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1.
Front Mol Biosci ; 11: 1341950, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38516193

RESUMO

Introduction: Parkinson's disease (PD) is the most common motor neurodegenerative disease worldwide. Given the complexity of PD etiology and the different metabolic derangements correlated to the disease, metabolomics profiling of patients is a helpful tool to identify patho-mechanistic pathways for the disease development. Dopamine metabolism has been the target of several previous studies, of which some have reported lower phenylalanine and tyrosine levels in PD patients compared to controls. Methods: In this study, we have collected plasma from 27 PD patients, 18 reference controls, and 8 high-risk controls to perform a metabolomic study using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Results: Our findings revealed higher intensities of trans-cinnamate, a phenylalanine metabolite, in patients compared to reference controls. Thus, we hypothesize that phenylalanine metabolism has been shifted to produce trans-cinnamate via L-phenylalanine ammonia lyase (PAL), instead of producing tyrosine, a dopamine precursor, via phenylalanine hydroxylase (PAH). Discussion: Given that these metabolites are precursors to several other metabolic pathways, the intensities of many metabolites such as dopamine, norepinephrine, and 3-hydroxyanthranilic acid, which connects phenylalanine metabolism to that of tryptophan, have been altered. Consequently, and in respect to Metabolic Control Analysis (MCA) theory, the levels of tryptophan metabolites have also been altered. Some of these metabolites are tryptamine, melatonin, and nicotinamide. Thus, we assume that these alterations could contribute to the dopaminergic, adrenergic, and serotonergic neurodegeneration that happen in the disease.

2.
BMC Neurol ; 23(1): 387, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37884861

RESUMO

BACKGROUND: Sleep difficulties following a cerebrovascular stroke are an interesting topic in the scientific community. Following a brain ischemic insult, a variety of sleep problems can occur. AIM OF WORK: To study the sleep architecture following stroke and to identify the impact of site, size and severity of ischemic cerebrovascular troke on sleep microstructure. SUBJECTS AND METHODS: this was a case control study; polysomnogram was done for 93 patients admitted to the stroke unit at El- Hadara university hospital with the first ever ischemic stroke. NIHSS was calculated immediately and 1 month after stroke onset. 50 age matched control subjects with no evidence of central nervous system or major psychiatric disorder by history or clinical examination. RESULTS: Total sleep time, sleep efficiency were lower in ischemic cerebrovascular stroke patients than in control group and this was statistically significant (p = .001* p = .0001* respectively). Arousal index limb movement index and snoring index were all higher among the ischemic cerebrovascular stroke group in comparison to the control group and this was statistically significant (p = .0001*p = .05*p = .0001). Both the REM(rapid eye movement) and REM latency were highest among brain stem stroke, and this was statistically significant p = .043*, p = .0.001*.cortical infarcts showed higher AHI (apnea hypopnea index)and this was statistically significant p = 0.002* Limb movement index was higher among sizable size stroke and this was statistically significant (p = 0.038). NIHSS National Institutes of Health Stroke Scale after 1 month follow up showed a significant indirect correlation with the lowest oxygen saturation during sleep (p = 0.047). Lowest oxygen saturation was lowest among sizable stokes and desaturation index was highest among sizable size strokes both were statistically significant p = 0.006. NIHSS2 had a significant negative correlation with the lowest oxygen saturation during sleep p = 0.047. CONCLUSION: The microstructure of sleep is significantly impacted by cerebrovascular stroke. Brain stem strokes had the highest REM and REM latency, while cortical strokes had the highest moderate-to-severe AHI. Sizable strokes displayed increased indices of limb movement, desaturation, and oxygen saturation.


Assuntos
AVC Isquêmico , Apneia Obstrutiva do Sono , Acidente Vascular Cerebral , Humanos , Estudos de Casos e Controles , Egito/epidemiologia , Sono , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/diagnóstico
3.
Mult Scler Relat Disord ; 79: 104962, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37714097

RESUMO

BACKGROUND: Multiple Sclerosis (MS) is an immune-mediated, chronic disease of the central nervous system that affects mainly adults. However, it is increasingly recognized that MS may start in childhood resulting in a relentlessly progressive disability and cognitive impairment. Registries across the globe are reporting inconstant data about their Pediatric-Onset Multiple Sclerosis (POMS) patients. Moreover, newer lines of treatments are emerging and showing efficacy in controlling the MS disease regardless of the onset. Therefore, there is a requirement for more research into the clinical profile of POMS in different populations and ethnicities. METHODS: This study was a cross-sectional study that included MS patients who visited the MS unit at Alexandria University from January 2019 to January 2021. We analyzed their epidemiological, clinical, radiological data, and cerebrospinal fluid (CSF) results from their updated records as well as follow-up interviews. RESULTS: Annual Relapse Rate (ARR) was marginally less in POMS than AOMS (0.72 ± 0.57 vs 1.04 ± 0.78 relapse/year, P =.008). POMS patients had a bigger gap to their first relapse (40.0 ± 47.35 vs 22.71 ± 34.33 months, p= .066). The difference in relapse rate between the two groups was abolished after the exclusion of patients who had a gap of more than 5 years to their first relapse. AOMS patients were significantly more likely to start with a second-line disease-modifying treatment (DMT) than POMS patients (11.5% vs 31%, p= .04), whereas POMS patients were more likely to be escalated to the second line (34.6% vs 19.3%, p= .07). ARR had a positive and significant correlation with expanded disability status scale (EDSS) progression per year (rs(24)= .57 p=.003). A Mann-Whitney test indicated that POMS patients who had infratentorial involvement in the initial MRI brain had higher EDSS (3.08 ± 1.99) than POMS who did not (1.07 ± 0.79) U=24 P =.013. IgG index had a significant and positive correlation with annual EDSS progression rate rs (8) = 0.8 p=.001. CONCLUSION: Early disease onset does not mean a higher relapse rate when including the full spectrum of POMS and longer follow-up duration. POMS patients relapsed more on the first-line DMT and escalation should be considered early. Infratentorial involvement in the initial magnetic resonance imaging (MRI) brain and high IgG index are potential predictors for aggressive disease course in POMS.


Assuntos
Esclerose Múltipla , Criança , Humanos , Adulto , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/terapia , Estudos Transversais , Idade de Início , Sistema de Registros , Recidiva , Imunoglobulina G
4.
J Egypt Public Health Assoc ; 98(1): 5, 2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36878998

RESUMO

BACKGROUND: The COVID-19 pandemic has impacted medical professionals' job satisfaction and was a call to adopt telemedicine. Finding out how far medical professionals are satisfied and ready to use telemedicine would be important to improve medical practice. METHODS: Data was collected from 959 medical professionals from both the governmental and private health sectors in Egypt in 2021 using a specifically designed online questionnaire, to evaluate job satisfaction, perception of telemedicine, and propose solutions to improve medical practice. RESULTS: The study revealed low to moderate job satisfaction at governmental (27.2%) and private (58.7%) sectors. Underpayment was the most reported challenge at both sectors (37.8% and 28.3%, respectively). Dissatisfaction with government salary was independently predicted by working at the Ministry of Health and Population (OR = 5.54, 95%CI = 2.39,12.8; p < 0.001). Wage increase (46.10%), medical training of professionals (18.1%), and management of non-human resources (14.4%) were the most proposed solutions to improve medical practice in Egypt. During the COVID-19 pandemic, 90.7% of medical professionals had practiced telemedicine with moderate level of perception of its benefits (56%). CONCLUSIONS: During the COVID-19 pandemic, medical professionals reported low to moderate job satisfaction and a moderate level of perception of telemedicine. It is recommended to analyze the healthcare financing system and provide continuous training of medical professionals to improve medical practice in Egypt.

5.
Epilepsy Res ; 191: 107089, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36801489

RESUMO

OBJECTIVE: MiRNAs are important gene-regulating agents in epilepsy development, according to new research. The purpose of this study is to investigate the relationship between serum expression of miR-146a-5p and miR-132-3p and epilepsy in Egyptian patients as potential diagnostic and therapeutic biomarkers. METHODS: MiR-146a-5p and miR-132-3p were measured in the serum of 40 adult epilepsy patients and 40 controls using real-time polymerase chain reaction. The comparative cycle threshold (CT) approach (2-ΔΔCT) was used to compute relative expression levels, which were normalized to cel-miR-39 expression and compared to healthy controls. The diagnostic performance of miR-146a-5p and miR-132-3p was assessed using receiver operating characteristic curve analysis. RESULTS: The relative expression levels of miR-146a-5p and miR-132-3p in serum were considerably greater in epilepsy patients than in the control group. There was a significant difference in the miRNA-146a-5p relative expression in the focal group when the non-responders were compared with the responders' groups, and a significant difference when comparing the non-responders' focal and the non-responders' generalized groups, however, univariate logistic regression analysis revealed that increased seizure frequency is the only risk factor among all factors affecting the drug response There was a significant difference in epilepsy duration between miR-132-3p high and low expression. With an area under the curve of 0.714 (95% C. I 0.598-0.830; P = 0.001), the combined miR-146a-5p and miR-132-3p serum levels performed better than each separately as a diagnostic biomarker to distinguish epilepsy patients from controls. SIGNIFICANCE: The findings imply that both miR-146a-5p and miR-132-3p may be involved in epileptogenesis regardless of epilepsy subtypes. Although the combined circulating miRNAs may be useful as a diagnostic biomarker, they are not a predictor of drug response. MiR-132-3p might be used to predict epilepsy's prognosis by demonstrating its chronicity.


Assuntos
MicroRNA Circulante , Epilepsia , MicroRNAs , Adulto , Humanos , MicroRNAs/metabolismo , Biomarcadores , Prognóstico , Curva ROC
6.
Eur Radiol Exp ; 6(1): 49, 2022 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-36074209

RESUMO

BACKGROUND: Though abnormal iron deposition has been reported in specific brain regions in multiple sclerosis (MS), no data exist about whether the overall quantity of iron in the brain is altered or not. We aimed to determine whether the noted aberrant iron deposition in MS brains was a problem of overall load or regional distribution in a cohort of MS patients. METHODS: An experienced neuroradiologist, a radiology software engineer, and four neurologists analysed data from quantitative susceptibility maps reconstructed from 3-T magnetic resonance brain images of 30 MS patients and 15 age- and sex-matched healthy controls. Global brain iron load was calculated, and the regional iron concentrations were assessed in 1,000 regions of interest placed in MS lesions in different locations, normal appearing white matter, thalami, and basal ganglia. RESULTS: Global brain iron load was comparable between patients and controls after adjustment for volume (p = 0.660), whereas the regional iron concentrations were significantly different in patients than in control (p ≤ 0.031). There was no significant correlation between global iron load and clinical parameters, whereas regional iron concentrations correlated with patients' age, disease duration, and disability grade (p ≤ 0.039). CONCLUSIONS: The aberrant iron deposition noted in MS seems to be a problem of regional distribution rather than an altered global brain iron load.


Assuntos
Esclerose Múltipla , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Humanos , Ferro/análise , Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla/diagnóstico por imagem
7.
Sleep Sci ; 15(1): 8-16, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35662958

RESUMO

Objectives: COVID-19 pandemic imposed a relevant number of stressful factors potentially impacting either daytime function or sleep quality. This study aimed to assess the sleep quality and anxiety among the general population living in Egypt. Material and Methods: A cross-sectional survey was conducted among 1,000 individuals who have been recruited via a convenience sample. A predesigned questionnaire was distributed online to collect data on sleep quality using the validated Arabic version of the Pittsburgh sleep quality index, anxiety disorders by the generalized anxiety disorder (GAD-7) scale, demographic characteristics, and clinical history. Results: Among the study participants (33.8% males, 46.2% healthcare workers, 25% had chronic diseases, 30.1% were physically active during lockdown, and 70.3% reported work termination due to COVID-19 infection, 68.4% complained of bad sleep and 70.3% showed clinically significant levels of anxiety). In multiple logistic regression analysis, bad sleep quality was significantly associated with moderate anxiety (OR: 1.88; [95% CI: 1.37-2.60]), severe anxiety (OR: 3.15; [95% CI: 2.18-4.55]), being physically active (OR: 0.53; [95% CI: 0.39-0.71]), received higher education as being postgraduate (OR: 0.56; [95% CI: 0.35-0.92]), or living with family (OR: 0.74; [95% CI :0.56-0.98]).The GAD-7 scale added 8% discrimination power for prediction of bad sleep quality compared to the model based on demographic and clinical data [with GAD: AUC=0.70, p<0.001; without GAD: AUC=0.62, p<0.001]. Conclusion: COVID-19 had a significant impact on sleep quality and anxiety among Egyptians. Since both the conditions may overlap and potentiate each other leading to chronic dysfunctional outcomes, an accurate assessment and clinical approach may favor a better prognosis.

8.
Mult Scler Relat Disord ; 57: 103354, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35158462

RESUMO

BACKGROUND: Multiple Sclerosis is the most common chronic demyelinating disease of the central nervous system, representing the main cause of non-traumatic disabling disorders in young adults. The etiology of Multiple Sclerosis is not fully appreciated, although strong evidence points to genetic and environmental factors. The role of the gut microbiome in Multiple Sclerosis pathogenesis is a rapidly emerging area of study in that field. AIM: The aim of the present study is to identify the gut microbiome that are likely related to Multiple Sclerosis as well as their possible role in the susceptibility and the course of the disease. METHODS: Thirty Egyptian patients with relapsing remitting multiple sclerosis, who presented to the Multiple Sclerosis Clinic of Alexandria University Hospital were enrolled in the study. These were diagnosed according to the McDonald 2017 criteria. A cross matching control group of 20 healthy subjects of similar age and sex was included. Stool specimens were taken from each for detection of gut microbiome profile by quantitative SYBR Green Real Time PCR assay. RESULTS: The present study demonstrate that RRMS patients have a distinct gut microbiome compared to healthy controls, with certain gut microbes showing decreased or increased abundance in Multiple Sclerosis patients compared to controls. Multiple Sclerosis patients have significantly higher B. fragilis than the normal control. Although the level of Prevotella, and Lactobacilli appear much less in MS patients than the control, the difference was not statistically significant. The same for C. perfringes which was higher in Multiple Sclerosis patients. CONCLUSION: The overall results of the study agree with previous studies reporting that patients with Multiple Sclerosis in Egypt exhibit microbial gut dysbiosis. However, the results of individual bacteria may differ, according to the age, treatment, level of physcial exercise and type of therapy at the time of enrollment.


Assuntos
Microbioma Gastrointestinal , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Disbiose , Egito , Humanos , Adulto Jovem
9.
J Clin Sleep Med ; 18(3): 721-729, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34605391

RESUMO

STUDY OBJECTIVES: Sleep apnea is a chronic disorder associated with multiple recognized comorbidities. Only a few studies focus on evaluating the cognitive profile in patients diagnosed with sleep apnea. The aim of the study was to assess the cognitive functions in this population using the Montreal Cognitive Assessment. METHODS: The study cohort was 1,445 adult patients who were referred for overnight polysomnography, 764 cases and 681 healthy controls. All participants' clinical data and comorbidities were taken, and they all performed overnight polysomnography and Montreal Cognitive Assessment. RESULTS: A significantly higher proportion (57.5%) of sleep apnea groups were males; 15.7% were illiterate compared to the non-sleep apnea group. Hypertension and diabetes mellitus were significantly more prevalent among studied patients with sleep apnea, and the mean total score for the Montreal Cognitive Assessment scale was significantly lower among those with sleep apnea at P < .001. Those with no sleep apnea showed a significantly higher function in all attributes compared to patients with sleep apnea-namely, language, orientation, abstraction, naming, attention, and recall (P < .05). CONCLUSIONS: Logistic regression analysis was conducted to investigate predictors for occurrence of cognitive impairment (Montreal Cognitive Assessment score < 26) among the studied sample (n = 1,445). The overall model was significant at P < .001. Variables that showed significance in univariate analysis were entered in the model. Significant predictors for cognitive impairment were being male, older age, diabetic, hypertensive, and with a lower level of education and having sleep apnea. CITATION: Mekky JF, Yousof S, Elsayed I, Elsemelawy R, Mahmoud H, Elweshahi H. Assessment of the cognitive functions in adult Egyptian patients with obstructive sleep apnea using the Montreal Cognitive Assessment: a retrospective large-scale study. J Clin Sleep Med. 2022;18(3):721-729.


Assuntos
Idioma , Apneia Obstrutiva do Sono , Adulto , Cognição , Egito/epidemiologia , Humanos , Masculino , Estudos Retrospectivos , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia
10.
Neurobiol Sleep Circadian Rhythms ; 11: 100069, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34258472

RESUMO

It is well established that certain alteration of sleep disorders occur in patients with wake-up stroke (WUS) such as sleep disordered breathing, periodic limb movements and sleep duration. However, the data are lacking about the microarchitecture of different sleep stages among those patients. AIM OF WORK: To compare the polysomnographic microarchitecture of rapid eye movement (REM) sleep between WUS and daytime stroke (DTS). METHODS: A cross-sectional polysomnographic study was conducted on 20 patients with WUS and 20 patients with DTS, with analysis of REM sleep microarchitecture in specific. RESULTS: Patients with WUS had significantly shorter REM stage (11.76 ± 5.48% in WUS versus 16.59 ± 5.33% in DTS, P = 0.008), longer early morning REM was (25.70 ± 13.13 min in WUS versus 4.15 ± 4.69 min in DTS, P=<0.001), higher apnea-hypopnea index (AHI) during REM (6.29 ± 10.18 in WUS versus 1.10 ± 4.57 in DTS, P = 0.009), and lower mean Oxygen saturation during REM (92.70 ± 3.63 WUS versus 95.45 ± 1.35 DTS, P = 0.012). The OR of early morning REM duration was 1.8 (CI 1.099-3.130, p = 0.021) for WUS. CONCLUSION: The microarchitecture of REM sleep is disrupted in patients with wake-up stroke.

11.
World Neurosurg ; 150: e279-e286, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33689851

RESUMO

OBJECTIVE: To study pattern and rate of neurological functional recovery after surgery for cervical spondylotic myelopathy (CSM). METHODS: This prospective study comprised 25 patients with CSM who underwent surgical decompression at our institution. Upper limb, lower limb, and sphincter functions were assessed using the modified Japanese Orthopaedic Association score (mJOA). Assessment was done before the operation and at 1 month, 3 months, and 1 year after surgery. RESULTS: The mJOA score did not significantly increase at 1 month after surgery (P = 0.051); however, increase in mJOA score was statistically significant at 3 and 1 year after surgery (P < 0.001 and P < 0.001, respectively). Upper limb motor dysfunction improved in 65% of patients, lower limb motor dysfunction improved in 52% of patients, upper limb sensory dysfunction improved in 48% of patients, and sphincter dysfunction improved in 14.2% of patients. There was a significant positive correlation between preoperative and postoperative mJOA score at 1 month, 3 months, and 1 year after surgery. CONCLUSIONS: Minimal improvement occurred in the first month after CSM surgery to reach a peak at 3 months after surgery and steady improvement up to 1 year after surgery. Upper limbs recovered better and earlier than lower limbs and sphincter function. Preoperative severity of CSM is one of the main predictors of postoperative neurological outcome.


Assuntos
Descompressão Cirúrgica/métodos , Procedimentos Neurocirúrgicos/métodos , Compressão da Medula Espinal/cirurgia , Espondilose/cirurgia , Adulto , Idoso , Canal Anal/fisiopatologia , Vértebras Cervicais/cirurgia , Egito , Feminino , Seguimentos , Humanos , Monitorização Neurofisiológica Intraoperatória , Extremidade Inferior/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recuperação de Função Fisiológica , Resultado do Tratamento , Extremidade Superior/fisiopatologia
12.
Neuropsychiatr Dis Treat ; 16: 3187-3196, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33376334

RESUMO

INTRODUCTION: Substance abuse is a complex issue requiring multi-disciplinary management. Protracted abstinence syndrome leads to persistent discomfort even after detoxification lasting months, resulting in poor sleep duration and quality. Despite being a major contributor to relapse and sleep disturbances, no objective assessment procedures to monitor sleep after the detoxification have been reported. The study aims to assess sleep structure after detoxification via polysomnography and psychometrically assess sleep over the next 6 months in abstinent and relapsing patients. METHODS: Sixty successfully detoxified males (35.8 ± 7.3 years) with a history of heroin abuse (DSM-V) (mean composite scores (ASI): 1.3 ± 0.06, 3.48 ± 0.38, 5.45 ± 0.63, 1.2 ± 0.19, 3.93 ± 0.9, and 2.61 ± 0.8 for medical status, employment/support status, alcohol/drugs status, legal status, family/social relationships, and psychiatric status, respectively) were recruited immediately following their detoxification, without giving additional psychoactive substances or medications. Polysomnography was done in the second week following detoxification to allow washout of medications, followed by a monthly sleep assessment through sleep diary and daytime sleepiness using a visual analog scale. Relapse was proved by a urine test. Polysomnographic parameters and ASI subscales for relapsing and non-relapsing participants were compared using a 2-tailed Student's t-test (p<0.05). RESULTS: Eighteen participants relapsed by 6 months (12 by 3 months). Only the ASI legal problems score was significantly different for the two groups (p=0.001). The differences were significant for NREM stages I (p=0.001) and II (p=0.002), bilateral limb movement (p=0.009), and arousal indices (p=0.001). CONCLUSION: Measuring polysomnographic parameters (percentage of NREM I and II, arousal index, and limb movement index) for sleep disturbance in detoxified heroin-abuse patients can be potential predictors for relapse in a 6-month follow-up.

13.
Epilepsy Behav ; 107: 107064, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32320932

RESUMO

BACKGROUND: Sleep and epilepsy are bedfellows, and they affect each other reciprocally. Despite the well-known relationship between sleep and epilepsy, data about the impact of sleep on seizure control and responsiveness to therapy are scarce. OBJECTIVE: The aim of this work was to study the impact of sleep architecture in drug-naïve patients with idiopathic generalized epilepsy (IGE) on seizure control and responsiveness to treatment. METHODS: This is a prospective cohort study conducted on thirty newly diagnosed patients with IGE attending the epilepsy clinic in Alexandria University Hospital in Egypt and thirty healthy controls. All recruited subjects had a baseline overnight polysomnographic study, then patients were given sodium valproate in therapeutic doses and followed up for six months for assessment of seizure control. After follow-up, they were classified into fully controlled and inadequately controlled patients, and a comparison between them was made. RESULTS: Of the recruited patients, 13 were fully controlled. Rapid eye movement (REM) sleep % was significantly lower among inadequately controlled patients (9.01 ±â€¯6.23) than fully controlled group (19.6 ±â€¯9.01) and controls (18.17 ±â€¯4.85) (p = 0.002), and the REM sleep latency was significantly longer among the inadequately controlled patients (115.7 ±â€¯72.8 min) than fully controlled patients (54.6 ±â€¯77.3 min) and controls (68.75 ±â€¯37.95 min) (p = 011). On univariate regression analysis, the Odd's ratio (OR) for REM sleep percentage was 3.04 (p = 0.001). CONCLUSION: Rapid eye movement sleep percentage and latency can contribute to seizure control in IGE.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia Generalizada/tratamento farmacológico , Epilepsia Generalizada/fisiopatologia , Convulsões/tratamento farmacológico , Convulsões/fisiopatologia , Sono REM/fisiologia , Adolescente , Adulto , Anticonvulsivantes/farmacologia , Criança , Estudos de Coortes , Egito/epidemiologia , Epilepsia Generalizada/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Convulsões/epidemiologia , Sono REM/efeitos dos fármacos , Ácido Valproico/farmacologia , Ácido Valproico/uso terapêutico , Adulto Jovem
14.
Seizure ; 78: 71-77, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32213443

RESUMO

PURPOSE: Therapeutic drug monitoring (TDM) is increasingly recommended in antiepileptic drug (AED) therapy, yet a complex relationship exists between the unbound-drug serum concentration (Cu.serum) as a monitoring biomarker and clinical efficacy. The study was designed to investigate the validity of the intracellular unbound-drug concentration in Peripheral Blood Mononuclear Cells (Cu.PBMC) as a feasible TDM tool in relation to levetiracetam (LEV). METHODS: Patients from epilepsy out-patient centre were included in a 4-month descriptive prospective study. Trough serum and PBMC LEV concentrations were monthly determined using HPLC and correlated with clinical features, demographic data, and P-glycoprotein (P-gp) expression. RESULTS: Seventy-patients completed the study with a LEV dose range of 500-3000 mg/day. An absolute range for LEV Cu.serum and Cu.PBMC was 1.00-26.99 and 0.33-4.43 µg/mL, respectively. Unlike Cu.serum, the average four-month LEV Cu.PBMC displayed a significant positive correlation with clinical features and P-gp expression; where patients with higher LEV Cu.PBMC experienced less number of seizure/month, better cognition and quality of life, and had a more reduction in P-gp expression, but no significant correlation with LEV daily dose was observed. A therapeutic response threshold of ≥ 0.82 µg/mL for LEV Cu.PBMCwas perceived by using a receiver operating characteristic curve that related the number of seizure/month to the LEV Cu.PBMC. The validity of this therapeutic threshold was significant in contrast to LEV Cu.serum. CONCLUSION: Levetiracetam PBMC concentration is a more sensitive biomarker for LEV efficacy and correlates better with clinical events than Cu.serum and could represent a novel tool for more precise LEV monitoring.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/sangue , Anticonvulsivantes/sangue , Monitoramento de Medicamentos/normas , Epilepsia/tratamento farmacológico , Epilepsia/fisiopatologia , Leucócitos Mononucleares , Levetiracetam/sangue , Adolescente , Adulto , Anticonvulsivantes/administração & dosagem , Biomarcadores , Monitoramento de Medicamentos/métodos , Epilepsia/sangue , Feminino , Humanos , Levetiracetam/administração & dosagem , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Estudos Prospectivos , Qualidade de Vida , Sensibilidade e Especificidade , Adulto Jovem
15.
IEEE Trans Neural Syst Rehabil Eng ; 26(2): 527-537, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29432118

RESUMO

Electrical stimulation optimization is a challenging problem. Even when a single region is targeted for excitation, the problem remains a constrained multi-objective optimization problem. The constrained nature of the problem results from safety concerns while its multi-objectives originate from the requirement that non-targeted regions should remain unaffected. In this paper, we propose a mixed integer linear programming formulation that can successfully address the challenges facing this problem. Moreover, the proposed framework can conclusively check the feasibility of the stimulation goals. This helps researchers to avoid wasting time trying to achieve goals that are impossible under a chosen stimulation setup. The superiority of the proposed framework over alternative methods is demonstrated through simulation examples.


Assuntos
Estimulação Elétrica/métodos , Programação Linear , Algoritmos , Encéfalo/fisiologia , Córtex Cerebral , Estimulação Elétrica/instrumentação , Eletrodos , Análise de Elementos Finitos , Humanos , Reprodutibilidade dos Testes
16.
Sleep Med ; 38: 116-121, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29031745

RESUMO

AIM: The aim is to analyze the sleep architecture using polysomnography (PSG) in patients with Juvenile Myoclonic Epilepsy (JME): (newly diagnosed and those on valproate drug) attending epilepsy clinic at Alexandria University Hospitals. METHODS: This study involved 20 patients with JME on valproate (age: 22.40 ± 5.80 years; M:F = 6:14), 20 newly diagnosed patients (age: 18.55 ± 6.0 years; M:F = 6:14), and 20 matched healthy controls (age: 22.10 ± 5.0 years; M:F = 6:14). Clinical assessment, electroencephalogram (EEG), evaluation with comprehensive sleep questionnaire, and PSG were done for all patients. RESULTS: PSG showed significant alterations in sleep architecture in the total JME group in the form of reduced mean sleep efficiency (p = 0.001∗), increased mean Rapid eye movement (REM) onset latency (p = 0.046∗), decrease mean REM percentage (p = 0.011∗), increased mean wakefulness after sleep onset (p = 0.018∗), increase the index of total arousal (p = 0.005∗), increased mean periodic limb movement index (P = 0.001∗), and reduced apnea hypopnea index (P = <0.001) in comparison to control group. Valproate treated group showed increased sleep efficiency (p = 0.040∗), decreased REM arousal index (P = 0.012), longer stage 3 (P = 0.038), and prolonged stage 2 (P = 0.049∗) than the newly diagnosed group. CONCLUSIONS: Sleep architecture was significantly disturbed in JME, with improvement in sleep efficiency in valproate treated patients.


Assuntos
Epilepsia Mioclônica Juvenil/fisiopatologia , Sono , Adolescente , Adulto , Anticonvulsivantes/uso terapêutico , Eletroencefalografia , Feminino , Humanos , Masculino , Epilepsia Mioclônica Juvenil/complicações , Epilepsia Mioclônica Juvenil/tratamento farmacológico , Polissonografia , Sono/efeitos dos fármacos , Sono/fisiologia , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/fisiopatologia , Inquéritos e Questionários , Ácido Valproico/uso terapêutico , Adulto Jovem
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