Real-world experiences of migraine patients on Erenumab: a Kuwait single center cohort.

BACKGROUND: Migraine is a prevalent headache disorder with a significant impact on the quality of life. This study aims to investigate the effectiveness and safety of erenumab, mAb targeting the CGRP receptor, in treating chronic (CM) and episodic (EM) migraine in clinical practice Kuwait, providing region-specific insights to treatment options. METHOD: This was a prospective observational cohort study of patients diagnosed with EM or CM treated with erenumab. The primary outcome of the study was to assess the proportion of patients achieving ≥ 50% reduction in monthly mean migraine days, and several changes including the mean number of monthly migraine days, the frequency of analgesic use, attack severity, AEs, and QoL. RESULTS: The study included 151 patients with a mean age of 44.0±11.4 years, and 81.9% female. The primary outcome was achieved in 74.2% of patients, with a significant (p < 0.001) reduction in headache frequency, pain severity, analgesic use, and improvement in QoL. Age and duration of migraine were significant predictors of achieving a ≥ 50% reduction in headache frequency after therapy (OR = 0.955; p = 0.009) and (OR = 0.965; p = 0.025), respectively. Treatment compliance was observed in 76.2% of patients, and 24.5% discontinued treatment. Constipation was the most commonly reported AEs (6.0%), and conservative management was the most common approach to managing AEs. CONCLUSION: Erenumab was effective in reducing the frequency and severity of migraine attacks and improving QoL, and safe with manageable AEs in a real-world setting in Kuwait. Further research is needed to better understand erenumab's effectiveness and safety in different populations and settings, as well as to compare it with other migraine prophylactic treatments.

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.

New-Onset Focal Task Specific Oromandibular Dystonia in Association with Quran Recitation: A Case Series.

Background: Focal task-specific dystonia is a form of isolated focal dystonia that occurs during the performance of a specific skilled motor task. The occurrence of oromandibular dystonia (OMD) specifically in association with the recitation of Quranic verses have been rarely reported in the literature, in non-native Arabic-speaking patients. This case series describe a rare type of focal task-specific dystonia that occurs exclusively by reciting Quran in native Arabic-speaking patients, which has never been reported, to the best of our knowledge. Methods: In this case series, we identified five patients with new-onset OMD that was exclusively induced by reciting Quran. Cases were evaluated in our Movement Disorders outpatient clinic at Ibn Sina hospital; the main tertiary neurology center in Kuwait, between 2015 and 2023. Results: Five cases (3 males, 2 females) were identified in this study. Mean age of onset of the symptoms was 52.3 ± 4.1 years, while the median duration of the symptoms prior to diagnosis was 3 years. All patients were native Arab-speaking, with no previous history of other types of dystonia. No identifiable risk factors could be obtained including exposure to dopamine blocking agents or antipsychotics, or history of oral or dental surgery. Patients underwent a full clinical, laboratory, and radiological evaluation. All patients had OMD dystonia in varying forms and severity, while two patients had additional spasmodic dysphonia/ blepharospasm on progressive recitation. Most patients had minimal improvement with combination of oral medications and speech therapy. Four patients received botulinum toxin injections with better results. Discussion: The mental and physical stress in attempting to recite the Quranic verses could have contributed to the development of OMD. Moreover, the increased demand on the muscles of the jaw, lips, and tongue during recitation can trigger the dystonic symptoms. Highlights: OMD exclusively during Quran recitation is a rare phenomenon, and expands the spectrum of task-specific focal dystonia described in the literature. It was found to be distressing to the patients and a challenge to treat. Prompt recognition could minimize unnecessary testing and procedures, and facilitate earlier treatment.

Unmet Needs of Patients Living with Migraine in the Gulf Cooperation Council (GCC) Countries.

The scale of migraine and its impact on the lives of patients in the Gulf Cooperation Council (GCC) countries may be underestimated by healthcare professionals and the public and unmet needs in the provision of migraine medical care may exist. This article reports the key outcomes from a meeting of migraine specialists and their patients organised by the Emirates Neurology Society to learn more about the patient diagnosis and treatment journey and the extent to which migraine affects daily life. Patient stories indicate that the burden of migraine is underestimated, migraine is not generally recognised as a disease, delayed and incorrect diagnoses are common, and that achieving symptom control is often more a question of good luck rather than good management. Disease awareness campaigns are recommended to elevate societal understanding of migraine and reduce stigma toward patients affected by migraine. Recommendations for an improved healthcare system experience for patients affected by migraine include education initiatives targeting patients and physicians as well as initiatives to address gaps in the diagnosis and treatment of migraine.

Population Pharmacokinetics of Topiramate in Patients with Epilepsy Using Nonparametric Modeling.

BACKGROUND: Topiramate (TPM) is used for the treatment of various epileptic seizures and the prevention of migraine. This study aimed to develop a population pharmacokinetic model and identify covariates that influence TPM behavior in patients with epilepsy in Kuwait. METHODS: Data were collected retrospectively from 108 patients (2 years old and above) with epilepsy who were treated with oral TPM and 174 TPM blood samples from 3 hospitals in Kuwait from 2009 to 2016. Data were randomly divided into 2 groups for model development and validation. The population pharmacokinetic model was built using the nonparametric modeling algorithm (Pmetrics). The model was evaluated internally through the visual predictive check method and externally using a new data set. RESULTS: A 1-compartment model with first-order elimination fitted the data well. Covariates showing a significant effect on the elimination rate constant were renal function and coadministration of carbamazepine (CBZ). The mean estimated clearance was 2.11 L/h; this was 50% higher for patients coadministered with CBZ. Age and sex were essential covariates for the volume of distribution (V). The visual predictive check of the final model could predict the measured concentrations. External validation further confirmed the favorable predictive performance of the model with low bias and imprecision for predicting the concentration in a particular population. CONCLUSIONS: TPM elimination was increased with CBZ coadministration and was affected by renal function. Meanwhile, age and sex were the main predictors for V. The predictive performance of the final model proved to be valid internally and externally.

Real world study of ocrelizumab in multiple sclerosis: Kuwait experience.

BACKGROUND: Ocrelizumab is a humanized anti-CD20 antibody that has been approved for the treatment of patients with multiple sclerosis (MS). Real-world data in the Middle East is very limited. OBJECTIVES: To describe the effectiveness and safety of ocrelizumab treatment in MS patients in a real clinical setting. METHODS: This is an observational, registry-based study. MS patients who were treated with ocrelizumab and completed at least one-year follow-up post-treatment were included. Baseline clinical and radiological characteristics were collected before ocrelizumab initiation. The relapse rate, disability measures, magnetic resonance image (MRI) activity (new T2 lesions and/or GD+ enhancing T1 lesions), and adverse events (AE) at the last follow-up visits were assessed. RESULTS: Data from 447 patients were analyzed, of which 260 (58.2%) were females. The mean age and mean disease duration were 37.39 ± 11.61 and 9.38 ± 7.57 years respectively. Most of the cohort was of a relapsing form (74.3%; n = 332), whereas active secondary and primary progressive forms represented 15.4% (n = 69) and 10.3% (n = 46) respectively. In the relapsing cohort, Ocrelizumab was prescribed in 162 (48.8%) patients due to highly active disease, and in 99 (29.8%) patients due to disease breakthrough while on prior therapies. In the last follow-up visits, most of the relapsing cohort was relapse-free (95.8% vs. 27.4%; p <0.001), had no evidence of MRI activity (3.6% vs. 67.5%; p <0.001) while EDSS score was stable (1.80+1.22 vs. 1.87+1.16; p < 0.104) when compared to baseline. NEDA-3 was achieved in 302 (91%) of RRMS patients. Confirmed disability progression was 27.5% and 23.9% in SPMS and PPMS respectively. Adverse events were observed in 139 (31.1%); infusion reactions and infections represented the most. CONCLUSION: This study showed that ocrelizumab is an effective and safe treatment for MS patients in a real clinical setting similar to what was observed in clinical trials.

Impact of the first Gulf war on multiple sclerosis risk in Kuwait: a quasi-experimental study.

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.

A prospective observational longitudinal study with a two-year follow-up of multiple sclerosis patients on Cladribine.

BACKGROUND: Cladribine was approved for the treatment of multiple sclerosis (MS). Real-world data is very limited. OBJECTIVES: To study the effectiveness and the safety of Cladribine treatment in only one group of MS patients after treatment with Cladribine for two years. METHODS: This observational, longitudinal prospective study. Eligible subjects were relapsing remitting MS patients who had at least two-year follow-up after Cladribine treatment. The primary endpoint was the proportion of relapse free patients. Secondary endpoints were ARR, change in EDSS scores, the proportion of patients with CDP, MRI activity, and NEDA-3 status, also the rate of occurrence of AEs. Patients were assessed for primary and secondary endpoints at the end of two years of follow-up. RESULTS: Of a total of seventy-two patients, 59 (81.9 %) were females, mean age of 36.32 + 10.06 years old, mean disease duration 7.21 + 6.19. Most patients (n = 32; 44.4 %) were naïve to any treatment. Forty patients (55.6 %) completed two courses of treatment. The primary endpoint showed that most of our cohort was relapse free (85 % versus 25 %; P < 0.001), Secondary endpoints showed that ARR was significantly reduced 0.15 + 0.36 versus 0.85 + 0.53; P < 0.01). Most of the cohort 90 % have no progression of disability. Few subjects had new T2 lesions (7.5 % versus 70.8 %; P < 0.001 and gadolinium enhancement 5 % versus 66.7 %; P < 0.001) in MRI compared to baseline. No evidence of disease activity 3 (NEDA-3) was achieved in 30 (75 %) patients. It was achieved in 87.5 % of naive patients versus 66.7 % in patients who received prior disease modification drugs before Cladribine initiation. Infections 6 (n = 6; 8.4 %) lymphocytopenia (n = 3; 4.2 %), and elevated liver enzymes (n = 1; 1.4 %) were reported. CONCLUSION: Cladribine treatment reduced significantly relapse rate and MRI activity. It was safe and tolerable. Early initiation of cladribine is associated with favorable outcomes.

Commentary: Consensus Guidelines on the Appropriate Use of Brand-Name and Generic Anti-Seizure Medication for the Management of Epilepsy in the Gulf Region.

INTRODUCTION: The clinical, social, and economic burden of epilepsy is undeniable. Local guidance on epilepsy management is limited and needed to address the both use of anti-seizure medication (ASM) and switching practices which influence clinical outcomes. AREAS COVERED: An expert panel composed of practicing neurologists and epileptologists from countries of the Gulf Cooperation Council (GCC) met in 2022 to discuss local challenges in the management of epilepsy and formulate recommendations for clinical practice. Published literature on the outcomes of ASM switching was reviewed along with clinical practice/gaps, international guidelines, and local treatment availabilities. EXPERT OPINION: Improper ASM use and inappropriate brand-name-to-generic or generic-to-generic switching can contribute to worsening clinical outcomes in epilepsy. ASMs should be used for the management of epilepsy based on patient clinical profile, underlying epilepsy syndrome, and drug availability to ensure optimal and sustainable treatment. Both first-generation and newer ASMs can be considered; appropriate use is recommended from the beginning of treatment. It is critical to avoid inappropriate ASM switching to avoid breakthrough seizures. All generic ASMs should fulfill strict regulatory requirements. If needed, ASM changes should always be approved by the treating physician. ASM switching (brand-name-to-generic, generic-to-generic, generic-to-brand-name) should be avoided in epilepsy patients who have achieved control but can be considered for those uncontrolled on current medication.

A real-life study of alemtuzumab in persons with multiple sclerosis: Kuwait's experience.

BACKGROUND: Alemtuzumab, a humanized anti-CD52 monoclonal antibody, has been approved as a treatment in persons with active relapsing-remitting multiple sclerosis (RRMS). Real-world data in middle east is very limited. We aimed to evaluate the effectiveness and safety of alemtuzumab in a real-world clinical setting. METHODS: This observational, registry based study assessed persons with multiple sclerosis (PwMS) who were treated with alemtuzumab and completed at least follow up one year after second course. Baseline clinical and radiological characteristics within one year prior to alemtuzumab initiation were collected. The relapse rate, disability measures, radiological activity and adverse events at last follow-up visits were assessed. RESULTS: Data of seventy-three persons with multiple sclerosis (MS) was analyzed, of which 53 (72.6%) were females. Mean age and mean disease duration were 34.25 ± 7.62 and 9.23 ± 6.20 years respectively. Alemtuzumab was started in 32 (43.8%) naïve patients due to highly active disease and in 25 (34.2%) (PwMS) who were on prior therapies and  in 16 (22%) patients due to adverse events on prior medications. Mean follow-up period was 4 ± 1.67 years. In the last follow-up visits, most of our cohort was relapse free (79.5% vs. 17.8%; p < 0.001) compared to baseline before alemtuzumab treatment while mean EDSS score was reduced (2.21 ± 2.15 vs. 2.41 ± 1.85; p < 0.059). The proportion of PwMS who had MRI activity (new T2/ Gd-enhancing) lesions were significantly reduced compared to baseline (15.1% vs. 82.2%; p < 0.001). NEDA-3 was achieved in 57.5% of (PwMS). NEDA-3 was significantly better in naïve patients (78% versus. 41.5%; p < 0.002) and in patients with disease duration < 5 years, (82.6% v 43.2%; p < 0.002). Several adverse events such as infusion reactions (75.3%), autoimmune thyroiditis (16.4%) and glomerulonephritis (2.7%) were reported. CONCLUSION: The effectiveness and safety profile of alemtuzumab in this cohort were consistent with data of clinical trials. Early initiation of Alemtuzumab is associated with favorable outcome.

Assessing the Usability of an Instagram Filter in Monitoring Essential Tremor: A Proof-of-Concept Study.

Background: Spiral drawing is an important test in monitoring essential tremor (ET). With the rise of telemedicine amid the coronavirus disease 2019 pandemic, a contactless tool for monitoring tremors was required. We aimed to assess the validity of a novel smartphone technology using a video-based social media platform for rapid and objective monitoring of ET. Methods: A prospective pilot study evaluated patients with ET in 2 clinic visits. Videos of tremors were recorded using a publicly available Instagram filter and were visually compared with spirals drawn by the patients. The level of agreement among the raters was evaluated. Results: A total of 12 patients with ET were recruited. A consensus between both raters was achieved for 11 patients (91.6%) for both spirals and videos with good interrater agreement (κ value, 0.755 ± 0.332). Conclusion: This novel method was found to be valid and easy to use in measuring ET in real-world settings. Further research in a larger cohort is needed to suggest its use as a home-based or clinic-based monitoring tool.

COVID-19 vaccination in people with multiple sclerosis, real-life experience.

BACKGROUND: Vaccination against the severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) virus is recommended in multiple sclerosis (MS) to reduce the risk of complications from Coronavirus disease 2019 (COVID-19) infection. These vaccines were not investigated in people with MS (PWMS). OBJECTIVE: This study aimed to report the short-term safety of the COVID-19 vaccines among PWMS. METHODS: Pfizer-BioNTech mRNA (BNT162b2) vaccine and Oxford-Astra Zenecaa chimpanzee adenovirus-vectored (ChAdOx1 nCoV-19) vaccine have been approved to be used in Kuwait since December 2021. PWMS registered in Kuwait national registry were contacted by phone, WhatsApp, or through face-to-face interviews and were invited to complete our questionnaire. Demographic, clinical data, symptoms following the vaccine, worsening of pre-existing MS symptoms, and occurrence of relapse were recorded. RESULTS: Of the 820 PWMS, 647 completed the questionnaire. Between January 2021 and 31 August 2021, 383 (59.28%) PWMS received at least one dose of the approved vaccinations versus 63.4% of the general population on the same date. Their mean age was 36.82 + 8.80, and most of them, 247 (64.3%), were females. A total of 356 vaccinated cohorts (92.6%) were treated with disease-modifying therapies. Adverse events were reported by 261 (68.15%) subjects. One case of COVID-19 infection was encountered after the first dose of the BNT162b2 vaccine. Twenty-one (5.48%) cases reported worsening of pre-existing MS symptoms after the vaccine. Five patients (1.31%) reported relapse after the COVID-19 vaccine. The most common adverse events of the COVID-19 vaccine were pain at the injection site, fatigue, low-grade fever, and body ache; and resolved within one week. There was no significant association between use of disease modifying therapy (DMT) and COVID-19 vaccine adverse events. CONCLUSION: BNT162b2 and ChAdOx1 nCoV-19 are safe for PWMS. No increased risk of relapse activity or worsening of pre-existing MS symptoms.

Post-dural puncture headache: a prospective study on incidence, risk factors, and clinical characterization of 285 consecutive procedures.

BACKGROUND: Lumbar puncture (LP) is a common and relatively safe neurological procedure. It can be complicated by post-dural puncture headache (PDPH) after both diagnostic and therapeutic procedures. The aim of this study is to identify the incidence, risk factors and clinical characterization of PDPH in the inpatient setting of the main tertiary neurology hospital in Kuwait. METHODS: We conducted a prospective observational cohort study that included patients who were admitted to neurology department at Ibn Sina hospital, Kuwait, from January 1, 2019 to December 31, 2020, on whom, LP was performed for diagnostic and/or therapeutic reasons. Multivariate logistic regression analysis was performed to evaluate the association between PDPH and different clinical parameters. RESULTS: A total of 285 patients were included; 225 females (78.9%), mean age of 32.9 ± 11.7 years. PDPH was reported by 84 patients (29.5%), with mean headache onset of 1.7 ± 0.8 days, and mean duration of 2.4 ± 2.1 days. The commonest headache type was dull aching in 49 patients (58.3%). Headache severity was mild to moderate in 64 patients (76.2%), with mean NRS of 4.1 ± 0.9. Most PDPH (99.3%) resolved with conservative medical management, with only 2 patients (0.7%) requiring epidural blood patch. In multivariate logistic regression model, there was a statistically significant correlation between development of PDPH and young age (p = 0.001), female gender (p = 0 .001), low BMI (p < 0 .001), pre-LP headache (p = 0.001), history of previous PDPH (p = 0.001), and number of LP attempts (p < 0.001). PDPH was statistically significantly higher in patients with optic neuritis (p = 0.009), and cerebral venous thrombosis (p = 0.007), and lower in patients with peripheral neuropathy (p = 0.011) and spinal muscular atrophy (p = 0.042). CONCLUSIONS: Findings from clinical practice in the main tertiary neurology hospital in Kuwait were in line with literature findings. Younger age, female gender, lower BMI, pre-procedural headache, previous history of PDPH, and number of LP attempts were found to be independent risk factors for developing PDPH. To our knowledge, this study represents the first comprehensive description of PDPH in a population from the Arabian Gulf Region.

A Multidisciplinary Perspective Addressing the Diagnostic Challenges of Late-Onset Pompe Disease in the Arabian Peninsula Region Developed From an Expert Group Meeting.

Pompe disease is a rare, metabolic, autosomal recessive disorder. Early diagnosis is critical for progressive Pompe disease as delays can significantly alter the clinical course of the disease. Diagnostic modalities, including dried blood spot testing and genetic testing, are available and are effective for diagnosing patients with late-onset Pompe disease (LOPD). However, clinicians face numerous clinical challenges related to the diagnosis of the disease. Two expert group committee meetings, involving 11 experts from the United Arab Emirates, Kuwait, the Kingdom of Saudi Arabia, and Oman, were convened in October 2019 and November 2020 respectively to develop a uniform diagnostic algorithm for the diagnosis of pediatric and adult LOPD in the Arabian Peninsula region. During the first meeting, the specialty-specific clinical presentation of LOPD was defined. During the second meeting, a diagnostic algorithm was developed after a thorough validation of clinical presentation or symptoms, which was performed with the aid of existing literature and expert judgement. A consensus was reached on the diagnostic algorithm for field specialists, such as neurologists, rheumatologists, general practitioners/internal medicine specialists, orthopedic specialists, and pulmonologists. This specialty-specific diagnostic referral algorithm for pediatric and adult LOPD will guide clinicians in the differential diagnosis of LOPD.

Late-Onset Pompe Disease Presenting with Isolated Tongue Involvement.

Late-onset Pompe disease (LOPD) is a rare autosomal recessive metabolic disorder that is caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), which is responsible for glycogen breakdown. It has a wide clinical spectrum but usually presents with limb girdle and respiratory muscles weakness. Tongue involvement has been rarely reported as the sole initial symptom of LOPD. A 65-year-old male presented with difficulty in speech and eating for a 4-year duration. He started to notice speech difficulty with production of particular speech sounds such as /l/, /d/, and /t/. Within 1 year, he developed difficulties in manipulating food with the tongue and oral residue in lateral sulci requiring digital manipulation, which was suggestive of tongue muscles weakness. Clinical examination showed tongue fasciculations, mild atrophic changes, and mild tongue weakness. Investigations showed mildly elevated creatine kinase levels, and electromyography of the tongue muscles revealed moderate spontaneous activity, denervation, chronic reinnervation with high-amplitude motor unit potentials, and positive sharp waves, with preserved recruitment. Given the diagnostic uncertainty, a screening for LOPD was performed using a dried blood spot, and GAA enzyme activity levels were found to be low; 1.06 µmol/L/h (reference values in adults: 2.10-29.00 µmol/L/h). Next-generation sequencing showed pathogenic variant in GAA gene, confirming the diagnosis of LOPD. This rare report of LOPD presenting with isolated tongue involvement adds to the expanding phenotypic variability of this disease. Tongue involvement is an important and early clinical sign of LOPD that needs careful evaluation and can aid in early diagnosis of this rare and treatable disease.

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.

Prevalence, severity, outcomes, and risk factors of COVID-19 in multiple sclerosis: An observational study in the Middle East.

A cross-sectional hospital records-based study was conducted to evaluate the prevalence, severity, outcomes, and identify demographic and clinical risk factors of coronavirus disease (COVID-19) in patients with MS. The study was conducted at multiple clinics in Oman, Kuwait, and the United Arab Emirates (UAE) from March 2020 to February 2021. The association of patient demographics, MS disease characteristics, and use of disease-modifying therapies with outcomes of COVID-19 illness were evaluated using odds ratio. A total of 134 MS patients with COVID-19 (prevalence rate of 3.7%) having a median age of 35.5 years were analyzed in the study. A majority (126 [94.0%]) of patients had mild COVID-19 illness and 122 (91.0%) made a full recovery, while 1 (0.7%) patient died. The median EDSS score reported in the study was low (1.0). Univariate regression analysis showed high EDSS scores, progressive MS disease, and use of anti-CD20 therapy such as rituximab as risk factors for moderate to severe COVID-19 requiring hospitalization. Comorbidities were associated with a higher risk of non-recovery from COVID-19 in both univariate and multivariate analyses. Age, sex, smoking history, and duration of MS did not show a significant association with severity or adverse COVID-19 disease outcome. Identification of risk factors can aid in improving the treatment and monitoring of pwMS and COVID-19.

Validation of the Arabic Version of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale.

BACKGROUND: The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) has become the gold standard for evaluating different domains in Parkinson's disease (PD), and it is commonly used in clinical practice, research, and clinical trials. OBJECTIVES: The objectives are to validate the Arabic-translated version of the MDS-UPDRS and to assess its factor structure compared with the English version. METHODS: The study was carried out in three phases: first, the English version of the MDS-UPDRS was translated into Arabic and subsequently back-translated into English by independent translation team; second, cognitive pretesting of selected items was performed; third, the Arabic version was tested in over 400 native Arabic-speaking PD patients. The psychometric properties of the translated version were analyzed using confirmatory factor analysis (CFA) as well as exploratory factor analysis (EFA). RESULTS: The factor structure of the Arabic version was consistent with that of the English version based on the high CFIs for all four parts of the MDS-UPDRS in the CFA (CFI ≥0.90), confirming its suitability for use in Arabic. CONCLUSIONS: The Arabic version of the MDS-UPDRS has good construct validity in Arabic-speaking patients with PD and has been thereby designated as an official MDS-UPDRS version. The data collection methodology among Arabic-speaking countries across two continents of Asia and Africa provides a roadmap for validating additional MDS rating scale initiatives and is strong evidence that underserved regions can be energically mobilized to promote efforts that apply to better clinical care, education, and research for PD. © 2022 International Parkinson and Movement Disorder Society.

The effects of coronavirus disease 2019 (COVID-19) pandemic on people with epilepsy (PwE): an online survey-based study.

During the unprecedented COVID-19 pandemic in 2020, the whole world faced an unusual health emergency. Medical care of chronic neurological diseases, such as Epilepsy, is being neglected. In this survey, we aimed to evaluate the impact of the COVID-19 pandemic on the care of people with Epilepsy (PwE) and to identify their risk factors for seizure worsening to direct better future medical care. We administered a web-based survey (submitted on August 5, 2020). It included socio-demographic, Epilepsy-related, and psychometric data (The Depression, Anxiety, and Stress Scale-21 Items(DASS21) and The Pittsburgh Sleep Quality Index (PSQI). Regression analysis identified predictors of seizure worsening. We collected responses from an online survey of PwE during the pandemic. Out of 151 responders, 71 patients complained of issues related to Epilepsy management and all of whom reached the treating physician and solved their problems. Sleep quality was compromised in 84 patients (55.6%). Two-thirds of the patients in our cohort (66.2%) reported depression, 72.2% reported anxiety, and 75.5% reported stress. Eight patients (5.3%) got COVID-19 infection, and only one patient suffered from mild worsening of the seizure. The main concerns were shortage of medications for 46 (30.5%) patients, getting Coronavirus infection for 67 (44.4%) patients, and seizure worsening for 32 (21.3%) patients. Thirty-five patients (23.2%) reported seizure worsening, which was best explained by retirement or jobless state, having moderate or severe stress, poor sleep quality, vagus nerve stimulation (VNS), fear of getting COVID-19 infection, fear of worsening of seizures, or shortage of medication. During the current COVID-19 pandemic, a significant percentage of PwE experienced worsening of their seizures. This unusual, challenging experience clarifies the urgent need to establish telemedicine services and home-based management of Epilepsy, including ambulatory EEG, home video, and medication delivery to patients' homes to provide continuous medical care.

Effect of Pre-exposure Use of Amantadine on COVID-19 Infection: A Hospital-Based Cohort Study in Patients With Parkinson's Disease or Multiple Sclerosis.

Background: Amantadine has been proposed to inhibit E-channel conductance in reconstituted lipid bilayers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to study whether patients on amantadine have altered risks of contracting COVID-19 infection. Methods: We conducted a hospital-based, observational, retrospective cohort study using data for patients on amantadine supported by data given by the patients through an online questionnaire. We included registered amantadine users in our hospital for 6 months or more on March 1, 2020, and non-amantadine users to act as the control group. We used forced entry, multiple logistic regression models to estimate adjusted ORs for amantadine adjusting for the confounders. Findings: Between September 1, 2019, and March 1, 2020, 212 patients with Parkinson's disease (PD) or multiple sclerosis (MS) received greater than one equal to two prescriptions of amantadine. We selected a random sample of diagnoses which matched 424 patients of non-amantadine users (1:2) as a control group (424 patients). Between March 1, 2020, and March 1, 2021, 256 patients responded to our online questionnaire, 87 patients were on amantadine (group I), and 169 patients were not (control group, group II). COVID-19 disease infection proved to be 5.7 and 11.8% in group I and II patients, respectively. Increased odds of COVID-19 in multivariable-adjusted models were associated with old age and history of contact with COVID cases. Amantadine was associated with a significantly reduced risk of COVID-19 disease infection (adjusted OR 0.256, 95% CI 0.074-0.888). Interpretation: Amantadine is associated with a reduced risk of COVID-19 infection after adjusting for a broad range of variables. History of contact with COVID cases and old age are risk factors for COVID-19 infection. Therefore, we recommended randomized clinical trials investigating amantadine use for the prevention of COVID-19.