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.

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.

[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.

Association of amyotrophic lateral sclerosis and Behcet's disease: is there a relationship? A multi-national case series.

Neurological involvement may be seen in 5-30% of the patients with Behcet's disease (BD). Occasionally, parenchymal neurological involvement in BD can present as a spinal cord syndrome. However, motor neuron disease-like presentation is extremely uncommon. Here we are reporting five patients (all male; median age, 38) fulfilling both International Study Group criteria for BD and El Escorial criteria for amyotrophic lateral sclerosis (ALS). These patients were identified by a questionnaire sent to the members of the Neuro-Behcet Study Group of the International Study Group for BD. Three out of five patients had only motor presentations. In two patients, sensory and urinary manifestations were present as well. Spinal cord MRIs were normal in all, and brain MRIs were normal in four patients; one patient had nonspecific white matter changes. Two patients passed away 1-3 years after diagnosis of ALS, and two patients were lost to follow-up 3 and 11 years after admission; one patient is still alive 3 years after onset. The patients that are presented here might represent a rare form of neurological involvement in BD as well as sole coincidence. Larger prospective series are needed to further answer this issue.

Systemic lupus erythematosus induced by interferon ß1 therapy in a patient with multiple sclerosis.

Drug-induced lupus erythematosus is defined as a lupus-like syndrome temporally related to a drug exposure. We report a 34-year-old woman with multiple sclerosis who developed, while being treated with interferon ß-1a, myalgia and associated with wrist synovitis. Clinical and immunologic investigations were in favor of systemic lupus erythematosus. Interferon therapy was maintained. Under corticosteroids and antipaludeen treatment, the patient did not develop any other lupic manifestations.

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.

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.

Epilepsy surgery program in Tunisia: an example of a Tunisian French collaboration.

OBJECTIVE: To describe the first Tunisian epilepsy surgery program establishment and to emphasize on its originality that is an exchange and surgery decision taken by two Mediterranean neurophysiological teams, via the Internet. METHODS: Patients with mesial temporal lobe epilepsy (MTLE) and refractory to antiepileptic drugs were included. A noninvasive protocol evaluation including a detailed history, neurological evaluation, brain imaging, scalp video-EEG monitoring and neuropsychological evaluation were performed. The different findings were discussed between the Neurophysiological Department of Charles Nicolle Hospital of Tunis and Rouen through the EUMEDCONNECT Internet network project. If cases of concordance of clinical, neuropsychological, neuroimaging data and video-EEG recordings, surgery was indicated. RESULTS: 15 patients (7 women and 8 men) with mean age of 30 years were included. 10 patients had right hippocampal sclerosis (HS) and 5 had left HS. MRI findings were concordant with the ictal EEG in 12 patients. One patient had bitemporal ictal EEG abnormalities and right HS on MRI. One patient had contralateral ictal clinical and EEG patterns to the side of HS. One patient had temporal 'plus' epilepsy. Surgery was performed in 10 cases. After surgery, all patients are seizure free, with no operative mortality or major surgery complications. CONCLUSION: Our model of twin affiliations between advanced epilepsy surgery programs in a developed country and starting programs in a developing country, using Internet technology, can be a model for collaboration in other countries.

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.

[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.

[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.

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.

[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.