Effects of EPHX1 and CYP3A4*22 genetic polymorphisms on carbamazepine metabolism and drug response among Tunisian epileptic patients.

The aim of this study was to evaluate the impact of polymorphisms in the EPHX1 (c.416A > G, c.337T > C) and CYP3A4*22 genes involved in carbamazepine (CBZ) metabolism and pharmacoresistance among 118 Tunisian patients with epilepsy under maintenance dose of CBZ. These genetic polymorphisms were analyzed by PCR-RFLP. Associations between plasma CBZ concentration, CBZ-E concentration, maintenance doses and metabolic ratio (CBZ-E:CBZ, CBZ-D:CBZ-E) were analyzed with each polymorphism. Both variants of EPHX1 c.416A > G and c.337T > C are significantly associated with higher metabolic ratio CBZ-E:CBZ and seem to decrease the activity of the epoxide hydrolase. The CYP3A4*22 variant allele is significantly associated with lower CBZ-D:CBZ-E ratio and seems also to be associated with less activity of the cytochrome. Our data suggest that certain polymorphisms of metabolizing enzyme genes could influence inter-individual variability of CBZ metabolism.

Hepatic myelopathy with spastic paraparesis: report of two cases and review of the literature.

PURPOSE: The present report illustrates two men aged for 59 and 43 years, respectively, who presented with slowly progressive spastic paraparesis. STUDY DESIGN: Two case reports and review of literature. METHODS: The patent's history, clinical examination, biology, magnetic resonance imaging (MRI) findings and treatment are reported. We also discuss the pathogenesis and various treatment options. RESULTS: Neurologic examination showed spastic paraparesis without other neurological disorders. MRI of the spinal cord and brain were normal. Cytologic examination of cerebrospinal fluid from each patient was normal. Hemogram disclosed a pancytopenia. Partial thromboplastin time was prolonged. Liver function tests revealed raised serum bilirubin, normal alanine aminotransferase and aspartate aminotransferase, reduced total protein and albumin. Plasma ammonia was elevated. Blood vitamin B12 and folate values were in normal ranges. Serum antibodies to human T cell lymphotropic virus, human immunodeficiency virus, syphilis and hepatitis C virus were absent. Hepatitis B virus antibody assay was positive. The electromyographic evaluation for second motor neuron involvement was also normal. Endoscopy revealed esophageal varices and a spleno-renal shunt. CONCLUSIONS: Hepatic myelopathy remains a default diagnosis assigned only after the exclusion of other causes of spastic paraparesis and partial transverse myelopathy. An accurate history, along with appropriate imaging and laboratory findings, is crucial.

Does acute aerobic exercise enhance selective attention, working memory, and problem-solving abilities in Alzheimer's patients? A sex-based comparative study.

Introduction: The present study aimed to evaluate the effect of acute aerobic exercise on certain cognitive functions known to be affected by Alzheimer's disease (AD), with a particular emphasis on sex differences. Methods: A total of 53 patients, with a mean age of 70.54 ± 0.88 years and moderate AD, voluntarily participated in the study. Participants were randomly assigned to two groups: the experimental group (EG), which participated in a 20-min moderate-intensity cycling session (60% of the individual maximum target heart rate recorded at the end of the 6-min walk test); and the control group (CG), which participated in a 20-min reading activity. Cognitive abilities were assessed before and after the physical exercise or reading session using the Stroop test for selective attention, the forward and backward digit span test for working memory, and the Tower of Hanoi task for problem-solving abilities. Results: At baseline, both groups had comparable cognitive performance (p > 0.05 in all tests). Regardless of sex, aerobic acute exercise improved attention in the Stroop test (p < 0.001), enhanced memory performance in both forward (p < 0.001) and backward (p < 0.001) conditions, and reduced the time required to solve the problem in the Tower of Hanoi task (p < 0.001). No significant differences were observed in the number of movements. In contrast, the CG did not significantly improve after the reading session for any of the cognitive tasks (p > 0.05). Consequently, the EG recorded greater performance improvements than the CG in most cognitive tasks tested (p < 0.0001) after the intervention session. Discussion: These findings demonstrate that, irrespective to sex, a single aerobic exercise session on an ergocycle can improve cognitive function in patients with moderate AD. The results suggest that acute aerobic exercise enhances cognitive function similarly in both female and male patients, indicating promising directions for inclusive therapeutic strategies.

A Simple Score for Predicting Paroxysmal Atrial Fibrillation in Patients with Embolic Stroke of Undetermined Source in a Tunisian Cohort Study.

BACKGROUND: The annualized recurrent stroke rate in patients with Embolic Stroke of Undetermined Source (ESUS) under antiplatelet therapy is around 4.5%. Only a fraction of these patients will develop atrial fibrillation (FA), to which a stroke can be attributed retrospectively. The challenge is to identify patients at risk of occult AF during follow-up. OBJECTIVE: This work aims to determine clinical factors and electrocardiographic and ultrasound parameters that can predict occult AF in patients with ESUS and build a simple predictive score applicable worldwide. METHODS: This is a single-center, registry-based retrospective study conducted at the stroke unit of Sahloul University Hospital, Sousse, Tunisia, between January 2016 and December 2020. Consecutive patients meeting ESUS criteria were monitored for a minimum of one year, with a standardized follow-up consisting of outpatient visits, including ECG every three months and a new 24-hour Holter monitoring in case of palpitations. We performed multivariate stepwise regression to identify predictors of new paroxysmal AF among initial clinical, electrocardiographic (ECG and 24-hour Holter monitoring) and echocardiographic parameters. The coefficient of each independent covariate of the fitted multivariable model was used to generate an integerbased point-scoring system. RESULTS: Three hundred patients met the criteria for ESUS. Among them, 42 (14%) patients showed at least one episode of paroxysmal AF during a median follow-up of two years. In univariate analysis, age, gender, coronary artery disease, history of ischemic stroke, higher NIHSS at admission and lower NIHSS at discharge, abnormal P-wave axis, prolonged P-wave duration, premature atrial contractions (PAC) frequency of more than 500/24 hours, and left atrial (LA) mean area of more than 20 cm2 were associated with the risk of occurrence of paroxysmal AF. We proposed an AF predictive score based on (1.771 x NIHSS score at admission) + (10.015 x P-wave dispersion; coded 1 if yes and 0 if no) + (9.841x PAC class; coded 1 if ≥500 and 0 if no) + (9.828x LA class surface; coded 1 if ≥20 and 0 if no) + (0.548xNIHSS score at discharge) + 0.004. A score of ≥33 had a sensitivity of 76% and a specificity of 93%. CONCLUSION: In this cohort of patients with ESUS, NIHSS at both admission and discharge, Pwave dispersion, PAC≥500/24h on a 24-hour Holter monitoring, and LA surface area≥20 cm2 provide a simple AF predictive score with very reasonable sensitivity and specificity and is applicable almost worldwide. An external validation of this score is ongoing.

Effectiveness of Simultaneous Combined Intervention for Enhancing Cognitive Function in Patients with Moderate Alzheimer's Disease.

Background: The evidence supporting the effectiveness of combined interventions in Alzheimer's disease (AD) patients remains inconclusive. Objective: The aim of this study was to evaluate the mid- and long-term effectiveness of physical training, alone or combined with cognitive games, on cognitive performance in patients with moderate AD. Methods: Seventy-nine AD patients (≈73% females, age of ≈70±1 years) were randomly divided into three groups: aerobic-based training (AT-group, n = 27), aerobic-based training plus cognitive games (ACT-group, n = 25), and a control group engaged in reading (CG, n = 26), two sessions per week. Cognitive performance was evaluated at the start, 4th week (W4), end of the 8th week (W8), and after a 4-week detraining period (W12), using problem-solving (Tower-of-Hanoi), selective attention (Stroop-test), and working memory (Digit-Span-test) assessments. Stress levels and quality of life were also evaluated.Results:: Aerobic and combined training induced a positive effect on all cognitive functions tested at W4 (except problem-solving) and W8 (all p < 0.001) with greater improvements in working-memory and problem-solving in ACT-group (p < 0.05). Depression levels also decreased significantly, and quality of life improved at W8 (p < 0.001) in both groups. After 4 weeks of detraining, the beneficial effect of AT and ACT was still observed. The CG did not show any significant improvements at all time points.Conclusions:: Physical and cognitive interventions appear effective for improving cognitive-functions, quality-of-life, and reducing depression in AD patients. Combined training emerges as a more effective strategy to mitigate AD progression. Further research is necessary to validate these results and explore their potential for preventing early cognitive decline.

Post varicella zoster virus myelitis in immunocompetent patients.

We report 2 immunocompetent patients with myelitis. The first was a 55-year old man who developed myelitis after intercostal herpes zoster. The second was a 19-year-old boy who presented with myelopathy after varicella infection. Varicella-zoster virus (VZV) myelitis was diagnosed based on the close temporal relationship between rash and onset of clinical symptoms, and by the elevated rate of anti-VZV IgG in the CSF without oligoclonal bands in the first case, and presence of VZV DNA in the second. The course was favorable after a 3-day course of corticosteroids and 3 weeks of acyclovir. Varicella-zoster virus myelitis is uncommon; it affects essentially immunodepressed patients. We highlight the importance of considering the possibility of VZV myelitis, even in immunocompetent patients. The combination of corticoids and acyclovir must be instituted, quickly, to improve functional outcome.

Spectrum of gastrointestinal lesions of neurofibromatosis type 1: a pictorial review.

Neurofibromatosis type 1 (NF1) is one of the most common genetic disorders. Gastrointestinal manifestations of NF-1 are seldom thought of in routine clinical practice and might thus be significantly under-recognised. Their heterogeneous spectrum ranges from localised microscopic proliferative lesions to grossly recognizable mass-forming neurofibromas, neuroendocrine and gastrointestinal stromal tumours (GIST). The aim of this study is discussing the imaging evaluation and characterisation of the abdomen lesions in patients with NF1. TEACHING POINTS: • Neurofibromatosis type (NF-1) is one of the most common single gene disorders. • Every organ system can be involved and intra-abdominal manifestations are underestimated. • The NF1 abdominal manifestations comprehend five categories of tumours. • Neurogenic tumours including with neurofibromas are the most common type. • Early diagnosis of abdominal manifestations of NF-1 based on imaging patterns is necessary for appropriate treatment to avoid serious organic complications related to tumour mass.

Effects of glutathione S-transferase M1 and T1 deletions on epilepsy risk among a Tunisian population.

Glutathione-S-transferases enzymes are involved in the detoxification of several endogenous and exogenous substances. In this present study, we evaluated the effects of two glutathione-S-transferase polymorphisms, (GSTM1 and GSTT1) on epilepsy risk susceptibility in a Tunisian population. These polymorphisms were analyzed in 229 healthy subjects and 98 patients with epilepsy, using a polymerase chain reaction (PCR). Odds ratio (ORs) was used for analyzing results. The study results demonstrated that individuals with the GSTM1 null genotype were at an increased risk of developing epilepsy [OR=3.80, 95% confidence interval (CI) (2.15-4.78)], whereas no significant effects were observed between individuals with GSTT1 null genotype and epilepsy risk [OR=1.15, 95% CI (0.62-2.12)]. These genotyping finding revealed that the absence of GSTM1 activity could be contributor factor for the development of epilepsy disease.

Modulation at age of onset in tunisian huntington disease patients: implication of new modifier genes.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. The causative mutation is an expansion of more than 36 CAG repeats in the first exon of IT15 gene. Many studies have shown that the IT15 interacts with several modifier genes to regulate the age at onset (AO) of HD. Our study aims to investigate the implication of CAG expansion and 9 modifiers in the age at onset variance of 15 HD Tunisian patients and to establish the correlation between these modifiers genes and the AO of this disease. Despite the small number of studied patients, this report consists of the first North African study in Huntington disease patients. Our results approve a specific effect of modifiers genes in each population.