Nusinersen Treatment for Spinal Muscular Atrophy: Retrospective Multicenter Study of Pediatric and Adult Patients in Kuwait.

Spinal muscular atrophy is a neuromuscular genetic condition associated with progressive muscle weakness and atrophy. Nusinersen is an antisense oligonucleotide therapy approved for the treatment of 5q spinal muscular atrophy in pediatric and adult patients. The objective of this clinical case series is to describe the efficacy and safety of nusinersen in treating spinal muscular atrophy in 20 pediatric and 18 adult patients across six treatment centers in Kuwait. Functional motor assessments (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders, Hammersmith Functional Motor Scale Expanded, and Revised Upper Limb Module) were used to assess changes in motor function following nusinersen treatment. The safety assessment involved clinical monitoring of adverse events. The results demonstrate clinically meaningful or considerable improvement in motor performance for nearly all patients, lasting over 4 years in some cases. A total of 70% of patients in the pediatric cohort and 72% of patients in the adult cohort achieved a clinically meaningful improvement in motor function following nusinersen treatment. Additionally, nusinersen was well-tolerated in both cohorts. These findings add to the growing body of evidence relating to the clinical efficacy and safety of nusinersen.

Efficacy and safety of stem cell transplantation for multiple sclerosis: a systematic review and meta-analysis of randomized controlled trials.

Multiple sclerosis (MS) is a common autoimmune neurological disease affecting patients' motor, sensory, and visual performance. Stem Cell Transplantation (SCT) is a medical intervention where a patient is infused with healthy stem cells with the purpose of resetting their immune system. SCT shows remyelinating and immunomodulatory functions in MS patients, representing a potential therapeutic option. We conducted this systematic review and meta-analysis that included randomized control trials (RCTs) of SCT in MS patients to investigate its clinical efficacy and safety, excluding observational and non-English studies. After systematically searching PubMed, Web of Science, Scopus, and Cochrane Library until January 7, 2024, nine RCTs, including 422 patients, were eligible. We assessed the risk of bias (ROB) in these RCTs using Cochrane ROB Tool 1. Data were synthesized using Review Manager version 5.4 and OpenMeta Analyst software. We also conducted subgroup and sensitivity analyses. SCT significantly improved patients expanded disability status scale after 2 months (N = 39, MD = - 0.57, 95% CI [- 1.08, - 0.06], p = 0.03). SCT also reduced brain lesion volume (N = 136, MD = - 7.05, 95% CI [- 10.69, - 3.4], p = 0.0002). The effect on EDSS at 6 and 12 months, timed 25-foot walk (T25-FW), and brain lesions number was nonsignificant. Significant adverse events (AEs) included local reactions at MSCs infusion site (N = 25, RR = 2.55, 95% CI [1.08, 6.03], p = 0.034) and hematological disorders in patients received immunosuppression and autologous hematopoietic SCT (AHSCT) (N = 16, RR = 2.33, 95% CI [1.23, 4.39], p = 0.009). SCT can improve the disability of MS patients and reduce their brain lesion volume. The transplantation was generally safe and tolerated, with no mortality or significant serious AEs, except for infusion site reactions after mesenchymal SCT and hematological AEs after AHSCT. However, generalizing our results is limited by the sparse number of RCTs conducted on AHSCT. Our protocol was registered on PROSPERO with a registration number: CRD42022324141.

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.

Efficacy of gelatin sponge in the prevention of post-surgical intra-abdominal adhesion in a rat model.

Although different products have been developed to prevent post-surgical adhesion, their efficacy remains unsatisfactory. This study aimed to evaluate the efficacy of the gelatin sponge in the prevention of post-surgical intra-abdominal adhesions in a rat model. Rats were randomly divided into sham, adhesion, and gelatin groups. All rats, except the sham group, underwent cecal abrasion to establish an adhesion model. After celiotomy, a sterile gelatin sponge was applied intra-abdominal on the abraded cecum in the gelatin group. Rats were sacrificed on day 14 post-surgery and intra-abdominal adhesions were evaluated and scored. Adhesion tissues were evaluated by histological, histochemical, and immunohistochemical analysis. Intra-abdominal adhesions were recorded in all rats of the adhesion group. Intra-abdominal application of gelatin sponge significantly (P < 0.001) reduced intra-abdominal adhesions by 91% in the gelatin group relative to the adhesion group. The histological analysis revealed a marked decrease (P < 0.001) in the inflammatory score and neovascularization in the gelatin group. The histochemical analysis found that gelatin sponge administration reduced adhesion formation and thickness of adhesion tissue. Moreover, gelatin sponge significantly (P < 0.0001) increased MMP-9 expression and decreased macrophage marker expression in adhesive tissue. This study revealed that the application of gelatin sponge markedly reduced the post-surgical intra-abdominal adhesions and suggests new guidance for using gelatin sponge as an anti-adhesive substance in clinical practice.

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 Efficacy and Safety of Pridopidine on Treatment of Patients with Huntington's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Pridopidine is a novel drug that helps stabilize psychomotor function in patients with Huntington's disease (HD) by activating the cortical glutamate pathway. It promises to achieve the unmet needs of current therapies of HD without worsening other symptoms. OBJECTIVE: To review the literature discussing the efficacy of pridopidine in alleviating motor symptoms and its safety in patients with HD. METHODS: We searched Scopus, Web of Science, the Cochrane Library, Wiley, and PubMed for randomized controlled trials (RCTs) of pridopidine on HD. Data from eligible studies were extracted and pooled as mean differences for efficacy and risk ratios (RRs) for safety using RevMan software version 5.3. RESULTS: A total of 4 relevant RCTs with 1130 patients were selected (816 in the pridopidine group and 314 in the placebo group). The pooled effect size favored pridopidine over placebo insignificantly in the Unified Huntington's Disease Rating Scale Total Motor Score (mean difference [MD], -0.93; 95% confidence interval [CI], -2.01 to 0.14; P = 0.09), whereas the effect size of 3 studies significantly favored pridopidine over placebo in the Unified Huntington's Disease Rating Scale Modified Motor Score (MD, -0.81; 95% CI, -1.48 to -0.13; P = 0.02). Pridopidine generally was well tolerated. None of the adverse effects were considerably higher in the case of pridopidine compared with placebo in overall adverse events (RR, 1.03; 95% CI, 0.94-1.13; P = 0.49) and serious adverse events (RR, 1.62; 95% CI, 0.88-2.99; P = 0.12). CONCLUSION: The effects of pridopidine on motor functions (especially voluntary movements) in patients with HD are encouraging and provide a good safety profile that motivates further clinical trials on patients to confirm its effectiveness and safety.

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.

Coronavirus disease 2019 infection and pituitary apoplexy: A causal relation or just a coincidence? A case report and review of the literature.

BACKGROUND: Pituitary tumor apoplexy (PA) is an emergency condition caused by hemorrhage or infarction of the preexisting adenoma. Many factors are currently well-known to predispose to PA. However, during the period of coronavirus disease 2019 (COVID-19) pandemic, case reports of PA associated with COVID-19 infection have been sequentially published. To the best of our knowledge, four cases have been reported so far in the English literature. We herein report the fifth case of this association and review the pertinent literature. CASE DESCRIPTION: A 55-year-old male patient with confirmed COVID-19 infection presented by progressive decrease in visual acuity and oculomotor nerve palsy. His medical history is notable for diabetes mellitus, hypertension, and pituitary macroadenoma resection 11 years ago. He was on hormonal replacement therapy for panhypopituitarism that complicated the surgery. Previous magnetic resonance (MR) imaging studies were consistent with enlarging residual pituitary adenoma. During the current hospitalization, computed tomography revealed hyperdensity of the sellar and suprasellar areas. MR imaging revealed PA in a recurrent large adenoma. Endoscopic endonasal transsphenoidal resection was uneventfully undertaken with near total excision of the adenoma and partial improvement of visual loss and oculomotor palsy. Histopathological examination demonstrated classic features of PA. However, his chest condition progressed and he had to be transferred to COVID-19 intensive care unit in the referring hospital where he was intubated and put on mechanical ventilation. One week later, the patient unfortunately passed away due to complications of severe COVID-19 pneumonia. CONCLUSION: We report the fifth case of PA associated with COVID-19 infection. Based on our patient's clinical findings, review of the other reported cases, as well as the available literature, we put forth a multitude of pathophysiological mechanisms induced by COVID-19 that can possibly lead to the development of PA. In our opinion, the association between both conditions is not just a mere coincidence. Although the histopathological features of PA associated with COVID-19 are similar to PA induced by other etiologies, future research may disclose unique pathological fingerprints of COVID-19 virus that explains its capability of inducing PA.

Surgical Management for Dystonia: Efficacy of Deep Brain Stimulation in the Long Term.

INTRODUCTION: Dystonia is a movement disorder substantially affecting the quality of life. Botulinum Neurotoxin (BoNT) is used intramuscularly as a treatment for dystonia; however, not all dystonia patients respond to this treatment. Deep brain stimulation (DBS) is an established treatment for Parkinson's disease (PD) and essential tremor, but it can help in dystonia as well. OBJECTIVES: We studied a total of 67 dystonia patients who were treated with DBS over a period of 7 years to find out the long-term efficacy of DBS in those patients. First, we calculated patient improvement in post-surgery follow-up programs using the Global Dystonia Severity scale (GDS) and Burke-Fahn-Marsden dystonia rating scale (BFMDRS). Secondly, we analyzed the scales scores to see if there was any statistical significance. METHODS: In our study we analyzed patients with ages from 38 to 78 years with dystonia who underwent DBS surgery between January 2014 and December 2020 in four different centers (India, Kuwait, Egypt, and Turkey). The motor response to DBS surgery was retrospectively measured for each patient during every follow-up visit using the GDS and the BFMDRS scales. RESULTS: Five to 7 years post-DBS, the mean reduction in the GDS score was 30 ± 1.0 and for the BFMDRS score 26 ± 1.0. The longitudinal change in scores at 12 and 24 months post-op was also significant with mean reductions in GDS and BFMDRS scores of 68 ± 1.0 and 56 ± 1.0, respectively. The p-values were <0.05 for our post-DBS dystonia patients. CONCLUSIONS: This study illustrates DBS is an established, effective treatment option for patients with different dystonias, such as generalized, cervical, and various brain pathology-induced dystonias. Although symptoms are not completely eliminated, continuous improvements are noticed throughout the post-stimulation time frame.

Unexplained worsening of parkinsonian symptoms in a patient with advanced Parkinson's disease as the sole initial presentation of COVID-19 infection: a case report.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative condition that has been reported following viral infections in rare occasions. Several neurological complications have emerged in association with coronavirus disease 2019 (COVID-19), since its declaration as a pandemic. Herein, we present a novel case of unexplained worsening of PD as the sole initial presentation of COVID-19, in the absence of fever or respiratory symptoms. CASE PRESENTATION: A 56-year-old male with advanced PD presented with severe rigidity, dystonic posturing of both feet, and confusion of 4 days duration. His condition progressed to an akinetic-rigid state and confusion during the following week, and a routine nasopharyngeal swab tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the 9th day of onset. He developed fever and dyspnea later and was intubated on the 10th day. CONCLUSION: To our knowledge, worsening of PD symptoms as the sole initial manifestation of SARS-CoV-2 infection, in the absence of other cardinal features of COVID-19, has not been reported in the literature. We suggest testing for COVID-19 infection in patients with PD, especially advanced cases, who present with unexplained worsening of symptoms, even in the absence of COVID-19 cardinal features.

Association of COVID-19 Pandemic and Rate of Cognitive Decline in Patients with Dementia and Mild Cognitive Impairment: A Cross-sectional Study.

Introduction: Since the declaration of coronavirus disease 2019 (COVID-19) as a pandemic, patients with dementia, were specifically vulnerable to the negative impact of the outbreak. Objective: To examine the association between lockdown amid COVID-19 pandemic and the rate of cognitive decline among patients with dementia and mild cognitive impairment (MCI). Methods: We conducted a cross-sectional observational study on patients with dementia and MCI who attended the outpatient clinic at Ibn Sina Hospital, the main tertiary neurology center in Kuwait, during the month of September 2020. The rate of cognitive decline, estimated by MMSE scores, was compared between the period prior to, and during lockdown. Results: We evaluated 36 consecutive patients with cognitive impairment (23 females [63.9%], mean age 71 ± 10.8 years, mean disease duration 34.6 ± 29 months). Eleven patients (30.6%) progressed to a more severe stage during the study period; 1 MCI (2.8%) converted to mild dementia, 6 (16.6%) mild to moderate, and 4 (11.1%) moderate to severe dementia. Monthly decline of MMSE scores before lockdown was 0.2 ± 0.1 points, while it was 0.53 ± 0.3 points during lockdown, which was statistically significant (p = .001). The most affected cognitive domain was the memory with a mean decline of 1.5 ± 0.8 points. Conclusions: This study provides "real-world" data suggesting rapid cognitive decline in patients with dementia during the lockdown period. Healthcare systems should pay more attention to this vulnerable group, to help them maintain their mental, physical and social well-being during this crisis.

Visual versus semiquantitative analysis of 18F- fluorodeoxyglucose-positron emission tomography brain images in patients with dementia.

Various studies have reported to the superiority of semiquantitative (SQ) analysis over visual analysis in detecting metabolic changes in the brain. In this study, we aimed to determine the limitations of SQ analysis programs and the current status of 18F- fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan in dementia. 18F- FDG-PET/computed tomography (CT) brain images of 39 patients with a history of dementia were analyzed both visually and semiquantitatively. Using the visually markedly abnormal 18F- FDG-PET images as standard, we wanted to test the accuracy of two commercially available SQ analysis programs. SQ analysis results were classified as matching, partially matching and nonmatching with visually markedly abnormal studies. On visual analysis, 18F- FDG-PET showed marked regional hypometabolism in 19 patients, mild abnormalities in 8 and was normal in 12 patients. SQ analysis-1 results matched with visual analysis in 8 patients (42.1%) and partially matched in 11. SQ analysis-2 findings matched with visual analysis in 11 patients (57.8%) and partially matched in 7 and did not match in 1. Marked regional hypometabolism was either on the left side of the brain or was more significant on the left than the right in 63% of patients. Preservation of metabolism in sensorimotor cortex was seen in various dementia subtypes. Reviewing images in color scale and maximum intensity projection (MIP) image was helpful in demonstrating and displaying regional abnormalities, respectively. SQ analysis provides less accurate results as compared to visual analysis by experts. Due to suboptimal image registration and selection of brain areas, SQ analysis provides inaccurate results, particularly in small areas and areas in close proximity. Image registration and selection of areas with SQ programs should be checked carefully before reporting the results.

MED27 Variants Cause Developmental Delay, Dystonia, and Cerebellar Hypoplasia.

The Mediator multiprotein complex functions as a regulator of RNA polymerase II-catalyzed gene transcription. In this study, exome sequencing detected biallelic putative disease-causing variants in MED27, encoding Mediator complex subunit 27, in 16 patients from 11 families with a novel neurodevelopmental syndrome. Patient phenotypes are highly homogeneous, including global developmental delay, intellectual disability, axial hypotonia with distal spasticity, dystonic movements, and cerebellar hypoplasia. Seizures and cataracts were noted in severely affected individuals. Identification of multiple patients with biallelic MED27 variants supports the critical role of MED27 in normal human neural development, particularly for the cerebellum. ANN NEUROL 2021;89:828-833.

Evaluation of clinical outcome and safety profile of edaravone in treatment of amyotrophic lateral sclerosis: a 72-week single-center experience.

Edaravone is a free radical scavenger that has been recently approved for treatment of Amyotrophic lateral sclerosis (ALS) to delay functional decline. We aim to evaluate edaravone efficacy and safety in ALS patients in the main neurology tertiary center in Kuwait over 72-week period. We conducted a prospective observational cohort study in the main tertiary hospital over 72-week period from July 2018 until January 2020. Patients were assessed at baseline, 24, 48 and 72 weeks of therapy using ALSFRS-R score, MRC sum score, FVC value, among other parameters. Seventeen consecutive patients were evaluated. All patients were assessed at baseline, 24 and 48 weeks, while 9 patients (52.9%) were further assessed at 72 weeks. There was a statistically significant decline of ALSFRS-R at 72 weeks, MRC sum score at 48 and 72 weeks, while the decline in FVC was not statistically significant. Glycosuria was found in only one patient. Our study showed significant functional decline after 1 year of edaravone therapy with preserved respiratory function. The drug had a high level of dissatisfaction among our cohort despite having a high safety profile.

Demographics, Clinical Characteristics, and Management of Idiopathic Intracranial Hypertension in Kuwait: A Single-Center Experience.

Background: Idiopathic intracranial hypertension (IIH) affects predominantly obese females during their reproductive age period. The demographics of this condition has not been studied in Kuwait before. Objectives: To determine the demographics, clinical features, risk factors, and treatment modalities of IIH in the main neurology tertiary referral hospital in Kuwait and to compare our data with literature. Methods: A retrospective study was conducted to identify cases of IIH seen between January 1, 2018, and December 31, 2018. Patients were diagnosed in and referred from the neurology and neuro-ophthalmology clinics. Results: Our cohort consisted of 139 patients. We estimated a crude annual incidence rate of IIH of 3.28 per 100,000 population. Female-to-male ratio was 9.6:1. Mean age was 32.1 ± 10.8 years. Mean age of males was 31.46 ± 12.63 and that of females was 32.11 ± 10.67. The median of the duration from the first symptoms till diagnosis was 6 weeks (2-10 weeks). Headache was the most common symptom in 134 (96.4%) patients, followed by visual disturbances in 85 (61.2%) patients, transient visual obscurations (TVOs) in 84 (60.4%) patients, pulsatile tinnitus in 72 (51.8%) patients, diplopia in 22 (15.8%) patients, other symptoms (e.g., nausea, vomiting, radicular neck, and back pain) in 19 (13.7%) patients, and 1 (0.7%) patient had facial weakness. High body mass index (BMI) was seen in 89.9% of patients, either overweight or obese, and it was the most common risk factors in both males (46.2%) and females (61.1%). Anemia was found in 38.1%; 21.6% of patients used OCPs and 7.9% used vitamin A. Bilateral transverse sinus stenosis (BTSS) was detected in 47 (33.8%) patients. Only 2 (1.4%) patients developed "fulminant IIH" characterized by rapidly progressive disease. All the patients received medical treatment and only 12 (8.6%) needed surgical management. Conclusion: Incidence of IIH in Kuwait is similar to other regional studies but higher than Western studies. Demographics and clinical features of IIH in our study are comparable to international and regional figures. Most of our patients had a benign course. IIH is more prevalent in females and strongly associated with obesity.