Youssef Sidhom

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.

Clinical features and disability progression in multiple sclerosis in Tunisia: Do we really have a more aggressive disease course?

BACKGROUND Few epidemiological data are available on multiple sclerosis (MS) patients in North Africa (NA). Studies of immigrants from NA showed a more aggressive course compared to European patients. OBJECTIVE The aim of this study is to describe clinical and long term course characteristics of MS in Tunisia and to compare it to European cohorts. METHOD A total of 437 MS patients from three hospital based cohorts in Tunisia and having prospective follow up between 2010 and 2012 were analyzed. We considered as endpoints the time to reach EDSS scores of 3, 4 and 6 in the different clinical forms of MS and the beginning of a secondary progressive (SP) phase. RESULTS Sex ratio was 2.34. Mean age of onset was 30.3 years. The course was relapsing-remitting (RR) in 91% of patients and primary progressive (PP) in 9%. The most frequent isolated onset symptoms were respectively motor (28%), optic neuritis (20%) and sensory (16%) dysfunction. Median time to SP onset was 19.1 years. Median times from onset of multiple sclerosis to assignment of a score of 3, 4 and 6 were 8, 10.7 and 15 years respectively. Benign form of MS represented 31.5%. Median interval from the onset of the disease to EDSS score of 3, 4 and 6 was shorter in PP-MS than in RR-MS. However, there was no difference between these two groups for the median time from the assignment of EDSS 4 to the assignment EDSS 6. CONCLUSIONS Our study shows that Tunisian MS patients have a quite similar clinical feature to European patients. Still, larger MS multicenter cohort studies in NA with longer follow-up duration could clearly respond to the issue.

Fast multiple sclerosis progression in North Africans Both genetics and environment matter

Objective: To compare multiple sclerosis (MS) disability progression among North Africans (NAs) living in France (NAF) and in Tunisia (NAT) and Caucasian patients born and living in France (CF). Methods: Patients with MS admitted to the day hospital in the Neurology Department at Pitié-Salpêtrière Hospital (France) and Razi Hospital (Tunisia) were questioned on their place of birth and the place of birth of their parents. To compare delay to outcomes, log-rank tests were used. Univariate and multivariate Cox models were used to determine factors influencing time to Expanded Disability Status Scale (EDSS) 6. Results: We consecutively included 462 patients: 171 CF, 151 NAT, and 140 NAF. Sex ratio, disease forms, and delay from disease onset to diagnosis were similar between the groups. NAF differed from other groups, with a shorter median time to reach EDSS 3, 4, and 6, and a more frequent incomplete recovery after first relapse (p < 0.0001). Furthermore, the NA second-generation group showed the youngest median age at onset (26.5 ± 8.8 years, p = 0.001), the shortest median time to EDSS 6 in relapsing-remitting patients, and an increased mean number of relapses during the first 5 years of the disease (6.1 ± 3.7, p = 0.01) compared to CF. The Cox proportional hazard models demonstrate that (1) NA ethnicity is a significant predictor of fast progression even when adjusting for major covariates and (2) treatment did not influence the models. Conclusion: Our study further supports severity of MS in NAs and unravels the particular severity in NAs living in France, mainly for the second generation.

Paraneoplastic opsoclonus-myoclonus-ataxia syndrome revealing dual malignancy

Dual malignancy has been rarely associated to paraneoplastic syndromes. We describe an unusual case of metachronous small cell lung carcinoma revealed by opsoclonus-myoclonus ataxia syndrome in a 69-year-old patient with known prostate adenocarcinoma, with positive anti-Hu and anti-Yo antibodies and good responsiveness to corticosteroids and chemotherapy.

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.

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.

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.