Vitamin D receptor gene BsmI (rs1544410) polymorphism: role in multiple sclerosis and genotype-phenotype correlations.

BACKGROUND: Multiple sclerosis (MS) has a complex pathophysiology which depends on many endogenous and exogenous factors. Vitamin D involvement has been largely studied in MS. The large distribution of the vitamin D receptor (VDR) in different immune cells is suggestive of an immunomodulatory role. The VDR gene polymorphisms have been proposed as potential risk factors for MS development or evolution with non-conclusive results. METHODS AND RESULTS: We conducted a cross-sectional study including patients ≥ 18 years, with a diagnosis of relapsing remitting MS according to the McDonald Criteria and having a minimum follow-up period of one year after starting a disease modifying therapy. Two study groups were compared based on the Multiple Sclerosis Severity Scale or MSSS: "a slow progressor" group for an MSSS ≤ 5, and a "fast progressor" group for an MSSS > 5. The rs1544410 VDR gene polymorphism was studied for all patients. Eighty patients were included. The fast progressor groups had a higher EDSS at onset, a higher total number of relapses, more frequent and shorter time to secondary progression. The progression profile was not statistically different between genotypes and alleles of the VDR gene polymorphism rs1544410. The CC genotype and wild-type allele exhibited a more aggressive disease phenotype with a higher number of relapses the first year, shorter time to secondary progression and cerebral atrophy on assessment. CONCLUSIONS: Our results suggest potential genotype-phenotype correlations for the rs1544410 VDR gene polymorphism in the disease course of MS. Future research on a larger scale is needed to confirm these findings.

Cognitive impairment in multiple sclerosis: Utility of electroencephalography.

OBJECTIVE: to evaluate associations between neurocognitive impairment and electroencephalography (EEG) data in Multiple Sclerosis (MS). METHODS: patients aged between 18 and 65 years, diagnosed with MS accordingly to the McDonald 2017 criteria and who were in remission for at least one month were included. Cognitive functions were evaluated by validated neuropsychological tests for Tunisian population. Electroencephalography data of each patient were analysed, Grand Total EEG (GTE) score was calculated and we evaluated their statistical links with cognitive impairment. RESULTS: Thirty five patients were included. Slower background activity was associated with presence of: reduced information processing speed (IPS) (p = 0,03), verbal memory impairment (p = 0,04) and executive dysfunction (p = 0,016). The score 3 of GTE (reactivity of background activity) was associated with reduced IPS (p = 0,007) and executive dysfunction (p = 0,014). We found a positive correlation between background activity and Tunisian Verbal Test (TVLT) (ρ =0,46 ; p = 0,005) and Symbol Digit Modalities Test (SDMT) (ρ =0,35 ; p = 0,03). Sensitivity of GTE score was 68,4% for executive dysfunction (cut-off=2,5) and 66,7% for reduced IPS (cut-off=2,5). CONCLUSIONS: Our results have shown utility of EEG in detecting cortical involvement and its correlation with cognitive impairment in MS patients. SIGNIFICANCE: EEG could be a tool for monitoring cortical involvement during MS and predict cognitive impairment.

Missing apolipoprotein E ε4 allele associated with nonamnestic Alzheimer's disease in a Tunisian population.

In this study, we investigate the impact of apolipoprotein E epsilon 4 (APOE ε4) as a major risk factor of Alzheimer's disease (AD), based on the clinical presentation of the disease in our population on the one hand, and comparison of the results with the findings from the literature on the other hand. Our study covered a population of 144 patients versus 90 healthy controls matched with each other in terms of age, gender, age of onset, etc. All patients underwent neurological examination, comprehensive neuropsychological assessment and brain magnetic resonance imaging. Controls were selected based on the neurological examination and the Arabic version of the minimental state examination (MMSE). Patients were classified as probable typical amnestic AD and atypical nonamnestic AD if the patient had logopenic variant primary aphasia, posterior cortical atrophy, behavioural or dysexecutive variants, corticobasal syndrome, nonfluent and semantic variants of primary progressive aphasia associated to biological diagnosis for AB42, Tau and Ptau biomarks in the cerebrospinal fluid. Genotyping was performed using the polymerace chain reaction restriction fragment length polymorphism (PCR-RFLP) method. The study of the allelic frequency of APOE in cases and controls show that APOE ε4 is associated with an increased risk for AD (P = 0.002). We observed that the distribution of APOE ε4 within the AD group differs depending on the phenotype. Nonamnestic AD was more common in patients not carrying APOE ε4 (APOE ε4 (-)) compared to carriers of homozygous or heterozygous APOE ε4 (APOE ε4 (+)) (P = 0.038). In addition to its known effect as a major risk factor, we found that patients with AD are APOE ε4 negative, they show cognitive decline in nonmemory domains (language, behaviour, attention, executive and visuospatial functions).

Association between H2 haplotype of microtubule associated protein tau gene (deletion / insertion) with Alzheimer Disease in Tunisian patients.

It is widely recognized that Alzheimer's disease (AD) is the main cause of dementia in the elderly. AD is typically characterized by the extraneuronal plaque made up essentially of the amyloid ß peptide and intraneuronal tangles of hyperphosphorylated microtubule-associated Tau protein. This study investigates the possible interaction between AD and the deletion/insertion polymorphism in intron 9 of the Tau gene haplotype and APOE state in a Tunisian AD cases population (n = 85) and control (n = 91). The H2/H2 genotype was higher in the AD group as compared to the controls (22.4% vs. 7.8%). The frequency of H2 allele is higher in the patients group, and the difference of allele frequency is statistically significant between the two groups (χ2 = 12.220, p < 0.05). H2 allele is correlated with the female gender within the patient group (χ2 = 7.649, p = 0.006) Tau H2 haplotype can be identified as a risk factor of AD in the studied Tunisian population and was associated to female gender. There is no significant correlation between the frequency of Tau gene ins/del polymorphism and cognitive profile distribution in the patient group (p > 0.05).

COVID-19 Infection and Recurrent Stroke in Young Patients With Protein S Deficiency: A Case Report.

INTRODUCTION: Protein S deficiency and coronavirus disease 2019 (COVID-19) are rare etiologies of ischemic stroke. We describe a case of an ischemic stroke revealing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a patient with a history of protein S deficiency and cerebral imaging suggestive of vasculitis. CASE REPORT: A 52-year-old woman, with history of protein S deficiency, was admitted for right hemiparesis and aphasia that happened 6 hours before her consultation. Her National Institutes of Health Stroke Scale (NIHSS) was 11. She had hypoxia (SpO2 93%). COVID-19 polymerase chain reaction was positive. Cerebral computed tomography scan showed an ischemic stroke in the territory of the superficial left middle cerebral artery. The recommended time period for thrombolysis was exceeded and we did not dispose of sufficient resources to deliver thrombectomy. She was treated with aspirin, statins, antibiotic therapy, and oxygen. Considering the high risk of thromboembolic complications and the history of protein S deficiency, anticoagulation treatment with heparin followed by acenocoumarol was started. Evolution was marked by the appearance of 24 hours regressive, acute symptoms of confusion. Brain magnetic resonance imaging showed new ischemic strokes in both anterior cerebral arteries and on magnetic resonance angiography narrowing of the left internal carotid artery and both anterior cerebral arteries suggestive of vasculitis was seen. We maintained anticoagulation and prescribed methylprednisolone 500 mg daily for 3 days. Evolution was marked by improvement of clinical deficit and respiratory status. CONCLUSIONS: SARS-CoV-2 infection potentializes the prothrombotic effect and vascular inflammation by accentuating protein S deficit. The place of steroids seems justifiable in the presence of symptoms of vasculitis in brain imaging.

Knowledge and attitudes toward epilepsy among teachers in Tunisia.

BACKGROUND: The importance of school teachers' knowledge of and attitudes toward epilepsy and its contribution in improving the links between the Education and Health fields, is well recognized and appreciated. In order to clarify the amount of misconceptions about epilepsy among Tunisian teachers, we conducted a web-based survey. The main objectives of our study were, first, to determine the knowledge about and attitudes toward epilepsy, and second, to specify factors associated with a better understanding of this disease. METHODS: Data were collected using a web-based survey "Google Forms". RESULTS: The study showed a positive correlation between the level of teachers' knowledge of epilepsy and their attitudes toward a person with epilepsy. Despite the knowledge gaps revealed in Tunisian teachers, the overall attitude was at large positive. Familiarity with epilepsy, whether through family or work environment, made a tremendous contribution in redressing misconceptions about epilepsy in our study. CONCLUSION: More educational interventions and programs are needed to increase teachers' familiarity with epilepsy and, consequently, increase their awareness and knowledge.

Utility of EEG on attention deficit-hyperactivity disorder (ADHD).

OBJECTIVE: The aim of our study was to analyze electrophysiological findings in patient with Attention Deficit Hyperactivity Disorder (ADHD) by electroencephalography (EEG) recording, estimate the prevalence of epilepsy in ADHD population and assess its clinical characteristics. METHODS: We conducted a retrospective and analytic study that concerned children with ADHD, followed for at least two-years in the Tunisian National Center for School and University Medicine (NCSUM). All patients recruited underwent at the diagnosis of ADHD, neurological examination and EEG recording in the department of Neurology of Charles Nicolle Hospital. Medical data including family history, ictal semiology and ADHD features were assessed. RESULTS: Thirty patients were enrolled in our study. Mean age was 12.27 years with a sex ratio of 3.28. Mean age at diagnosis of ADHD was 6.6 years. Attention Deficit Hyperactivity Disordercombined subtype was seen in 18/30 patients, Hyperactive/ Impulsive subtype in 7/30 patients and Inattentive subtype in 5/30 patients. Epilepsy-disease was reported in 20% (Seizures preceded the diagnosis of ADHD in 3/6 cases and appeared after an average of 3.67 years in 3/6 cases). Mean age of seizure onset was 7 years. Seizure-types were generalized (motor 4/6 cases, absence-type (1/6 case)) and focal (1/6 case). Electroencephalography revealed Epileptiform discharges in 30% with frontal and left dominance. Interictal discharges were significantly associated with younger age of onset (p: 0.02), inattentive subtype (p: 0.04) and intellectual disability (p: 0.04). These discharges was not associated with epilepsy. CONCLUSION: Our results have shown that epileptiform discharges could be used as risk factor for seizures and cognitive impairment which may influence outcome in ADHD population.

Refractory epilepsy in PSEN 1 mutation (I83T).

Mutations in the presenilin-1 gene (PSEN1) on chromosome 14 are the most common cause of autosomal dominant Alzheimer's disease (ADAD), which has a broad clinical phenotype, encompassing not only dementia but a variety of other neurological features. We report the case of a 32 years old man with a family history of  early onset AD associated with a PSEN1 mutation in the exon 4 (I83T). The proband's, carrying the mutation,  present a refractory epilepsy predating cognitive decline. We discuss the physiopathological mechanisms of epilepsy during AD associated with PSEN 1 mutation, the possibility of linking this epilepsy to the mutation?.

Association between ACE polymorphism, cognitive phenotype and APOE E4 allele in a Tunisian population with Alzheimer disease.

Angiotensin-converting enzyme (ACE) has shown altered activity in patients with neurological diseases. An insertion/deletion (I/D) polymorphism of the ACE gene encoding angiotensin-converting enzyme has been reported to be associated with the risk for Alzheimer's disease (AD), and is generally considered to be a disorder primarily affecting memory. We conducted a case-control study in a sample composed of 85 sporadic AD patients and 90 age- and sex-matched controls to investigate the possible effect of the polymorphism and cognitive profile. Our data revealed an association between the ACE polymorphism and AD risk. There was a significant difference in the ACE allele or genotype frequencies between cases and controls. The D/D genotype showed an increased risk for AD and in the amnestic group and the effect was independent on ApoE genotypes.

Early psychiatrics symptoms in familial Alzheimer's disease with presenilin 1 mutation (I83T).

Several clinical phenotypes were associated with presenilin 1 (PSEN1) mutation in early-onset familial Alzheimer's disease (EOFAD). We report the clinical phenotype of two members of a familial dementia kindred who presented with EOFAD and early psychiatric syndrome as behavioral abnormalities. Sequence analysis of the index patient and his brother's PSEN1 transcript revealed a novel T > C transition in exon 4 which was determined as a missense substitution at position 248 of the coding sequence (cDNA. 248T > C).

Novel presenilin 1 mutation (p.I83T) in Tunisian family with early-onset Alzheimer's disease.

A minority of Alzheimer disease (AD) patients begin presenting symptoms before the age of 65 years. A familial aggregation is often found in this group of early-onset AD, and, in a subset of families, the pattern of inheritance is consistent with autosomal dominant inheritance. Fully penetrant variants in amyloid precursor protein, presenilin 1 (PSEN1), and presenilin 2 are the only causative mutations reported for autosomal dominant AD. This study is to explore the PSEN1 gene mutation in a Tunisian familial Alzheimer's disease. The patient in this family showed a novel missense mutation in exon 4 of the PSEN1 gene (complementary DNA 248T>C), altering isoleucine to threonine at 83 position. Because the change occurred in conserved domains of this gene, and cosegregated with affected family member, we suggested that this change may have a mutagenic and probably pathogenic effect.

Parkinsonism and Sjögren's Syndrome: A Fortuitous Association or a Shared Immunopathogenesis?

Background. The Sjögren Syndrome (SS) can include various manifestations of central nervous system impairment. Extrapyramidal signs are known to be very rare and unusually discovered on early onset in this pathology. Observation. A 46-year-old woman with a history of progressive Parkinsonism for 6 years and a normal brain magnetic resonance imaging was partially improved with levodopa therapy. The later discovery of a sicca syndrome led to performing of further investigations, which revealed the presence of anti-SSA antibodies and a sialoadenitis of grade 4 according to Chisholm's classification on labial salivary gland biopsy. The diagnosis of primary SS was established and the adjunction of corticotherapy has remarkably improved Parkinson's signs without use of other immunosuppressive agents. Conclusion. Based on these findings, we discuss the hypothesis of either a causal link between SS and Parkinsonism or a fortuitous association of two distinct pathologies with or without a shared immunopathogenesis.