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1.
Sci Rep ; 14(1): 19049, 2024 08 17.
Article de Anglais | MEDLINE | ID: mdl-39152190

RÉSUMÉ

Patients recovering from COVID-19 commonly exhibit cognitive and brain alterations, yet the specific neuropathological mechanisms and risk factors underlying these alterations remain elusive. Given the significant global incidence of COVID-19, identifying factors that can distinguish individuals at risk of developing brain alterations is crucial for prioritizing follow-up care. Here, we report findings from a sample of patients consisting of 73 adults with a mild to moderate SARS-CoV-2 infection without signs of respiratory failure and 27 with infections attributed to other agents and no history of COVID-19. The participants underwent cognitive screening, a decision-making task, and MRI evaluations. We assessed for the presence of anosmia and the requirement for hospitalization. Groups did not differ in age or cognitive performance. Patients who presented with anosmia exhibited more impulsive alternative changes after a shift in probabilities (r = - 0.26, p = 0.001), while patients who required hospitalization showed more perseverative choices (r = 0.25, p = 0.003). Anosmia correlated with brain measures, including decreased functional activity during the decision-making task, thinning of cortical thickness in parietal regions, and loss of white matter integrity. Hence, anosmia could be a factor to be considered when identifying at-risk populations for follow-up.


Sujet(s)
Anosmie , Encéphale , COVID-19 , Imagerie par résonance magnétique , SARS-CoV-2 , Humains , COVID-19/complications , COVID-19/psychologie , COVID-19/physiopathologie , COVID-19/imagerie diagnostique , COVID-19/anatomopathologie , Anosmie/étiologie , Anosmie/physiopathologie , Mâle , Femelle , Adulte d'âge moyen , Adulte , Encéphale/imagerie diagnostique , Encéphale/anatomopathologie , Encéphale/physiopathologie , SARS-CoV-2/isolement et purification , Sujet âgé , Prise de décision , Cognition/physiologie
2.
Mult Scler Relat Disord ; 79: 105012, 2023 Nov.
Article de Anglais | MEDLINE | ID: mdl-37797392

RÉSUMÉ

INTRODUCTION: Multiple Sclerosis (MS) is a chronic disease affecting around 2.8 million people worldwide. Two-thirds are women, and the mean age at diagnosis is about 30 years old. Social trends are moving towards older age at first pregnancy, both in women with and without MS. OBJECTIVES: To determine the frequency of diminished ovarian reserve (DOR) through anti-Mullerian Hormone (AMH) measurement in women with MS at fertile age and Healthy Females (HF) in Chile. METHODS: Case-control, multicentric, cross-sectional study including relapsing-remitting people with MS (pwMS) between 18 and 40 years and sex and age-matched HF. We obtained a blood sample to determine AMH levels. We defined DOR as AMH <1.5 ng/mL and very-low AMH levels as <0.5 ng/mL. Also, we performed questions regarding reproductive decision-making. RESULTS: We included 79 sex and age-matched HF and 92 pwMS, median age 32(19-40) years, median disease duration 6 (1-17)years, median EDSS 1.0 (0-6), 95% were receiving disease-modifying therapy (DMT), 70% high-efficacy DMT and 37% with a treatment that contraindicates pregnancy. DOR was observed in 24% (n = 22) of the pwMS, compared to 14% (n = 11) of the HF (p = 0.09), while very-low AMH levels were observed in 7.6% (n = 7) of pwMS and none of the HF (p = 0.0166). We observed an inverse correlation between age and AMH levels. Age was the only significant risk factor for low AMH levels in pwMS (OR 1.14 95%CI(1.00-1-31), p = 0.04), including smoking, body mass index (BMI), hormonal contraception, autoimmune comorbidity, high/low-moderate efficacy DMT, and active disease as covariables. We did not find statistically significant differences in age at diagnosis, BMI, disease duration, EDSS, autoimmune comorbidity, use of hormonal contraception, or percentage of active disease between MS women with normal vs DOR. Over 70% of pwMS desired to become pregnant in the future, while 60% considered that the diagnosis of MS was a limitation for pregnancy planning. CONCLUSIONS: No differences in DOR, measured by levels of AMH, were observed between pwMS MS and HF in Chile. As expected, AMH levels were correlated only with ageing. This information may be evaluated early during the disease course to help patients and neurologists with fertility counselling and family planning considerations regarding DMT use.


Sujet(s)
Sclérose en plaques , Réserve ovarienne , Grossesse , Humains , Femelle , Adulte , Mâle , Sclérose en plaques/épidémiologie , Études transversales , Chili/épidémiologie , Vieillissement
3.
Mult Scler Relat Disord ; 69: 104442, 2023 Jan.
Article de Anglais | MEDLINE | ID: mdl-36521387

RÉSUMÉ

BACKGROUND: Anti-Myelin Oligodendrocyte Glycoprotein (MOG) Antibody Associated Disease (MOGAD) is an emerging disorder recognized as a clinical entity distinct from Multiple Sclerosis and Aquaporin-4-positive Neuromyelitis Optica Spectrum Disorders (NMOSD-AQP4+), and its phenotypic spectrum continues to expand. Most information about its clinical course has emerged from retrospective studies, and treatment response both in acute and chronic-relapsing disease is still limited. We aimed to describe the clinical and paraclinical characteristics of monophasic and relapsing, paediatric and adult patients with MOGAD under regular clinical care in Chile, highlighting some challenging cases that are far from being considered benign. METHODS: Observational, retrospective, and prospective longitudinal multicentre study including patients with positive serum MOG-IgG assessed by cell-based assay. RESULTS: We include 35 patients, 71% women, median age at onset 30 years (range 1-68), 23% had paediatric onset, with a median disease-duration 24 months (range 12-348). In the whole cohort, the most frequent symptoms at onset were isolated optic neuritis (ON) (34%) and myelitis (22%). Encephalitis with seizures or encephalomyelitis was the most common presentation in paediatric-onset patients 75% (n = 6), compared to 11% (n = 3) of the adult-onset patients (p < 0.001). A relapsing course was observed in 34%, these patients were younger (25 vs. 34 years, p = 0.004) and with a longer disease duration (64 vs. 6 months, p = 0.004) compared to monophasic patients. Two patients developed encephalitis with seizures/status epilepticus, with concomitant positive CSF anti-NMDAR-IgG. Chronic immunotherapy was ever prescribed in 77%, the most frequent was rituximab (35%). Relapses under chronic immunotherapy occurred in 5/27 patients (18.5%), two of them under rituximab, one paediatric patient who started combined therapy with monthly IVIG and one adult patient that switched to satralizumab plus mycophenolate. The median EDSS at the last follow-up was 1.5 (range 0-6.0). CONCLUSION: In Chile, patients with MOGAD exhibit a wide spectrum of clinical presentations at disease onset and during relapses. Close monitoring is needed, particularly in younger patients with short follow-up periods.


Sujet(s)
Encéphalite , Neuromyélite optique , Femelle , Mâle , Humains , Études rétrospectives , Études prospectives , Rituximab , Chili/épidémiologie , Glycoprotéine MOG , Aquaporine-4 , Crises épileptiques , Autoanticorps , Immunoglobuline G , Oligodendroglie
6.
Mult Scler Relat Disord ; 48: 102682, 2021 Feb.
Article de Anglais | MEDLINE | ID: mdl-33321343

RÉSUMÉ

INTRODUCTION: Women represent two-thirds of the MS population and are usually diagnosed during childbearing age. Collection of local information about pregnancy outcomes is fundamental to support individual decision-making. OBJECTIVE: To explore the trends in pregnancy decision making and pregnancy outcomes before (PreMS) and after (PostMS) MS diagnosis. METHODS: We developed a questionnaire for retrospective assessment of pregnancy outcomes in PreMS and PostMS patients under regular care at the Programa de Esclerosis Multiple UC in Chile. RESULTS: From the 218 women who responded to the questionnaire, 67 women did not have pregnancies. The total number of pregnancies registered was 299, 223 were PreMS (97 women, mean 2.5 ± 1.3 per/woman), and 76 PostMS (59 women, mean 1.9 ± 1.1 per/woman, p = 0.003). Mean age at first pregnancy was 27.6 ± 6.2 in PreMS, and 32.6 ± 4.6 years in PostMS women (p < 0.001). Significant differences between PreMS and PostMS pregnancy outcomes were cesarean section (37% vs. 66%; OR 2.74 95%CI(1.5-52), p=0.002), suspected relapse during 6 months after birth (7% vs. 18%, p<0.001), and breastfeeding (83% vs 67%, p=0.005). Gestational age, weight/size at birth, were not different between groups. Major malformations were observed similarly in both groups. CONCLUSIONS: Changes in pregnancy decision-making after MS diagnosis occur, having fewer children and at an older age. It also changes obstetrician decisions for cesarean sections, with a 3 fold increase. Regarding newborn outcomes, there were no differences between groups.


Sujet(s)
Sclérose en plaques , Issue de la grossesse , Sujet âgé , Césarienne , Enfant , Chili , Femelle , Humains , Nouveau-né , Sclérose en plaques/épidémiologie , Grossesse , Issue de la grossesse/épidémiologie , Études rétrospectives
7.
Mult Scler Relat Disord ; 46: 102565, 2020 Nov.
Article de Anglais | MEDLINE | ID: mdl-33039942

RÉSUMÉ

BACKGROUND: Comorbidities are prevalent among Multiple Sclerosis (MS) patients. Few studies have characterized their prevalence and impact in Latin American populations. OBJECTIVE: We aim to assess the prevalence of comorbidities and their impact on the risk of physical disability across different MS phenotypes. METHODS: Cross-sectional multicenter study of patients under regular clinical care at the Programa de Esclerosis Múltiple UC and Hospital Dr. Sótero del Río in Chile. Prevalence of comorbidities was estimated from the retrospective assessment of electronic medical charts. Disease phenotypes were categorized into two groups: clinically isolated syndrome/relapsing-remitting (inflammatory group) and primary/secondary progressive MS patients (progressive group). A multivariable analysis using binary logistic regression for assessing the risk of EDSS ≥ 6.0 in each group was performed. RESULTS: A total of 453 patients was included, 71% female, mean age at onset 31 years, mean disease duration 10 years, and median EDSS 2.0 (range 0-10). In the whole sample, most prevalent comorbidities were ever-smoking (42.2%), depression/anxiety (34.9%), thyroid disease (15.7%), hypertension (11.3%) and insulin resistance/type 2 diabetes mellitus (11.0%). When assessing the risk of EDSS ≥ 6, in the inflammatory group (N = 366), age at onset (OR 1.06, 95%CI(1.02-1.11), p = 0.008), disease duration (OR 1.06, 95%CI(1.00-1.12), p = 0.039) and epilepsy comorbidity (OR 5.36, 95%CI(1.33-21.5), p = 0.018) were associated with a higher risk of disability. In the progressive group (N = 87), disease duration was a risk factor (OR 1.08 95%CI(1.02-1.16), p = 0.014), while shorter diagnostic delay (OR 0.91 95%CI(0.85-0.99), p = 0.025) and insulin resistance/type 2 diabetes mellitus comorbidity were protective factors (OR 0.18 95%CI(0.04-0.83), p = 0.028), 72% of these patients were receiving metformin. CONCLUSIONS: Comorbidities are common across different MS disease phenotypes. Epilepsy seems particularly related with a higher risk of physical disability in relapsing-remitting patients, while the role of insulin resistance/type 2 diabetes mellitus or the impact of metformin use as a protective factor should be further studied. Prospective and larger studies are still needed in order to assess the real impact of comorbidities and their management in MS outcomes.


Sujet(s)
Diabète de type 2 , Sclérose en plaques récurrente-rémittente , Sclérose en plaques , Adulte , Chili , Comorbidité , Études transversales , Retard de diagnostic , Évaluation de l'invalidité , Évolution de la maladie , Femelle , Humains , Mâle , Sclérose en plaques/épidémiologie , Sclérose en plaques récurrente-rémittente/épidémiologie , Phénotype , Prévalence , Études prospectives , Études rétrospectives
8.
Seizure ; 83: 1-4, 2020 Dec.
Article de Anglais | MEDLINE | ID: mdl-33075670

RÉSUMÉ

PURPOSE: Our objective is to describe the most prevalent electroencephalographic findings in COVID-19 hospitalized patients, and to determine possible predictors of mortality including EEG and clinical variables. METHODS: A multicentric prospective observational study in patients with COVID-19 requiring EEG during hospitalization. RESULTS: We found 94 EEG from 62 patients (55 % men, mean age 59.7 ± 17.8 years) were analyzed. Most frequent comorbidity was cardiac (52 %), followed by metabolic (45 %) and CNS disease (39 %). Patients required ICU management by 60 %, with a mortality of 27 % in the whole cohort. The most frequent EEG finding was generalized continuous slow-wave activity (66 %). Epileptic activity was observed in 19 % including non-convulsive status epilepticus, seizures and interictal epileptiform discharges. Periodic patterns were observed in 3 patients (3.2 %). Multivariate analysis found that cancer comorbidity and requiring an EEG during the third week of evolution portended a higher risk of mortality CONCLUSION: We observed that the most prevalent EEG finding in this cohort was generalized continuous slow-wave activity, while epileptic activity was observed in less than 20 % of the cases. Mortality risk factors were comorbidity with cancer and requiring an EEG during the third week of evolution, possibly related to the hyperinflammatory state.


Sujet(s)
COVID-19/mortalité , Électroencéphalographie , SARS-CoV-2/pathogénicité , Crises épileptiques/physiopathologie , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , COVID-19/diagnostic , COVID-19/physiopathologie , Électroencéphalographie/méthodes , Épilepsie/physiopathologie , Épilepsie/virologie , Femelle , Hospitalisation/statistiques et données numériques , Humains , Patients hospitalisés , Mâle , Adulte d'âge moyen , Pronostic , Crises épileptiques/virologie , État de mal épileptique/mortalité , État de mal épileptique/physiopathologie , État de mal épileptique/virologie
9.
Neurosurgery ; 88(1): 113-121, 2020 12 15.
Article de Anglais | MEDLINE | ID: mdl-32735677

RÉSUMÉ

BACKGROUND: Accurate localization of the probable Epileptogenic Zone (EZ) from presurgical studies is crucial for achieving good prognosis in epilepsy surgery. OBJECTIVE: To evaluate the degree of concordance at a sublobar localization derived from noninvasive studies (video electroencephalography, EEG; magnetic resonance imaging, MRI; 18-fluorodeoxyglucose positron emission tomography FDG-PET, FDG-PET) and EZ estimated by stereoEEG, in forecasting seizure recurrence in a long-term cohort of patients with focal drug-resistant epilepsy. METHODS: We selected patients with a full presurgical evaluation and with postsurgical outcome at least 1 yr after surgery. Multivariate Cox regression analysis for seizure freedom (Engel Ia) was performed. RESULTS: A total of 74 patients were included, 62.2% were in Engel class Ia with a mean follow-up of 2.8 + 2.4 yr after surgery. In the multivariate analysis for Engel Ia vs >Ib, complete resection of the EZ found in stereoEEG (hazard ratio, HR: 0.24, 95%CI: 0.09-0.63, P = .004) and full concordance between FDG-PET and stereoEEG (HR: 0.11, 95%CI: 0.02-0.65, P = .015) portended a more favorable outcome. Most of our results were maintained when analyzing subgroups of patients. CONCLUSION: The degree of concordance between noninvasive studies and stereoEEG may help to forecast the likelihood of cure before performing resective surgery, particularly using a sublobar classification and comparing the affected areas in the FDG-PET with EZ identified with stereoEEG.


Sujet(s)
Épilepsie pharmacorésistante/chirurgie , Électroencéphalographie/méthodes , Neuroimagerie/méthodes , Crises épileptiques/prévention et contrôle , Résultat thérapeutique , Adolescent , Adulte , Enfant , Études de cohortes , Femelle , Fluorodésoxyglucose F18 , Prévision , Humains , Imagerie par résonance magnétique/méthodes , Mâle , Adulte d'âge moyen , Tomographie par émission de positons/méthodes , Études rétrospectives , Jeune adulte
10.
Mult Scler Relat Disord ; 45: 102411, 2020 Oct.
Article de Anglais | MEDLINE | ID: mdl-32711299

RÉSUMÉ

BACKGROUND: Fingolimod is a high-efficacy disease-modifying therapy for multiple sclerosis (MS) and was the first oral treatment approved for the disease. Adverse events include bradyarrhythmia, hypertension, macular oedema and increased risk of infections, mainly due to its main mechanism of action, the non-selective modulation of sphingosine-1-phosphate receptor. METHODS AND RESULTS: We report the baseline characteristics, effectiveness outcomes and adverse events of a prospective cohort of 177 patients with a median treatment duration of 24 months, in which four patients (2.3%) presented with otherwise non-provoked peripheral vascular events (PVE). CONCLUSIONS: Further studies are still needed to evaluate the frequency and severity of PVE in fingolimod patients.


Sujet(s)
Sclérose en plaques récurrente-rémittente , Sclérose en plaques , Études de cohortes , Chlorhydrate de fingolimod/effets indésirables , Humains , Immunosuppresseurs/effets indésirables , Sclérose en plaques/traitement médicamenteux , Sclérose en plaques/épidémiologie , Études prospectives
13.
Sci Rep ; 10(1): 9310, 2020 06 09.
Article de Anglais | MEDLINE | ID: mdl-32518271

RÉSUMÉ

Working Memory (WM) impairment is the most common cognitive deficit of patients with Multiple Sclerosis (MS). However, evidence of its neurobiological mechanisms is scarce. Here we recorded electroencephalographic activity of twenty patients with relapsing-remitting MS and minimal cognitive deficit, and 20 healthy control (HC) subjects while they solved a WM task. In spite of similar performance, the HC group demonstrated both a correlation between temporoparietal theta activity and memory load, and a correlation between medial frontal theta activity and successful memory performances. MS patients did not show theses correlations leading significant differences between groups. Moreover, cortical connectivity analyses using granger causality and phase-amplitude coupling between theta and gamma revealed that HC group, but not MS group, presented a load-modulated progression of the frontal-to-parietal connectivity. This connectivity correlated with working memory capacity in MS groups. This early alterations in the oscillatory dynamics underlaying working memory could be useful for plan therapeutic interventions.


Sujet(s)
Lobe frontal/physiopathologie , Troubles de la mémoire/physiopathologie , Mémoire à court terme/physiologie , Sclérose en plaques/physiopathologie , Sclérose en plaques/psychologie , Lobe pariétal/physiopathologie , Adulte , Études cas-témoins , Électroencéphalographie , Femelle , Lobe frontal/imagerie diagnostique , Humains , Traitement d'image par ordinateur , Mâle , Troubles de la mémoire/imagerie diagnostique , Troubles de la mémoire/étiologie , Sclérose en plaques/imagerie diagnostique , Sclérose en plaques récurrente-rémittente/imagerie diagnostique , Sclérose en plaques récurrente-rémittente/étiologie , Sclérose en plaques récurrente-rémittente/physiopathologie , Lobe pariétal/imagerie diagnostique , Temps de réaction , Lobe temporal/imagerie diagnostique , Lobe temporal/physiopathologie
14.
BMC Neurol ; 20(1): 173, 2020 May 07.
Article de Anglais | MEDLINE | ID: mdl-32380977

RÉSUMÉ

BACKGROUND: Multiple sclerosis (MS) is a chronic immune mediated disease and the progressive phase appears to have significant neurodegenerative mechanisms. The classification of the course of progressive MS (PMS) has been re-organized into categories of active vs. not active inflammatory disease and the presence vs. absence of gradual disease progression. Clinical trial experience to date in PMS with anti-inflammatory medications has shown limited effect. Andrographolide is a new class of anti-inflammatory agent, that has been proposed as a potential drug for autoimmune disorders, including MS. In the present trial, we perform an exploratory pilot study on the efficacy and safety of andrographolide (AP) compared to placebo in not active PMS. METHODS: A pilot clinical trial using 140 mg oral AP or placebo twice daily for 24 months in patients with not active primary or secondary progressive MS was conducted. The primary efficacy endpoint was the mean percentage brain volume change (mPBVC). Secondary efficacy endpoints included 3-month confirmed disability progression (3-CDP) and mean EDSS change. RESULTS: Forty-four patients were randomized: 23 were assigned to the AP group, and 21 were assigned to the placebo group. The median baseline EDSS of both groups was 6.0. Annualized mPBVC was - 0.679% for the AP group and - 1.069% for the placebo group (mean difference: -0.39; 95% CI [- 0.836-0.055], p = 0.08, relative reduction: 36.5%). In the AP group, 30% had 3-CDP compared to 41% in the placebo group (HR: 0.596; 95% CI [0.200-1.777], p = 0.06). The mean EDSS change was - 0.025 in the AP group and + 0.352 in the placebo group (mean difference: 0.63, p = 0.042). Adverse events related to AP were mild rash and dysgeusia. CONCLUSIONS: AP was well tolerated and showed a potential effect in reducing brain atrophy and disability progression, that need to be further evaluated in a larger clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT02273635 retrospectively registered on October 24th, 2014.


Sujet(s)
Anti-inflammatoires non stéroïdiens/usage thérapeutique , Encéphale/effets des médicaments et des substances chimiques , Diterpènes/usage thérapeutique , Sclérose en plaques chronique progressive/traitement médicamenteux , Sujet âgé , Andrographis , Anti-inflammatoires non stéroïdiens/pharmacologie , Encéphale/imagerie diagnostique , Évolution de la maladie , Diterpènes/pharmacologie , Méthode en double aveugle , Femelle , Humains , Imagerie par résonance magnétique , Mâle , Adulte d'âge moyen , Sclérose en plaques , Phytothérapie , Projets pilotes , Études prospectives
15.
Rev. chil. neuro-psiquiatr ; Rev. chil. neuro-psiquiatr;57(4): 365-376, dic. 2019. tab, ilus
Article de Espagnol | LILACS | ID: biblio-1092733

RÉSUMÉ

Resumen El creciente interés en los mecanismos que determinan el funcionamiento social de los seres humanos ha emergido como un desafío a la hora de obtener un concepto adecuado de cognición social y sus mecanismos relacionados, debido a que diversas patologías neurológicas y psiquiátricas se relacionan con deterioros de estas funciones desde etapas tempranas. Cognición Social se define como la integración de procesos mentales que permiten la interacción entre sujetos, incluyendo fenómenos como el de la Percepción Social, la Teoría de la Mente y la Empatía (o respuesta afectiva a los estados mentales de otros sujetos). En este artículo, como objetivo principal, exponemos los principales conceptos y las bases neurales para facilitar una primera aproximación de quienes busquen una aplicación con poblaciones clínicas.


The growing interest in the mechanisms determining the social functioning of human beings has raised the challenge of obtaining an accurate concept of social cognition and its related mechanisms, because several neurologic and psychiatric diseases exhibit related impairments since earliest stages. Social Cognition is defined as the integration of mental processes allowing the interaction among subjects and it includes phenomena as Social Perception, Theory of Mind and Empathy (or the affective response to the mental state of other people). In this article, as the primary aim, we expose the main concepts and neural basis in order to make easier the first approach for those who are looking for an application in the research with clinical populations.


Sujet(s)
Humains , Perception sociale , Cognition , Empathie , Théorie de l'esprit , Processus mentaux
16.
Rev. chil. radiol ; 25(1): 5-18, mar. 2019. tab, ilus
Article de Espagnol | LILACS | ID: biblio-1003745

RÉSUMÉ

La esclerosis múltiple (EM) es la enfermedad inflamatorio-desmielinizante del Sistema nervioso central más prevalente en adultos. La resonancia magnética (RM) juega un rol cada vez más importante en el estudio de esta patología, en especial en su diagnóstico precoz, por lo que la diferenciación imagenológica de variantes frecuentes e infrecuentes de EM con otras patologías de sustancia blanca que comprometen encéfalo y médula espinal es esencial. Mediante una revisión pictórica se ilustrarán características típicas en RM del compromiso por EM y de variantes menos habituales de lesión desmielinizante, y se ilustrarán hallazgos característicos de lesiones relacionadas a vasculopatías inflamatorias y no inflamatorias, encefalomielitis diseminada aguda (ADEM), neuromielitis óptica (NMO) y enfermedades vasculares de la médula espinal que pueden simular EM, con énfasis en el diagnóstico diferencial radiológico.


Multiple sclerosis (MS) is the most prevalent inflammatory-demyelinating disease of the central nervous system in adult population. Magnetic resonance imaging (MRI) has an increasingly important role, especially in early diagnosis, so the imaging differentiation of frequent and infrequent variants of MS with other white matter diseases of brain and spinal cord is essential. Through a pictorial essay we show typical MR features of MS and more infrequent variants of demyelinating lesions and illustrate characteristic imaging findings of inflammatory and non-inflammatory vasculopathies, acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO) and vascular diseases of spinal cord that may simulate MS, with emphasis on imaging differential diagnosis.


Sujet(s)
Humains , Sclérose en plaques/imagerie diagnostique , Imagerie par résonance magnétique , Tomodensitométrie , Neuromyélite optique/imagerie diagnostique , Diagnostic différentiel , Encéphalomyélite aigüe disséminée/imagerie diagnostique , Syndrome de Susac/imagerie diagnostique
17.
Front Immunol ; 8: 753, 2017.
Article de Anglais | MEDLINE | ID: mdl-28713377

RÉSUMÉ

Multiple sclerosis (MS) is a chronic, inflammatory, and demyelinating disease of the central nervous system. It is a heterogeneous pathology that can follow different clinical courses, and the mechanisms that underlie the progression of the immune response across MS subtypes remain incompletely understood. Here, we aimed to determine differences in the immunological status among different MS clinical subtypes. Blood samples from untreated patients diagnosed with clinically isolated syndrome (CIS) (n = 21), different clinical forms of MS (n = 62) [relapsing-remitting (RRMS), secondary progressive, and primary progressive], and healthy controls (HCs) (n = 17) were tested for plasma levels of interferon (IFN)-γ, IL-10, TGF-ß, IL-17A, and IL-17F by immunoanalysis. Th1 and Th17 lymphocyte frequencies were determined by flow cytometry. Our results showed that IFN-γ levels and the IFN-γ/IL-10 ratio were higher in CIS patients than in RRMS patients and HC. Th1 cell frequencies were higher in CIS and RRMS than in progressive MS, and RRMS had a higher Th17 frequency than CIS. The Th1/Th17 cell ratio was skewed toward Th1 in CIS compared to MS phenotypes and HC. Receiver operating characteristic statistical analysis determined that IFN-γ, the IFN-γ/IL-10 ratio, Th1 cell frequency, and the Th1/Th17 cell ratio discriminated among CIS and MS subtypes. A subanalysis among patients expressing high IL-17F levels showed that IL-17F and the IFN-γ/IL-17F ratio discriminated between disease subtypes. Overall, our data showed that CIS and MS phenotypes displayed distinct Th1- and Th17-related cytokines and cell profiles and that these immune parameters discriminated between clinical forms. Upon validation, these parameters might be useful as biomarkers to predict disease progression.

18.
PLoS One ; 12(6): e0177472, 2017.
Article de Anglais | MEDLINE | ID: mdl-28650992

RÉSUMÉ

Galectin-8 (Gal-8) is a member of a glycan-binding protein family that regulates the immune system, among other functions, and is a target of antibodies in autoimmune disorders. However, its role in multiple sclerosis (MS), an autoimmune inflammatory disease of the central nervous system (CNS), remains unknown. We study the consequences of Gal-8 silencing on lymphocyte subpopulations and the development of experimental autoimmune encephalitis (EAE), to then assess the presence and clinical meaning of anti-Gal-8 antibodies in MS patients. Lgals8/Lac-Z knock-in mice lacking Gal-8 expression have higher polarization toward Th17 cells accompanied with decreased CCR6+ and higher CXCR3+ regulatory T cells (Tregs) frequency. These conditions result in exacerbated MOG35-55 peptide-induced EAE. Gal-8 eliminates activated Th17 but not Th1 cells by apoptosis and ameliorates EAE in C57BL/6 wild-type mice. ß-gal histochemistry reflecting the activity of the Gal-8 promoter revealed Gal-8 expression in a wide range of CNS regions, including high expression in the choroid-plexus. Accordingly, we detected Gal-8 in human cerebrospinal fluid, suggesting a role in the CNS immune-surveillance circuit. In addition, we show that MS patients generate function-blocking anti-Gal-8 antibodies with pathogenic potential. Such antibodies block cell adhesion and Gal-8-induced Th17 apoptosis. Furthermore, circulating anti-Gal-8 antibodies associate with relapsing-remitting MS (RRMS), and not with progressive MS phenotypes, predicting clinical disability at diagnosis within the first year of follow-up. Our results reveal that Gal-8 has an immunosuppressive protective role against autoimmune CNS inflammation, modulating the balance of Th17 and Th1 polarization and their respective Tregs. Such a role can be counteracted during RRMS by anti-Gal-8 antibodies, worsening disease prognosis. Even though anti-Gal-8 antibodies are not specific for MS, our results suggest that they could be a potential early severity biomarker in RRMS.


Sujet(s)
Autoanticorps/immunologie , Encéphalomyélite auto-immune expérimentale/immunologie , Galectines/immunologie , Sclérose en plaques/immunologie , Lymphocytes T régulateurs/immunologie , Cellules Th17/immunologie , Animaux , Apoptose/physiologie , Encéphale/immunologie , Encéphale/métabolisme , Adhérence cellulaire/physiologie , Encéphalomyélite auto-immune expérimentale/génétique , Encéphalomyélite auto-immune expérimentale/métabolisme , Femelle , Galectines/génétique , Galectines/métabolisme , Extinction de l'expression des gènes , Humains , Souris , Souris de lignée C57BL , Souris transgéniques , Sclérose en plaques/génétique , Sclérose en plaques/métabolisme , Pronostic , Lymphocytes T régulateurs/métabolisme , Cellules Th17/métabolisme
19.
Mult Scler ; 23(13): 1791-1795, 2017 Nov.
Article de Anglais | MEDLINE | ID: mdl-28397579

RÉSUMÉ

Secondary paroxysmal dyskinesias (SPDs) are short, episodic, and recurrent movement disorders, classically related to multiple sclerosis (MS). Carbamazepine is effective, but with risk of adverse reactions. We identified 7 patients with SPD among 457 MS patients (1.53%). SPD occurred in face ( n = 1), leg ( n = 2), or arm +leg ( n = 4) several times during the day. Magnetic resonance imaging (MRI) showed new or enhancing lesions in thalamus ( n = 1), mesencephalic tegmentum ( n = 1), and cerebellar peduncles ( n = 5). Patients were treated with clonazepam and then acetazolamide ( n = 1), acetazolamide ( n = 5), or levetiracetam ( n = 1) with response within hours (acetazolamide) to days (levetiracetam). No recurrences or adverse events were reported after a median follow-up of 33 months.


Sujet(s)
Anticonvulsivants/pharmacologie , Cervelet/imagerie diagnostique , Dyskinésies , Dystonie , Sclérose en plaques , Tegmentum du mésencéphale/imagerie diagnostique , Thalamus/imagerie diagnostique , Acétazolamide/pharmacologie , Adulte , Anticonvulsivants/administration et posologie , Clonazépam/pharmacologie , Dyskinésies/imagerie diagnostique , Dyskinésies/traitement médicamenteux , Dyskinésies/étiologie , Dyskinésies/physiopathologie , Dystonie/imagerie diagnostique , Dystonie/traitement médicamenteux , Dystonie/étiologie , Dystonie/physiopathologie , Femelle , Études de suivi , Humains , Lévétiracétam , Imagerie par résonance magnétique , Mâle , Sclérose en plaques/complications , Sclérose en plaques/imagerie diagnostique , Sclérose en plaques/physiopathologie , Piracétam/analogues et dérivés , Piracétam/pharmacologie , Résultat thérapeutique
20.
Epilepsy Behav Case Rep ; 4: 70-3, 2015.
Article de Anglais | MEDLINE | ID: mdl-27195219

RÉSUMÉ

Gelastic epilepsy or laughing seizures have been historically related to children with hypothalamic hamartomas. We report three adult patients who had gelastic epilepsy, defined as the presence of seizures with a prominent laugh component, including brain imaging, surface/invasive electroencephalography, positron emission tomography, and medical/surgical outcomes. None of the patients had hamartoma or other hypothalamic lesion. Two patients were classified as having refractory epilepsy (one had biopsy-proven neurocysticercosis and the other one hippocampal sclerosis and temporal cortical dysplasia). The third patient had no lesion on MRI and had complete control with carbamazepine. Both lesional patients underwent resective surgery, one with complete seizure control and the other one with poor outcome. Although hypothalamic hamartomas should always be ruled out in patients with gelastic epilepsy, laughing seizures can also arise from frontal and temporal lobe foci, which can be surgically removed. In addition, we present the first case of gelastic epilepsy due to neurocysticercosis.

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