RESUMEN
BACKGROUND: Domains encompassing emotional disorders in relapsing-remitting MS (RRMS) patients are still unclear. METHODS: We performed a 24-month, multicenter, single-arm, prospective study. RRMS patients started IFN-ß treatment at baseline. The primary endpoint was lack of emotional control, measured using the "Echelle d'HumeurDépressive" (EHD) scale three times at baseline and at 10 post-treatment visits. Secondary endpoints were emotional blunting, irritability, fatigue, depression and anxiety. A linear mixed covariance model assessed change from baseline on an intention-to-treat basis, under the assumption of no mood disorder effect (one-sided 97.5% level), in which autoregressive type of autocorrelation was tested. RESULTS: Out of 79 recruited patients, 70 were analyzed: 80% female; mean (SD) age, 37.0 (11.5) years. Mean (SD) lack of emotional control score at baseline and Month 24 was 12.7 (4.4) and 12.6 (5.5), respectively, versus 10.1 (3.2) in a healthy control population matched for age and sex. Stepwise analysis identified younger age, male sex and antidepressant use as significant predictors of higher lack of emotional control values. CONCLUSIONS: Based on 24â¯months of prospective follow-up, the results of this study highlights a broad spectrum of emotional disorders in the MS population at the time of disease modifying drugs initiation but no major IFN-ß-related emotional disorders (mood dyscontrol, anxiety, depression) were observed. However, sporadic occurrences of severe mood disorders and suicidality cannot be excluded.
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Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Adulto , Femenino , Humanos , Interferón beta/uso terapéutico , Masculino , Trastornos del Humor/tratamiento farmacológico , Trastornos del Humor/etiología , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Estudios ProspectivosRESUMEN
BACKGROUND: Cerebellar and cognitive dysfunction can occur early in clinically isolated syndrome (CIS). Eye tracking is a reliable tool for the evaluation of both subtle cerebellar symptoms and cognitive impairment. OBJECTIVES: To investigate the early cognitive profile using neuropsychological and ocular motor (OM) testing in CIS with and without cerebellar dysfunction with OM testing compared to healthy subjects (HS). METHODS: Twenty-eight patients and 12 HC underwent OM and neuropsychological testing. Cerebellar impairment was defined by the registration of saccadic intrusions and/or at least 10% of dysmetria during ocular motor recording. Visually guided saccade (VGS), memory-guided saccade (MGS) and antisaccade (AS) paradigms were compared to neuropsychological assessments. RESULTS: The group of patients with cerebellar dysfunction (n=16) performed worse on MGS latencies and error rates, and had worse working memory, executive function and information processing speed (IPS) z scores than patients without cerebellar dysfunction. IPS was correlated with the AS error rate in all patients and with the VGS error rate and the MGS final eye position ratio in cerebellar patients. CONCLUSION: Eye tracking is a sensitive tool to assess cognitive and cerebellar dysfunctions in CIS. In CIS patients, cerebellar impairment is associated with working memory, executive functions and IPS slowness.
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Enfermedades Cerebelosas/diagnóstico , Enfermedades Cerebelosas/etiología , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Enfermedades Desmielinizantes/complicaciones , Adulto , Atención , Enfermedades Desmielinizantes/diagnóstico por imagen , Enfermedades Desmielinizantes/psicología , Función Ejecutiva , Movimientos Oculares , Femenino , Humanos , Imagenología Tridimensional , Masculino , Memoria a Corto Plazo , Persona de Mediana Edad , Neuroimagen , Pruebas Neuropsicológicas , Estudios Prospectivos , Escalas de Valoración Psiquiátrica , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: The posterior cerebellar lobules seem to be the anatomical substrate of cognitive cerebellar processes, but their microstructural alterations in multiple sclerosis (MS) remain unclear. OBJECTIVES: To correlate diffusion metrics in lobules VI to VIIIb in persons with clinically isolated syndrome (PwCIS) and in cognitively impaired persons with MS (CIPwMS) with their cognitive performances. METHODS: Sixty-nine patients (37 PwCIS, 32 CIPwMS) and 36 matched healthy subjects (HS) underwent 3T magnetic resonance imaging, including 3D T1-weighted and diffusion tensor imaging (DTI). Fractional anisotropy (FA) and mean diffusivity (MD) were calculated within each lobule and in the cerebellar peduncles. We investigated the correlations between cognitive outcomes and the diffusion parameters of cerebellar sub-structures and performed multiple linear regression analysis to predict cognitive disability. RESULTS: FA was generally lower and MD was higher in the cerebellum and specifically in the vermis Crus II, lobules VIIb and VIIIb in CIPwMS compared with PwCIS and HS. In hierarchical regression analyses, 31% of the working memory z score variance was explained by FA in the left lobule VI and in the left superior peduncle. Working memory was also associated with MD in the vermis Crus II. FA in the left lobule VI and right VIIIa predicted part of the information processing speed (IPS) z scores. CONCLUSION: DTI indicators of cerebellar microstructural damage were associated with cognitive deficits in MS. Our results suggested that cerebellar lobular alterations have an impact on attention, working memory and IPS.
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Corteza Cerebelosa/diagnóstico por imagen , Disfunción Cognitiva/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Adulto , Disfunción Cognitiva/complicaciones , Imagen de Difusión Tensora , Evaluación de la Discapacidad , Escolaridad , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Imagenología Tridimensional , Modelos Lineales , Imagen por Resonancia Magnética , Masculino , Memoria a Corto Plazo , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/complicaciones , Esclerosis Múltiple Recurrente-Remitente/psicología , Análisis Multivariante , Pruebas Neuropsicológicas , Pronóstico , Adulto JovenRESUMEN
OBJECTIVE: We investigated whether diffusion tensor imaging (DTI) could reveal early hippocampal damage and clinically relevant correlates of memory impairment in persons with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). METHODS: A total of 37 persons with CIS, 32 with MS and 36 controls prospectively included from 2011 to 2014 were tested for cognitive performances and scanned with 3T-magnetic resonance imaging (MRI) to assess volumetric and DTI changes within the hippocampus, whole brain volume and T2-lesion load. RESULTS: While there was no hippocampal atrophy in the CIS group, hippocampal fractional anisotropy (FA) was significantly decreased compared to controls. Decrease in hippocampal FA together with increased mean diffusivity (MD) was even more prominent in MS patients. In CIS, hippocampal MD was correlated with episodic verbal memory performance ( r = -0.57, p = 0.0002 and odds ratio (OR) = 0.058, 95% confidence interval (CI) = 0.0057-0.59, p = 0.016 adjusted for age, gender, depression and T2-lesion load), but not with cognitive tasks unrelated to hippocampal functions. Hippocampal MD was the only variable discriminating memory-impaired from memory-preserved persons with CIS (area under the curve (AUC) = 0.77, sensitivity = 90.0%, specificity = 70.3%, positive predictive value (PPV) = 52.9%, negative predictive value (NPV) = 95.0%). CONCLUSION: DTI alterations within the hippocampus might reflect early neurodegenerative processes that are correlated with episodic memory performance, discriminating persons with CIS according to their memory status.
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Enfermedades Desmielinizantes/patología , Enfermedades Desmielinizantes/fisiopatología , Hipocampo/patología , Trastornos de la Memoria/fisiopatología , Memoria Episódica , Adulto , Enfermedades Desmielinizantes/diagnóstico por imagen , Imagen de Difusión Tensora , Femenino , Hipocampo/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Esclerosis Múltiple/fisiopatología , Adulto JovenRESUMEN
Cerebellar impairment is frequent and predictive of disability in multiple sclerosis (MS). The Nine-Hole Peg Test (NHPT) is commonly used to assess cerebellar symptoms despite its lack of specificity for cerebellar ataxia. Eye-tracking is a reliable test for identifying subtle cerebellar symptoms and could be used in clinical trials, including those involving early MS patients. To evaluate, by the use of eye-tracking, the accuracy of the NHPT in detecting subtle cerebellar symptoms in patients with clinically isolated syndrome with a high risk of conversion to MS (HR-CIS). Twenty-nine patients and 13 matched healthy controls (HC) underwent an eye-tracking protocol. Cerebellar impairment was defined by registration of saccadic intrusions or at least 10 % dysmetria in a saccadic movement recording. These criteria were compared to NHPT performance. Sixteen patients fulfilled saccadic criteria for cerebellar impairment. NHPT performance was significantly increased in HR-CIS patients (p < 0.01) versus HC. However, NHPT performance did not differ between cerebellar and non-cerebellar groups. NHPT performance with the dominant hand could differentiate patients, particularly cerebellar patients, from HC, but it could not discriminate cerebellar from non-cerebellar patients who were classified according to saccadic criteria. These findings should be considered in future clinical trials involving HR-CIS patients.
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Cerebelo/fisiopatología , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/fisiopatología , Adulto , Evaluación de la Discapacidad , Progresión de la Enfermedad , Medidas del Movimiento Ocular , Femenino , Mano/fisiopatología , Humanos , Masculino , Síntomas Prodrómicos , Pronóstico , Curva ROC , Movimientos Sacádicos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Cerebellar damage has been implicated in information processing speed (IPS) impairment associated with multiple sclerosis (MS) that might result from functional disconnection in the frontocerebellar loop. Structural alterations in individual posterior lobules, in which cognitive functioning seems preponderant, are still unknown. Our aim was to investigate the impact of grey matter (GM) volume alterations in lobules VI to VIIIb on IPS in persons with clinically isolated syndrome (PwCIS), MS (PwMS) and healthy subjects (HS). METHODS: 69 patients (37 PwCIS, 32 PwMS) and 36 HS underwent 3â T MRI including 3-dimensional T1-weighted MRIs. Cerebellum lobules were segmented using SUIT V.3.0 to estimate their normalised GM volume. Neuropsychological testing was performed to assess IPS and main cognitive functions. RESULTS: Normalised GM volumes were significantly different between PwMS and HS for the right (p<0.001) and left lobule VI (p<0.01), left crus I, right VIIb and entire cerebellum (p<0.05 for each comparison) and between PwMS and PwCIS for all lobules in subregions VI and left crus I (p<0.05). IPS, attention and working memory were impaired in PwMS compared with PwCIS. In the whole population of patients (PwMS and PwCIS), GM loss in vermis VI (R2=0.36; p<0.05 when considering age and T2 lesion volume as covariates) were associated with IPS impairment. CONCLUSIONS: GM volume decrease in posterior lobules (especially vermis VI) was associated with reduced IPS. Our results suggest a significant impact of posterior lobules pathology in corticocerebellar loop disruption resulting in automation and cognitive optimisation lack in MS. TRIAL REGISTRATION: Clinicaltrail NCT01207856, NCT01865357; Pre-results.
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Cerebelo/diagnóstico por imagen , Cognición/fisiología , Memoria a Corto Plazo/fisiología , Esclerosis Múltiple/diagnóstico por imagen , Tiempo de Reacción/fisiología , Adulto , Atención/fisiología , Progresión de la Enfermedad , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/psicología , Pruebas Neuropsicológicas , Tamaño de los Órganos/fisiología , Adulto JovenRESUMEN
BACKGROUND: The assessment of cognitive impairment in multiple sclerosis (MS) requires large neuropsychological batteries that assess numerous domains. The relevance of these assessments to daily cognitive functioning is not well established. Cognitive ecological evaluation has not been frequently studied in MS. OBJECTIVES: The aim of this study was to determine the interest of cognitive evaluation in a virtual reality environment in a sample of persons with MS with cognitive deficits. METHODS: Thirty persons with MS with at least moderate cognitive impairment were assessed with two ecological evaluations, an in-house developed task in a virtual reality environment (Urban DailyCog®) and a divided attention task in a driving simulator. Classical neuropsychological testing was also used. RESULTS AND CONCLUSION: Fifty-two percent of the persons with MS failed the driving simulator task and 80% failed the Urban DailyCog®. Virtual reality assessments are promising in identifying cognitive impairment in MS.
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Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/genética , Esclerosis Múltiple/complicaciones , Interfaz Usuario-Computador , Adulto , Simulación por Computador , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/rehabilitación , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Estadística como AsuntoRESUMEN
BACKGROUND: Depressive mood and other emotional symptoms are common in multiple sclerosis (MS). The patient-reported outcome version of the "Echelle d'Humeur Dépressive" (EHD-PRO) aims to differentiate between two dimensions of depressive mood in people living with MS (PwMS). OBJECTIVES: First, to compare EHD-PRO assessment and its two dimensions, lack of emotional control and emotional blunting, between a large sample of healthy controls (HCs) and two samples of PwMS, relapsing-remitting MS (RRMS) and primary progressive MS (PPMS); and second, to analyse the relationships between EHD-PRO scores with neurological disability, cognitive function, fatigue and health-related quality of life (HR-QOL). RESULTS: Regardless of their phenotype, PwMS had significantly higher EHD-PRO scores than HCs. EHD-PRO scores did not differ between the two MS groups. EHD-PRO scores did not correlate with disability and fatigue scores, disease duration or cognitive z scores. In RRMS, the lack of emotional control was independently associated with a decrease in HR-QOL. CONCLUSION: The EHD-PRO is able to easily detect depressive mood and to differentiate between two clinical dimensions, emotional blunting and lack of emotional control. The scale is sensitive and seems robust to confounding factors. Lack of emotional control seems to contribute significantly to altered HR-QOL in RRMS.