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Essential tremor (ET) encompasses a wide spectrum of motor and non-motor features. Eye movement abnormalities were first reported two decades ago as an atypical finding in ET. Today, a growing number of publications about eye movement abnormalities in neurodegenerative diseases have helped understand their pathophysiology and the basis of their phenotypic variability. Thus, addressing such aspect in ET may disentangle, based on the oculomotor network abnormalities, the dysfunctional brain pathways in ET. In this study, we aimed to describe neurophysiological eye movement abnormalities in ET and their clinical correlates in terms of cognition and other associated clinical signs. We conducted a cross-sectional study in a tertiary neurology referral center including consecutive ET patients and cognitively normal healthy controls (HC) matched for age and sex. The study protocol included the assessment of voluntary horizontal saccades, smooth pursuit, anti-saccades and saccadic intrusions. We assessed the associated motor signs, cognitive functions and the presence of rapid eye movement disorder (RBD). Sixty-two ET patients and 66 HC were enrolled in the study. Eye movement examination showed significant abnormalities in comparison with HC (46.7% vs 20%, p = 0.002). Prolonged saccadic latency (38.7%, p = 0.033) and altered smooth pursuit (38.7%, p = 0.033) were the most common abnormalities in ET patients. Anti-saccadic errors (16% vs 0% in HC, p = 0.034) correlated with the presence of rigidity (p = 0.046), bradykinesia (p = 0.001), cognitive dysfunction (p = 0.006), executive dysfunction (p = 0.0002), apraxia (p = 0.0001), altered verbal fluency (p = 0.013) and altered backward digit span (p = 0.045) along with the presence of RBD (p = 0.035). Square-wave jerks (11.5% vs 0% in HC, p = 0.0024) correlated with rest tremor. A distinctive phenotype of ET could emerge out of this study characterized by anti-saccadic errors and a sub-cortical cognitive profile, consecutive to the disruption of the cerebello-thalamo-cortical loop. Patients with anti-saccadic errors could be cognitively vulnerable and in need of a close monitoring of their cognitive efficiency during the disease's progression. They may as well convert to Parkinson disease if they present with parkinsonism, RBD and square-wave jerks and require, consequently, a close observation of their motor progression.
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Tremor Essencial , Movimentos Oculares , Humanos , Estudos Transversais , Movimentos Sacádicos , Acompanhamento Ocular UniformeRESUMO
BACKGROUND: Tobacco use and alcohol consumption are the primary risk factors for laryngeal cancer (LC). In most populations, occupational exposures are likely to play a minor role in laryngeal carcinogenesis. We aimed to investigate the association between occupational exposure and laryngeal cancer. METHODS: It is a case-control study that included 140 cases diagnosed between January 2013 and December 2016 and 140 controls matched by sex, age, alcohol consumption, and tobacco consumption. RESULTS: Significantly increased risks were found amongst workers of the building sector (OR=4.621; 95% CI [1.826-11.693]) and the mechanical industry sector (OR=5.074; 95% CI [1.425-18.072]). Significant association of laryngeal cancer with various carcinogens was observed such as asbestos (p=0.009; OR=3.68; 95% CI [1.29-10.46]), paint vapors (p=0.005; OR=3.35; 95% CI [1.37-8.16]), solvents (p=0.001; OR=3.29: 95% CI [1.61-6.68]) and cement dust (p=0.003; OR=3.19: 95% CI [1.43-7.12]). After binary logistic regression, cement dust was independently correlated with LC (p=0.042; OR=3.93; 95% CI [1.04-14.78]. The administration sector was associated with decreased risk (p=0.001; OR=0.07; 95% CI [0.03-0.15]) as well as the health sector (p=0.001; OR=0.098; 95% CI [0.02-0.43]). CONCLUSIONS: Our results supported the role of occupational factors in developing LC. Further studies enabling an in-depth analysis of occupational exposures are necessary to provide a clearer definition of the etiological associations between single agents and circumstances of exposure and the genesis of LC.
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Amianto , Neoplasias Laríngeas , Doenças Profissionais , Exposição Ocupacional , Humanos , Neoplasias Laríngeas/etiologia , Neoplasias Laríngeas/induzido quimicamente , Estudos de Casos e Controles , Tunísia/epidemiologia , Fatores de Risco , Exposição Ocupacional/efeitos adversos , Amianto/efeitos adversos , Poeira , Doenças Profissionais/etiologia , Doenças Profissionais/induzido quimicamenteRESUMO
INTRODUCTION: Atypical Parkinsonian syndromes (APS) encompass a spectrum of neurodegenerative diseases including dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal syndrome (CBS). The effects of the Apolipoprotein E (APOE) gene on APS clinical features are controversial and understudied in several populations. We aimed to explore the influence of APOE genotype on clinical features in an APS Tunisian cohort. METHODS: We included clinically diagnosed APS patients genotyped for APOE, and analyzed the clinical and APOE genotype associations. RESULTS: A total of 328 APS patients were included, comprising 184 DLB, 58 PSP, 49 MSA, and 37 CBS. Significant differences in initial Mini-Mental State Examination and Frontal Assessment Battery scores according to APOE genotypes (P=0.05 and 0.0048) were found. Executive dysfunction (P=0.026) disorientation (P=0.025), and hallucinations (P<0.001) were more pronounced among APOE-É4 carriers particularly in DLB. Memory disorders were also correlated to APOE-É4 allele (P=0.048) and were more frequent among DLB and PSP carriers. Depression was associated to APOE-ε4 (P=0.042), more markedly in APOE-ε4-CBS and MSA carriers. CONCLUSIONS: Our findings suggested a role of APOE-ε4 in defining a more altered cognitive phenotype with variable degrees across subgroups in APS patients, especially in DLB carriers. This effect mainly concerned executive, memory and orientation functions as well as hallucinations.
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Apolipoproteínas E/genética , Atrofia de Múltiplos Sistemas , Transtornos Parkinsonianos , Paralisia Supranuclear Progressiva , Apolipoproteína E4/genética , Humanos , Atrofia de Múltiplos Sistemas/diagnóstico , Atrofia de Múltiplos Sistemas/genética , Transtornos Parkinsonianos/diagnóstico , Transtornos Parkinsonianos/genética , Paralisia Supranuclear Progressiva/genéticaRESUMO
BACKGROUND: Midline essential tremor (Mid-ET) is a distinctive group of essential tremor (ET) in which tremor affects the neck, jaw, tongue, and/or voice. For long, it has been considered as an ultimate stage of the disease and a marker of its severity. However, recent studies pointed its complexity in terms of non-motor presentation. Thus, we aimed to investigate the non-motor signs (NMS) in Mid-ET. DESIGN: We conducted a cross-sectional study in a tertiary neurology referral center including ET patients classified into two groups based on the presence or not of midline tremor (Mid-ET vs. No-Mid-ET). We assessed NMS using the non-motor severity scale (NMSS), a large battery of cognitive tests, clinical and electrophysiological study of the autonomic nervous system along with the evaluation of sleep disturbances. RESULTS: A total of 163 patients were included: Mid-ET (n = 79) and No-Mid-ET (n = 84) matched in gender and age of onset. Mid-ET patients had higher proportion of late-onset ET (> 60 years old, p = 0.002) and more extrapyramidal signs (p = 0.005). For NMS, Mid-ET was marked with cognitive dysfunction (p = 0.008). The hallmarks of the neuropsychiatric profile of Mid-ET were executive dysfunction (p = 0.004), attention problems (p < 0.000), episodic memory impairment (p = 0.003), and greater depression (p = 0.010). The presence of RBD was a trait of Mid-ET (p = 0.039). In both Mid-ET and No-Mid-ET phenotypes, clinical and neurophysiological dysautonomia correlated with cognitive dysfunction. CONCLUSION: Mid-ET patients had greater cognitive dysfunction, depression, RBD, higher proportion of late-onset ET, and more extrapyramidal signs. Taken all together, these findings could provide a redesigned insight into the underlying physiopathology of Mid-ET indicative of a greater cerebellar dysfunction.
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Tremor Essencial , Estudos Transversais , Tremor Essencial/complicações , Humanos , Pescoço , Testes Neuropsicológicos , TremorRESUMO
Aims: The present survey aims to assess the overall mood disorder prevalence and identify associated socio-demographic and clinical factors in a Tunisian community sample, with special attention to the COVID-19 pandemic. Background: Mood disorders are one of the leading causes of all non-fatal burdens of disease, with depression being at the top of the list. The COVID-19 pandemic may have increased the prevalence of mood disorders, especially in Low and Middle-income countries (LMICs) and in vulnerable populations. Objective: 1/ Assess point and lifetime prevalence of depressive and bipolar disorders as well as subthreshold bipolarity in a representative population sample of La Manouba governorate and assess treatment patterns for these disorders; 2/Study socio-demographic and clinical correlates of mood disorders 3/ Assess the association between mood disorders and quality of life 4/ Study the impact of the COVID-pandemic on the prevalence of mood disorders 5/ Assess coping mechanisms to the COVID-pandemic and whether these mechanisms moderate the appearance of mood disorders or symptoms since the beginning of the pandemic. Methods: This is a household cross-sectional observational survey to be conducted in La Manouba Governorate in a sample of 4540 randomly selected individuals aged ≥ 15 years. Data collection will be carried out by trained interviewers with clinical experience, through face-to-face interviews and the use of the computer assisted personal interviewing approach (CAPI). The following assessment tools are administered. Results: Structured clinical Interview for DSM IV-TR (Mood disorder section and Screening questions on Anxiety), Mood Disorder Questionnaire (MDQ), Suicide Behaviors Questionnaire-Revised (SBQ), 12-item Short Form Survey (SF-12), the Brief-COPE, and a questionnaire about a headache. In addition, socio-demographic and clinical data will be collected. Conclusion: This will be one of the very few household surveys in a general population sample to assess mental health problems and COVID-19-related variables since the beginning of the pandemic. Through this research, we aim to obtain an epidemiological profile of mood disorders in Tunisia and an estimation of the impact of the COVID-19 pandemic on their prevalence. Results should contribute to improving mental health care in Tunisia.
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Few studies have reported abnormal ocular movements in cases of amyotrophic lateral sclerosis (ALS) and their link with other disease features. Our study aimed to describe and analyse eye movement abnormalities in ALS patients. Specifically, we set out to investigate the correlation between non-motor signs and oculomotor impairment in order to understand the pathogenesis of the disease. All ALS patients seen from 2018 to 2020 in the department of Neurology of Razi hospital underwent the recording of saccadic eye movements. Results were compared with healthy controls. Sixty-two patients were included. Altered saccadic eye movements (72.6%) correlated with tongue atrophy and bladder dysfunction. The most common finding was altered smooth pursuit (56.5%), which showed correlation with bladder dysfunction and altered frontal assessment battery (FAB) scores. Prolonged latencies of horizontal saccades (34%) correlated with sensory and extrapyramidal signs. Our study is the first to examine the characteristics of eye movements in a large African cohort of ALS patients and to show correlations with extra-motor clinical signs. Our findings showed extra-motor cortex dysfunction in ALS with greater frequency of eye movement abnormalities in comparison with previous studies. Altered horizontal pursuit, the core abnormality, confirmed the extension of the neurodegenerative process to the frontal and prefrontal cortices. Prolonged horizontal saccade latencies reflect mainly the involvement of the parietal eye field. Anti-saccadic abnormalities were the least common finding and showed, paradoxically, no link with executive dysfunction.
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BACKGROUND: A wide range of neurological manifestations has been described in COVID-19. METHODS: In this nationwide retrospective observational study, patients in Tunisia diagnosed with COVID-19 between the 2nd of March and the 16th of May 2020 were contacted by telephone. We collected demographic and clinical data and specified characteristics and evolution of main neurological symptoms. RESULTS: Of 1034 confirmed COVID-19 patients, 646 were included (mean age 42.17 years old) and 466 (72.1%) had neurological symptoms. Neurological symptoms were isolated 22.7% (n = 106). Headache was the most frequent neurological symptom (n = 279, 41.1%): mainly frontotemporal (n = 143, 51.1%) and mild or moderate (n = 165, 59.1%). When associated with fever (n = 143, 51.3%), headache was more likely to be severe and present at onset. Recovery was reported in 83.2%. Smell and taste impairment were found in 37.9% (n = 245) and 36.8% (n = 238) respectively. Among them, 65.3% (156/239) were anosmic and 63.2% (146/231) were ageusic. A complete improvement was found in 72.1% (174/240) of smell impairment and in 76.8% (179/233) of taste impairment. Myalgia (n = 241, 37.3%) and sleep disturbances (n = 241, 37.3%) were also frequent. Imported cases had more neurological symptoms (p = 0.001). In 14.5%, neurological symptoms preceded the respiratory signs (RS). RS were associated with more frequent (p = 0.006) and numerous (p < 0.001) neurological symptoms. CONCLUSIONS: Neurological symptoms in COVID-19 are frequent, can be isolated and present at onset. A total recovery is the most recorded outcome. RS are predictive of neurological symptoms. Studies in to virus and host genetics should be considered to understand the different phenotypes.
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Ageusia/etiologia , COVID-19/complicações , Cefaleia/etiologia , Mialgia/etiologia , Transtornos do Olfato/etiologia , Transtornos do Sono-Vigília/etiologia , Adulto , Idoso , Ageusia/epidemiologia , Ageusia/fisiopatologia , COVID-19/epidemiologia , Feminino , Cefaleia/epidemiologia , Cefaleia/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Mialgia/epidemiologia , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/fisiopatologia , Estudos Retrospectivos , Transtornos do Sono-Vigília/epidemiologia , Tunísia/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: We describe and compare the sociodemographic and clinical features, treatments, and prognoses and survival times of patients with amyotrophic lateral sclerosis (ALS) in Africa. METHODOLOGY: We conducted a multicentre, hospital-based cohort study in Africa. Patients with ALS diagnosed in the neurology departments of participating hospitals from 2005 to 2017 were included. Subgroup analysis was performed by subcontinent. Survival analyses were conducted using the Cox proportional hazards model. RESULTS: Nine centres from eight African countries participated. A total of 185 patients with ALS were included: 114 from Northern Africa, 41 from Western Africa and 30 from Southern Africa. A male predominance (male to female ratio 2.9) was evident. The median age at onset was 53.0 years (IQR 44.5-64.0 years). The onset was bulbar in 22.7%. Only 47 patients (26.3%) received riluzole, mainly in Northern and Western Africa. The median survival from the time of diagnosis was 14.0 months (95% CI 10.7 to 17.2 months). The median survival was longer in Northern Africa (19.0 months, 95% CI 10.8 to 27.2 months) than in Western (4.0 months, 95% CI 0.8 to 7.1 months) and Southern (11.0 months, 95% CI 5.6 to 16.4 months) Africa (Breslow test, p<0.0001). Both subcontinental location and riluzole treatment independently affected survival. CONCLUSION: More African patients with ALS were male and younger and exhibited a lower proportion of bulbar onset compared with patients with ALS from Western nations. Survival was consistent with that in Western registers but far shorter than what would be expected for young patients with ALS. The research improves our understanding of the disease in Africa.
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Esclerose Lateral Amiotrófica/fisiopatologia , Adulto , África do Norte/epidemiologia , África Austral/epidemiologia , África Ocidental/epidemiologia , Idade de Início , Idoso , Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/epidemiologia , Esclerose Lateral Amiotrófica/mortalidade , Estudos de Coortes , Humanos , Pessoa de Meia-Idade , Fármacos Neuroprotetores/uso terapêutico , Prognóstico , Modelos de Riscos Proporcionais , Riluzol/uso terapêutico , Distribuição por Sexo , Taxa de SobrevidaRESUMO
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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Canais de Cálcio Tipo T/genética , Epilepsia Generalizada/genética , Proteínas Associadas aos Microtúbulos/genética , Proteínas Serina-Treonina Quinases/genética , Adolescente , Adulto , Idade de Início , Criança , Estudos de Coortes , Consanguinidade , Epilepsia Generalizada/epidemiologia , Família , Feminino , Estudos de Associação Genética , Ligação Genética , Predisposição Genética para Doença , Humanos , Masculino , Herança Multifatorial , Linhagem , Tunísia/epidemiologia , Adulto JovemRESUMO
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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Doença de Alzheimer/genética , Glicoproteínas de Membrana/genética , Receptores Imunológicos/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Técnicas de Genotipagem , Humanos , Masculino , Fatores de Risco , Análise de Sequência , Tunísia , População BrancaRESUMO
Non-motor symptoms (NMS) of Parkinson Disease (PD) are common and can cause severe disability. They are often under-recognized and remain untreated. Tools to evaluate these symptoms in Arabic-speaking patients are still lacking. The objective of this study was to evaluate an Arabic version of the non-motor symptoms scale (NMSS) of PD as an instrument for measuring NMS in Arabic-speaking patients. Sixty-two PD patients clustered around Hoehn & Yahr Stages 2-3 were evaluated by the Arabic version of NMSS. They also underwent a battery of standard psychometric assessment measures that included the scales for outcomes of Parkinson's disease-autonomic (SCOPA-AUT), the Pittsburgh sleep quality index (PSQI), the Beck depression inventory, the geriatric depression scale (GDS), the mini-mental state examination (MMSE), the visual analogical scale for pain(VAS) and the neuro-psychiatric inventory (NPI). The metric properties of the NMSS were studied as well as its correlation with other standard tests evaluating NMS. The mean NMSS score was 82 ± 56 (skewness 0.88). There were highly significant correlations between the NMSS and the SCOPA-AUT as well as the NMSS and PSQI scores. Significant positive correlations between NMSS and GDS, BECK and VAS were also observed. The sleep/fatigue domain significantly correlated with the PSQI, the cardiovascular/urinary/sexual function/gastrointestinal domains significantly correlated with the SCOPA-AUT, the mood/cognition domain significantly correlated with the GDS and BECK findings. The mean Cronbach's alpha coefficient was 0.87, showing a satisfactory internal consistency. The Arabic version of NMSS can be considered a comprehensive and reliable measure for non-motor symptoms in Arabic-speaking PD patients.
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Doenças do Sistema Nervoso Autônomo/diagnóstico , Transtornos do Humor/diagnóstico , Índice de Gravidade de Doença , Transtornos do Sono-Vigília/diagnóstico , Tradução , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças do Sistema Nervoso Autônomo/etiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/etiologia , Doença de Parkinson/complicações , Escalas de Graduação Psiquiátrica , Psicometria , Reprodutibilidade dos Testes , Transtornos do Sono-Vigília/etiologia , Estatística como Assunto , Tunísia , Escala Visual AnalógicaRESUMO
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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Progressão da Doença , Esclerose Múltipla , Humanos , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/etiologia , Fatores de Risco , Exposição Ambiental/efeitos adversos , Animais , Infecções por Vírus Epstein-Barr/complicaçõesRESUMO
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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Transtornos Parkinsonianos , Centros de Atenção Terciária , Humanos , Masculino , Feminino , Transtornos Parkinsonianos/genética , Transtornos Parkinsonianos/mortalidade , Transtornos Parkinsonianos/diagnóstico , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Tunísia/epidemiologia , Prognóstico , População do Norte da ÁfricaRESUMO
OBJECTIVE: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disorder encompassing several phenotypes with various motor and cognitive deficits. We aimed to study motor and cognitive characteristics across PSP phenotypes and to assess the influence of apolipoprotein E (APOE) gene variants on PSP phenotypic expression. METHODS: In this 20-year cross-sectional study, we retrospectively reviewed the charts of all patients classified as PSP patients and recategorized them according to phenotype using the Movement Disorder Society criteria (2017). Phenotypes were divided into three subgroups, Richardson's syndrome (PSP-RS), PSP-cortical (PSP with predominant frontal presentation [PSP-F] + PSP with predominant speech/language disorder [PSP-SL] + PSP with predominant corticobasal syndrome [PSP-CBS]) and PSP-subcortical (PSP with predominant parkinsonism [PSP-P] + PSP with progressive gait freezing [PSP-PGF] + PSP with predominant postural instability [PSP-PI] + PSP with predominant ocular motor dysfunction [PSP-OM] + PSP with cerebellar ataxia [PSP-C] + PSP with primary lateral sclerosis [PSP-PLS]), based on clinical presentation during the first 3 years after symptom onset, which defines the early disease stage. Clinical and neuropsychological assessment data were collected. Genotyping of APOE was performed using restriction fragment length polymorphism polymerase chain reaction and verified by Sanger sequencing. RESULTS: We included 112 PSP patients comprising 10 phenotypes classified into 48 PSP-RS, 34 PSP-cortical (PSP-CBS, 17.6%; PSP-F, 9.4%; PSP-SL, 8.2%) and 30 PSP-subcortical (PSP-P, 11.6%; PSP-PI, 8%; PSP-OM, 2.7%; PSP-PGF, 1.8%; PSP-C, 1.8%; PSP-PLS, 0.9%) subgroups. PSP-RS patients were older at disease onset (p = 0.009) and had more akinetic-rigid and levodopa-resistant parkinsonism (p = 0.006), while PSP-cortical patients had more tremors and asymmetric and/or levodopa-responsive parkinsonism (p = 0.025). Cognitive domains were significantly less altered in the PSP-subcortical subgroup. Overall, PSP-APOEε4 carriers developed parkinsonism earlier (p = 0.038), had earlier oculomotor dysfunction (p = 0.052) and had more altered cognitive profiles. The APOEε4 allele was also associated with a younger age of parkinsonism onset in the PSP-RS phenotype group (p = 0.026). CONCLUSION: This study demonstrated the wide phenotypic spectrum of PSP among Tunisians. Disease onset and akinetic-rigid and levodopa-resistant parkinsonism were the hallmarks of the PSP-RS phenotype, while milder cognitive impairment was characteristic of the PSP-subcortical subgroup. The APOEε4 allele was associated with earlier parkinsonism and oculomotor dysfunction and seemed to play a role in defining a more altered cognitive profile in PSP patients.
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Elevated rates of consanguinity and inbreeding are responsible for the high prevalence of recessively inherited diseases among inbred populations including Tunisia. In addition, the co-occurrence of two of these conditions, called also comorbidity, within the same individual or in members of the same family are often described in Tunisia which is challenging for diagnosis. The high throughput sequencing has improved the diagnosis of inherited diseases. We report here on a 32-year-old woman born to consanguineous parents. She presented with congenital ichthyosis and muscular dystrophy. She was primarily suspected as suffering from Chanarin-Dorfman syndrome (CDS) with unusual form. Screening of founder mutations allowed only the elucidation of the molecular etiology of Ichthyosis. As the result was inconclusive, Whole Exome Sequencing (WES) was conducted. WES data analysis led to the identification of a mutation in the CAPN3 gene underlying limb-girdle muscular dystrophy type 2A (LGMD2A). Sanger sequencing confirmed the familial segregation of mutations. This work presents the first case worldwide of individual comorbidity of bathing suit ichthyosis and LGMD2A. The co-occurrence of two diseases should be systematically considered when establishing a diagnosis especially in consanguineous populations. WES is a powerful tool for molecular diagnosis in particular for revealing comorbidities and rectifying the diagnosis.
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Distrofia Muscular do Cíngulo dos Membros , Feminino , Humanos , Adulto , Sequenciamento do Exoma , Distrofia Muscular do Cíngulo dos Membros/genética , Mutação , ComorbidadeRESUMO
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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BACKGROUND: The clinical spectrum of stiff-person syndrome (SPS) encompasses a wide range of signs including psychiatric symptoms (PS). OBJECTIVE: Our objective was to provide an overview of the spectrum of PS in SPS through a systematic literature search and 2 illustrative case reports. METHODS: We reported 2 anti-glutamic acid decarboxylase-positive SPS cases that presented with phobic disorder, and we performed a systematic review by following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles published in PubMed, MEDLINE on Ovid, Embase, and via a manual search before October 20, 2020, were selected by 2 independent reviewers. Original studies, case reports, editorials, commentaries, and letters to the editor reporting cases of SPS with PS were all included. Conference abstracts, reviews and book chapters, unavailable articles, and those not reporting SPS cases or PS were excluded. Quantitative summary data were calculated. RESULTS: In addition to our 2 cases, we identified 237 cases of SPS with PS from 74 additional included publications totaling 239 patients. Anxiety (56%) and depression (45%) were the most common PS in SPS. Mean diagnostic delay was 4.7 years. Among the 3 SPS phenotypes, the classic form was predominant (77%), followed by stiff-limb syndrome (13%) and progressive encephalomyelitis with rigidity and myoclonus (10%). The most frequent etiology of SPS with PS was autoimmune (90%), followed by cryptogenic (7%) and paraneoplastic forms (7%). These patients were mainly treated with immune-mediated therapies and GABAergic drugs. CONCLUSIONS: Our review revealed that the most common PS of SPS are anxiety and depression occurring mostly in autoimmune and classic forms, allowing a clearer understanding of this entity, which may lead to earlier diagnosis and better outcome.
Assuntos
Encefalomielite , Rigidez Muscular Espasmódica , Humanos , Rigidez Muscular Espasmódica/complicações , Rigidez Muscular Espasmódica/diagnóstico , Diagnóstico Tardio , AutoanticorposRESUMO
AIMS: The aims of this study were to analyze retinal and choroidal changes on optical coherence tomography (OCT) and OCT-Angiography (OCT-A) in Alzheimer's disease (AD) patients and compare them to other forms of major dementia. We also aimed to analyze the correlation between clinical severity of global cognitive deficiency assessed by the mini-mental state exam (MMSE) score and OCT/OCT-A parameters. METHODS: Retrospective cross-sectional evaluative study of AD, and age-and gender-matched patients with other dementias. Fundus examination, OCT and OCT-A were compared. RESULTS: Ninety-one eyes of AD patients and 53 eyes of patients with other dementias were included. Retinal deposits were found in 6.59% of AD cases. OCT highlighted the presence of hyperreflective deposits and localized areas of outer retina and ellipsoid zone disruption, respectively in 20.87% and 15.38% of AD cases. Hyperreflective foci were noted within inner retinal layers in 4.39% of AD cases. Quantitative analysis revealed a thicker nasal retinal nerve fiber layer (p = 0.001) and ganglion cell complex in superior (p = 0.011) and temporal quadrants (p = 0.009) in eyes of AD patients, compared to other dementias. OCT-A showed a significantly higher fractal dimension of both superficial and deep capillary plexus (p = 0.005), with lower choriocapillaris density (p = 0.003) in AD patients. CONCLUSIONS: Structural OCT could highlight the presence of hyperreflective deposits in AD, probably reflecting beta-amyloid deposits, associated to outer retinal disruptions. Quantitative OCT analysis showed structural differences between AD patients and other dementias, and combined OCT-A could identify microvascular changes in AD patients representing new potential differential diagnosis criteria.
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Doença de Alzheimer , Disfunção Cognitiva , Humanos , Tomografia de Coerência Óptica/métodos , Estudos Retrospectivos , Doença de Alzheimer/diagnóstico , Estudos Transversais , Retina , Disfunção Cognitiva/diagnóstico , Angiografia , Angiofluoresceinografia/métodos , Vasos RetinianosRESUMO
Background: Dementia with Lewy bodies (DLB) is a progressive neurodegenerative disease with various clinical symptoms. Limited data have described the clinical subtypes of DLB. Objective: We aimed to compare clinical subtypes of DLB according to initial symptoms and to study the effect of Apolipoprotein E (APOE) gene in DLB. Methods: We included DLB patients classified into three groups based on initial symptoms: non-motor onset (cognitive and/or psychiatric) (NMO-DLB), motor onset (parkinsonism and/or gait disorders) (MO-DLB), and mixed onset (non-motor and motor symptoms) (MXO-DLB). Clinical and APOE genotype associations and survival were analyzed. Results: A total of 268 patients were included (NMO-DLB = 75%, MXO-DLB = 15.3%, MO-DLB = 9.7%). Visual hallucinations were more frequent (p = 0.025), and attention was less commonly impaired in MXO-DLB (p = 0.047). When adjusting with APOE É4 status (APOE genotype performed in 155 patients), earlier falls and frontal lobe syndrome were more common in MXO-DLB (p = 0.044 and p = 0.023, respectively). The median MMSE decline was 2.1 points/year and the median FAB decline was 1.9 points/year, with no effect of clinical subtypes. Median survival was 6 years. It was similar in DLB subtypes (p = 0.62), but shorter for patients with memory symptoms at onset (p = 0.04) and for males (p = 0.0058). Conclusions: Our study revealed a few differences between DLB clinical subtypes. APOE É4 appears to be associated with earlier falls and a higher prevalence of frontal syndrome in MXO-DLB. However, DLB clinical subtypes did not impact on survival. Nevertheless, survival analysis identified other poor prognosis factors, notably inaugural memory impairment and male gender.