Mouna Ben Djebara

Bipolar disorder and multiple sclerosis: a case series.

Background. The prevalence of psychiatric disturbance for patients with multiple sclerosis (MS) is higher than that observed in other chronic health conditions. We report three cases of MS and bipolar disorder and we discuss the possible etiological hypothesis and treatment options. Observations. All patients fulfilled the McDonald criteria for MS. Two patients were followed up in psychiatry for manic or depressive symptoms before developing MS. A third patient was diagnosed with MS and developed deferred psychotic symptoms. Some clinical and radiological features are highlighted in our patients: one manic episode induced by high dose corticosteroids and one case of a new orbitofrontal MRI lesion concomitant with the emergence of psychiatric symptoms. All patients needed antipsychotic treatment with almost good tolerance for high dose corticosteroids and interferon beta treatment. Conclusions. MRI lesions suggest the possible implication of local MS-related brain damage in development of pure “psychiatric fits” in MS. Genetic susceptibility is another hypothesis for this association. We have noticed that interferon beta treatments were well tolerated while high dose corticosteroids may induce manic fits.

Using KASP technique to screen LRRK2 G2019S mutation in a large Tunisian cohort

BackgroundIn North African populations, G2019S mutation in LRRK2 gene, encoding for the leucine-rich repeat kinase 2, is the most prevalent mutation linked to familial and sporadic Parkinson’s disease (PD). Early detection of G2019S by fast genetic testing is very important to guide PD’s diagnosis and support patients and their family caregivers for better management of their life according to disease’s evolution.MethodsIn our study, a genetic PD’s diagnosis tool was developed for large scale genotyping using Kompetitive Allele Specific PCR (KASP) technology. We investigated G2019S’s frequency in 250 Tunisian PD patients and 218 controls.ResultsWe found that 33.6% of patients and 1.3% of controls were carriers. Demographic characteristics of patients with G2019S had no differences compared with non-carrier patients. Thereby, we could emphasize the implication of G2019S in PD without any distinctive demographic factors in the studied cohort. Sixty patients out of 250 were genotyped using Taqman assay and Sanger sequencing. The genotyping results were found to be concordant with KASP assay.ConclusionsThe G2019S mutation frequency in our cohort was similar to that reported in previous studies. Comparing to Taqman assay and Sanger sequencing, KASP was shown to be a reliable, time and cost effective genotyping assay for routine G2019S screening in genetic testing laboratories.

Hot water epilepsy with pachygyria

Hot water epilepsy (HWE) refers to a specific type of reflex epilepsy precipitated by the stimulus of bathing in hot water. Pathogenesis is still unknown and temporal lobe has been thought to take part in the epileptogenesis. HWE can be symptomatic of focal cortical malformation, and few cases were reported. This is the third report of HEW in which a parietal malformation has been observed. Our hypothesis that sensory cortex might be implicated in the epileptogenic process is corroborated by two previous reports on patients with HWE and malformation of the parietal cortical development.

Season of birth and multiple sclerosis in Tunisia

BACKGROUND Recent studies on date of birth of multiple sclerosis (MS) patients showed an association between month of birth and the risk of developing MS. This association has not been investigated in an African country. OBJECTIVE We aimed to determine if the risk of MS is associated with month of birth in Tunisia. METHODS Data concerning date of birth for MS patients in Tunisia (n = 1912) was obtained. Birth rates of MS patients were compared with all births in Tunisia matched by year of birth (n = 11,615,912). We used a chi-squared analysis and the Hewitts non-parametric test for seasonality. RESULTS The distribution of births among MS patients compared with the control population was not different when tested by the chi-squared test. The Hewitts test for seasonality showed an excess of births between May and October among MS patients (p = 0.03). The peak of Births of MS patients in Tunisia was in July and the nadir in December. CONCLUSION Our data does support the seasonality hypothesis of month of birth as risk factor for MS in Tunisia. Low vitamin D levels during pregnancy could be a possible explanation that needs further investigation.

Clinical and genetic study of Tunisian families with genetic generalized epilepsy: contribution of CACNA1H and MAST4 genes

Genetic generalized epilepsies (GGE) (childhood absence epilepsy (CAE), juvenile myoclonic epilepsy (JME) and epilepsy with generalized tonic-clonic seizures (GTCS)) are mainly determined by genetic factors. Since few mutations were identified in rare families with autosomal dominant GGE, a polygenic inheritance was suspected in most patients. Recent studies on large American or European cohorts of sporadic cases showed that susceptibility genes were numerous although their variants were rare, making their identification difficult. Here, we reported clinical and genetic characteristics of 30 Tunisian GGE families, including 71 GGE patients. The phenotype was close to that in sporadic cases. Nineteen pedigrees had a homogeneous type of GGE (JME-CAE-CGTS), and 11 combined these epileptic syndromes. Rare non-synonymous variants were selected in probands using a targeted panel of 30 candidate genes and their segregation was determined in families. Molecular studies incriminated different genes, mainly CACNA1H and MAST4. The segregation of at least two variants in different genes in some pedigrees was compatible with the hypothesis of an oligogenic inheritance, which was in accordance with the relatively low frequency of consanguineous probands. Since at least 2 susceptibility genes were likely shared by different populations, genetic factors involved in the majority of Tunisian GGE families remain to be discovered. Their identification should be easier in families with a homogeneous type of GGE, in which an intra-familial genetic homogeneity could be suspected.

Genetic Analysis of TREM2 Variants in Tunisian Patients with Alzheimer's Disease

Objective: Rare variants in the TREM2 gene have been reported to significantly increase the risk of Alzheimer’s disease in Caucasian populations. Hitherto, this association was not studied in North African populations. In this work, we aimed to study the association between TREM2 exon 2 variants and the risk of late-onset Alzheimer’s disease (LOAD) in a Tunisian population. Subjects and Methods: We sequenced exon 2 of TREM2 in a Tunisian cohort of 172 LOAD patients and 158 control subjects. We used the Fisher exact test to compare the distribution of allelic frequencies between the two groups. Results: We identified 4 previously reported nonsynonymous variants (p.Asp39Glu, p.Arg62His, p.Thr96Lys, and p.Val126Gly) and 1 novel synonymous variant (p.Gln109Gln), none of which was significantly associated with the risk of Alzheimer’s disease. Moreover, the rare TREM2 variant (p.Arg47His), which was considered to be a risk factor for Alzheimer’s disease in European descent populations, was not detected in our cohort. Conclusion: These findings do not support a major role for TREM2 in the pathogenesis of LOAD in the Tunisian population.

Isolated spinal cord compression syndrome revealing delayed extensive superficial siderosis of the central nervous system secondary to cervical root avulsion

Context: Cervical root avulsion secondary to traumatic plexus injury is a rare etiology of superficial siderosis (SS) of the central nervous system (CNS). We describe the case of an isolated progressive compressive myelopathy revealing this complication and discuss the pathogenesis of such a presentation, its clinical and imaging peculiarities with a literature review. Findings: We report on the case of a 48-year-old man with history of left brachial plexus injury at the age of 2 years. Since the age of 38 years, he had presented with a progressive paraplegia, bladder and erectile dysfunction, neuropathic pain and sensory level. The diagnosis was made by spinal cord and brain magnetic resonance follow-up imaging revealing hypointensity T2-weighted gradient echo linear dark rim around the entire neuraxis and cervical dural pseudomeningoceles. These MRI findings were suggestive of extensive hemosiderin deposition consolidating the diagnosis of SS of CNS. Conclusion/Clinical relevance: Our case report illustrates diagnosis difficulties in unusual or paucisymptomatic presentations of SS. A history of brachial plexus trauma with nerve root avulsion should prompt gradient-echo T2-weighted imaging to bring out such a complication. Superficial siderosis of the CNS should be included in the panel of differential diagnosis of the parethospastic syndromes and compressive myelopathy.

LRRK2 G2019S Parkinson's disease with more benign phenotype than idiopathic

The LRRK2‐G2019S mutation is the most common cause of Parkinsons disease (PD) in North Africa. G2019S‐PD has been described as similar to idiopathic with minor clinical differences. The aim of this study was to determine the G2019S‐related phenotype and to investigate gender and gene dosage effects on clinical features of G2019S carriers.

Early-onset versus late-onset Alzheimer’s disease in tunisia

to unknown time of symptom onset. The head MRI demonstrated acute infarction at the left posterior insular cortex. MRA of the head and neck showed only hypoplastic A1 segment of the right anterior cerebral artery and 50 % stenosis of the right internal carotid artery which were not contributory to the acute infarction. 48 hours later, facial droop, disarticulation and word-finding difficulty completely improved. However, multiple domains of cognitive impairment were detected. He scored 20/30 on the Montreal Cognitive Assessment. He had significant impairment in delayed recall, letter & animal fluency and repetition tasks. The memory impairment characterized as retrieval deficit which improved with word cues. Naming was intact either in the MoCA or shortened version of Boston Naming Test. Conclusions: Isolated left posterior insular infarction is extremely rare. This case demonstrates the role of this area in multiple cognitive domains including language-related and verbal memory function. Moreover, this is the first report of the verbal fluency deficit associated with isolated left posterior insular lesion. This area is a convergent structure connecting with multiple brain regions, thus the deficits caused by the left posterior insular lesion is more likely to be a consequence of diaschisis rather than the damage of a specialized or isolated center.