Impact of primary headache disorder on quality of life among school students in Kuwait.

BACKGROUND: Primary headache disorders have being increasingly reported in younger populations. They can have significant effects on their quality of life and academic achievement and may cause significant distress to their families. AIMS AND OBJECTIVES: To assess the burden of primary headache disorder and its impact on the quality of life on school student in Kuwait. METHODS: A cross-sectional study was conducted among Kuwaiti primary and middle school students of both genders in randomly selected schools located in two governorates in 2018/2019 academic year. Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire for children and adolescents was used to assess the impact of primary headaches on the quality of life. RESULTS: One thousand and ninety-one questionnaires were completed by primary and middle school students of both genders; of whom 466 students (girls 321 (68.88%) were diagnosed with primary headache disorders with mean age 11.98 ± 2.03 years. In the month prior to the survey, the effect of the headache was variable. The students lost a mean of 1.99 ± 2.015 days of school while they could not perform their usual activities for a mean of 2.84 ± 4.28 days. Their parents lost a mean of 2 ± 2.03 days of work because of headaches of their children and parents prohibited 5.7% of the students to engage in any activity due to their headaches. Difficulties in concentrations were reported as never sometimes (39.1%), often (24.8%), and always (26%). Majority of the students (51.5%) experienced a feeling of sadness ranging from sometimes to always. Most of the students (67.3%) struggled to cope with the headache and 22.4% were never able to cope. Additionally, 19.4% of students reported they did not want others noticing their headache. CONCLUSION: Primary headache disorder can have a significant impact on the quality of life in children. It can affect their engagement in activities and academic achievement. Implementing strategies to properly manage schoolchildren with primary headaches can have profound effects on their quality of life.

Prognostic indicators of secondary progression in a paediatric-onset multiple sclerosis cohort in Kuwait.

BACKGROUND: The frequency of paediatric-onset multiple sclerosis (POMS) and the precise risk of secondary progression of disease are largely unknown in the Middle East. This cross-sectional cohort study assessed the risk and examined prognostic factors for time to onset of secondary progressive multiple sclerosis (SPMS) in a cohort of POMS patients. METHODS: The Kuwait National MS Registry database was used to identify a cohort of POMS cases (diagnosed at age <18 years) from 1994 to 2013. Data were abstracted from patients' records. A Cox proportional hazards model was used to evaluate the prognostic significance of the variables considered. RESULTS: Of 808 multiple sclerosis (MS) patients, 127 (15.7%) were POMS cases. The median age (years) at disease onset was 16.0 (range 6.5-17.9). Of 127 POMS cases, 20 (15.8%) developed SPMS. A multivariable Cox proportional hazards model showed that at MS onset, brainstem involvement (adjusted hazard ratio 5.71; 95% confidence interval 1.53-21.30; P=0.010), and POMS patient age at MS onset (adjusted hazard ratio 1.38; 95% confidence interval 1.01-1.88; P=0.042) were significantly associated with the increased risk of a secondary progressive disease course. CONCLUSIONS: This study showed that POMS patients with brainstem/cerebellar presentation and a relatively higher age at MS onset had disposition for SPMS and warrant an aggressive therapeutic approach.

Retrospective Cohort Study of Gender Differential in Risk of Multiple Sclerosis in Kuwait.

BACKGROUND: Despite an increase in the incidence of multiple sclerosis (MS) in the Middle-East, there is a paucity of published data on sex ratio among MS patients in the region. Therefore, this retrospective cohort study determined sex ratio by year of birth of MS patients born from January 1, 1950, to December 31, 2000, who were diagnosed and registered in the Kuwait National MS Registry till April 30, 2013. METHODS: Patients were classified into 5-year periods according to their year of birth. Sex ratio (female:male) and its 95% CI for each period were computed. Using binomial logistic regression, sex ratio in MS patients was modeled with respect to year of birth and nationality. RESULTS: Of 1,035 patients with MS, 675 (65.2%) were women and 798 (77.1%) Kuwaiti. Sex ratio (female:male) of MS cases for entire study period was 1.9 (range 0.4-3.0). Multivariable logistic regression model showed that with each passing year of birth, there was statistically significant 8% increase in sex ratio (female:male) for vulnerability to MS risk (adjusted OR 1.08; 95% CI 1.06-1.09; p < 0.001). CONCLUSIONS: There was a statistically significant steady increase on logarithmic scale in the gender disparity for MS risk over the study period. This study from the Middle-East adds to the existing persuasive evidence of enhanced MS risk in women. Further insight in the context of differential risk factors including the role of sex hormones and vitamin D deficiency in MS pathogenesis may help designing preventive strategies.

Risk Factors, Subtypes, and Outcome of Ischemic Stroke in Kuwait: A National Study.

BACKGROUND AND PURPOSE: Epidemiological studies of stroke burden in Kuwait are scarce. We aimed to identify the risk factors, subtypes, and outcome of ischemic stroke in the 6 major hospitals in Kuwait between 2008 and 2013. METHODS: A cross-sectional survey was carried out using randomly selected ischemic stroke patients. It included data of sociodemographic status, stroke risk factors, stroke subtypes, treatment, and outcomes. RESULTS: A total of 1257 ischemic stroke patients (811 men and 446 women; mean age 60.2 ± 13.1) were included. Small-artery ischemic stroke was the most common stroke subgroup (69.8%) whereas hypertension was the most prevalent risk factor (80.9%). History of heart disease was significantly associated (P < .001) with cardioembolic strokes (58.3%) compared to large-artery stroke (37.5%) and small-artery stroke (32.5%). Atrial fibrillation was significantly prevalent (P < .001) in cardioembolic stroke (54.2%) compared to large-artery stroke (13%) and small-artery stroke (7.6%). Presentation at ages less than 45 years was significantly (P < .001) associated with improved neurological status at discharge (82.6%) when compared to patients aged 45-70 years (78.5%) and more than 70 years (63.8%). Similar findings were observed at 6 months follow-up (78.4% versus 72.8% and 46%; P < .001). Cardioembolic stroke was significantly associated with higher mortality rates (25% versus 12.4% and 6.8%; P < .061) in large-vessel and small-vessel strokes, respectively. CONCLUSIONS: Small-artery ischemic stroke was the most common stroke subgroup, and hypertension was the most common risk factor. The outcome was better in younger patients. Cardioembolic stroke was associated with worse outcome.

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

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.

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

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 ±â€¯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.

Economic burden of multiple sclerosis on Kuwait health care system.

BACKGROUND: Multiple Sclerosis (MS) is a chronic neurological disease with heavy economic and social burdens resulting in significant disability. OBJECTIVE: This 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. METHODS: A cross-sectional study using Kuwait National MS registry was conducted to estimate the costs of utilization of resources from 2011 to 2015. RESULTS: Between 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 <0.0001). During this same period, ambulatory relapse treatment increased by 5.8% while hospitalizations decreased by 2.6%. Patients with a moderate EDSS score (3.5-6) had the highest average cost (p<0.0001) compared to mild and severe EDSS scores. CONCLUSIONS: Multiple sclerosis has been a significant economic burden on the Kuwait healthcare system. DMTs are the main driver of cost.

Risk of relapses during pregnancy among multiple sclerosis patients.

BACKGROUND: Relapse rate in women with Multiple Sclerosis (MS) is reduced during pregnancy especially in the third trimester according to the previous studies. OBJECTIVES: To measure the annual relapse rate (ARR) in women with MS during pregnancy. METHODS: A retrospective study was conducted using prospectively collected data from two MS registries in Kuwait and Lebanon. Demographics, clinical characteristics including relapses, disease modifying therapies (DMTs) and their washout periods were extracted. The annual relapse rates pre and post pregnancies were compared and the relationship between relapses and prior use of different DMTs was assessed. RESULTS: Data of 164 pregnancies (132 MS patients) was reviewed. Mean age and disease duration at the time of pregnancy confirmation were 32.4 ±â€¯5.3 and 7.8 ±â€¯4.7 years respectively. Most patients (91.7%; n = 121) were on DMTs in the year prior to pregnancy. The pre-pregnancy ARR was 0.10 (95% CI: 0.04 - 0.13), which increased to 0.20 (95% CI: 0.13- 0.29) during pregnancy. Most relapses occurred either during the 1st (ARR = 0.24; 95% CI: 0.12 - 0.44) or 3rd (ARR = 0.32; 95%CI: 0.17 - 0.53) trimesters. Fingolimod (31.8%) and natalizumab (22.7%) were the most commonly prescribed DMTs in patients who sustained relapses during pregnancy. The mean washout period was significantly longer among subjects with relapses (9.3 ±â€¯6.6 vs. 2.5 ±â€¯3.9; p < 0.001) than those of without relapses. CONCLUSIONS: Relapse rate during pregnancy was higher than previous studies conducted in patients on platform therapies or untreated. Longer washout period prior to conception was associated with increased relapses especially in fingolimod and natalizumab treated patients.

Relapse occurrence in women with multiple sclerosis during pregnancy in the new treatment era.

OBJECTIVE: To determine the rate of relapse occurrence during pregnancy and postpartum. METHODS: In a cross-sectional study using the national multiple sclerosis (MS) registry, pregnant women with relapsing MS were identified. Data on demographics, clinical characteristics, and disease-modifying therapies (DMTs), including washout periods, were collected. Timings and durations of relapses were extracted. A multivariate logistic regression was used to assess the relationship between relapses and prior use of different DMTs. RESULTS: Completed data were available for 99 pregnancies (87 patients). Mean age and mean age at onset were 31.8 ± 5 and 24.4 ± 5.6 years, respectively, while the mean disease duration was 7.4 ± 4.6 years. Most pregnancies (89.9%) occurred in patients who were on DMTs in the year preceding pregnancy with a mean treatment duration of 63.4 ± 29 months. The rates of occurrence of relapses during pregnancy and postpartum were 17.2% and 13.7%, respectively. Most of the relapses occurred during the first (n = 6) and third (n = 7) trimesters. Rate of relapse was highest among patients receiving natalizumab and fingolimod before pregnancy. A longer washout period was significantly associated with relapse occurrence. CONCLUSION: The relapse occurrence during pregnancy is higher than the previously published rates. The use of high-efficacy therapies with long washout periods before conception was associated with an increased risk of relapses during pregnancy. Postpartum relapse occurrence was similar to that in previous reports.

JC virus seroprevalence and seroconversion in multiple sclerosis cohort: A Middle-Eastern study.

OBJECTIVES: To estimate JCV seroprevalence and risk of seroconversion against JCV among MS patients in the Middle East. METHODS: This multicenter study was conducted by implementing a cross-sectional design to assess JCV seroprevalence, and a longitudinal design to assess the risk of JCV seroconversion. Multivariable logistic and Poisson regression analyses were used to assess the relationship between clinical variables and JCV seropositivity and risk of seroconversion. RESULTS: Of 581 MS patients, 64.9% patients were females. Mean age and mean disease duration were 33.9 and 8.4years respectively. JCV seroprevalence was 48.7%. Male gender (p=0.002), age at onset (p=0.001) and disease duration of 20 or more years (p=0.007) were significantly associated with JCV seropositivity. Among patients (n=125), followed longitudinally, the risk of JCV seroconversion was 17.6% (95% CI: 11.4%-25.4%) during a median follow-up of 18months. The proportion of seroreverted and pseudoconverted patients was 4% and 3.2% respectively. CONCLUSIONS: JCV seroprevalence among MS patients in the Middle East was lower than international figures. Male gender, age at onset and disease duration were significantly associated with JCV seropositivity. Risk of JCV seroconversion was higher than previously reported figures. Observed JCV sero-reversion or pseudo-conversion entail watchful period before embarking on a clinical decision.

Pediatric-Onset Multiple Sclerosis Disease Progression in Kuwait: A Retrospective Analysis.

BACKGROUND: Pediatric and adults patients share basic aspects of multiple sclerosis; however, pediatric patients may have distinctive clinical features and disease course. OBJECTIVE: To compare the demographic and clinical characteristics between patients of pediatric-onset and adult-onset multiple sclerosis. METHODS: Using the Kuwait National Multiple Sclerosis Registry , multiple sclerosis patients with disease onset at age ≤ 17 years (pediatric-onset multiple sclerosis) or >17 years (adult-adult multiple sclerosis) were identified. Several demographics and clinical characteristics were analyzed. Disability measures and time to reach secondary progressive multiple sclerosis were compared between the two cohorts using chi-square and Student t tests. RESULTS: A total of 984 records of multiple sclerosis patients were assessed, of which 111 (11.3%) had disease onset at age ≤ 17 years. The female to male ratio did not differ between the two groups (P = 0.19). The mean age at onset of pediatric- and adult-onset multiple sclerosis was 14.9 and 27.68 years, respectively. Pediatric-onset multiple sclerosis patients were more likely to have brainstem/cerebellar (P < 0.03) and multifocal (P < 0.01) presentations at onset. The mean number of relapses did not differ between the two cohorts (3.4 ± 2.1 versus 3.05 ± 2.2; P = 0.14). The mean expanded disability status scale score at last visit was lower in the pediatric-onset cohort compared with the adult-onset cohort (2.38 ± 1.72 versus 3.02 ± 2.18; P = 0.003). The time to develop secondary progressive multiple sclerosis was longer in the pediatric-onset cohort (14.6 ± 4.6 years versus 11.0 ± 5.3 years; P < 0.04). CONCLUSIONS: Pediatric-onset multiple sclerosis patients were more likely to have brainstem/cerebellar and multifocal symptoms at onset. Although the number of relapses was comparable to the adult-onset cohort, multiple sclerosis patients with pediatric-onset had lower expanded disability status scale scores and a longer time to reach secondary progressive course at last follow-up visits.

Status migrainosus as an initial presentation of multiple sclerosis.

BACKGROUND: Demyelinating plaques may induce headache through disruption of the pathways, which are implicated in the pathogeneses of migraine. We report a case of 25-year-old female patient, who presented with status migrainosus fulfilling the criteria of international classification of headache disorder. She was eventually diagnosed with multiple sclerosis (MS) after an extensive work-up and long-term clinical and radiological follow-up. FINDINGS: At the onset of status migrainosus, magnetic resonance imaging (MRI) revealed the presence of several demyelinating lesions fulfilling Swanton criteria. She was started on migraine prophylactic treatment but there was no subsequent response. One year later, she presented with recurrent status migrainosus and a follow-up MRI revealed multiple gadolinium-enhancing lesions in the brain. She was treated with abortive migraine medications. Within the following 2 year, she developed ascending parasthesia and weakness of both lower limbs indicative of incomplete transverse myelitis in association with recurrent status migrainosus. A diagnosis of MS was established based on a follow-up MRI that satisfied the revised 2010 McDonald criteria. Both the headache and neurological signs improved with IV methylprednisolone therapy. Her headache entered remission after initiation of a disease modifying therapy. CONCLUSION: Status migrainosus can be the initial presentation of MS. Unresponsiveness to migraine prophylactic therapy in the presence of active demyelinating plaque in MRI brain may pose a diagnostic challenge and a diagnosis of MS might be considered.

Real-world use of fingolimod in patients with relapsing remitting multiple sclerosis: a retrospective study using the national multiple sclerosis registry in Kuwait.

BACKGROUND: Fingolimod is an oral sphingosine-1-phosphate-receptor modulator, which has demonstrated efficacy in clinical trials and has recently been approved for multiple sclerosis (MS) treatment in Kuwait. Post-marketing studies are important to demonstrate real-life efficacy and safety. OBJECTIVE: The objective of this study was to examine the efficacy and safety of fingolimod treatment in a clinical setting. METHODS: Using the national Kuwait MS registry, relapsing remitting MS patients who had been prescribed fingolimod for ≥6 months were retrospectively identified. Three-monthly clinical evaluations and 6-monthly magnetic resonance imagings (MRIs) were performed. Patient status pre- and post-treatment was compared using chi-square and Student t-tests. RESULTS: A total of 175 patients were included: 75.4 % female (n = 132); mean age 33.3 ± 9.2 years; mean disease duration 7.2 ± 5.2 years; mean fingolimod use 21.7 ± 9.1 months. Most had used previous disease-modifying therapy (78.9 %; n = 138), mainly interferons (66.9 %; n = 117). Twenty-three patients (11.4 %) discontinued/withdrew fingolimod; of whom eight had relapses. The proportion of relapse-free patients improved significantly (86.3 % vs. 32.6 %; p < 0.001), while the proportion of patients with MRI activity decreased (18.3.6 % vs. 77.7 %; p < 0.001). Mean expanded disability status scale (EDSS) score at the last visit improved when compared with pre-treatment (2.26 ± 1.49 vs. 2.60 ± 1.44; p = 0.03). Forty-three (24.6 %) patients experienced adverse events; headaches and lymphopenia were the most commonly reported adverse events. CONCLUSION: Fingolimod treatment was associated with reduced relapse and MRI activity, and an improved EDSS score. Discontinuation/withdrawal rates and adverse events were low. Fingolimod presents a promising treatment for MS in Kuwait.