Whole-exome sequencing analyses in a Saudi Ischemic Stroke Cohort reveal association signals, and shows polygenic risk scores are related to Modified Rankin Scale Risk.

Ischemic stroke represents a significant societal burden across the globe. Rare high penetrant monogenic variants and less pathogenic common single nucleotide polymorphisms (SNPs) have been described as being associated with risk of diseases. Genetic studies in Saudi Arabian patients offer a greater opportunity to detect rare high penetrant mutations enriched in these consanguineous populations. We performed whole exome sequencing on 387 ischemic stroke subjects from Saudi Arabian hospital networks with up to 20,230 controls from the Saudi Human Genome Project and performed gene burden analyses of variants in 177 a priori loci derived from knowledge-driven curation of monogenic and genome-wide association studies of stroke. Using gene-burden analyses, we observed significant associations in numerous loci under autosomal dominant and/or recessive modelling. Stroke subjects with modified Rankin Scale (mRSs) above 3 were found to carry greater cumulative polygenic risk score (PRS) from rare variants in stroke genes (standardized PRS mean > 0) compared to the population average (standardized PRS mean = 0). However, patients with mRS of 3 or lower had lower cumulative genetic risk from rare variants in stroke genes (OR (95%CI) = 1.79 (1.29-2.49), p = 0.0005), with the means of standardized PRS at or lower than 0. In conclusion, gene burden testing in Saudi stroke populations reveals a number of statistically significant signals under different disease inheritance models. However, interestingly, stroke subjects with mRS of 3 or lower had lower cumulative genetic risk from rare variants in stroke genes and therefore, determining the potential mRS cutoffs to use for clinical significance may allow risk stratification of this population.

Neurobehcet with cerebral aneurysm.

Neuro-behcets disease (NBD) is an uncommon, serious presentation of behcets disease (BD) causing long-term morbidity and mortality. Cerebral aneurysms are rare in BD, with only a handful of cases reported worldwide. A 39-year-old female experienced slurring of speech, numbness, and reduced sensation in the left face, arm, and leg 90 minutes prior to presentation. She provided a history of recurrent oral and genital ulcers associated with intermittent joints pain and blurring of vision. erythrocyte sedimentation rate was elevated, but all other autoimmune workup was negative. Neuro-behcets disease was diagnosed. Brain magnetic resonance imaging demonstrated acute right periventricular infarction. Magnetic resonance angiogram revealed M1 segment stenosis and right internal carotid artery saccular aneurysm. Catheter angiography confirmed its presence measuring 4.8 mm X 6.1 mm. She was stabilized after coiling of the aneurysm and was started on medical therapy. Brain imaging should be carried out in young patients with BD presenting with an ischemic event, and intervention may be lifesaving.

Stroke and seizure continue to be the major brunt of in patient neurology care. An observation from teaching hospital.

OBJECTIVE: To assess the burden and describe the pattern of neurological disorders requiring admissions in a teaching hospital of Al Khobar. METHODS: This is a retrospective, cross sectional study, carried out in the Neurology Department of King Fahd Hospital of the University from January 2009 to December 2016. Neurological disorders were grouped as ischemic stroke, intracerebral hemorrhage, transient ischemic attack, cerebral venous sinus thrombosis, seizure disorders, central nervous system infection, multiple sclerosis, neuropathies, myopathies, headache, dementia and miscellaneous group. Data was entered and analyzed by Statistical Package for the Social Science (SPSS) version 22.0 (IBM Corp., Armonk, NY, USA). RESULTS: The records of 1,317 patients admitted under Neurology Service were analyzed. Out of that, 740 (56.2%) were male and 577 (43.8%) were female. Mean age was 46.9+\-24 years (mean+\-standard deviation). Ischemic stroke was the most common diagnosis (32%) followed by seizures (20%). Multiple sclerosis accounted for around 8% and central nervous system infections 5% of neurological admission. CONCLUSION: Ischemic stroke was found to be the most common etiology for hospitalization in our study. The results of our study are similar to previous literature. An urgent need to control major risk factors such as diabetes and hypertension is warranted to minimize the burden of stroke.

Characteristics and outcomes of large artery occlusion-related stroke due to intracranial atherostenosis: An experience from a single center in Saudi Arabia.

BACKGROUND: Literature on the frequency, response to treatment, and outcomes of acute ischemic stroke (AIS) due to intracranial atherostenosis (ICAS)-related intracranial large artery occlusion (ILAO) from Saudi Arabia is scarce. The aim of this study was to identify the percentage, describe the characteristics, and observe the treatment response in patients with AIS attributed to ICAS-related ILAO. MATERIALS AND METHODS: This cross-sectional study included all adult patients from 2017-2021 who fulfilled the inclusion criteria for the diagnosis of ICAS-related AIS. Patients were dichotomized based on ILAO. Mortality and functional outcomes (FOCs) based on 90 days' dependence level were compared between the two groups. The association between ILAO and other variables was assessed using the Chi-squared test, odds ratios (OR), and 95% confidence interval (CI). RESULTS: ILAO was found in 38.7% of patients with ICAS-related AIS. Men comprised three-fourths of the cohort and were more frequent in the ILAO group. Smoking was associated with increased (P = 0.04) likelihood of ILAO. Patients with ILAO had more severe strokes (P ≤ 0.001) than patients without. Middle cerebral artery was the most common occluded vessel (52%). Functional dependence (P = 0.003, OR = 2.87, CI = 1.42-5.77), malignant transformation (P = 0.001, OR = 8.0, CI = 1.82-35.9), and mortality (P ≤ 0.001, OR = 7.67, CI = 2.40-24.5) were significantly higher among ILAO group. Patients with ILAO with unfavorable FOC were older than those who achieved better FOC (P ≤ 0.001). Thrombolysis (P = 0.02, OR = 2.50, CI = 1.15-5.41) and mechanical thrombectomy (MT) improved FOC in patients with ILAO (P = 0.04, OR = 2.33, CI = 1.10-4.92). CONCLUSION: ILAO is common in patients with ICAS-related AIS. Timely hyperacute stroke treatment can help improve the FOC of otherwise disabling stroke due to ILAO. Raising awareness of the community about stroke is needed, so that a higher number of patients can arrive at hospital within the golden hours. Further data from the region are required to recognize the efficacy of MT in ICAS-related ILAO.

Influence of Sex Difference on Distribution of Risk Factors and Etiologic Subtypes of Acute Ischemic Stroke: Reality of Facts.

BACKGROUND AND PURPOSE: Sex-related differences have been documented in risk factors distribution, etiologic subtypes, diagnostic evaluation, offered management, and outcome of patients with acute ischemic stroke (AIS) from all over the world. Nevertheless, studies from Saudi Arabia are lacking. This study aimed to investigate the influence of sex on distribution of risk factors and etiologic subtype of AIS in patients admitted to our hospital. MATERIALS AND METHODS: Record of patients admitted to King Fahd Hospital of the University between 2010 and 2017 with ischemic stroke (IS) were reviewed. Base line characteristics, risk factors, and etiologic subtypes according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification were compared between men and women. RESULTS: Among 453 patients with IS, 300 (66.2%) were men and 153 (33.7%) were women. The mean age of all patients was 61.5 ± 14.5 years. Women were older than men (P = 0.00). Hypertension (P = 0.00), atrial fibrillation (P = 0.00), and past history of stroke (P = 0.03) were more frequent in women compared to men. Fewer carotid Doppler studies (47.1 vs. 68.3%, P = 0.00) and echocardiogram (75.1 vs. 83%, P = 0.01) were done in women as compared to men. Cardioembolic etiologic subtype (26.1 vs. 17.7%) was found more frequently, whereas small vessel occlusive (23.5 vs. 31%) and large artery disease less (10.5 vs. 16.3%) frequently in women. CONCLUSION: Significant sex-related differences were found in risk factors and subtypes of AIS in our cohort of patients. Findings of our study are in general comparable with studies from all over the world.