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Multiple Sclerosis (MS) is a complex neurological disease which prevalence is increasing worldwide. The impact of environmental factors on MS susceptibility has already been defined and highlighted in many previous reports, particularly vitamin D or ultraviolet B light exposure, Epstein-Barr virus (EBV) infection, obesity, and smoking. There is increasing evidence that environmental and lifestyle factors are not only important in triggering MS but are also implicated in MS progression. Low sun exposure and vitamin D deficiency exhibit a strong relationship with disease progression in both animal and human studies. The gestational period seems also to impact long-term disease progression as January's babies had a higher risk of requiring walking assistance than those born in other months. The implication of EBV in neurodegeneration and MS progression was also suggested even though its specific targets and mechanisms are still unclear. Cigarette smoking is correlated with faster clinical progression. The association of obesity and smoking seems to be associated with a faster progression and an increased rate of brain atrophy. Although the effect of air pollution on MS pathogenesis remains not fully understood, exposure to polluted air can stimulate several mechanisms that might contribute to MS severity. People with MS with active disease have an altered microbiota compared to patients in the remission phase. Cardiovascular comorbidities, epilepsy, and depression are also associated with a more severe disability accrual. Knowledge about MS modifiable risk factors of progression need to be incorporated into everyday clinical practice in order to ameliorate disease outcomes.
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Progresión de la Enfermedad , Esclerosis Múltiple , Humanos , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple/etiología , Factores de Riesgo , Exposición a Riesgos Ambientales/efectos adversos , Animales , Infecciones por Virus de Epstein-Barr/complicacionesRESUMEN
INTRODUCTION: Atypical Parkinsonian Syndromes(APS) are challenging neurodegenerative disorders due to their heterogeneous phenotypic overlaps.So far,there are no validated biomarkers that can accurately predict disease progression,and survival studies were highly different and contradictory. AIM: To investigate clinical and molecular survival factors among Tunisian APS patients. METHODS: A retrospective study included Tunisian APS-patients.Using clinical and molecular parameters,survival was explored by Kaplan-Meier analysis. RESULTS: We included 409-APS patients divided into 166-DLB,112-PSP,81-MSA and 50-CBS.Survival rate was similar in synucleinopathies, while it differed in tauopathies,being shorter in PSP compared to CBS.Median survival in DLB was different according to gender(p = 0.0048),early parkinsonism and cognitive disorders. Among MSA, prognosis was worse in MSA-C-patients(p = 0.012) and those with stridor(p = 0.0049),oculomotor and neuropsychiatric disorders. For tauopathies, survival was shorter in PSP-RS(p = 0.027),cerebellar phenotype, those with tremor and swallowing problems at onset, early parkinsonism and memory impairment. For CBS,prognosis was worse in patients with tremor,swallowing and cognitive problems.Significant differences were noted in terms of survival across APS non-carriers of APOE-ε4(p < 0.001) as well APS patients carriers of MAPT-H1.PSP patients had lower survival rate according to MAPT haplotype carriage. Moreover, the number of copies had an influence as patients with H1/H2-MAPT profile had better prognosis than those with H1/H1. CONCLUSION: This study determined survival rates in APS subgroups,which were comparable across synucleinopathies but shorter in PSP and longer in CBS.It also characterized demographic,phenotypic,and genetic profiles identifying more aggressive forms within APS subgroups.These findings address clinical gaps,aiding counseling for patients and families and guiding clinical management.Furthermore,they could facilitate patient stratification in clinical trials where mortality is an outcome measure.
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Trastornos Parkinsonianos , Centros de Atención Terciaria , Humanos , Masculino , Femenino , Trastornos Parkinsonianos/genética , Trastornos Parkinsonianos/mortalidad , Trastornos Parkinsonianos/diagnóstico , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Túnez/epidemiología , Pronóstico , Pueblo NorteafricanoRESUMEN
OBJECTIVE: LRRK2-G2019S is the most frequent mutation in North African Parkinson's disease (PD) patients. Data on its impact on disease progression and treatment response remain elusive. Therefore, we investigated the clinical features, treatments, and complications of PD in Tunisian patients according to their LRRK2-G2019S profile. METHODS: This longitudinal retrospective study was performed in the Department of Neurology, Razi University Hospital. We included clinically diagnosed PD patients according to the Movement Disorders Society criteria and reviewed their medical records for clinical, treatment, and neuropsychological assessments. All patients were screened for the LRRK2-G2019S mutation using Sanger sequencing. The correlation between LRRK2-G2019S and clinical PD features was evaluated. RESULTS: We included 393 PD patients, 41.5% of whom had LRRK2-G2019S mutations. Patients with mutations were younger (p = 0.017), and female PD patients had a greater mutation frequency (p = 0.008). Mutation carriers exhibited distinct clinical features, with a greater frequency of postural instability gait difficulty forms (adjusted-p < 0.001). During disease progression, carriers showed a faster annual progression in the Unified Parkinson's Disease Rating Scale Section III scores (adjusted-p = 0.009), and significantly higher levodopa equivalent dose values in later stages (1060.81 vs. 877.83 for 6-8 years). Motor complications, such as dyskinesia (adjusted-p < 0.001) and motor fluctuations (31.9% vs. 25.7%, adjusted-p < 0.001), were more prevalent in carriers, particularly in the later stages. LRRK2-G2019S carriers also exhibited a lower prevalence of non-motor symptoms, including episodic memory (adjusted-p < 0.001), attention (adjusted-p < 0.001), and dysexecutive disorders (adjusted-p = 0.038), as well as neuropsychiatric symptoms and dysautonomic signs. CONCLUSION: The present study demonstrated that the variability of the clinical profile among Tunisian PD patients was explained by the incomplete penetrance of LRRK2-G2019S, which increased with age. Further studies using biomarker and disease progression data are necessary to improve PD management.
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INTRODUCTION: The relationship between epilepsy and psychiatric disorders has been highlighted for a long time. Idiopathic epilepsy is known to have a benign course in most cases. However, the association of psychiatric disturbances could worsen the disease outcome. AIM: To study the frequency of psychiatric symptoms in patients with idiopathic epilepsy, and to assess the determinant factors in the patient group with these manifestations. METHODS: In one-year prospective study, consecutive patients diagnosed with idiopathic epilepsy were included. Those with a known psychiatric follow-up or with post ictal psychiatric disturbances were excluded. Psychiatric symptoms were evaluated with the Neurological Disorders Depression Inventory for Epilepsy, the Generalized Anxiety Disorder - 7 and the Neuropsychiatric Inventory Scale. Demographic and clinical data were collected and analyzed. RESULTS: Among 101 consecutive patients with idiopathic epilepsy, psychiatric symptoms were diagnosed in 61% of them. Anxiety (36.6%), psychotic features (21%) and depression (15.8 %) were the most commonly found psychiatric manifestations. Female gender (p < 10-3) and longer duration of epilepsy (p = 0.046) were significantly associated with occurrence of psychiatric disturbances. Patients under Carbamazepine and Valproic acid showed a lower frequency of depression (respectively p = 0.018 and p = 0.003). CONCLUSIONS: Occurrence of psychiatric disturbances was frequent in idiopathic epilepsy, with psychotic manifestations and anxiety being the most common of them. Female gender and long disease course were the main determining factors of psychiatric manifestations and should be considered in management of idiopathic epilepsy.
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Epilepsia , Humanos , Femenino , Estudios Prospectivos , Epilepsia/complicaciones , Epilepsia/diagnóstico , Epilepsia/epidemiología , Trastornos de Ansiedad/complicaciones , Trastornos de Ansiedad/epidemiología , Ansiedad/epidemiología , Ansiedad/etiologíaRESUMEN
Painful ophthalmoplegia is a common presenting symptom in neuro-ophthalmology emergencies. We report an unusual case of a recurrent painful ophthalmoplegia due to a third nerve schwannoma mimicking « ophthalmoplegic migraine ¼. A 18 year-old girl had presented 4 episodes of left eye painful ophthalmoplegia respectively in 8, 13, 16 and 17 years old. One year after the last episode, neurological examination was normal. Brain MRI focused on the oculomotor nerve showed an enhancing nodular lesion suggesting a third nerve schwannoma. Thus, recurrent painful ophthalmoplegia revealing oculomotor nerve schwannoma, as described in our case, is exceptional. To our knowledge, only thirteen cases have been reported in the literature. Third nerve schwannoma is a rare cranial nerve tumor, typically revealed by progressive palsy of the oculomotor nerve. Recurrent painful ophthalmoplegia with persistent headache and enhancement in brain imaging should suggest tumoral lesions.
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Neurilemoma , Oftalmoplejía , Migraña Oftalmopléjica , Síndrome de Tolosa-Hunt , Adolescente , Femenino , Humanos , Imagen por Resonancia Magnética , Neurilemoma/complicaciones , Neurilemoma/diagnóstico , Nervio Oculomotor , Oftalmoplejía/diagnóstico , Oftalmoplejía/etiología , Migraña Oftalmopléjica/complicaciones , Migraña Oftalmopléjica/diagnóstico , Síndrome de Tolosa-Hunt/complicaciones , Síndrome de Tolosa-Hunt/diagnósticoRESUMEN
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.
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Canales de Calcio Tipo T/genética , Epilepsia Generalizada/genética , Proteínas Asociadas a Microtúbulos/genética , Proteínas Serina-Treonina Quinasas/genética , Adolescente , Adulto , Edad de Inicio , Niño , Estudios de Cohortes , Consanguinidad , Epilepsia Generalizada/epidemiología , Familia , Femenino , Estudios de Asociación Genética , Ligamiento Genético , Predisposición Genética a la Enfermedad , Humanos , Masculino , Herencia Multifactorial , Linaje , Túnez/epidemiología , Adulto JovenRESUMEN
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.
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Enfermedad de Alzheimer/genética , Glicoproteínas de Membrana/genética , Receptores Inmunológicos/genética , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Técnicas de Genotipaje , Humanos , Masculino , Factores de Riesgo , Análisis de Secuencia , Túnez , Población BlancaRESUMEN
BACKGROUND: In 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. METHODS: In 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. RESULTS: We 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. CONCLUSIONS: The 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.
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Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/genética , Enfermedad de Parkinson/genética , Adulto , Anciano , Estudios de Cohortes , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Mutación , Tasa de Mutación , Reacción en Cadena de la Polimerasa , TúnezRESUMEN
OBJECTIVES: To describe the EEG characteristics of patients with Unverricht-Lundborg disease (ULD) and their changes during the long-term evolution of the disease. METHODS: A retrospective study including all patients with ULD confirmed by molecular biology and more than 15 years' duration of disease progression at the time of inclusion. EEGs were recorded at inclusion, 2 years and 5 years of follow-up. Patients who discontinued treatment during follow-up had an EEG monitoring 1 year after reintroduction of therapy. RESULTS: Forty-seven EEGs were performed in 17 patients. The mean age at onset was 12.0±5.5 years. The mean duration of follow-up was 26.5±6.9 years. The average background rhythm was 8.2 c/s, and was normal in 30 EEGs (64%), slow in 17 (36%) and disorganized in 11 (23%). Epileptic abnormalities were found in 22 EEGs (47%). Myoclonic jerks were found in 13 EEGs (28%). After re-adaptation of antiepileptic medication in patients who had previously stopped treatment, control EEG showed a normal background rhythm with no epileptic abnormalities throughout the monitoring period. CONCLUSION: This study shows that the progressive disappearance of EEG abnormalities is rather due to antiepileptic treatment than a gradual spontaneous tendency to decrease over time.
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Corteza Cerebral/fisiopatología , Progresión de la Enfermedad , Electroencefalografía , Síndrome de Unverricht-Lundborg/diagnóstico , Síndrome de Unverricht-Lundborg/fisiopatología , Adulto , Anticonvulsivantes/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Síndrome de Unverricht-Lundborg/tratamiento farmacológicoRESUMEN
INTRODUCTION: Carpal tunnel syndrome (CTS) is the most frequent entrapment neuropathy reported in patients with renal failure undergoing periodic haemodialysis. The role of arteriovenous fistula was discussed. The aim of this study was to investigate this relationship. METHODS: Subjects for this study were hemodialysis patients who underwent systematic electroneuromyography between January 2003 and December 2010. Only patients with unilateral fistulae were included for the study. RESULTS: One hundred and thirty-four out of 155 patients were examined. CTS was noted in 106 patients and was detectable only in ENMG in 42% of cases. It was more frequent (P<0.001) and more severe in the side of fistulae (P=0.08). Besides, development of CTS was only correlated with the longer duration of dialysis (P=0.005). This duration was significantly shorter in patients with CTS and diabetes. CONCLUSION: The positive correlation between CTS and aretriovenous fistulae confirms the pathogenic role of this latter. The risk rises in these patients with the duration of hemodialysis and the presence of diabetes.