Association between Alzheimer disease and the -491T allele of regulatory region polymorphism of Apolipoprotein E in a Tunisian population.

The apolipoprotein E (APOE) is a well-established risk factor for late-onset Alzheimer's disease (AD). Several studies have attempted to confirm the association between the polymorphism located at position -491 in the transcriptional regulatory region of the APOE gene and AD. We examined in 85 AD patients and 90 control subjects of a Tunisian population the potential involvement of this polymorphism as a risk factor for AD, either through an independent effect or through interaction with the existing APOE ε4 allele risk. The T allele frequency was significantly higher in the AD patients group (45.3 %) than in the controls group (32.78 %) and may possibly constitute a significant risk factor for AD. The APOE ε4 allele did not influence the distribution of the -491 polymorphism after stratification.

A new locus on chromosome 22q13.31 linked to recessive genetic epilepsy with febrile seizures plus (GEFS+) in a Tunisian consanguineous family.

BACKGROUND: Genetic epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome with extremely variable expressivity. The aim of our study was to identify the responsible locus for GEFS+ syndrome in a consanguineous Tunisian family showing three affected members, by carrying out a genome-wide single nucleotide polymorphisms (SNPs) genotyping followed by a whole-exome sequencing. We hypothesized an autosomal recessive (AR) mode of inheritance. RESULTS: Parametric linkage analysis and haplotype reconstruction identified a new unique identical by descent (IBD) interval of 527 kb, flanking by two microsatellite markers, 18GTchr22 and 15ACchr22b, on human chromosome 22q13.31 with a maximum multipoint LOD score of 2.51. Our analysis was refined by the use of a set of microsatellite markers. We showed that one of them was homozygous for the same allele in all affected individuals and heterozygous in healthy members of this family. This microsatellite marker, we called 17ACchr22, is located in an intronic region of TBC1D22A gene, which encodes a GTPase activator activity. Whole-exome sequencing did not reveal any mutation on chromosome 22q13.31 at the genome wide level. CONCLUSIONS: Our findings suggest that TBC1D22A is a new locus for GEFS+.

No association between an intronic polymorphism in the presenilin-1 gene and Alzheimer disease in a Tunisian population.

We examined the potential involvement of the polymorphism in intron 8 of the presenilin-1 (PSEN1) gene as a risk factor for Alzheimer disease (AD), both through independent effect and interaction with the apolipoprotein E (APOE) ε4 allele risk, in 85 patients and 90 controls. We found no significant differences in the distribution of PSEN1 genotype and allele frequency between both groups; and post stratification distribution with APOE ε4 allele. Age of onset suggests that this polymorphism influences AD progression.

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.

[Carpal tunnel syndrome. A Tunisian series]. / Le syndrome du canal carpien : A propos d'une série hospitalière Tunisienne.

BACKGROUND: Carpal tunnel syndrome (CTS) is the most frequent ductal syndrome. Few epidemiological studies in Tunisia exist. AIM: To describe clinical, biological and electromyographic data of Tunisian patients with CTS METHODS: A retrospective study including 80 patients with CTS, during the period going from 2009 to 2010. RESULTS: A female predominance was observed with an average age of 52 years. Acroparesthesia was the main complaint, followed by night awakenings and muscular weakness. Physical examination showed a positive Tinel (91.2%) and Phalen (82.5%) tests, a decrease of tactile sensitivity (26.2%) and a thenar amyotrophy (10%). The Electromyography was abnormal in 85% cases. The most revealing lesions were demyelinating, sensitivo-motor predominance (66%) abnormalities. on Biology, hyperglycemia (12.5%), hyperuricemia (8.7%) and renal failure (7.5%) were the most observed. Medical treatment was drawn on analgesics and anti-inflammatory for 90% of our patients. Local steroid injections were indicated for 35% of patients, leading to a clinical improvement in 90% of cases. Surgery was made in only 13.8% patients. CONCLUSION: Tunisian patients with CTS were female patients, housewifes with obesity or overweight. No other differences were observed in comparison with the literature.

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.

Childhood occipital epilepsy of Gastaut: a case report.

BACKGROUND: Idiopathic childhood occipital epilepsy of Gastaut is a rare but well defined syndrome within the group of idiopathic focal epilepsies in childhood. Clinical manifestations are characterized by simple partial seizures with mainly visual symptoms followed by secondary generalization. AIM: Report of a case of Childhood Occipital Epilepsy. CASE REPORT: We report a case of 10-year-old-girl, with no history. At the age of 9 years, the patient started experiencing repetitive events without fever. The first event consisted of several episodes of loss of consciousness with hypotonia and post ictal amnesia. The second type was three episodes of stereotyped, elaborated complex visual hallucinations, during 10 minutes. One month later, a third type of tonico-clonic generalized seizures appeared. Neurological examination and routine laboratory investigation were normal. Brain neuroimaging was normal. Interictal EEG showed bilateral discharges of slow generalized waves activated by hyperventilation. She has been treated by Sodium Valproate. All seizures stopped and she remained free of seizures. CONCLUSION: This epileptic syndrome must be identified, and treated without delay. In fact, without appropriate treatment, the evolution may lead to a continuous spike-wave during the sleep with cognitive deterioration.

Death in Unverricht-Lundborg disease.

The objective of this study is to report cases of unexpected deaths in Unverricht-Lundborg disease (ULD) patients, a comparatively benign form of progressive myoclonus epilepsy. We performed a multicentric study of the circumstances of death in ULD patients seen in the last 16 years. We assessed age, sex, severity and duration of disease, antiepileptic drugs, circumstances and presumed cause of death. Nineteen observations (12 females, 7 males) were collected from four centers (Tunis, Marseille, Milan, Belgrade). The most common causes of death are (1) SUDEP (six cases, all female), with 4/6 on phenobarbital alone, and (2) complications of severe ULD (six cases). Two patients committed suicide. Only one death was clearly unrelated to ULD (car accident), while four patients died of stroke, drowning, complications of chronic alcoholism and Wernicke encephalopathy, respectively. In conclusion, although the prognosis of ULD has progressed, there are still spontaneously severe forms and high risk of early death, including SUDEP.

[Particularities of epileptic women's care]. / Particularités de la prise en charge des femmes epileptiques.

AIM: Development on the epileptic women's care. METHOD: A research in the medical literature on PubMed and an exhaustive review of the published summaries and reports of Epileptology International Meetings, in the last five years. We included cohort studies, reviews and randomized double blinded therapeutic trials. Case reports and fundamental research studies have been excluded. RESULTS: sensitizing of the epileptic women starts with adolescence with an education and a preparation to sexual life and available contraceptive methods, in order to avoid undesired pregnancies and the serious consequences which they are likely to generate. Approximately 1/3 of the epileptic women have variations of their disease related to the menstrual cycle, probably because of a neurotoxic effect of estrogens (not counterbalanced by progestational hormones). Antiepileptic teratogenicity issue is not, yet, solved, in spite of new molecules commercialisation. The upkeep of a register concerning the use of AED during pregnancy makes it possible to better identify the problems and to establish an optimal therapeutic control for the mother and the child. CONCLUSION: Epilepsy impact on women's life is very different compared to men, because it interferes with the fields of sexuality, reproduction, menstrual cycle and contraception, in addition of AED teratogenicity. A close cooperation between obstetricians and neurologist and a sensitizing of health professionals are essential for the global care of the epileptic pregnant women or in age of procreation.

[Neurovascular progress in the dawn of the 21st century]. / Progrès en neurovasculaire a l'aube du 21ème siècle.

AIM/BACKGROUND: Development on progress in cerebral vascular pathology. METHOD: Research on PubMed concerning advances on Neurovascular diseases during the last twenty years. RESULTS: Stroke incidence and prevalence have shown an increase for a few years. High blood pressure (HBP) is well the main risk factor; the implication of tabagism, even passive, and of hormone substitutive therapy were also proven. Vascular and cellular mechanisms are implied in cerebral ischemia. The definition of transient ischemic attack (TIA) is currently based on a lesion criterion, conveying the emergency concept. The physiological rise in blood pressure on stroke early phase must be respected for the majority of patients. Progress of radiological explorations revolutionized stroke's care. Biological markers at the early stage of stroke are under development. New causes of stroke are reported. Stroke Units reduced the morbi-mortality by 50%. The treatment profited from solid clinical trials data and is now more effective. Physical rehabilitation benefitted from new movement and balance evaluation technologies and neuroplasticity concept, for better adapting the patient's rehabilitation. CONCLUSION: Neuro-vascular research knew a formidable renewed interest during two last decades. Stroke constitutes today a major public health's stake. It is important to organize the stroke channel's care in order to shorten hospitalization delay, not to harm and carry out urgent clinical and paraclinic expertise for optimal therapeutic choice.

[Epilepsy progress in the dawn of the 21st century]. / L'epilepsie a l'aube du 21eme siècle.

AIM: Review of development on recent acquisitions in Epileptology. METHODS: A research in the medical literature on PubMed and an exhaustive review of the Published summaries and reports of Epileptology International Meetings, in the last five years. We included cohort studies, reviews and randomized double blinded therapeutic trials publications related to the pathogenic, diagnostic and therapeutic advances. Case reports and pure research studies have been excluded. RESULTS: Defective genes and/or physiopathological mechanisms were identified for some clinical forms of epilepsy. New antiepileptics drugs (AED) with a more accurate pathogenic target were, therefore, developed. Modern technologies of cerebral explorations and in particular the MRI (magnetic resonance imagery) and the PET (Positron Emission Tomography) constitute a progress not only for research but also for the diagnostic and therapeutic evaluation in particular for patients candidates to surgery. Five new drugs are on sale, several others are being studied. Diets would be alternatives to the AED in case of intractable epilepsy. Surgery indication is currently extended to the elderly. The global care of epileptic patients implies also the fight against exclusion. CONCLUSION: The formidable development in epilepsy knowledge in fundamental and in clinical research, is not an exclusive matter of researchers and specialists in this discipline but also with the generalists, the pediatric and all the professionals of health implicated on epileptic's care; thus allowing an improvement of the prognosis and the quality of life of these patients.

[Progress in child epilepsy]. / Progrès en epilepsie pédiatrique.

Child epilepsy continues to concern the researchers and the clinicians and carried out these last years of important progress as well in the genetic field, as in physiopathology, clinic and therapeutic one. The identification of new genes of epilepsy, epilepsies related to channelopathy and new phenotypes related to precise genetic mutations, constitutes a major progress of paediatric epilepsy. The debate around the role of febrile convulsions in the development of hippocampal sclerosis is started again thanks to Diffusion MRI techniques. In utero exposure to antiepileptic drugs (AED), and its effects on neurodevelopment, is a very active field of research. An exposure to a polytherapy or to valproate would increase the risk of development delay. The ketogenic diet could be an alternative therapeutic during refractory epilepsies but can have serious consequences on the growth. Temporal lobe surgery is a good therapeutic option for refractory epilepsies of the child and offers, to him, better chances of social integration.

Epilepsy surgery program in Tunisia, the Charles Nicolle Hospital experience.

BACKGROUND: Epilepsy surgery is the best treatment in case of intractable epilepsy. However, it is underused in developing countries, creating an enormous treatment gap. On 2006, an epilepsy surgery program was set up in the Neurological Department of Charles Nicolle Hospital, Tunis, Tunisia. AIM: To describe its establishment and to emphasize on its originality that is an exchange and surgery decision taken by two Neurological teams via the internet. METHODS: Patients underwent a phase 1 presurgical evaluation at the Neurological Department of Charles Nicolle Hospital of Tunis. It included a detailed clinical history, a neurological evaluation, brain MRI, a continuous video EEG scalp monitoring and a neuropsychological evaluation. RESULTS: According to the different electro clinical and radiological findings, the surgery indication was taken between the Neurological department of Charles Nicolle Hospital of Tunis and the Neurophysiological Department of Charles Nicolle Hospital in Rouen through the EUMEDCONNECT network project. ATL was performed and the four patients are actually seizure free. CONCLUSION: Epilepsy surgery is actually a possible treatment option in Tunisia and should be indicated in patients with intractable partial seizures.

An Arabic Version of the Cognitive Subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog): Reliability, Validity, and Normative Data.

The Alzheimer's Disease Assessment Scale's cognitive subscale (ADAS-Cog) is the most widely used instrument for screening cognitive dysfunction in Alzheimer's disease. The aim of the present study was to develop an Arabic version of this scale (A-ADAS-Cog), examine its psychometric properties (reliability and validity), and provide normative data. The A-ADAS-Cog), an Arabic version of the Mini-Mental State Examination (A-MMSE), and a Standardized Clinical Dementia Rating Scale (CDR) were administered to three Tunisian groups: 124 normal controls (NC), 33 patients with non-Alzheimer dementia (N-AD), and 25 patients with Alzheimer's disease (AD). The A-ADAS-Cog scores were significantly affected by age and education. A correction table was constructed to control these effects. The results showed that the A-ADAS-Cog has good internal consistency and reliability (α= 0.82 for AD). The test-retest reliability of the A-ADAS-Cog was stable over time (r = 0.97). An evaluation of the construct validity of the A-ADAS-Cog using principal component analysis led to a solution with three factors (memory, language and praxis), which explained 72% of the variance. The concurrent validity of the A-ADAS-Cog was established using the A-MMSE score (r = -0.86), CDR Sum of Boxes score (CDR-SB; r = 0.87), and global CDR score (CDR-Global; r = 0.74). Finally, the A-ADAS-Cog has an excellent discriminating power in the diagnosis of AD (ROC area = 0.92). A cut-off score of 10 (sensitivity = 84% and specificity = 91%) is indicated for the screening of the AD. Overall, the results indicated that the A-ADAS-Cog is psychometrically reliable and valid and provides promising results for screening of dementia in Arabic speaking patients.

[Xeroderma pigmentosum. Cutaneous, ocular, and neurologic abnormalities in 49 Tunisian cases]. / Xeroderma pigmentosum: manifestations cutanées, oculaires et neurologiques à partir de 49 patients tunisiens.

This is a retrospective study about 49 cases of xeroderma pigmentosum (XP). The goal was to determine the clinical features of XP in Tunisia. Our study revealed the predominance of a moderate form. Malignant skin tumors showed early. Squamous cell carcinoma (SCC) remainsed the most frequent skin malignancy in all clinical forms. Neurological abnormalities were more frequent in the moderate form. Mental retardation and peripheral neuropathy were the most common signs.

[School failure and epilepsy: a case-control study]. / Echec scolaire et epilepsie: a propos d'une étude cas-témoin.

School difficulties and educational inadequacy usually correlate with the child's epilepsy. The target of our study is to discover the most precocious possible the epilepsy and to prevent educational failure in the population of children from 6 to 15 years old. We have carried out a retrospective study on 162 children of an educational age. This population was made up of 100 epileptic children followed over a period of 3 years (1995-1997) and a witness group made up of 62 children selected from brothers and sisters of the study group, with the same sex in default of the opposed sex who are educated. We have noted that at the same age between children from the group of study and children from the witness group. The class of study was significantly inferior in the group of study: the educational average class is 4th against 5th in the witness group P = 0.11. The difference was about one year. The difference of educational results was significant. For the last educational year, the educational mark was 8.99/20 in the group of study against 12/20 in the witness one. P < 10-5. For the last educational semester, the educational mark was 9.5/20 in the group of study against 11.9/20 in the witness group. (P = 3 x 10(-4)).

[Cerebral venous thrombosis and Behcet's disease]. / Thrombose veineuse cerebrale et maladie de Behcet.

Behcet's disease is a chronic relapsing multisystem disorder of unknown etiology. Neurological complications are frequent, occurring in 10 to 49% of cases. We report 4 cases with Behcet's disease (3 females and 1 male) who had symptomatic intracranial hypertension due to cerebral venous sinus thrombosis within a mean delay of 2 years. The mean age at onset was 31 years and the mean age on referral was 39.5 years. The predominant manifestation in our series were headache, papilledema, seizures and pyramidal syndromes. CT Scan showed non specific abnormalities in all of them and the sinus venous thrombosis was confirmed by MRI in 3 cases. The authors emphasize on the importance of MRI with angio MRI for the diagnosis, the outcome and the evaluation of the cerebral venous thrombosis after treatment.

[Mesial temporal lobe epilepsy. Nine case reports]. / Les épilepsies temporo-mésiales. A propos de 9 cas.

INTRODUCTION: Mesiotemporal epilepsy (MTLE) is a clinical syndrome characterised by the association of a history of febrile seizures, a homogenous clinical presentation of seizures, temporal interictal and ictal EEG recordings and an underlying pathology that is mesial sclerosis. MTLE is the most common type of medically intractable partial epilepsy with a drug-resistance in 90% of cases. OBJECT: The aim of this study is to describe the clinical, EEG and MRI findings of 9 patients with MTLE attending the outpatient clinic of Charles Nicolle Hospital. RESULTS: The median age of our study population was 30 years. A history of febrile seizures was found in 5 patients. Hippocampal atrophy was found in all the cases right in 4 cases and left in 5 cases. Drug-resistance was observed in 7 patients. No patient underwent surgery. CONCLUSION: It is important in front of medically intractable partial epilepsy to evoke MTLE, to confirm the diagnosis with neuro-imaging and to propose an interdisciplinary therapeutic approach including neurologists, epileptologists and neurosurgeons.