Risk factors of white matter hyperintensities in migraine patients.

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 < 0.013). Patients with WMHs were significantly older (43.50 + 8.71 versus. 35.92+ 8.55 years, P < 0.001), have a longer disease duration (14.54+ 7.76versus 8.58+ 6.89 years, P < 0.002), higher monthly migraine attacks (9.27+ 4. 31 versus 7.78 + 2.41 P < 0.020) and high serum homocysteine level (11.05+ 5.63 versus 6.36 + 6.27, P < 0.006) compared to those without WMHs. WMHs were more frequent in chronic migraine compared to episodic migraine (75% versus 34.6%; P < 0.030) and migraine with aura compared to those without aura (38.3% versus 29,2; P < 0.001). WMHs were mostly situated in the frontal lobes (83.4%), both hemispheres (70.8%), and mainly subcortically (83.3%). CONCLUSION: Older age, longer disease duration, frequent attacks, and high serum homocysteine level are main the risk factors for WMHs in this cohort. The severity or duration of migraine attacks did not increase the frequency of WMHs. The number of WMHs was significantly higher in chronic compared to episodic migraineurs.

A guide to best practice in faculty development for health professions schools: a qualitative analysis.

BACKGROUND: This is a practice guide for the evaluation tool specifically created to objectively evaluate longitudinal faculty development programs (FDP) using the "5×2 -D backward planning faculty development model". It was necessary to create this tool as existing evaluation methods are designed to evaluate linear faculty development models with a specific endpoint. This backward planning approach is a cyclical model without an endpoint, consisting of 5 dynamic steps that are flexible and interchangeable, therefore can be a base for an evaluation tool that is objective and takes into account all the domains of the FDP in contrast to the existing, traditional, linear evaluation tools which focus on individual aspects of the program. The developed tool will target evaluation of longitudinal faculty development programs regardless of how they were planned. METHODOLOGY: Deductive qualitative grounded theory approach was used. Evaluation questions were generated and tailored based on the 5 × 2-D model followed by 2 Delphi rounds to finalize them. Based on the finalized evaluation questions from the results of the Delphi rounds, two online focus group discussions (FGDs) were conducted to deduce the indicators, data sources and data collection method. RESULTS: Based on the suggested additions, the authors added 1 new question to domains B, with a total of 42 modifications, such as wording changes or discarding or merging questions. Some domains received no comments, therefore, were not included in round 2. For each evaluation question, authors generated indicators, data sources and data collection methods during the FGD. CONCLUSION: The methodology used to develop this tool takes into account expert opinions. Comprehensiveness of this tool makes it an ideal evaluation tool during self-evaluation or external quality assurance for longitudinal FDP. After its validation and testing, this practice guide can be used worldwide, along with the provided indicators which can be quantified and used to suit the local context.

Serum YKL-40 and IL 17 in Psoriasis: Reliability as prognostic markers for disease severity and responsiveness to treatment.

YKL-40, a mammalian chitinase 3- like protein that was associated with multiple inflammatory and immune diseases. Previous studies have suggested a role for YKL-40 in psoriasis based on its significantly higher levels in the serum of psoriatic patient compared with healthy controls. The aim of this study was to determine the correlation between serum YKL-40, psoriasis severity using PASI score and serum levels of IL-17 before and after narrow-band UVB therapy. 28 patients with moderate to severe plaque psoriasis, as defined by PASI scores, were enrolled in this prospective cohort study. All cases received NB-UVB phototherapy twice weekly for 3 months. Serum YKL-40 and IL-17 levels were evaluated before and after 3 months of treatment. Clinical photographs were taken both at baseline and after 3 months. There was a statistical positive correlation between serum levels of YKL-40 and serum IL-17 levels as well as PASI score in patients with moderate to severe psoriasis before and after treatment. YKL-40 represents a reliable marker for psoriasis severity estimated by PASI and positively correlated with IL 17 as an inflammatory marker in psoriasis.

A guide for evaluation of online learning in medical education: a qualitative reflective analysis.

BACKGROUND: With the strike of Covid-19, an unprecedented rapid shift to remote learning happened worldwide with a paradigm shift to online learning from an institutional adjuvant luxury package and learner choice into a forced solo choice. This raises the question of quality assurance. While some groups have already established standards for online courses, teaching and programs yet very little information is included on methodology of their development and very little emphasis is placed on the online learning experience. Nevertheless, no work has been done specifically for medical education institutions. AIM: To develop a set of descriptors for best practice in online learning in medical education utilizing existing expertise and needs. METHODS: This work utilizes a qualitative multistage approach to identify the descriptors of best practice in online learning starting with a question guided focus group, thematic analysis, Delphi technique and an expert consensus session done simultaneously for triangulation. This was done involving 32 institution in 19 countries. RESULTS: This materialized into the development of a set of standards, indicators, and development of a checklist for each standard area. The standard areas identified were organizational capacity, educational effectiveness, and human resources each of which listed a number of standards. Expert consensus sessions identified the need for qualification of data and thus the development of indicators for best practice. CONCLUSION: Standards are needed for online learning experience and their development and redesign is situational and needs to be enhanced methodologically in axes that are pertaining to the needs of the education community. Taking such axes into consideration by educators and institutions will lead to planning and implementing successful online learning activities, while taking them into consideration by the evaluators will help them conduct comprehensive audits and provide stakeholders with highly informative evaluation reports.

Coronavirus disease-19 and headache; impact on pre-existing and characteristics of de novo: a cross-sectional study.

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 (X2) 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 < 0.006). Post Coronavirus disease-19, the usage of analgesic increased significantly by the patient with migraine (2.31 ± 1.65 vs 3.05 ± 2.09, p = 0.002) while the patient with tension type headache had statistically significant increase in severity (5.556 ± 1.86 vs 7 ± 2.25, p = 0.033) and frequency (7 ± 6.29 vs 12.72 ± 7.96, p = 0.006) of headache attacks. Bi-frontal and temporal headache are the most reported (40.6% each) headache site among de novo headache group. Patients younger than 40 years had longer duration of the headache attack (18.50 ± 16.44 vs 5.5 ± 9.07, p = 0.045) post COVID-19. Male patients compared to females (8.66 ± 1.15 versus 5.93 ± 2.01 p = 0.04) had more severe headache post Coronavirus disease-19. De novo headache resolved within 1 month in most of patients (65.3%). CONCLUSION: Primary headache get worse after Coronavirus disease-19. De novo primary headache is frequent post Coronavirus disease-19 and resolve within 1 month. Headaches related to Coronavirus disease-19 are severe, present as migraine phenotype. Young male patients with Coronavirus disease-19 tend to have worse headache.

Model for utilizing distance learning post COVID-19 using (PACT)™ a cross sectional qualitative study.

BACKGROUND: COVID - 19 pandemic pressured medical schools globally to shift to Distance learning (DL) as an alternative way to ensure that the content delivered is satisfactory for student progression. AIM OF THE WORK: This work aims at mapping priorities for post-COVID planning for better balance between distance learning and face to face learning. METHODS: This qualitative study aimed to develop a model for utilizing DL using The Polarity Approach for Continuity and Transformation (PACT)™. A virtual mapping session was held with 79 faculty from 19 countries. They worked in small groups to determine upsides and downsides of face-to-face and DL subsequently. An initial polarity map was generated identifying five tension areas; Faculty, Students, Curriculum, Social aspects and Logistics. A 63-item assessment tool was generated based on this map, piloted and then distributed as a self-administered assessment. The outcomes of this assessment were utilized for another mapping session to discuss warning signs and action steps to maintain upsides and avoid downsides of each pole. RESULTS: Participants agreed that face-to-face teaching allows them to inspire students and have meaningful connections with them. They also agreed that DL provides a good environment for most students. However, students with financial challenges and special needs may not have equal opportunities to access technology. As regards social issues, participants agreed that face-to-face learning provides a better chance for professionalism through enhanced team-work. Cognitive, communication and clinical skills are best achieved in face-to-face. Participants agreed that logistics for conducting DL are much more complicated when compared to face-to-face learning. Participants identified around 10 warning signs for each method that need to be continuously monitored in order to minimize the drawbacks of over focusing on one pole at the expense of the other. Action steps were determined to ensure optimized use of in either method. CONCLUSION: In order to plan for the future, we need to understand the dynamics of education within the context of polarities. Educators need to understand that the choice of DL, although was imposed as a no-alternative solution during the COVID era, yet it has always existed as a possible alternative and will continue to exist after this era. The value of polarity mapping and leveraging allows us to maximize the benefit of each method and guide educators' decisions to minimize the downsides for the good of the learning process.

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.

Use of traditional medicine for primary headache disorders in Kuwait.

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 < 0.05 is considered significant. RESULTS: A total of 279 patients were included. The mean age is 40.32 ± 11.75 years; females represented 79.6% of the cohort. Most patients (n = 195; 69.9%) reported the use of TM before presentation to headache clinic, mainly Hijama (47.3%). Cultural / religious beliefs were the cause of seeking TM in 51.3% versus 10% used it due to ineffective medical treatment and 8.6% used it because of intolerance of medical treatment. Patients used TM were older at the onset of headache (24.24 ± 10.67 versus 20.38 ± 8.47; p < 0.003), and had longer headache disease duration (19.26 ± 13.13 versus 16.12 ± 11.39; p < 0.044). All patients with chronic headache (100%) and most of episodic migraine patients (90.4%) sought TM while only (31.5%) of Tension type headache sought TM; p < 0.047. Patients who sought TM had more frequent episodes of headache, longer duration of attacks and higher number of days of analgesic-usage respectively over last 3 months before presentation to our side (9.66 ± 7.39 versus 4.14 ± 2.72; p < 0.001), (41.23 ± 27.76 versus 32.19 ± 23.29; p <. 0009), (8.23 + 7.70 versus 3.18 ± 3.06; p < 0.001). At 3 months after the final TM session, there was no significant reduction of frequency of headache days per month (9.19 ± 7.33 versus 8.99 ± 7.59; p < 0.50), days of analgesic use per month (7.45 ± 7.43 versus 6.77 ± 6.93; p < 0.09) and duration of headache (41.23 ± 27.76 versus 41.59 ± 27.69; p < 0.78). However, there was a significant reduction of the severity of headache (p < 0.02). Few patients (17.9%) reported adverse events with TM. Most of TM cohorts were not satisfied after receiving this type of medicine. CONCLUSION: TM was widely used in Kuwait for primary headache. Patients sought TM before seeking physician because they found them more congruent with their own cultural and religious beliefs. Health care professionals involved in the management of headache should be aware of this and monitor potential benefits or adverse events of TM. The usage of TM was not effective in reducing headache attacks and severity.

Prevalence of Primary Headache Disorders in Kuwait.

BACKGROUND: Only an insignificant quantum of data exists on the prevalence of primary headaches among those living in Kuwait. We aimed to determine the prevalence of primary headaches among the Kuwaiti population. METHODS: This community-based study included Kuwaiti population aged 18-65 years. Using systematic random sampling, data was collected by the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation questionnaire. Responses to the diagnostic questions were transformed into diagnoses algorithmically to confirm the diagnosis of primary headache. RESULTS: A total of 15,523 patients were identified of whom 9,527 (61%) were diagnosed with primary headache disorder; a female predominance of 62.2% was observed. The mean age was 34.84 ± 10.19. Tension-type headache (TTH) was the most prevalent at 29% followed by episodic migraine (23.11%), chronic migraine (5.4%), and medication overuse headache (2.4%). Primary headache prevalence declined steadily from 71% in those aged 18-30 years to 23% in those over 50 (p < 0. 037). The female:male ratio was 1.7:1. Frequency and severity of primary headache were correlated significantly with lost work days (r = 0.611, p < 0.001 and r = 0.102, p = 0.001, respectively). CONCLUSIONS: In Kuwait, primary headache disorder is more frequent in young adults and females. TTH followed by episodic migraine were the more prevalent types of headache. Higher frequency and severe headaches were associated with increasing social and work-related burden.

Burden of migraine in a Kuwaiti population: a door-to-door survey.

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 < 0.01) with a mean age of 34.56 ± 10.17 years. Most of migraine cohort (64.4%) sought medical advice with respect to their migraine headaches and the majority (62.4%) were seen by general practitioners (GPs) while 17.2% were assessed by neurologists and 3.7% was seen by other specialties. Tension type headache and sinus-related headaches were diagnosed in 8.9% and 2.1% of migraine subjects respectively. The majority (94.6%) of migraine subjects used symptomatic drugs for headache attacks, whereas 39.9% were taking preventive medication. In the preceding 3 months to the survey, subjects with episodic migraine had lost a mean of 1.97 days from their paid work or school attendance compared to 6.62 days in chronic headache sufferers (P < 0.001). Additionally, subjects with episodic migraine lost a mean of 1.40 days from household work compared to 5.35 days in subjects with chronic headache (P < 0.001). Participants with episodic migraine and chronic headache missed a mean of 2.81 and 3.85 days on social occasions, in the preceding 3 months (P < 0.001). CONCLUSIONS: Migraine in Kuwait is highly prevalent and it has a significant impact on activity of daily living, schooling/ employment and social occasions of patients. Accurate diagnosis, effective abortive and preventive treatments of migraine are paramount to improve quality of life and as well as cost saving.

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.

Spinal segmental myoclonus as an unusual presentation of multiple sclerosis.

BACKGROUND: Unusual presentations of multiple sclerosis (MS) at onset may post a diagnostic dilemma to the treating neurologists. Spinal myoclonus is rare in MS and may lead to perform extensive investigations to rule out other etiologies affecting the spinal cord. CASE PRESENTATION: We described a 31-year-old male who presented with involuntary brief jerky movements of the left shoulder and arm with significant wasting of shoulder muscles. In retrospect, the patient had a progressive right leg weakness one year prior to his presentation. Needle electromyography confirmed the presence of rhythmic irregular burst discharges in motor units of muscles expanding from the third to the sixth cervical region with normal nerve conduction parameters. There was no evidence of cortically generated myoclonic jerks using time-locked electroencephalogram. Magnetic Resonance Imaging of the brain and cervical cord along with the presence of oligoclonal bands in cerebral spinal fluid confirmed the diagnosis of MS. Based on the history and progressive clinical features, a diagnosis of primary progressive MS was established. CONCLUSION: Spinal myoclonus can be the presenting manifestation of MS in association with demyelinating plaques in the root exit zones of the spinal cord. Spinal myoclonus may pose a diagnostic challenge when it presented at the disease onset and especially in patients with progressive course at onset. Our patient represents the first reported primary progressive MS case in the literature with spinal myoclonus presentation.

Skeletal muscle dysfunction in idiopathic pulmonary arterial hypertension.

Despite improvements in survival with disease-targeted therapies, the majority of patients with pulmonary arterial hypertension (PAH) have persistent exercise intolerance that results from impaired cardiac function and skeletal muscle dysfunction. Our intent was to understand the molecular mechanisms mediating skeletal muscle dysfunction in PAH. A total of 12 patients with PAH and 10 matched control subjects were assessed. Patients with PAH demonstrated diminished exercise capacity (lower oxygen uptake max, lower anaerobic threshold and higher minute ventilation/CO2) compared with control subjects. Quadriceps muscle cross-sectional area was significantly smaller in patients with PAH. The vastus lateralis muscle was biopsied to enable muscle fiber morphometric assessment and to determine expression levels/activation of proteins regulating (1) muscle mass, (2) mitochondria biogenesis and shaping machinery, and (3) excitation-contraction coupling. Patients with PAH demonstrated a decreased type I/type II muscle fiber ratio, with a smaller cross-sectional area in the type I fibers. Diminished AKT and p70S6 kinase phosphorylation, with increased atrogin-1 and muscle RING-finger protein-1 transcript levels, were evident in the PAH muscle, suggesting engagement of cellular signaling networks stimulating ubiquitin-proteasome-mediated proteolysis of muscle, with concurrent depression of networks mediating muscle hypertrophy. Although there were no differences in expression/activation of proteins associated with mitochondrial biogenesis or fission (MTCO2 [cytochrome C oxidase subunit II]/succinate dehydrogenase flavoprotein subunit A, mitochondrial transcription factor A, nuclear respiratory factor-1/dynamin-related protein 1 phosphorylation), protein levels of a positive regulator of mitochondrial fusion, Mitofusin2, were significantly lower in patients with PAH. Patients with PAH demonstrated increased phosphorylation of ryanodine receptor 1 receptors, suggesting that altered sarcoplasmic reticulum Ca(++) sequestration may impair excitation-contraction coupling in the PAH muscle. These data suggest that muscle dysfunction in PAH results from a combination of muscle atrophy and intrinsically impaired contractility.

Migraine among medical students in Kuwait University.

BACKGROUND: Medical students routinely have triggers, notably stress and irregular sleep, which are typically associated with migraine. We hypothesized that they may be at higher risk to manifest migraine. We aimed to determine the prevalence of migraine among medical students in Kuwait University. METHODS: This is cross-sectional, questionnaire-based study. Participants who had two or more headaches in the last 3 months were subjected to two preliminary questions and participants with at least one positive response were asked to perform the validated Identification of Migraine (ID Migraine™) test. Frequency of headache per month and its severity were also reported. RESULTS: Migraine headache was suggested in 27.9% subjects based on ID-Migraine™. Migraine prevalence (35.5% and 44%, versus 31.1%, 25%, 21.1%, 14.8%, 26.5%, p < 0.000), frequency (5.55 + 1.34 and 7.23 + 1.27, versus 3.77 ± 0.99, 2.88 ± 0.85, 3.07 ± 0.96, 2.75 ± 0.75, 4.06 ± 1.66, p < 0.000); and severity of headache (59.1% and 68.2%, versus 28.3%,8.3%, 6.7%,16.7%, p < 0.000; were significantly increased among students in the last 2 years compared to first five years of their study. Stress 43 (24.9%), irregular sleep 36 (20.8%), and substantial reading tasks 32 (18.5%), were the most common triggering factors cited by the students. CONCLUSION: The prevalence of migraine is higher among medical students in Kuwait University compared to other published studies. The migraine prevalence, frequency and headache severity, all increased in the final two years of education.

Substantial and comparable suppression of disease activity following early initiation of cladribine tablets, ocrelizumab or alemtuzumab as first pharmacologic treatment for relapsing multiple sclerosis: A real world study.

BACKGROUND: We describe the efficacy and safety of recent high efficacy disease DMTs in DMT-naive patients with highly active RMS. METHODS: This was a retrospective, cross sectional study from the Kuwait national MS registry. Patients with RMS who received alemtuzumab, cladribine tablets or ocrelizumab as their first DMT for RMS, with ≥2 year of follow up were included. The primary endpoint was the change in relapse rate from treatment initiation to 1 year; changes in disability (Expanded Disability Status Scale [EDSS]), radiologic activity, the proportion with no evidence of disease activity-3 (NEDA-3), and the frequency of adverse events were secondary endpoints. RESULTS: Among 123 RRMS patients, 59 received ocrelizumab, 32 received cladribine tablets and 32 received alemtuzumab. About two-thirds (65%) were women. Substantial and similar (p>0.05) reductions occurred at the end of follow-up in annual relapse rate (by 93.2% for ocrelizumab, 87.5% for cladribine tablets, and 90.6% for alemtuzumab). The proportion with new T2 of gadolinium-enhancing MRI lesions across the three groups was reduced from 85-100% to 7-13%. Rates of confirmed disability progression were low (ocrelizumab 6.9%, cladribine tablets 3.1%, alemtuzumab 0%; p=0.280); disability was reduced in 15%, 22% and 38%, respectively. NEDA-3 was observed in 89.8%, 87.5%, and 84.4, respectively (p=0.784). No new or unexpected safety issues occurred. CONCLUSION: Ocrelizumab, cladribine tablets and alemtuzumab reduced relapse rates and MRI activity, and prevented disease progression, when are initiated early in DMT-naive RMS patients. These data support the early use of high-efficacy DMTs for people with highly active RMS.