A Tangled Autoimmune Trio: Multiple Sclerosis, Systemic Lupus Erythematosus and Antineutrophil Cytoplasmic Antineutrophil Cytoplasmic Antibody Vasculitis.

The coexistence of multiple autoimmune diseases in the same individual is unusual and has received little attention in the literature. We present a young female patient with multiple sclerosis, systemic lupus erythematosus, and biopsy-proven renal proteinase 3 antineutrophil cytoplasmic antibodyassociated vasculitis who responded well to intravenous rituximab clinically and serologically.

Multicentre Observational Study of Treatment Satisfaction with Cladribine Tablets in the Management of Relapsing Multiple Sclerosis in the Arabian Gulf: The CLUE Study.

INTRODUCTION: Inconvenient administration and side effects of some disease-modifying therapies (DMTs) for relapsing multiple sclerosis (RMS) can deter adherence. We evaluated treatment satisfaction with cladribine tablets (CladT) for RMS in the Arabian Gulf. METHODS: This was a non-interventional, multicentre, prospective observational study in non-pregnant/lactating adults (aged ≥ 18 years) with RMS eligible for 1st treatment with CladT (EU labelling). The primary outcome was overall treatment satisfaction at 6 months (Treatment Satisfaction Questionnaire for Medication [TSQM]-14, v. 1.4), Global Satisfaction subscale. Secondary endpoints were TSQM-14 scores for convenience, satisfaction with side effects and satisfaction with effectiveness. Patients provided written informed consent. RESULTS: Of 63 patients screened, 58 received CladT and 55 completed the study. Mean age was 33 ± 9 years; mean weight 73 ± 17 kg; 31% male/69% female; mostly from the United Arab Emirates (52%) or Kuwait (30%). All had RMS (mean 0.9 ± 1.1 relapses in the past year), mean Expanded Disability Status Scale (EDSS) 1.4 ± 1.2; 36% were DMT-naïve. Mean [95% CI] score was high for overall treatment satisfaction (77.8 [73.0-82.6]), ease of use (87.4 [83.7-91.0]), tolerability (94.2 [91.0-97.3]) and effectiveness (76.2 [71.6-80.7]). Scores were similar irrespective of DMT history, age, gender, relapse history or EDSS. No relapses or serious treatment-emergent adverse events (TEAE) occurred. Two severe TEAE occurred (fatigue, headache) and 16% reported lymphopenia (two cases of grade 3 lymphopenia). Absolute lymphocyte counts at baseline and 6 months were 2.2 ± 0.8 × 109/L and 1.3 ± 0.3 × 109/L, respectively. CONCLUSIONS: Treatment satisfaction, ease of use, tolerability and patient-perceived effectiveness for CladT were high, irrespective of baseline demographics, disease characteristics and prior treatment.

Global Differences in Risk Factors, Etiology, and Outcome of Ischemic Stroke in Young Adults-A Worldwide Meta-analysis: The GOAL Initiative.

BACKGROUND AND OBJECTIVES: There is a worldwide increase in the incidence of stroke in young adults, with major regional and ethnic differences. Advancing knowledge of ethnic and regional variation in causes and outcomes will be beneficial in implementation of regional health care services. We studied the global distribution of risk factors, causes, and 3-month mortality of young patients with ischemic stroke, by performing a patient data meta-analysis from different cohorts worldwide. METHODS: We performed a pooled analysis of individual patient data from cohort studies that included consecutive patients with ischemic stroke aged 18-50 years. We studied differences in prevalence of risk factors and causes of ischemic stroke between different ethnic and racial groups, geographic regions, and countries with different income levels. We investigated differences in 3-month mortality by mixed-effects multivariable logistic regression. RESULTS: We included 17,663 patients from 32 cohorts in 29 countries. Hypertension and diabetes were most prevalent in Black (hypertension, 52.1%; diabetes, 20.7%) and Asian patients (hypertension 46.1%, diabetes, 20.9%). Large vessel atherosclerosis and small vessel disease were more often the cause of stroke in high-income countries (HICs; both p < 0.001), whereas "other determined stroke" and "undetermined stroke" were higher in low and middle-income countries (LMICs; both p < 0.001). Patients in LMICs were younger, had less vascular risk factors, and despite this, more often died within 3 months than those from HICs (odds ratio 2.49; 95% confidence interval 1.42-4.36). DISCUSSION: Ethnoracial and regional differences in risk factors and causes of stroke at young age provide an understanding of ethnic and racial and regional differences in incidence of ischemic stroke. Our results also highlight the dissimilarities in outcome after stroke in young adults that exist between LMICs and HICs, which should serve as call to action to improve health care facilities in LMICs.

Position of Cladribine Tablets in the Management of Relapsing-Remitting Multiple Sclerosis: An Expert Narrative Review From the United Arab Emirates.

The use of immune reconstitution therapies (IRT) in patients with relapsing-remitting multiple sclerosis (RRMS) is associated with a prolonged period of freedom from relapses in the absence of continuously applied therapy. Cladribine tablets is a disease-modifying treatment (DMT) indicated for highly active relapsing multiple sclerosis (MS) as defined by clinical or imaging features. Treatment with cladribine tablets is effective and well tolerated in patients with active MS disease and have a low burden of monitoring during and following treatment. In this article, an expert group of specialist neurologists involved in the care of patients with MS in the United Arab Emirates provides their consensus recommendations for the practical use of cladribine tablets according to the presenting phenotype of patients with RRMS. The IRT approach may be especially useful for patients with highly active MS insufficiently responsive to treatment with a first-line DMT, those who are likely to adhere poorly to a continuous therapeutic regimen, treatment-naïve patients with high disease activity at first presentation, or patients planning a family who are prepared to wait until at least 6 months after the end of treatment. Information available to date does not suggest an adverse interaction between cladribine tablets and COVID-19 infection. Data are unavailable at this time regarding the efficacy of COVID-19 vaccination in patients treated with cladribine tablets. Robust immunological responses to COVID-19 infection or to other vaccines have been observed in patients receiving this treatment, and treatment with cladribine tablets per se should not represent a barrier to this vaccination.

Clinical characteristics and admission patterns of stroke patients during the COVID 19 pandemic: A single center retrospective, observational study from the Abu Dhabi, United Arab Emirates.

OBJECTIVE: To compare ischemic and hemorrhagic stroke patients with COVID-19 to non-COVID-19 controls, and to describe changes in stroke admission patterns during the pandemic. METHODS: This is a single center, retrospective, observational study. All consecutive patients admitted with primary diagnosis of ischemic/ hemorrhagic stroke between March1st -May10th 2020 were included and compared with the same time period in 2019. RESULTS: There was a 41.9% increase in stroke admissions in 2020 (148 vs 210,P = .001). When comparing all ischemic strokes, higher rate of large vessel occlusion (LVO) (18.3% vs 33.8%,P = .008) and significant delay in initiation of mechanical thrombectomy after hospital arrival (67.75 vs 104.30 minutes,P = .001) was observed in 2020. When comparing all hemorrhagic strokes, there were no differences between the two years. Among 591 COVID-19 admissions, 31 (5.24%) patients with stroke including 19 with ischemic (3.21%) and 12 with hemorrhagic stroke (2.03%) were identified. Patients with COVID-19 and ischemic stroke were significantly younger (58.74 vs 48.11 years,P = .002), predominantly male (68.18% vs 94.74%,P = .016), had lesser vascular risk factors, had more severe clinical presentation (NIHSS 7.01 vs 17.05,P < .001), and higher rate of LVO (23.6% vs. 63.1%,P = .006). There was no difference in the rate of endovascular thrombectomy, but time to groin puncture was significantly longer in COVID-19 patients (83.41 vs 129.50 minutes,P = .003). For hemorrhagic stroke, COVID-19 patients did not differ from non-COVID-19 patients. CONCLUSIONS: Stroke continues to occur during this pandemic and stroke pathways have been affected by the pandemic. Stroke occurs in approximately 5% of patients with COVID-19. COVID-19 associated ischemic stroke occurs in predominantly male patients who are younger, with fewer vascular risk factors, can be more severe, and have higher rates of LVO. Despite an increase in LVO during the pandemic, treatment with mechanical thrombectomy has not increased. COVID-19 associated hemorrhagic stroke does not differ from non-COVID-19 hemorrhagic stroke patients.

Call to Action: SARS-CoV-2 and CerebrovAscular DisordErs (CASCADE).

BACKGROUND AND PURPOSE: The novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), now named coronavirus disease 2019 (COVID-19), may change the risk of stroke through an enhanced systemic inflammatory response, hypercoagulable state, and endothelial damage in the cerebrovascular system. Moreover, due to the current pandemic, some countries have prioritized health resources towards COVID-19 management, making it more challenging to appropriately care for other potentially disabling and fatal diseases such as stroke. The aim of this study is to identify and describe changes in stroke epidemiological trends before, during, and after the COVID-19 pandemic. METHODS: This is an international, multicenter, hospital-based study on stroke incidence and outcomes during the COVID-19 pandemic. We will describe patterns in stroke management, stroke hospitalization rate, and stroke severity, subtype (ischemic/hemorrhagic), and outcomes (including in-hospital mortality) in 2020 during COVID-19 pandemic, comparing them with the corresponding data from 2018 and 2019, and subsequently 2021. We will also use an interrupted time series (ITS) analysis to assess the change in stroke hospitalization rates before, during, and after COVID-19, in each participating center. CONCLUSION: The proposed study will potentially enable us to better understand the changes in stroke care protocols, differential hospitalization rate, and severity of stroke, as it pertains to the COVID-19 pandemic. Ultimately, this will help guide clinical-based policies surrounding COVID-19 and other similar global pandemics to ensure that management of cerebrovascular comorbidity is appropriately prioritized during the global crisis. It will also guide public health guidelines for at-risk populations to reduce risks of complications from such comorbidities.

Characteristics of Large-Vessel Occlusion Associated with COVID-19 and Ischemic Stroke.

The mechanisms and phenotype of ischemic stroke associated with coronavirus disease 2019 (COVID-19) remain uncertain. A retrospective study was conducted in patients with COVID-19 presenting with ischemic stroke from March 1 to May 25, 2020, and cases with large-vessel occlusion were identified. To provide baseline institutional stroke data within and outside the COVID-19 pandemic, all consecutive ischemic stroke and TIA admissions (COVID and non-COVID) to the hospital during a 10-week period from March 1 to May 10, 2020, were collected and compared with data from the same time period in 2019. Among 20 patients with COVID-19 and acute ischemic stroke, 15 (75%) had large-vessel occlusion. These patients were young (mean age, 46.5 years), male (93%), without major burden of traditional cardiovascular risk factors, and had a severe stroke presentation. Large-vessel occlusions were observed in multiple vessels (40%), uncommonly affected vessels, and atypical locations with a large thrombus burden. Systemic thrombosis separate from large-vessel occlusion was not uncommon (26%). At short-term follow-up, stroke etiology remained undetermined in 46% of patients and functional outcome was poor. The above findings raise the possibility of stroke related to mechanisms induced by the COVID-19 infection itself, including a hypercoagulable state and/or endothelial damage. In addition, they document the severe presentation and poor outcomes of large-vessel occlusion in COVID-19 ischemic stroke.

Demographic and clinical characteristics of familial and sporadic multiple sclerosis: A single center exploratory study from Abu Dhabi.

Demographic and clinical characteristics of Familial Multiple Sclerosis (FMS) have not been fully investigated yet in Abu Dhabi. The aim of this single center exploratory study was to investigate demographic and clinical characteristics of FMS compared to sporadic MS (SMS) in Abu Dhabi. A chart review single center study was conducted in 98 patients with MS. Group comparisons were performed using Mann-Whitney and Chi-Square tests as appropriate. A p < 0.05 was considered statistically significant. 24.5% were patients with FMS and 83% were Emirates. No significant differences in demographic and clinical characteristics were found between patients with FMS and SMS in overall all MS patients and in the Emirati group analyzed alone. Patients with FMS did not differ in demographic and clinical characteristics compared to patients with SMS. Further prospective studies are needed to elucidate environmental and genetic risk factors contributing to FMS in the Emirati population.

Short term real-world Fingolimod efficacy and safety in Emirati patients with multiple sclerosis.

In clinical trials, Fingolimod was an efficacious and safe treatment for multiple sclerosis (MS). Despite this, few studies have explored its real-world efficacy and safety in the Middle East. The aim of this study was to describe our clinical experience with Fingolimod at Cleveland Clinic Abu Dhabi in Emirati patients with MS. We retrospectively collected clinical and brain and spinal cord MRI activity over time in 30 Emirati MS patients [F/M = 22/8, mean (SD) disease duration at treatment initiation = 3.3 (3.6) years, age at onset = 25.9 (6.9) years] who were commenced on Fingolimod from 2015 and followed for 18 months. The proportion of MS patients clinically and radiologically silent after Fingolimod initiation over time was assessed together with annualized relapse rate (ARR) reduction and adverse events (AEs) occurrence. 70% of MS patients who started Fingolimod were naïve. The baseline ARR [mean (SD; range)] was [1.2 (0.8; 0-4)] and 23.3% of MS patients had Gadolinium enhancing lesions at baseline MRI. Overall, the ARR was reduced by 72% and, relapses and MRI activity were found in only 24% and 38% of MS patients respectively. Mild to moderate AEs were observed in 33% of MS patients. No severe AEs were recorded. In Emirati MS patients, Fingolimod is safe and efficacious as an early treatment choice.

Seropositive neuromyelitis optica spectrum disorder in Emirati patients: A case series.

OBJECTIVE: To describe clinical and radiological characteristics of seropositive neuromyelitis optica (NMO) in Emirati patients. While epidemiology of seropositive NMO in Abu Dhabi has been reported in a previous paper, its clinical and MRI profiles among Emirati patients have not been previously fully investigated. METHODS: In our case series, we describe clinical and MRI characteristics of 5 Emirati patients with NMO, consecutively admitted at Cleveland Clinic Abu Dhabi, a major tertiary hospital in Abu Dhabi, United Arab Emirates. RESULTS: Patients were all females, mean age of onset (SD) was 41 (11) years, and 67% had autoimmune comorbidities. Most patients initially presented with acute myelitis (80%) while 20% got optic neuritis. Mean (SD) number of further relapses after onset was 3 (1) and mean (SD) disease duration was 12 (11) years. At MRI, apparent longitudinal extensive transverse myelitis was present in all patients affecting mostly the central gray matter of the cervical cord but extending as well to the thoracic portion. Furthermore, seropositive NMO related brain lesions were also observed. CONCLUSIONS: Our work provides valuable information regarding seropositive NMO with the potential to increase recognition of this disorder in Abu Dhabi and confirms NMO findings described in the other populations with this disorder. Further research is needed to advance clinical and MRI characterization of seronegative NMO in the region.

Global Outcome Assessment Life-long after stroke in young adults initiative-the GOAL initiative: study protocol and rationale of a multicentre retrospective individual patient data meta-analysis.

INTRODUCTION: Worldwide, 2 million patients aged 18-50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients. METHODS AND ANALYSIS: The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18-50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence. ETHICS AND DISSEMINATION: Ethical approval for the GOAL study has already been obtained from the Medical Review Ethics Committee region Arnhem-Nijmegen. Additionally and when necessary, approval will also be obtained from national or local institutional review boards in the participating centres. When needed, a standardised data transfer agreement will be provided for participating centres. We plan dissemination of our results in peer-reviewed international scientific journals and through conference presentations. We expect that the results of this unique study will lead to better understanding of worldwide differences in risk factors, causes and outcome of young stroke patients.