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.

Risk factors and subtypes of acute ischemic stroke. A study at King Fahd Hospital of the University.

OBJECTIVE: To identify the different subtypes of acute ischemic stroke, and estimate the frequency of various risk factors among these patients. METHODS: In this retrospective, cross-sectional study, we reviewed the medical records of patients admitted with the diagnosis of acute ischemic stroke at King Fahd Hospital of the University, Al-Khobar, Saudi Arabia from March 2008 till December 2015. The demographic characteristics, subtypes of stroke, risk factors (hypertension, diabetes mellitus, hyperlipidemia, coronary artery disease, atrial fibrillation, valvular heart disease) and other relevant data were documented on pre-defined data sheets. RESULTS: The records of 343 patients were included in the study; 64.4% were male and 35.6% were female. The mean age was 59.3+/-13.6 (mean+/-SD) years for males, and 66.8+/-14.9 years for females. Small vessel occlusion was the most common etiologic subtype of ischemic stroke (32.1%), followed by cardio embolic (21.9%), and large artery atherosclerosis (14.6%). The middle cerebral artery was the most commonly affected territory. Hypertension was found in 78.1%, diabetes mellitus in 62.7%, hyperlipidemia in 54.8%, and ischemic heart disease in 24.2% of patients. CONCLUSION: Small vessel occlusion was the most common etiology in our cohort. The onset of stroke at a relatively younger age group in the male population is of great concern and needs to be verified by further epidemiological studies. Adequate control of modifiable risk factors may help in reducing the disease burden caused by stroke.

Characteristics of Stroke-related Seizures and their Predictive Factors: A Tertiary Care Center Experience.

BACKGROUND AND PURPOSE: Various risk factors have been described in the literature that increase the risk of seizures associated with stroke. This study was aimed to determine the occurrence rate of poststroke seizures (PSSs) and the associated risk factors in Arab population. MATERIALS AND METHODS: Study included all stroke patients aged >18 years with a minimum follow-up of 24 months following stroke to identify seizure occurrence. Patient's hospital records for all admissions and clinic visits were reviewed. Seizures were classified into early PSS if they occur within 1 week of stroke, and late PSS if they occur after 1 week of stroke. RESULTS: Out of 594 patients, 380 were males. Seizure occurrence was higher in anterior circulation infarctions (94.8%, P < 0.05), cortical location (80.5%, P < 0.05), large artery atherosclerosis (63.8%, P < 0.05), lower activated partial thromboplastin time (APTT) (P = 0.0007), patients with ischemic heart disease (IHD) (P = 0.01), and those who underwent craniotomy (P = 0.001). Nonhigh-density lipoprotein cholesterol was inversely related to PSS (P = 0.01). Higher stroke severity (89%) and confusion (67%) at the time of presentation were independently related to PSS. CONCLUSIONS: Eighty-two (13.8%) patients had PSS. Greater stroke severity at presentation with altered sensorium was independent risk factors for the development of PSS. Patients with underlying IHD, lower APTT, and undergoing neurosurgical intervention require vigilant monitoring for PSS.

Résumé Ontexte et objectif:Divers facteurs de risque ont été décrits dans la littérature qui augmentent le risque de convulsions associées à un AVC. Cette étude visait à déterminer le taux d'occurrence des crises post-AVC (PSS) et les facteurs de risque associés dans la population arabe.Matériels et Méthodes:L'étude a inclus tous les patients victimes d'AVC âgés de plus de 18 ans avec un suivi minimum de 24 mois après l'AVC pour identifier la survenue d'une crise. Les dossiers hospitaliers des patients pour toutes les admissions et visites à la clinique ont été examinés. Les saisies ont été classées en premiers PSS s'ils surviennent dans la semaine suivant l'AVC, et PSS tardif s'ils surviennent après 1 semaine de l'AVC.Résultats:Sur 594 patients, 380 étaient des hommes. Crise d'épilepsie la fréquence était plus élevée dans les infarctus de la circulation antérieure (94,8 %, P < 0,05), la localisation corticale (80,5 %, P < 0,05), l'athérosclérose des grandes artères (63,8 %, P < 0,05), un temps de thromboplastine partielle activé (APTT) inférieur (P = 0,0007), les patients atteints de cardiopathie ischémique (IHD) (P = 0,01) et ceux ayant subi une craniotomie (P = 0,001). Le cholestérol des lipoprotéines non de haute densité était inversement lié au PSS (P = 0,01). Course supérieure la gravité (89 %) et la confusion (67 %) au moment de la présentation étaient indépendamment liées au PSS.Conclusions:Quatre-vingt-deux (13,8 %) patients avait PSS. Une plus grande gravité de l'AVC lors de la présentation avec un sensorium altéré était un facteur de risque indépendant pour le développement du PSS. Les patients avec une IHD sous-jacente, un APTT inférieur et une intervention neurochirurgicale nécessitent une surveillance vigilante du PSS.

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.

The efficacy of new neuronal growth factor in the healing of the sciatic nerves in rabbits.

Background and Objective: Regeneration of nervous tissue is unpredictable and an ideal growth factor to influence the healing of the injured nerves is not available. A recent study in rats had shown that a new neuronal growth factor (NNGF) was effective in the early healing of the sciatic nerves. The aim of this experimental study is to test the efficacy of NNGF in the healing of iatrogenic division of the sciatic nerves in a larger animal (rabbits). Methods: White New Zealand 20 male rabbits of 6 months of age were divided into two groups. Intramuscular ketamine and xylazine were used to anesthetize the animals. The sciatic nerves were divided using scalpel blade 15 and 10/0 Vicryl was used to repair the divided neural tissue. In the study group, 10 mg/kg body weight of NNGF was instilled on the top of the divided nerves and the wound was closed. At 4 weeks, the operated limbs were observed for any trophic skin changes. Nerve conduction studies were carried out using train-of-four-Watch SX, Organon (Ireland) Ltd., and Ireland. The rabbits were put to death humanely and the sciatic nerves were removed and delivered to the pathologist in 2% formalin. The pathologists were blinded about the two groups. Results: Electromyographic study done at 4 weeks showed in the untreated group; the mean twitches 1-T4 was 0.45 ± 0.31% and in the treated group, the average was 77.912 ± 5% (P > 0.001). Microscopic anatomy in the treated group revealed prominent healing by regeneration was evidenced by showing growth of its proximal segments into an empty endoneurial tube which was not seen in the control group. In the control group, the nerves showed no histological element of healing by regeneration. Conclusions: NNGF proves that in a larger animal at 4 weeks profoundly influenced early regeneration of experimentally created divisions of myelinated nerve tissue.

Résumé Contexte et objectif: La régénération des tissus nerveux est imprévisible et un facteur de croissance idéal pour influencer la guérison des nerfs blessés n'est pas disponible. Une étude récente chez le rat a montré qu'un nouveau facteur de croissance neuronal (NNGF) était efficace dans la guérison précoce des nerfs sciatiques. L'objectif de cette étude expérimentale est de tester l'efficacité du NNGF dans la guérison de la division iatrogène des nerfs sciatiques chez un animal plus grand (lapin). Méthodes: White New Zealand 20 lapins mâles de 6 mois ont été divisés en deux groupes. La kétamine intramusculaire et la xylazine ont été utilisées pour anesthésier les animaux. Les nerfs sciatiques ont été divisés en utilisant la lame scalpel 15 et 10/0 vicryl ont été utilisés pour réparer le tissu neural divisé. Dans le groupe d'étude, 10 mg / kg de poids corporel du NNGF ont été inculqués sur le dessus des nerfs divisés et la plaie a été fermée. À 4 semaines, les membres opérés ont été observés pour tout changement de peau trophique. Des études de conduction nerveuse ont été menées à l'aide de SX Train-of-Nat-Watch, Organon (Ireland) Ltd. et Ireland. Les lapins ont été mis à mort avec humanité et les nerfs sciatiques ont été retirés et livrés au pathologiste dans 2% de formol. Les pathologistes ont été aveuglés sur les deux groupes. Résultats: électromyographique L'étude réalisée à 4 semaines a montré dans le groupe non traité; Les contractions moyennes 1 à T4 étaient de 0,45 ± 0,31% et dans le groupe traité, la moyenne était de 77,912 ± 5% (p> 0,001). L'anatomie microscopique dans le groupe traité a révélé une guérison importante par régénération a été mise en évidence en montrant la croissance de ses segments proximaux dans un tube endoneurial vide qui n'a pas été observé dans le groupe témoin. Dans le groupe témoin, les nerfs n'ont montré aucun élément histologique de guérison par régénération. Conclusions: NNGF prouve que chez un animal plus grand à 4 semaines, a profondément influencé la régénération précoce des divisions créées expérimentalement du tissu nerveux myélinisé. Mots-clés: Facteurs de croissance, régénération nerveuse, nerfs sciatiques.

Prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup.

OBJECTIVES: To mitigate the incidence of recurrent stroke in patients, dual antiplatelet therapy comprising aspirin and clopidogrel is usually administered. Clopidogrel is a prodrug and its bioactivation is catalyzed by cytochrome P450 (CYP)2C19. The main objective of this work was to determine the prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and assess the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup. METHODS: This prospective (2018-2019) study was conducted on 256 patients (age 61 ± 12.5) clinically diagnosed with ischemic stroke who were genotyped using Spartan RX CYP2C19 assay. RESULTS: From the total patient group (256), upon admission, 210 patients were prescribed either aspirin, clopidogrel or dual antiplatelet therapy. Of the 27 patients with the CYP2C19*2 allele who were prescribed clopidogrel (18) or dual antiplatelet therapy (9), only 21 patients could be followed up for a period of six months post stroke event, in addition to 21 age- and sex-matched patients with the normal allele. The CYP2C19*2 allele carriers had a statistically significant increased risk of recurrent stroke compared to patients carrying the normal allele. CONCLUSIONS: This study shows the suitability of using genotyping to guide antiplatelet therapy in ischemic stroke patients in a clinical setting.

Prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup.

OBJECTIVES: To mitigate the incidence of recurrent stroke in patients, dual antiplatelet therapy comprising aspirin and clopidogrel is usually administered. Clopidogrel is a prodrug and its bioactivation is catalyzed by cytochrome P450 (CYP)2C19. The main objective of this work was to determine the prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and assess the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup. METHODS: This prospective (2018-2019) study was conducted on 256 patients (age 61 ± 12.5) clinically diagnosed with ischemic stroke who were genotyped using Spartan RX CYP2C19 assay. RESULTS: From the total patient group (256), upon admission, 210 patients were prescribed either aspirin, clopidogrel or dual antiplatelet therapy. Of the 27 patients with the CYP2C19*2 allele who were prescribed clopidogrel (18) or dual antiplatelet therapy (9), only 21 patients could be followed up for a period of six months post stroke event, in addition to 21 age- and sex-matched patients with the normal allele. The CYP2C19*2 allele carriers had a statistically significant increased risk of recurrent stroke compared to patients carrying the normal allele. CONCLUSIONS: This study shows the suitability of using genotyping to guide antiplatelet therapy in ischemic stroke patients in a clinical setting.

Psychometric properties of an Arabic version of the fatigue severity scale in patients with stroke.

Background: Post-stroke fatigue is a common symptom which needs to be assessed by a psychometrically sound tool. Objectives: To investigate the psychometric properties of an Arabic version of the fatigue severity scale (FSS-A) in patients with stroke. Methods: An observational, cross-sectional design was applied to 147 survivors of first-time stroke and 70 healthy participants. Internal consistency was measured by Cronbach's α, while test-retest reliability was measured by intraclass correlation coefficients (ICCs). To assess validity, the FSS-A was correlated with the Fatigue Visual Analogue Scale (VAS-F), the Short Form 36 (SF-36) and its vitality domain (SF-36V), the stroke specific quality of life (SSQOL-A) and its energy domain (SSQOL-A-E), and the Beck Depression Inventory II (BDI-II). Results: The FSS-A showed excellent internal consistency (Cronbach's α = 0.934) and test-retest reliability (ICC = 0.920, 95% confidence interval (CI): 0.85-0.96). Exploratory factor analysis confirmed that the FSS-A is unidimensional. The FSS-A had high positive correlation with VAS-F, moderate positive correlation with BDI-II, high negative correlation with SSQOL-A-E and moderate negative correlations with SF-36, SF-36V, and SSQOL-A. It differentiated patients from healthy participants with a sensitivity of 78.4% and a specificity of 77.1%. The minimal detectable change with 95% CI was 1.02 (22.4%). Conclusions: The FSS-A showed good psychometric properties suggesting its usefulness as a fatigue evaluation tool in patients diagnosed with stroke.

Nonadherence to Antiepileptic Medications: Still a Major Issue to be Addressed in the Management of Epilepsy.

CONTEXT: Medication nonadherence is a significant barrier in achieving seizure freedom in patients with epilepsy. There is a deficiency of data about the reasons for nonadherence in Saudi population. AIMS: The aim of this study is to prove the existence of nonadherence to antiepileptic drugs (AEDs) in patients with epilepsy and identify the responsible factors. SETTING AND DESIGN: This is a prospective, cross-sectional study carried in the Department of Neurology at King Fahd Hospital of the University affiliated with Imam Abdulrahman Bin Faisal University. SUBJECTS AND METHODS: Patients of all ages diagnosed to have epilepsy as mentioned in their medical record and taking antiepileptic medications were interviewed using a questionnaire. STATISTICAL ANALYSIS USED: Statistical analysis was performed using IBM Statistical Package for the Social Sciences version 21 (IBM Corp., Armonk, NY, USA). Statistical significance was defined as two-tailed with a P ≤ 0.05. RESULTS: Among 152 participants, 52.6% were male and 47.4% were female. Mean age of the patients was 28 ± 14.3 (mean ± standard deviation) years. Of 152 patients, 48.7% were found to be nonadherent to their AED therapy. The most commonly identified factor was forgetfulness. Nonadherence was significantly associated with poor seizure control (P = 0.002). CONCLUSION: Nonadherence to the AED is common among patients with epilepsy and affects seizure control adversely.