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.

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.

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.

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.

Physicians' attitude towards webinars and online education amid COVID-19 pandemic: When less is more.

BACKGROUND: Since the declaration of COVID-19 as a pandemic, all scientific medical activities were shifted to an online format, in the form of webinars, to maintain continuing medical education (CME). We aimed to assess physicians' attitude among different medical specialties towards this sudden and unexpected shift of traditional face-to-face meetings into webinars, and to suggest future recommendations. METHODS: We conducted a cross-sectional, internet-based survey study using a 25-item questionnaire, from November 1 and November 15, 2020. The survey was created and distributed to physicians from different medical and surgical specialties and from different countries via several social media platforms, using a snowball technique. RESULTS: A total of 326 physicians responded; 165 (50.6%) were females, mean age of responders was 38.7 ± 7.5 years. The majority of responses (93.2%) came from Arab countries. Of them, 195 (59.8%) reported attending more webinars compared to the same period last year, with average of 3 per month. As regard to the general impression; 244 (74.8%) were "strongly satisfied" or "satisfied", with the most satisfaction for "training courses: by 268 (82.2%), and "International conferences" by 218 (66.9%). However, 246 respondents (75.5%) felt overwhelmed with the number and frequency of webinars during the pandemic, 171 (52.5%) reported attending less than 25% of webinars they are invited to, 205 (62.8%) disagreed that webinars can replace in-person meetings after the pandemic, and 239 (73.3%) agreed that online meetings need proper regulations. CONCLUSIONS: Webinars comprised a major avenue for education during COVID-19 pandemic, with initial general satisfaction among physicians. However, this paradigm shift was sudden and lacked proper regulations. Despite initial satisfaction, the majority of physicians felt overwhelmed with the number and frequency of webinars. Physicians' satisfaction is crucial in planning future educational activities, and considering that this current crisis will most likely have long lasting effects, webinars should be viewed as complementing traditional in-person methods, rather than replacement. In this study, we are suggesting recommendations to help future regulation of this change.

Seronegative limbic encephalitis manifesting as subacute amnestic syndrome: a case report and review of the literature.

BACKGROUND: Limbic encephalitis (LE), a variant of autoimmune encephalitis, is inflammation of the limbic system of the brain. The disorder presents with subacute impairment of short-term memory, psychiatric manifestations, confusion and seizures. "Seronegative LE" is a challenging diagnosis in the absence of well-characterized autoantibodies. CASE PRESENTATION: A 33-year-old Kuwaiti woman with no relevant past history presented with subacute progressive amnesia of 6-month duration. Magnetic resonance imaging (MRI) showed bilateral hyperintensity of the limbic structures. An extensive workup of the blood and cerebrospinal fluid (CSF) failed to identify paraneoplastic or autoimmune antibodies. The diagnosis of seronegative LE was made, and immunotherapy was initiated, with improvement in cognitive function. CONCLUSION: Seronegative LE is a challenging diagnosis. Inability to detect autoantibodies, especially early in the disease course, should not rule out the diagnosis of autoimmune encephalitis. Early diagnosis and treatment with immunotherapy may prevent irreversible brain damage.

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.

CNS demyelination during tofacitinib therapy: First report.

Iatrogenic demyelination is a distinct clinical subtype of central nervous system inflammatory disorders. The Janus kinase inhibitor, tofacitinib, is an oral disease-modifying antirheumatic drug that has shown contradictory effects on multiple sclerosis in animal models. In this report, we describe a novel case of reversible multifocal CNS demyelination in a patient with seropositive rheumatoid arthritis on tofacitinib. Although the mechanism is not completely understood, activation of T17 cells by tofacitinib and the subsequent increased production of interleukin-17 could be the cause. Moreover, a link between TNF-α and JAK/STAT pathways has been suggested, which may further explain the occurrence of iatrogenic demyelination in this case.

Monomelic Amyotrophy (Hirayama Disease): A Rare Case Report and Literature Review.

Hirayama disease is a rare neurological entity that is characterized by initial progressive muscular wasting and weakness of the distal upper limb in young men, followed by a spontaneous arrest within several years. The disease is believed to be a result of forward displacement of the cervical dural sac and spinal cord induced by neck flexion. It is commonly seen in Asia and rarely encountered in the Middle East countries. We report a rare case of a 20-year-old Kuwaiti patient presenting with a 10-month duration of gradual left upper limb weakness and wasting. We describe his electrophysiological and radiological findings that confirmed the diagnosis, and conducted a literature review. Hirayama disease is rarely encountered in clinical settings and should be suspected in male patients presenting with unilateral or asymmetrical bilateral lower motor weakness of hands and forearms. It is a benign entity, and cervical collar is usually the only treatment needed in most cases.

Impact of coronavirus disease 2019 (COVID-19) pandemic on patients with migraine: a web-based survey study.

BACKGROUND: Since the declaration COVID-19 as a pandemic, healthcare systems around the world have faced a huge challenge in managing patients with chronic diseases. Patients with migraine were specifically vulnerable to inadequate medical care. We aimed to investigate the "real-world" impact of COVID-19 pandemic on migraine patients, and to identify risk factors for poor outcome. METHODS: We administered an online, self-reported survey that included demographic, migraine-related, COVID-19-specific and overall psychosocial variables between July 15 and July 30, 2020. We recruited a sample of patients with migraine from headache clinic registry and via social media to complete an anonymous survey. Outcomes included demographic variables, change in migraine frequency and severity during the lockdown period, communication with treating physician, compliance to migraine treatment, difficulty in getting medications, medication overuse, symptoms of anxiety and/or depression, sleep and eating habits disturbance, screen time exposure, work during pandemic, use of traditional medicine, effect of Botox injection cancellation, and overall worries and concerns during pandemic. RESULTS: A total of 1018 patients completed the survey. Of the respondents, 859 (84.3%) were females; 733 (71.9%) were aged 20 to 40 years, 630 (61.8%) were married, and 466 (45.7%) reported working during the pandemic. In comparison to pre-pandemic period, 607 respondents (59.6%) reported increase in migraine frequency, 163 (16%) reported decrease in frequency, and 105 (10.3%) transformed to chronic migraine. Severity was reported to increase by 653 (64.1%) respondents. The majority of respondents; 626 (61.5%) did not communicate with their neurologists, 477 (46.9%) reported compliance to treatment, and 597 (58.7%) reported overuse of analgesics. Botox injections cancellation had a negative impact on 150 respondents (66.1%) from those receiving it. Forty-one respondents (4%) were infected with COVID-19; 26 (63.4%) reported worsening of their headaches amid infection period. Sleep disturbance was reported by 794 (78.1%) of respondents, and 809 (79.5%) reported having symptoms of anxiety and/or depression. CONCLUSIONS AND RELEVANCE: COVID-19 pandemic had an overall negative impact on patients with migraine. Several risk factors for poor outcome were identified. Long-term strategies should be validated and implemented to deliver quality care for patients with migraine, with emphasis on psychosocial well-being.

Fluoroscopic Epidural Steroid Injection: Pain Relief in Discogenic Sciatica Versus Lumbar Spinal Stenosis. A Study on Middle Eastern Patients.

OBJECTIVE: To compare the effect of epidural steroid injections (ESI) in patients with discogenic sciatica (Sci) versus patients with lumbar canal stenosis (LSS), not controlled by conservative treatment. MATERIALS AND METHODS: In our study, 80 patients with Sci and 66 with LSS were included. A single ESI (10 mg dexamethasone in 3 cc 0.25% bupivacaine) was applied under fluoroscopic control: one level above the highest stenotic level, in the posterior epidural space, via interlaminar approach in LSS and at the prolapse level, in the anterior epidural space, via transforaminal route in Sci. Pain intensity was assessed by VAS at baseline and on days 1, 15 and 30 after intervention. RESULTS: The procedure was successful in 78 Sci and 63 LSS patients. Patients with Sci responded significantly better. At one month, pain reduction over 50% was achieved in 63% (52.3-73.7% at p = 0.95) of Sci but only in 35% (23.2-46.8%) of LSS (p = 0.03). Return to pre-intervention level happened in 47% (34.7-59.3%) of LSS versus 14% (6.3-21.7%) of Sci patients (p = 0.01). In 5 patients the procedure failed, without resulting morbidity. CONCLUSION: ESI are more effective in patients with Sci than in single level LSS. In multiple level LSS, results are disappointing.

Radiological characteristics of neuromyelitis optica spectrum disorder in Kuwait.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disorder of the central nervous system that predominantly targets optic nerves and spinal cord. Studies of NMOSD are scarce in the Middle East. OBJECTIVE: To evaluate the MRI characteristics of NMOSD patients in Kuwait. PATIENT AND METHODS: This is an observational, retrospective study on NMOSD patients who attended the MS clinic. Patients who fulfilled the 2015 diagnostic criteria of NMOSD were included. Patients` clinical, radiological and serological data were extracted from the medical records. The radiological variables were compared according to gender and AQP4 serostatus. RESULTS: Forty-two patients fulfilling the NMOSD diagnostic criteria. The mean age and mean age of onset were 32.6 ± 11.4 and 28.9 ± 9.8 years respectively. Females represented 83.3 % of the cohort with female-to-male ratio of 5:1. Thirty-one patients (73.8 %) tested positive for AQP4 antibody. Nineteen patients (45.2 %) had bilateral optic nerve involvement, while chiasmal involvement was seen in 8 (19.0 %) patients. Spinal cord was involved in 36 (85.7 %) patients; of whom 27 (64.3 %) had LETM. The most common spinal segment involved was the cervical (72.2 %) followed by the dorsal (25.0 %) regions. The brain was involved in 39 (92.8 %) patients and the periventricular region around fourth and lateral ventricles was the most commonly involved site (n = 35; 83.3 %), along with periaqueductal (n = 25; 61.9 %) and corpus callosal (n = 24; 57.1 %) regions. Isolated area postrema involvement was observed in 9 (21.4 %) patients. CONCLUSION: This is the first study describing the radiological characteristics of NMOSD in Kuwait. Although our data is comparable with the previous international studies, a higher percentage of bilateral optic nerve, brain, and callosal involvement was observed. Further multicenter studies with a larger cohort are needed to confirm our results.

LCIG in treatment of non-motor symptoms in advanced Parkinson's disease: Review of literature.

BACKGROUND: For managing nonmotor symptoms (NMS) in advanced Parkinson's disease (PD), levodopa-carbidopa intestinal gel (LCIG) infusion is of interest as it shows lesser plasma fluctuations of both drugs as compared to oral levodopa-carbidopa (LC). OBJECTIVES: To highlight LCIG effect in NMS among advanced PD patients and appraise the currently available literature. METHODS: PubMed screening (till 2020) of 184 articles was done, of which 51 were selected. Among them, 23 original articles relevant to the research question were included, of which 6 were then excluded after careful reading of full articles. The 17 relevant studies of the review provide Grade C level of evidence of efficacy. RESULTS: LCIG is beneficial in improving or relieving various NMS especially (mood, cognition/memory, sleep, gastrointestinal symptoms, urinary symptoms, and quality of life questionnaires) in patients with advanced PD. Amelioration of motor functions or direct relations may lead to improvement in NMS PD patients using LCIG. Adverse events noted in patients treated with LCIG include pneumoperitoneum, abdominal pain, stoma infection, reversible peripheral neuropathy, local tube problems, impulse control disorder, and weight loss. Serious adverse events were mostly found to be unrelated to LCIG. CONCLUSIONS: LCIG provides an uninterrupted intestinal levodopa infusion by percutaneous endoscopic gastrojejunostomy (PEG-J). It effectively decreases plasma fluctuations of levodopa and reduces motor instability and NMS burden in advanced PD. However, adequate dose modification and individualization of therapy are essential for optimal effect.

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.