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).

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.

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.

High APOE epsilon 4 allele frequencies associated with Alzheimer disease in a Tunisian population.

The goal of the study was to examine the Apolipoprotein E (APOE) genotypes in a Tunisian sample of patients with Alzheimer disease (AD) and normal controls, and to compare the results with the findings from the literature. A hospital-based case-control study of two groups (58 patients with AD, 71 controls) was conducted. Patients received a detailed clinical history, neurological examination, neuropsychological testing and brain imaging. A neurological examination and the Arabic version of the Mini-Mental State Examination were made for controls. Genotyping was performed using the PCR restriction fragment length polymorphism (PCR-RFLP) method. There were no statistical differences in age (p = 0.05) and gender (p = 0.046) between the two groups. The APOE ε4/4 genotype was over represented in the AD group in comparison with the controls (13.3 vs. 2.8%). A significant increased risk of AD among APOE ε4 allele carriers was observed. The odds ratio for the association of AD patients with homozygous and heterozygous ε4 allele was, respectively, 5.40 (1.35-21.48) and 2.90 (1.27-6.62). Our results in addition to previously published genetic studies suggest that AD disease is multifactor in origin. Ethnicity, genetic and environmental factors contribute to AD risk in different ethnic groups.

Increased T-bet/GATA-3 and ROR-γt /Foxp3 Ratios in Cerebrospinal Fluid as Potential Criteria for Definite Neuro-Behçet's Disease.

When the central nervous system (CNS) is the primary affected site in an initial attack of Behçet's disease (BD), the differential diagnosis is particularly challenging. Some cases remain unclassified or qualified as probable neuro-Behçet's disease (NBD). Several cytokines are involved in the immunopathogenesis of this disease; however, studies establishing the differential cytokine pattern between probable and definite NBD are scarce. Twenty-eight parenchymal NBD patients, diagnosed according to the International Consensus Recommendation (ICR) criteria and classified into definite (D-NBD; n = 17) and probable (P-NBD; n = 11), were sampled at their first neurological symptoms, and compared with healthy control subjects (n = 20). Oligoclonal bands (OCB) of IgG were detected by isoelectric focusing on agarose, and immunoblotting of matched serum and cerebrospinal fluid (CSF) sample pairs. T cell cytokines (INF-γ, IL-4, IL-17, and IL-10) and transcription factors related to Th1, Th2, Th17, and T regulatory populations (respectively T-bet, GATA-3, ROR-γt, and Foxp3) were studied by quantitative RT-PCR in peripheral blood mononuclear cells (PBMCs) and CSF cells. Inflammatory cytokines such as IL-6, TNF-α, and IL-1ß were also analyzed. CSF OCB pattern 2 was present in only 1 out of 28 neuro-Behçet's patients who belonged to the P-NBD group. Two D-NBD patients had OCB in CSF showing pattern 4. In the D-NBD CSF samples, IL-17 and IL-10 expressions were significantly elevated compared to P-NBD. Moreover, D-NBD patients had increased levels of T-bet/GATA-3 and ROR-γt/Foxp3 ratios compared to P-NBD. Furthermore, a significant increase of CSF IL-6 in D-NBD, compared to P-NBD and the controls, was found. In addition to the increased IL-6 level, the data obtained suggest the existence in D-NBD patients of a significantly disrupted balance between Th17 effector and T regulatory cells, as reflected by the enhanced ROR-γt/Foxp3 ratio. This could be considered as an additional criterion for definite neuro-Behçet's disease.

Obsessive-compulsive disorder: a new risk factor for Alzheimer disease?

We describe a case of a 75-year-old woman referred to the Memory Clinic of the neurological Department of Charles Nicolle Hospital, Tunis, for cognitive decline and behavioral disturbances. Her past medical history was marked by severe obsessive-compulsive disorder (OCD) with contamination obsessions and washing compulsions. She has a family history for OCD and/or of dementia in 15 members. Clinical features, along with neuropsychological findings and Brain imaging were in favor of Alzheimer disease (AD). The present report is the first family study reporting the possible association of OCD and AD. The glutamatergic dysfunction may be a common pathophysiology of OCD and AD explaining this association.

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.