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Protein-protein interactions, or PPIs, are a part of every biological activity and have been linked to a number of diseases, including cancer, infectious diseases, and neurological disorders. As such, targeting PPIs is considered a strategic and vital approach in the development of new medications. Nonetheless, the wide and flat contact interface makes it difficult to find small-molecule PP inhibitors. An alternative strategy would be to use the PPI interaction motifs as building blocks for the design of peptide-based inhibitors. Herein, we designed 12-mer peptide inhibitors to target p25-inducing-cyclin-dependent kinase (Cdk5) hyperregulation, a PPI that has been shown to perpetuate neuroinflammation, which is one of the major causal implications of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and frontotemporal dementia. We generated a library of 5 062 500 peptide combination sequences (PCS) derived from the interaction motif of Cdk5/p25 PP interface. The 20 amino acids were differentiated into six groups, namely, hydrophobic (aliphatic), aromatic, basic, acidic, unique, and polar uncharged, on the basis of their physiochemical properties. To preserve the interaction motif necessary for ideal binding, de novo modeling of all possible peptide sequence substitutions was considered. A set of filters, backed by the Support Vector Machine (SVM) algorithm, was then used to create a shortlisted custom peptide library that met specific bioavailability, toxicity, and therapeutic relevance, leading to a refined library of 15 PCS. A greedy algorithm and coarse-grained force field were used to predict peptide structure and folding before subsequent modeling studies. Molecular docking was performed to estimate the relative binding affinities, and out of the top hits, Pep15 was subjected to molecular dynamics simulations and binding free-energy calculations in comparison to a known peptide inhibitor with experimental data (template peptide). Interestingly, the identified peptide through our protocol, Pep15, was found to show a significantly higher binding affinity than the reference template peptide (-48.10 ± 0.23 kcal/mol and -17.53 ± 0.27 kcal/mol, respectively). In comparison to the template peptide, Pep15 was found to possess a more compact and buried surface area, tighter binding landscape, and reduced conformational variability, leading to enhanced structural and kinetic stability of the Cdk5/p25 complex. Notably, both peptide inhibitors were found to have a minimal impact on the architectural integrity of the Cdk5/p25 secondary structure. Herein, we propose Pep15 as a novel and potentially disruptive peptide drug for Cdk5/p25-mediated neurodegenerative phenotypes that require further clinical investigation. The systematic protocol and findings of this report would serve as a valuable tool in the identification of critical PPI interface reactive residues, designing of analogs, and identification of more potent peptide-based PPI inhibitors.
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Hsp27 is a member of the small heat-shock proteins (sHSPs) - the known cellular line of defence against abnormal protein folding behaviors. Nevertheless, its upregulation is linked to a variety of pathological disorders, including several types of cancers. The ceramide synthases (CerS) mediate the synthesis of ceramide, a critical structural and signaling lipid. Functionally, downstream ceramide metabolites are implicated in the apoptosis process and their abnormal functionality has been linked to anticancer resistance. Studies showed that CerS1 are possibly inhibited by Hsp27 leading to biochemical anticancer effects in vitro. Nevertheless, the nature of such protein-protein interaction (PPI) has not been considerably investigated in molecular terms, hence, we present the first description of the dynamics CerS1-Hsp27 interaction landscapes using molecular dynamics simulations. Time-scale molecular dynamics simulation analysis indicated a system-wide conformational events of decreased stability, increased flexibility, reduced compactness, and decreased folding of CerS1. Analysis of binding energy showed a favorable interaction entailing 56 residues at the interface and a total stabilizing energy of -158 KJ/mol. The CerS1 catalytic domain experienced an opposite trend compared to the protein backbone. Yet, these residues adopted a highly compact conformation as per DCCM and DSSP analysis. Furthermore, conserved residues (SER 212, ASP 213, ALA 240, GLY 243, ASP 319) comprising the substrate shuttling machinery showed notable rigidity implying a restrained ceramide precursor access and assembly; hence, a possible inhibitory mechanism. Findings from this report would streamline a better molecular understanding of CerS1-Hsp27 interactions and decipher its potential avenue toward unexplored anti-cancer mechanisms and therapy.
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INTRODUCTION: In the United States, it is reported that 1.4% of the general population commits suicide. It has been postulated that antiseizure medications (ASMs) can lead to the development of suicidal ideation and suicidal behavior; however, this risk is still very low and has yet to be precisely established. AREAS COVERED: This narrative review evaluates the risk of suicide-related events (SREs) in subjects taking ASMs for various neurological disorders. Screening tools for suicidal ideation and suicidal behavior are also discussed. References for this article were found using PubMed/MEDLINE. EXPERT OPINION: Although some ASMs can be associated with SREs, this is not yet clearly established. The mechanisms involved in suicide risk in subjects taking ASMs are multifactorial. The bidirectional relationship between depression and epilepsy, as well as other associations, should be kept in mind when interpreting any impact of ASMs in PWE. Screening for SREs, close monitoring of subjects taking ASMs are the most appropriate strategies to minimize suicide risk. More efforts should be made to achieve accurate risk stratification through prognostic models that could be applied to subjects taking ASMs. Studies exploring the association between ASMs and suicide should consider ASMs individually and control for prior SREs.
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Anticonvulsivantes , Epilepsia , Suicidio , Humanos , Suicidio/psicología , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Epilepsia/psicología , Ideación Suicida , Factores de RiesgoRESUMEN
Safe delivery and optimal peripartum and postpartum care in women with epilepsy (WWE) is a major concern which has received limited attention in recent years. A diagnosis of epilepsy per se is not an indication for a planned cesarean section or induction of labor, even though epidemiological studies indicate that cesarean delivery is more common among WWE compared to the general population. Pregnancy in WWE is associated with an increased risk of obstetrical complications and increased perinatal morbidity and mortality, and these risks may be greater among WWE taking ASMs. Wherever feasible, pregnant WWE should be directed to specialist care. Risk minimization includes, when appropriate, dose adjustment to compensate for pregnancy-related changes in the pharmacokinetics of some ASMs. With respect to postpartum management, WWE should be advised that the benefits of breastfeeding outweigh the small risk of adverse drug reactions in the infant.
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Lactancia Materna , Epilepsia , Complicaciones del Embarazo , Humanos , Femenino , Embarazo , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/uso terapéutico , Parto Obstétrico , Resultado del Embarazo/epidemiologíaRESUMEN
BACKGROUND: Diabetes mellitus and central obesity are more common among South Asian populations than among White British people. This study explores the differences in diabetes and obesity in South Asians with stroke living in the United Kingdom, India, and Qatar compared with White British stroke patients. METHODS: The study included the UK, Indian, and Qatari arms of the ongoing large Bio-Repository of DNA in Stroke (BRAINS) international prospective hospital-based study for South Asian stroke. BRAINS includes 4580 South Asian and White British recruits from UK, Indian, and Qatar sites with first-ever ischemic stroke. RESULTS: The study population comprises 1751 White British (WB) UK residents, 1165 British South Asians (BSA), 1096 South Asians in India (ISA), and 568 South Asians in Qatar (QSA). ISA, BSA, and QSA South Asians suffered from higher prevalence of diabetes compared with WB by 14.5% (ISA: 95% confidence interval (CI) = 18.6-33.0, p < 0.001), 31.7% (BSA: 95% CI = 35.1-50.2, p < 0.001), and 32.7% (QSA: 95% CI = 28.1-37.3, p < 0.001), respectively. Although WB had the highest prevalence of body mass index (BMI) above 27 kg/m2 compared with South Asian patients (37% vs 21%, p < 0.001), South Asian patients had a higher waist circumference than WB (94.8 cm vs 90.8 cm, p < 0.001). Adjusting for traditional stroke risk factors, ISA, BSA, and QSA continued to display an increased risk of diabetes compared with WB by 3.28 (95% CI: 2.53-4.25, p < 0.001), 3.61 (95% CI: 2.90-4.51, p < 0.001), and 5.24 (95% CI: 3.93-7.00, p < 0.001), respectively. CONCLUSION: South Asian ischemic stroke patients living in Britain and Qatar have a near 3.5-fold risk of diabetes compared with White British stroke patients. Their body composition may partly help explain that increased risk. These findings have important implications for public health policymakers in nations with large South Asian populations.
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Diabetes Mellitus , Accidente Cerebrovascular Isquémico , Obesidad , Personas del Sur de Asia , Humanos , Diabetes Mellitus/epidemiología , Pueblo Europeo , Accidente Cerebrovascular Isquémico/epidemiología , Obesidad/epidemiología , Estudios Prospectivos , Factores de Riesgo , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: The incidence of stroke in the Middle East is high, given its relatively young population. Smoking is a well-recognized risk factor for ischaemic stroke, and its high regional prevalence may partly account for this increased stroke risk. This research aims to determine whether young male South Asian migrants in Qatar were adversely affected by stroke depending on their smoking status. METHODS: Data from the ongoing international prospective BRAINS study was analysed. Male South Asian migrants to Qatar with a history of ischaemic stroke were recruited. Multivariate regression analysis was used to estimate the effects of comorbidities, such as BMI, hypertension, diabetes, hypercholesterolemia, alcohol consumption, and ischemic heart disease, on the association of age of stroke onset and smoking status. RESULTS: We identified 778 (mean age 49.5±10.2) migrant male workers of South Asian descent with ischaemic stroke in Qatar, of which 41.3% of the sample were current smokers. Compared to non-smokers, current smokers suffered a stroke 2.03 years earlier (95%CI: 0.60-3.46, P=0.005). Multivariate regression analysis demonstrated that only current smoking status was associated with an earlier age of stroke onset (ß=2.03, SE=0.74, P=0.006). CONCLUSION: Smoking is associated with at least a two-year earlier onset of ischaemic stroke in male South Asian migrants to the Middle East. Our study has important implications for the public health management of migrants in host countries.
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Purpose of Review: This article provides a review of the recent literature related to the FDA-approved drugs that had been repurposed as potential drug candidates against COVID-19. Moreover, we performed a quality pharmacophore study for frequently studied targets, namely, the main protease, RNA-dependent RNA polymerase, and spike protein. Recent Findings: Ever since the COVID-19 pandemic, the whole spectrum of scientific community is still unable to invent an absolute therapeutic agent for COVID-19. Considering such a fact, drug repurposing strategies seem a truly viable approach to develop novel therapeutic interventions. Summery: Drug repurposing explores previously approved drugs of known safety and pharmacokinetics profile for possible new effects, reducing the cost, time, and predicting prospective side effects and drug interactions. COVID-19 virulent machinery appeared similar to other viruses, making antiviral agents widely repurposed in pursuit for curative candidates. Our main protease pharmacophoric study revealed multiple features and could be a probable starting point for upcoming research.
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OBJECTIVES: Rheumatoid arthritis is a chronic inflammatory autoimmune disease. This study aimed to determine the association of interleukin-17A-197G/A polymorphism with rheumatoid arthritis in Sudanese patients. METHODS: A case-control study was conducted between March and December 2018. Clinical and demographic data of the study participants were collected and analyzed. Polymerase chain reaction restriction fragment length polymorphism molecular technique was done to investigate interleukin-17A-197G/A polymorphisms. All statistical tests were considered statistically significant when p < 0.05. RESULTS: The study population included 266 participants aged between 1 and 85 years, with an average of 40 years, classified into 85 (31.2%) cases (mean age 48.5 ± 11.3 years), and 181 (68.8%) controls (mean age 35.3 ± 15.9 years). The interleukin-17A homozygote AA genotype was more frequent among the control group compared to the case group; 95 (52.5%) and 7 (8.2%), respectively. The homozygote GG and the heterozygote AG genotypes were proportionally not different among the cases and control groups; 13 (54.2%) and 11 (45.8%), and 65 (46.4%) and 75 (53.6%), respectively. According to the distribution of interleukin-17A genotypes, a statistically significant difference was observed among cases with the interleukin-17A AA and AG genotypes, p values 0.001 and 0.004, respectively. For the association interleukin-17A genotypes and family history a negatively significant association was reported (95% confidence interval, -0.219, p value = 0.001). There was also a negatively significant association of interleukin-17A genotypes and anti-cyclic citrullinated peptide (95% confidence interval, -0.141, p value = 0.002). CONCLUSION: This study is the first study in Sudan established the association between interleukin-17A-197G/A (rs2275913) polymorphisms and susceptibly to rheumatoid arthritis. These findings appeal for further research in Sudan to investigate the exact role of IL-17A in immunopathology and disease severity among Sudanese rheumatoid arthritis.
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Plasmodium vivax malaria was thought to be rare in Africa, but an increasing number of P. vivax cases reported across Africa and in Duffy-negative individuals challenges this dogma. The genetic characteristics of P. vivax in Duffy-negative infections, the transmission of P. vivax in East Africa, and the impact of environments on transmission remain largely unknown. This study examined genetic and transmission features of P. vivax from 107 Duffy-negative and 305 Duffy-positive individuals in Ethiopia and Sudan. No clear genetic differentiation was found in P. vivax between the 2 Duffy groups, indicating between-host transmission. P. vivax from Ethiopia and Sudan showed similar genetic clusters, except samples from Khartoum, possibly due to distance and road density that inhibited parasite gene flow. This study is the first to show that P. vivax can transmit to and from Duffy-negative individuals and provides critical insights into the spread of P. vivax in sub-Saharan Africa.
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Sistema del Grupo Sanguíneo Duffy/sangre , Eritrocitos/parasitología , Malaria Vivax/sangre , Plasmodium vivax/aislamiento & purificación , África Oriental/epidemiología , Sistema del Grupo Sanguíneo Duffy/genética , Pool de Genes , Variación Genética , Humanos , Malaria Vivax/epidemiología , Malaria Vivax/genética , Plasmodium vivax/genética , Plasmodium vivax/patogenicidad , Receptores de Superficie Celular/genética , SudánRESUMEN
INTRODUCTION: The aim of this study is to provide the reader with a review on Complementary and Alternative Medicine (CAM) treatment in epilepsy in the Middle East and North Africa (MENA) region, to describe the extent and factors associated with its use among patients with epilepsy (PWE), and to recommend how effectively we will be able to reduce this alarming use. MATERIAL AND METHODS: Retrospective literature search from 1945 to December 2019, regarding CAM use in the MENA region, using electronic databases (PubMed, Scopus, Google Scholar, Web of Science). CONCLUSION: The use of CAM and consultation of traditional healers for the treatment of epilepsy has so far been widespread practice for centuries in the MENA region. Lack of health professionals and non-adherence to conventional epilepsy treatment are strongly associated with the use of CAM. Improvement in the level of knowledge of epilepsy among PWE, healthcare professionals, including traditional healers, will educate PWE and their caregivers on potentially unsafe practices and promote adherence to Antiseizure Drugs (ASDs). Additionally, randomized controlled trials are needed to study the role and value of various CAM treatment options in PWEs.
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Terapias Complementarias , Epilepsia , África del Norte/epidemiología , Epilepsia/terapia , Humanos , Medio Oriente , Estudios RetrospectivosRESUMEN
OBJECTIVE: To investigate the prevalence of intracerebral hemorrhage (ICH) using stroke database from the main tertiary hospital in Qatar (Hamad General Hospital) over the period of Dec 2013 to Oct 2017. METHODS: The prevalence of ICH was calculated based on age groups and ethnicity (Qatari nationals, non-Qatari Arab, South east Indian (SI) and Far East Asians (FE)). Thirty-day case fatality rate, poor clinical outcome at discharge (modified Rankin scale (mRS):3-6) and poor long-term outcome (mRS at 90 days: 3-6) were calculated per each age group sex and ethnicity. RESULT: There were 653/4039 (16 %) with ICH. The median age was 53 (IQ range: 45-64) with a male/female ratio: 557/96 (85.3/14.7 %). The 30-day mortality rate was 14.7 % (96/653), poor outcome at discharge (mRS 3-6): 66.8 % (436/653) and poor long-term outcome (mRS 90 days:3-6) 50.1 % (199/397). The prevalence of ICH in Qatar was 24.9 per 100 000. The highest mortality rate was seen in the elderly (≥ 70 years old) (16/67 (23.9 %)) and young group (48/291 (16.5 %)). The most common ethnic group among our ICH population are the following: FE (40.59 per 100 000), Qatari (25.26 per 100 000) and SI ethnic group (24.97 per 100 000). In multiple logistic regression analysis only, old age (≥ 70 years old) was associated with 30 days mortality (adj OR: 2.51, 95 % CI: 1.14-5.54, P = 0.023). Similar regression analysis was also observed that age ≥ 70 years old (adj. OR: 4.18, 95 % CI: 1.27-13.77, P = 0.019), sex (male) (adj. OR: 0.21, 95 % CI: 0.08-0.56, P = 0.002), and ethnicity (SI vs Qatari: adj. OR: 4.08, 95 % CI: 1.28-12.92, P = 0.017); (FE vs Qatari: adj. OR: 2.22, 95 % CI: 0.65-7.67, P = 0.203) are statistically associated with poor outcome. CONCLUSION: The prevalence of ICH was high in the elderly and in the FE, Qatari, and SI ethnic group. Further studies are needed to better understand the differences in ICH prognosis in multiethnic groups.
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Hemorragia Cerebral/etnología , Hemorragia Cerebral/mortalidad , Etnicidad , Recuperación de la Función/fisiología , Adulto , Factores de Edad , Anciano , Hemorragia Cerebral/terapia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Mortalidad/tendencias , Prevalencia , Estudios Prospectivos , Qatar/etnología , Factores Sexuales , Resultado del TratamientoRESUMEN
PURPOSE: To explore various social aspects of life (i.e., employment, education, and driving) in a large sample of patients with functional seizures (FS) living in seven countries from four continents. METHODS: In this retrospective study, we investigated adult patients with FS, who were admitted to the epilepsy monitoring units at centers in Iran, Qatar, USA, France, Georgia, Egypt, and United Arab Emirates (UAE). We studied the social aspects of life in the whole cohort. Then, we compared the social aspects of life between different world regions. RESULTS: Four hundred and forty patients were included (241 from Iran, 56 from Qatar, 52 from France, 41 from the USA, 19 from UAE, 18 from Egypt, and 13 from Georgia). One hundred and twenty six people (30%) had college education, 142 (33%) were employed, and 101 (28%) drove a motor vehicle in their routine daily lives. People with FS and college education were more likely to report a history of sexual abuse compared with those with a lower education. Patients with no loss of responsiveness with their FS were more likely to be employed. Male patients and patients without aura were more likely to drive a motor vehicle in their routine daily lives. None of the social characteristics of the patients with FS showed significant differences among the two large culturally different groups (Muslim nations vs. Christian nations). CONCLUSION: It appears that patients with FS across cultures have significant problems in their social aspects of life.
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Electroencefalografía , Convulsiones , Adulto , Egipto/epidemiología , Francia/epidemiología , Humanos , Irán , Masculino , Qatar , Estudios Retrospectivos , Convulsiones/epidemiología , Emiratos Árabes UnidosRESUMEN
BACKGROUND: Information on the epidemiology of temporal lobe epilepsy associated with hippocampal sclerosis (TLE-HS) from Qatar and the developing countries is scarce. To acquire knowledge on the incidence and prevalence of drug-resistant TLE-HS in Qatar, we designed this analytical and extrapolative systematic review of the existing literature. MATERIAL AND METHODS: We searched the electronic database PubMed from 1947 until April, 2018, using the following search terms in the title: "epilepsy" OR "temporal lobe" OR "hippocampal sclerosis" AND "epidemiology" OR "incidence" OR "prevalence." Relevant original studies, reviews, and their references, were included. We extrapolated from the previous international literature to estimate the epidemiology of drug-resistant TLE-HS in Qatar. RESULTS: The estimated Qatar incidence of epilepsy varies from 50 to 61 per 100 000 persons per year, and the estimated prevalence of epilepsy is 6.54 per 1000 population; the estimated incidence of TLE varies from 9.5 to 11.6 patients per 100 000 population per year and the estimated prevalence of TLE is 1.76 patients per 1000 people, with 4721 patients having TLE in Qatar. Finally, the reviewed studies also helped in making an estimate of the Qatar prevalence of drug-resistant TLE-HS to be between 0.3 and 0.6 cases per 1000 people (804-1609 current patients) and the Qatar incidence of drug-resistant TLE-HS (2.3-4.3 cases per 100 000 people, per year) with 62 to 116 new patients per year. CONCLUSION: Our study suggests that 804 to 1609 current patients (with 62-116 additional patients per year) in Qatar are suffering from drug-resistant TLE-HS; emphasis should be placed on the surgical aspect of the current Qatar Comprehensive Epilepsy Program.
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PURPOSE: We conducted a multicenter international cross-cultural comparative study to investigate clinical semiology and predisposing factors of functional seizures in a large cohort of patients living in different countries around the world. We hypothesized that semiology and predisposing factors of functional seizures differ between various world regions. METHODS: We conducted this retrospective observational study in adults with functional seizures admitted to epilepsy centers in Iran, Qatar, USA, France, Georgia, Egypt, and United Arab Emirates (UAE). We assessed and compared the demographic and clinical seizure characteristics of these patients, according to the patients' reports and review of the ictal recordings during video-electroencephalogram (EEG) monitoring. RESULTS: Five hundred nine patients were included (270 from Iran, 74 from Qatar, 63 from France, 43 from the USA, 22 from Egypt, 20 from UAE, and 17 from Georgia). Although all major manifestations of functional seizures (e.g., aura, loss of responsiveness, generalized motor seizures, ictal injury) were seen in all world regions, seizure semiology differed significantly across countries. Auras, ictal urinary incontinence, and ictal injury were more commonly reported by the American patients than patients from other world regions, whereas loss of responsiveness and generalized motor seizures were more frequently observed in the Iranian and American patients than the European and Arab patients. CONCLUSION: Semiology of functional seizures seems to vary across various regions of the world; socioeconomic, cultural, ethnic, and religious differences may play an essential role in the modulation of functional seizures semiology across different nations and cultures.
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Comparación Transcultural , Internacionalidad , Trastornos Psicofisiológicos/etnología , Trastornos Psicofisiológicos/psicología , Convulsiones/etnología , Convulsiones/psicología , Adolescente , Adulto , Anciano , Estudios Transversales , Electroencefalografía/métodos , Electroencefalografía/tendencias , Femenino , Hospitalización/tendencias , Humanos , Masculino , Anamnesis/métodos , Persona de Mediana Edad , Trastornos Psicofisiológicos/fisiopatología , Estudios Retrospectivos , Convulsiones/fisiopatología , Adulto JovenRESUMEN
In this narrative review, we will discuss some of the significant risks and dramatic consequences that are associated with epilepsy: depression, suicide, seizure-related injuries, and mortality, both in adults and in children. Considering the high prevalence of depression among people with epilepsy (PWE), routine and periodic screening of all PWE for early detection and appropriate management of depression is recommended. PWE should be screened for suicidal ideation regularly and when needed, patients should be referred for a psychiatric evaluation and treatment. When starting an antiepileptic drug (AED) or switching from one to another AED, patients should be advised to report to their treating physician any change in their mood and existence of suicidal ideation. The risk of injuries for the general epilepsy population is increased only moderately. The risk is higher in selected populations attending epilepsy clinics and referral centers. This being said, there are PWE that may suffer frequent, severe, and sometimes even life-threatening seizure-related injuries. The most obvious way to reduce risk is to strive for improved seizure control. Finally, PWE have a 2-3 times higher mortality rate than the general population. Deaths in PWE may relate to the underlying cause of epilepsy, to seizures (including sudden unexpected death in epilepsy [SUDEP] and seizure related injuries) and to status epilepticus, as well as to other conditions that do not appear directly related to epilepsy. Improving seizure control and patient education may be the most important measures to reduce epilepsy related mortality in general and SUDEP in particular.
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Depresión/etiología , Epilepsia/complicaciones , Suicidio , Heridas y Lesiones/etiología , Anticonvulsivantes/efectos adversos , Depresión/epidemiología , Epilepsia/tratamiento farmacológico , Epilepsia/mortalidad , Epilepsia/psicología , Humanos , Prevalencia , Convulsiones/tratamiento farmacológico , Suicidio/psicología , Heridas y Lesiones/epidemiologíaRESUMEN
BACKGROUND AND PURPOSE: Patients with acute stroke and mild or rapidly improving symptoms frequently show progression. The role of reperfusion treatment in such patients is not clear. We hypothesized that progression was most likely in patients with cortical localization and such patients may benefit from thrombolysis. MATERIAL AND METHODS: We interrogated Hamad Stroke Database to evaluate 90-days outcome in patients with acute ischemic stroke admitted within 4 hours and a NIHSS score of ≤6. Evaluation was based on localization (lacunar or cortical), multi-model imaging abnormalities and whether they received rt-PA. The 90-day mRS was used to determine outcome. RESULTS: During study period 6381 patients were admitted with acute stroke. Mild stroke within 4 hours was diagnosed in 506 [no thrombolysis: 381(lacunar: 213; cortical: 168), thrombolysis: 125 (lacunar: 45; cortical: 80)]. The rt-PA treated patients had significantly higher NIHSS (2.94±3.9 versus 1.28±2.46, p<0.0001), increased rates of complications (16.0% versus 3.9%, p<0.0001) and longer hospital stay (6.05±8.1 versus 3.78±3.6 days; p<0.001). In patients with cortical stroke, intracranial arterial occlusions (11.6% vs 3.9%, p<0.0001) and CTP mismatch (22.2% vs 4.4%, p<0.0001) were more frequent in rt-PA treated patients. Discharge mRS (33.6% versus 13.9%, p<0.001) and 90-days mRS (23.2% versus 11.8%, p = 0.002) was significantly worse in patients with cortical stroke (rt-PA-treated and untreated patients). CONCLUSIONS: The outcome in patients with mild stroke depends on lesion location (lacunar versus cortical) and severity of symptoms. Patients who receive rt-PA have significantly larger deficits, increased imaging abnormalities and higher rates of hospital complication, explaining the poor outcome in such subjects.
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Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/patología , Isquemia Encefálica/etiología , Isquemia Encefálica/patología , Progresión de la Enfermedad , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Terapia Trombolítica/métodos , Factores de Tiempo , Activador de Tejido Plasminógeno/metabolismo , Resultado del TratamientoRESUMEN
Although pregnancy is potentially protective against relapses of multiple sclerosis, severe rebound of disease activity after withdrawal of fingolimod may occur. We report a woman with multiple sclerosis who discontinued fingolimod in the first month of her pregnancy. She developed severe disease rebound which responded poorly to steroids. She was started on rituximab, which was continued during the rest of her pregnancy and beyond. Rituximab appeared safe and well tolerated by both mother and infant, and could be considered in pregnancy for those patients with multiple sclerosis who are at high risk of gestational and postpartum relapse.
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Malignant middle cerebral artery [MMCA] infarction has a different topographic distribution that might confound the relationship between lesion volume and outcome. Retrospective study to determine the multivariable relationship between computerized tomographic [CT] infarct location, volume and outcomes in decompressive hemicraniectomy [DHC] for MMCA infarction. The MCA infarctions were classified into four subgroups by CT, subtotal, complete MCA [co-MCA], Subtotal MCA with additional infarction [Subtotal MCAAI] and co-MCA with additional infarction [Co-MCAAI]. Maximum infarct volume [MIV] was measured on the pre-operative CT. Functional outcome was measured by the modified Rankin Scale [mRS] dichotomized as favourable 0-3 and unfavourable ≥4, at three months. In 137 patients, from least favourable to favourable outcome were co-MCAAI, subtotal MCAAI, co-MCA and subtotal MCA infarction. Co-MCAAI had the worst outcome, 56/57 patients with additional infarction had mRS ≥ 4. Multiple comparisons Scheffe test showed no significant difference in MIV of subtotal infarction, co-MCA, Subtotal MCAAI but the outcome was significantly different. Multivariate analysis confirmed MCAAI [7.027 (2.56-19.28), p = 0.000] as the most significant predictor of poor outcomes whereas MIV was not significant [OR, 0.99 (0.99-01.00), p = 0.594]. Other significant independent predictors were age ≥ 55 years 12.14 (2.60-56.02), p = 0.001 and uncal herniation 4.98(1.53-16.19), p = 0.007]. Our data shows the contribution of CT infarction location in determining the functional outcome after DHC. Subgroups of patients undergoing DHC had different outcomes despite comparable infarction volumes.
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Craniectomía Descompresiva/métodos , Infarto de la Arteria Cerebral Media/patología , Procedimientos Neuroquirúrgicos/métodos , Accidente Cerebrovascular/patología , Tomografía Computarizada por Rayos X/métodos , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Infarto de la Arteria Cerebral Media/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/cirugía , Tasa de Supervivencia , Factores de TiempoRESUMEN
BACKGROUND: Qatar is located on the north-eastern coast of the Arabian Peninsula. Qatari natives account for less than 15% of the population while the largest migrant group comprising 60% derives from South Asia. Despite projections that stroke burden in Qatar will increase with population ageing, epidemiological studies focusing on stroke in Qatar are relatively scarce. METHOD: We reviewed the available epidemiological publications relating to Qatar. In addition, we have added to this knowledge by incorporating Qatari data from the on-going Bio-Repository of DNA in Stroke, an independent multinational database of stroke patients. RESULTS: Qatar has low reported incidence and mortality rates of 58 and 9.17 per 100,000 per year, respectively, which may be explained by its middle-aged migrant worker majority population. Correspondingly, South Asian migrants in Qatar suffered younger strokes than Qatari natives (48.7 vs 63.4 years, P < 0.001). Among the most common risk factors identified in stroke patients were hypertension (77.9%), diabetes (43.8%) and hypercholesterolemia (28.5%). Ischaemic stroke was the most frequent subtype amongst migrant South Asians (71.1%). The majority of stroke cases had computed tomography and/or magnetic resonance imaging scans, but only 11.1% of ischaemic strokes were thrombolysed. Qataris on one-year follow up were more often found to have died (6.5% vs 0.3%) and had further stroke/transient ischaemic attack events (17.4% vs 6.4%, P = 0.009) compared to South Asians. CONCLUSION: The burden of stroke is increasing in Qatar, and considerable disparities are observed between the native and migrant populations which likely will require different approaches to management by its healthcare system.