated. In total, 439 patients from four Arabic-speaking countries were included. The mean age was 32.44 (±0.34) years, 71.5% were female, and 63.1% had an education level of university or above. The mean MS duration was 4.13 (±0.12) years, mean age at first attack was 27.35 (±0.26) years, and mean baseline EDSS score was 2.05 (±0.04). MusiQoL total score significantly improved at 6 months; however, this diminished at 12 months (65.67±0.8 at baseline vs. 67.21±0.79 at 6 months and 65.75±0.8 at 12 months; p=0.0015). Several aspects of patients’ HRQoL including activity of daily living, physical well-being, symptoms, and coping improved. Overall HRQoL measured using SF-36 remained generally unchanged over time (p=0.215). There was a statistically significant inverse relationship between change in EDSS score over time and change in overall MusiQoL score over time. In summary, findings confirm the utility of using MusiQoL for assessing changes in HRQoL during treatment with sc IFN β-1a in Arabic-speaking patients with MS.

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.

Background: 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.Aims and objectives: To examine the impact of puberty on the prevalence of primary headache disorders among female schoolchildren in Kuwait.Methods: 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.Results: 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%; p < 0.0001). All types of primary headaches were more significantly prevalent among postpubertal girls compared to those who are prepubertal.Conclusion: 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.

Neuromyelitis Optica Spectrum Disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system (CNS) primarily affecting the optic nerves and spinal cord, but also involving other regions of the CNS including the area postrema, periaqueductal gray matter, and hypothalamus. Knowledge related to pediatric manifestations of NMOSD has grown in recent years, particularly in light of newer information regarding the importance of not only antibodies to aquaporin 4 (AQP4-IgG) but also myelin oligodendrocyte glycoprotein (MOG-IgG) in children manifesting clinically with this syndrome. In this review, we describe the current state of the knowledge related to clinical manifestations, diagnosis, and chronic therapies for children with NMOSD, with emphasis on literature that has been published in the last 5 years. Following the review, we propose recommendations for the assessment/follow up clinical care, and treatment of this population.

Abstract Background Traditional Medicine (TM) is widely accepted to be used for the treatment headache disorders in Kuwait however, researches remain poorly documented. We aimed to study the frequency of TM use and its impact in the primary headache patients. Methods This is a cross sectional self-reported efficacy study, which was conducted in Headache clinic in Kuwait throughout 6 months. Patients who were diagnosed with primary headache disorders of both genders aged from 18 to 65 years were included. Self-reported questionnaires were distributed to patients who used TM in the previous year. It included demographic, and characteristics of headache (headache frequency, duration, number of analgesic used in days per month and severity of headache). TM queried included blood cupping (Hijama), head banding, herbal medicine (sabkha), and diet modification. It assessed characters of headache before and 3 months after the final TM session. Independent sample t test, paired sample t test and Chi-square test were used to compare between different values. P

Abstract Background Pediatric-onset multiple sclerosis (POMS) prevalence and incidence rates are increasing globally. No disease-modifying therapy are approved for MS pediatric population. Hence, we aim to review the literature on POMS to guide treating physicians on the current understanding of diagnosis and management of pediatric MS. Methods The authors performed a literature search and reviewed the current understanding on risk factors and disease parameters in order to discuss the challenges in assessing and implementing diagnosis and therapy in clinical practice. Results The revised International Pediatric MS group diagnostic criteria improved the accuracy of diagnosis. Identification of red flags and mimickers (e.g. acute disseminated encephalomyelitis and neuromyelitis optica) are vital before establishing a definitive diagnosis. Possible etiology and mechanisms including both environmental and genetic risk factors are highlighted. Pediatric MS patients tend to have active inflammatory disease course with a tendency to have brainstem / cerebellar presentations at onset. Due to efficient repair mechanisms at early life, pediatric MS patients tend to have longer time to reach EDSS 6 but reach it at earlier age. Although no therapeutic randomized clinical trials were conducted in pediatric cohorts, open-label multi-center studies reported efficacy and safety results with beta interferons, glatiramer acetate and natalizumab in similar adult cohorts. Several randomized clinical trials assessing the efficacy and safety of oral disease-modifying therapies are ongoing in pediatric MS patients. Conclusion Pediatric MS has been increasingly recognized to have a more inflammatory course with frequent infratentorial presentations at onset, which would have important implications in the future management of pediatric cohorts while awaiting the results of ongoing clinical trials.

Abstract Background Migraine prevalence and disability imprints on Kuwaiti population are underreported. We aimed to measure the prevalence of migraine and to assess its burden in Kuwait. Methods A cross-sectional community-based study was conducted which included biologically unrelated Kuwaiti adult population aged 18–65 years. They were randomly recruited from all six governments of Kuwait using stratified multistage cluster sampling. Trained interviewers visited the samples in door-to-door approach. The Headache-Attributed Restriction, Disability, and Social Handicap and Impaired Participation (HARDSHIP) questionnaire was used to collect the data. Demographic enquires were followed by diagnostic and disability questions. Results A total of 15,523 subjects were identified; of whom 3588 (23%) were diagnosed as episodic migraine and 845 (5.4%) as chronic headache. Prevalence of episodic migraine was 31.71% in female versus 14.88% in males (P

Abstract Background Evidence on the use of fingolimod in real-world clinical practice and data on patient-reported health-related quality of life (HRQoL) in countries such as the Middle East are sparse. The Prospective Evaluation of Treatment with Fingolimod for Multiple Sclerosis (PERFORMS) study assessed HRQoL and effectiveness and safety of fingolimod in patients with relapsing-remitting multiples sclerosis (RRMS), primarily in Middle Eastern countries. Methods This 12-month, observational, multicentre, prospective, real-world study was conducted in patients with RRMS who initiated fingolimod or another approved disease-modifying treatment (DMT) within 4 weeks before study entry. Patients were enrolled in a 2:1 ratio to obtain more data in fingolimod and parallel in other DMTs cohort by physicians during routine medical care. Key study outcomes included HRQoL assessed using MS International QoL (MusiQoL), MS relapses and disability. Safety was assessed throughout the study period. Due to the observational nature of the study, no neuroimaging assessments were mandated and central reading was not performed. Results Of 249 enrolled patients, 247 were included in the analysis (fingolimod cohort 172; other DMTs cohort 75). Overall, the mean age of patients was 36.5 years, 64.4% were women and ~90% were Caucasians. At baseline, mean MS duration since diagnosis was 7.2 years in the fingolimod and 4.8 years in the other DMTs cohorts. Overall, mean changes in MusiQoL index scores were −2.1 in the fingolimod cohort and −0.7 in the other DMTs cohort at Month 12, but improvement was not significant vs. baseline in both cohorts. Proportion of relapse-free patients increased significantly during the study vs. 0–12 months before the study in the fingolimod cohort (80.2% vs. 24.4%; p

An amendment to this paper has been published and can be accessed via the original article.

Background/Objective: 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.Methods: 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.Results: 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%; P < 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 %; p < 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; P < 0.79), while it was significantly higher in female vs. males (38.1% vs. 15.8%; P < 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.Conclusions: 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.

BackgroundMultiple Sclerosis (MS) is a chronic neurological disease with heavy economic and social burdens resulting in significant disability.ObjectiveThis study aims to (1) measure the cost of health resources utilization by MS patients and (2) to examine the difference in utilization and its attributed costs amongst patients who may have a different course of MS and expanded disability status scale (EDSS) scores.MethodsA cross-sectional study using Kuwait National MS registry was conducted to estimate the costs of utilization of resources from 2011 to 2015.ResultsBetween the period 2011-2015, 1344 MS patients were included in the registry. The average annual cost per MS patient has increased from $10,271 in 2011 to $17,296 in 2015. Utilization of disease-modifying therapies (DMTs) was the main driver of costs reaching 89.9% in 2015. Throughout the five-year period, the occurrence of relapses decreased from 21.8% to 12.2% (p ConclusionsMultiple sclerosis has been a significant economic burden on the Kuwait healthcare system. DMTs are the main driver of cost.

INTRODUCTION:Optical coherence tomography (OCT) with retinal segmentation analysis is a valuable tool in assessing axonal loss and neuro-degeneration in multiple sclerosis (MS) by in-vivo imaging, delineation and quantification of retinal layers. There is evidence of deep retinal involvement in MS beyond the inner retinal layers. The ultra-structural retinal changes in MS in different MS phenotypes can reflect differences in the pathophysiologic mechanisms. There is limited data on the pattern of deeper retinal layer involvement in progressive MS (PMS) versus relapsing remitting MS (RRMS). We have compared the OCT segmentation analysis in patients with relapsing-remitting MS and progressive MS. METHODS:Cross-sectional study of 113 MS patients (226 eyes) (29 PMS, 84 RRMS) and 38 healthy controls (72 eyes). Spectral domain OCT (SDOCT) using the macular cube acquisition protocol (Cirrus HDOCT 5000; Carl Zeiss Meditec) and segmentation of the retinal layers for quantifying the thicknesses of the retinal layers. Segmentation of the retinal layers was carried out utilizing Orion software (Voxeleron, USA) for quantifying the thicknesses of individual retinal layers. RESULTS:The retinal nerve finer layer (RNFL) (p = 0.023), the ganglion-cell/inner plexiform layer (GCIPL) (p = 0.006) and the outer plexiform layer (OPL) (p = 0.033) were significantly thinner in PMS compared to RRMS. There was significant negative correlation between the outer nuclear layer (ONL) and EDSS (r = -0.554, p = 0.02) in PMS patients. In RRMS patients with prior optic neuritis, the GCIPL correlated negatively (r = -0.317; p = 0.046), while the photoreceptor layer (PR) correlated positively with EDSS (r = 0.478; p = 0.003). CONCLUSIONS:Patients with PMS exhibit more atrophy of both the inner and outer retinal layers than RRMS. The ONL in PMS and the GCIPL and PR in RRMS can serve as potential surrogate of disease burden and progression (EDSS). The specific retinal layer predilection and its correlation with disability may reflect different pathophysiologic mechanisms and various stages of progression in MS.

Published natural history data on late-onset of multiple sclerosis are limited. We aimed to assess the risk of attaining EDSS 6.0 among patients with late-onset (> 40 years) MS (LOMS) and young-onset (18-40 years) MS (YOMS).This cross-sectional cohort study was conducted to identify LOMS and YOMS patients' with relapsing remitting course at MS diagnosis. Time (years) to reach sustained EDSS 6.0 was compared between LOMS and AOMS patients. Cox proportional hazards model was used to evaluate the demographic and clinical predictors of time to EDSS 6.0 in these cohorts.LOMS and YOMS cohorts comprised 99 (10.7%) and 804 (89.3%) patients respectively. Spinal cord presentation at MS onset was more common among LOMS patients (46.5% vs. 32.3%). The proportions of LOMS and YOMS patients reaching EDSS 6.0 during the follow-up period were 19.2% and 15.7% respectively. In multivariable Cox proportional hazards model, older age at MS onset (adjusted hazard ratio (aHR) = 3.96; 95% CI: 2.14-7.32; p < 0.001), male gender (aHR = 1.85; 95% CI: 1.22-2.81; p = 0.004) and spinal cord presentation at onset (aHR = 1.47; 95% CI: 0.98-2.21; p = 0.062) were significantly associated with shorter time to EDSS 6.0.LOMS patients attained EDSS 6.0 in a significantly shorter period that was influenced by male gender and spinal cord presentation at MS onset.

The burden of multiple sclerosis (MS) in women of childbearing potential is increasing, with peak incidence around the age of 30 years, increasing incidence and prevalence, and growing female : male ratio. Guidelines recommend early use of disease-modifying therapies (DMTs), which are contraindicated or recommended with considerable caution, during pregnancy/breastfeeding. Many physicians are reluctant to prescribe them for a woman who is/is planning to be pregnant. Interferons are not absolutely contraindicated during pregnancy, since interferon-β appears to lack serious adverse effects in pregnancy, despite a warning in its labelling concerning risk of spontaneous abortion. Glatiramer acetate, natalizumab, and alemtuzumab also may not induce adverse pregnancy outcomes, although natalizumab may induce haematologic abnormalities in newborns. An accelerated elimination procedure is needed for teriflunomide if pregnancy occurs on treatment or if pregnancy is planned. Current evidence supports the contraindication for fingolimod during pregnancy; data on other DMTs remains limited. Increased relapse rates following withdrawal of some DMTs in pregnancy are concerning and require further research. The postpartum period brings increased risk of disease reactivation that needs to be carefully addressed through effective communication between treating physicians and mothers intending to breastfeed. We address the potential for use of the first- and second-line DMTs in pregnancy and lactation.

Vitamin D deficiency is associated with several diseases including multiple sclerosis (MS). Several factors influence vitamin D levels and its optimal multi-function maintenance. Our objective was to assess quantifiable variables influencing vitamin D level and metabolism in MS patients from Kuwait. In a case-control study involving 50 MS patients, and 50 healthy control individuals for which plasma vitamin D levels, supplement use, vitamin D receptor (VDR) variants, and skin pigmentation indices were ascertained; we found overall vitamin D levels to be deficient in both groups, and supplement use to be common practice. VDR variants TaqI and BsmI associated with MS risk, and ApaI associated with low disease progression. VDR variant FokI associated with higher vitamin D levels in both groups. We conclude that several quantifiable variables related to vitamin D associate with MS suggesting a possible clinical immuno-modulatory application of vitamin D for MS patients in Kuwait.

Multiple Sclerosis is more common in women than men and females have more relapses than men. In a large international cohort we have evaluated the effect of gender on disability accumulation and disease progression to determine if male MS patients have a worse clinical outcome than females.Using the MSBase Registry, data from 15,826 MS patients from 25 countries was analysed. Changes in the severity of MS (EDSS) were compared between sexes using a repeated measures analysis in generalised linear mixed models. Kaplan-Meier analysis was used to test for sex difference in the time to reach EDSS milestones 3 and 6 and the secondary progressive MS.In relapse onset MS patients (n = 14,453), males progressed significantly faster in their EDSS than females (0.133 vs 0.112 per year, P

ObjectivesTo compare treatment persistence between two dosages of interferon β-1a in a large observational multiple sclerosis registry and assess disease outcomes of first line MS treatment at these dosages using propensity scoring to adjust for baseline imbalance in disease characteristics.MethodsTreatment discontinuations were evaluated in all patients within the MSBase registry who commenced interferon β-1a SC thrice weekly (n = 4678). Furthermore, we assessed 2-year clinical outcomes in 1220 patients treated with interferon β-1a in either dosage (22 µg or 44 µg) as their first disease modifying agent, matched on propensity score calculated from pre-treatment demographic and clinical variables. A subgroup analysis was performed on 456 matched patients who also had baseline MRI variables recorded.ResultsOverall, 4054 treatment discontinuations were recorded in 3059 patients. The patients receiving the lower interferon dosage were more likely to discontinue treatment than those with the higher dosage (25% vs. 20% annual probability of discontinuation, respectively). This was seen in discontinuations with reasons recorded as "lack of efficacy" (3.3% vs. 1.7%), "scheduled stop" (2.2% vs. 1.3%) or without the reason recorded (16.7% vs. 13.3% annual discontinuation rate, 22 µg vs. 44 µg dosage, respectively). Propensity score was determined by treating centre and disability (score without MRI parameters) or centre, sex and number of contrast-enhancing lesions (score including MRI parameters). No differences in clinical outcomes at two years (relapse rate, time relapse-free and disability) were observed between the matched patients treated with either of the interferon dosages.ConclusionsTreatment discontinuations were more common in interferon β-1a 22 µg SC thrice weekly. However, 2-year clinical outcomes did not differ between patients receiving the different dosages, thus replicating in a registry dataset derived from "real-world" database the results of the pivotal randomised trial. Propensity score matching effectively minimised baseline covariate imbalance between two directly compared sub-populations from a large observational registry.

The prevalence of multiple sclerosis (MS) is now considered to be medium-to-high in the Middle East and is rising, particularly among women. While the characteristics of the disease and the response of patients to disease-modifying therapies are generally comparable between the Middle East and other areas, significant barriers to achieving optimal care for MS exist in these developing nations. A group of physicians involved in the management of MS in ten Middle Eastern countries met to consider the future of MS care in the region, using a structured process to reach a consensus. Six key priorities were identified: early diagnosis and management of MS, the provision of multidisciplinary MS centres, patient engagement and better communication with stakeholders, regulatory body education and reimbursement, a commitment to research, and more therapy options with better benefit-to-risk ratios. The experts distilled these priorities into a single vision statement: “Optimization of patient-centred multidisciplinary strategies to improve the quality of life of people with MS.” These core principles will contribute to the development of a broader consensus on the future of care for MS in the Middle East.