RESUMEN
BACKGROUND: Posterior fossa lesions are common in pediatric-onset multiple sclerosis (MS), which is of concern, given the known role of the cerebellum in cognition. OBJECTIVES: To investigate the relationship between cerebellar pathology and cognitive function in youth with pediatric-onset MS. METHODS: Twenty-eight pediatric-onset relapsing-remitting MS patients (21 girls; mean age 16.2 years; mean disease duration 4.3 years, median Expanded Disability Status Scale 1.25) were compared to 33 age- and sex-matched healthy controls. Participants underwent structural magnetic resonance imaging (MRI) and neuropsychological evaluation to assess intelligence, attention, processing speed, language, visuo-motor integration, and fine-motor dexterity. Associations between cognitive outcomes and cerebellar volume independent of cerebral volume were examined. RESULTS: Cognitive and motor performance of the MS group was reduced relative to controls (all p<0.003). While cerebellar volumes did not differ between groups, cerebellar posterior lobe volume and infratentorial lesion volume accounted for extra variance on measures of information processing (R(2)=0.43; p=0.02) and vocabulary (R(2)=0.56; p=0.04) in patients (controlling for cerebral volume and sex), but not in controls. CONCLUSION: Smaller cerebellar posterior lobe volume, a known region for cognitive processing, and increased lesion burden in the posterior fossa adversely impact cognitive function, an important functional consequence of MS onset during childhood.
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Cerebelo/diagnóstico por imagen , Trastornos del Conocimiento/diagnóstico por imagen , Inteligencia/fisiología , Esclerosis Múltiple/diagnóstico por imagen , Adolescente , Trastornos del Conocimiento/fisiopatología , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Esclerosis Múltiple/fisiopatología , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: Acquired demyelinating syndromes (ADS) have the potential to negatively impact cerebellar growth, given the proclivity for infratentorial lesions in pediatric-onset multiple sclerosis (MS) and ADS. OBJECTIVE: To investigate cerebellar growth longitudinally in pediatric ADS. METHODS: Cerebellar volumes from 472 magnetic resonance imaging (MRI) scans of 98 patients with monophasic ADS (monoADS), monophasic acute disseminated encephalomyelitis (ADEM), and MS (49 girls; mean age: 11.4 years at first scan, mean follow-up: 3.1 years) imaged serially from onset and 897 MRI scans of 418 healthy children (223 girls, mean age: 11.3 years, mean follow-up: 2.9 years) were segmented automatically, analyzed with mixed-effect models, and compared with cerebral volume. RESULTS: Cerebellar developmental trajectories followed a U-shaped curve, showing larger volumes in boys (p < 0.001). Cerebellar volumes in all three patient groups failed to reach age-expected trajectories, leading to significantly smaller volumes, notably in the posterior lobes. Cerebellar volume reductions were of a similar magnitude to cerebral volume reductions. Cerebellar white matter volume declined in MS and ADEM patients over time, while in monoADS patients it remained similar to controls. Cerebellar volumes did not correlate either with lesion volumes at onset or with physical disability. CONCLUSION: MonoADS, ADEM, and MS in childhood lead to impaired age-expected growth of the cerebellum.
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Cerebelo/crecimiento & desarrollo , Encefalomielitis Aguda Diseminada/diagnóstico por imagen , Esclerosis Múltiple/diagnóstico por imagen , Adolescente , Estudios de Casos y Controles , Cerebelo/diagnóstico por imagen , Niño , Preescolar , Enfermedades Autoinmunes Desmielinizantes SNC/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Humanos , Masculino , Tamaño de los ÓrganosRESUMEN
We performed voxel-guided morphometry (VGM) investigating the mechanisms of brain atrophy in multiple sclerosis (MS) related to focal lesions. VGM maps detect regional brain changes when comparing 2 time points on high resolution T1-weighted (T1w) magnetic resonace imaging (MRI). Two T1w MR datasets from 92 relapsing-remitting MS patients obtained 12 months apart were analysed with VGM. New lesions and volume changes of focal MS lesions as well as in the surrounding tissue were identified by visual inspection on colour coded VGM maps. Lesions were dichotomized in active and inactive lesions. Active lesions, defined by either new lesions (NL) (volume increase > 5% in VGM), chronic enlarging lesions (CEL) (pre-existent T1w lesions with volume increase > 5%), or chronic shrinking lesions (CSL) (pre-existent T1w lesions with volume reduction > 5%) in VGM, were accompanied by tissue shrinkage in surrounding and/or functionally related regions. Volume loss within the corpus callosum was highly correlated with the number of lesions in its close proximity. Volume loss in the lateral geniculate nucleus was correlated with lesions along the optic radiation. VGM analysis provides strong evidence that all active lesion types (NL, CEL, and CSL) contribute to brain volume reduction in the vicinity of lesions and/or in anatomically and functionally related areas of the brain.
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Encéfalo/patología , Esclerosis Múltiple/patología , Adulto , Anciano , Atrofia/patología , Cuerpo Calloso/patología , Femenino , Cuerpos Geniculados/patología , Humanos , Procesamiento de Imagen Asistido por Computador , Modelos Logísticos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico por imagenRESUMEN
OBJECTIVE: To examine the temporal evolution of spinal cord (SC) atrophy in multiple sclerosis (MS), and its association with clinical progression in a large MS cohort. METHODS: A total of 352 patients from two centres with MS (relapsing remitting MS (RRMS): 256, secondary progressive MS (SPMS): 73, primary progressive MS (PPMS): 23) were included. Clinical and MRI parameters were obtained at baseline, after 12 months and 24 months of follow-up. In addition to conventional brain and SC MRI parameters, the annualised percentage brain volume change and the annualised percentage upper cervical cord cross-sectional area change (aUCCA) were quantified. Main outcome measure was disease progression, defined by expanded disability status scale increase after 24 months. RESULTS: UCCA was lower in SPMS and PPMS compared with RRMS for all time points. aUCCA over 24 months was highest in patients with SPMS (-2.2% per year) and was significantly higher in patients with disease progression (-2.3% per year) than in stable patients (-1.2% per year; p=0.003), while annualised percentage brain volume change did not differ between subtypes (RRMS: -0.42% per year; SPMS -0.6% per year; PPMS: -0.46% per year) nor between progressive and stable patients (p=0.055). Baseline UCCA and aUCCA over 24 months were found to be relevant contributors of expanded disability status scale at month-24, while baseline UCCA as well as number of SC segments involved by lesions at baseline but not aUCCA were relevant contributors of disease progression. CONCLUSIONS: SC MRI parameters including baseline UCCA and SC lesions were significant MRI predictors of disease progression. Progressive 24-month upper SC atrophy occurred in all MS subtypes, and was faster in patients exhibiting disease progression at month-24.
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Vértebras Cervicales/patología , Esclerosis Múltiple/patología , Médula Espinal/patología , Adulto , Atrofia , Encéfalo/patología , Estudios de Cohortes , Evaluación de la Discapacidad , Progresión de la Enfermedad , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
In multiple sclerosis (MS), cerebellar signs and symptoms as well as cognitive dysfunction are frequent and contribute to clinical disability with only poor response to symptomatic treatment. The current consensus paper highlights the broad range of clinical signs and symptoms of MS patients, which relate to cerebellar dysfunction. There is considerable evidence of cerebellar involvement in MS based on clinical, histopathological as well as structural and functional magnetic resonance imaging (MRI) studies. The review of the recent literature, however, also demonstrates a high variability of results. These discrepancies are, at least partially, caused by the use of different techniques and substantial heterogeneity among the patient cohorts in terms of disease duration, number of patients, and progressive vs. relapsing disease courses. Moreover, the majority of studies were cross-sectional, providing little insight into the dynamics of cerebellar involvement in MS. Some links between the histopathological changes, the structural and functional abnormalities as captured by MRI, cerebellar dysfunction, and the clinical consequences are starting to emerge and warrant further study. A consensus is formed that this line of research will benefit from advances in neuroimaging techniques that allow to trace cerebellar involvement at higher resolution. Using a prospective study design, multimodal high-resolution cerebellar imaging is highly promising, particularly in patients who present with radiologically or clinically isolated syndromes or newly diagnosed MS.
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Cerebelo/patología , Cognición , Imagen por Resonancia Magnética , Esclerosis Múltiple/patología , Esclerosis Múltiple/fisiopatología , Enfermedades Desmielinizantes/patología , Progresión de la Enfermedad , Humanos , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: In relapsing-remitting multiple sclerosis (RRMS), the cerebellum is a known predilection site for atrophy. Neuromyelitis optica (NMO) is characterized by extensive lesions in the spinal cord and optic nerve; however, cerebellar involvement has been less studied. Secondary degeneration of the spinocerebellar tract could impact the cerebellum in NMO. OBJECTIVE: We aimed to investigate whether spinal cord and cerebellar volume measures differ between patients with NMO and RRMS. METHODS: Volumetric analyses of the cerebellum (TCV), the upper cervical cord (UCV) as well as the whole brain (NBV) of age- and gender-matched patients with NMO (n=30; 56% AQP4 +ve) and RRMS (n=25) were performed on 3T brain magnetic resonance imaging (MRI) and compared with 34 healthy controls (HC). RESULTS: UCV was significantly reduced in NMO patients (6.3 cm(3)) as compared with HC (6.7 cm(3)), while patients with MS had reduced brain volumes compared with HC (NBV=1482 cm(3); p<0.001; TCV=188 cm(3); p=0.042), but UCV close to normal values. Patients with RRMS and NMO differed in NBV (p=0.001; lower in RRMS) and by trend (towards reduction in RRMS) in cerebellar volume (p=0.06). CONCLUSIONS: While atrophy seems to be diffuse in MS patients, a rather focussed pattern with predominant involvement of the UCV was observed in NMO patients.
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Encéfalo/patología , Cerebelo/patología , Médula Cervical/patología , Esclerosis Múltiple Recurrente-Remitente/patología , Neuromielitis Óptica/patología , Adulto , Atrofia/patología , Femenino , Voluntarios Sanos , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Reliable and fast segmentation of the human cerebellum with its complex architecture of lobes and lobules has been a challenge for the past decades. Emerging knowledge of the functional integration of the cerebellum in various sensori-motor and cognitive-behavioral circuits demands new automatic segmentation techniques, with accuracies similar to manual segmentations, but applicable to large subject numbers in a reasonable time frame. This article presents the development and application of a novel pipeline for rapid automatic segmentation of the human cerebellum and its lobules (RASCAL) combining patch-based label-fusion and a template library of manually labeled cerebella of 16 healthy controls from the International Consortium for Brain Mapping (ICBM) database. Leave-one-out experiments revealed a good agreement between manual and automatic segmentations (Dice kappa = 0.82). Intraclass correlation coefficients (ICC) were calculated to test reliability of segmented volumes and were highest (ICC > 0.9) for global measures (total and hemispherical grey and white matter) followed by larger lobules of the posterior lobe (ICC > 0.8). Further we applied the pipeline to all 152 young healthy controls of the ICBM database to look for hemispheric and gender differences. The results demonstrated larger native space volumes in men then women (mean (± SD) total cerebellar volume in women = 217 cm(3) (± 26), men = 259 cm(3) (± 29); P < 0.001). Significant gender-by-hemisphere interaction was only found in stereotaxic space volumes for white matter core (men > women) and anterior lobe volume (women > men). This new method shows great potential for the precise and efficient analysis of the cerebellum in large patient cohorts.
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Mapeo Encefálico , Cerebelo/anatomía & histología , Reconocimiento de Normas Patrones Automatizadas , Adulto , Algoritmos , Conjuntos de Datos como Asunto , Femenino , Humanos , Imagenología Tridimensional , Imagen por Resonancia Magnética , Masculino , Adulto JovenRESUMEN
Deep gray matter (DGM) atrophy has been reported in patients with multiple sclerosis (MS) already at early stages of the disease and progresses throughout the disease course. We studied DGM volume and shape and their relation to disability in a large cohort of clinically well-described MS patients using new subcortical segmentation methods and shape analysis. Structural 3D magnetic resonance images were acquired at 1.5 T in 118 patients with relapsing remitting MS. Subcortical structures were segmented using a multiatlas technique that relies on the generation of an automatically generated template library. To localize focal morphological changes, shape analysis was performed by estimating the vertex-wise displacements each subject must undergo to deform to a template. Multiple linear regression analysis showed that the volume of specific thalamic nuclei (the ventral nuclear complex) together with normalized gray matter volume explains a relatively large proportion of expanded disability status scale (EDSS) variability. The deformation-based displacement analysis confirmed the relation between thalamic shape and EDSS scores. Furthermore, white matter lesion volume was found to relate to the shape of all subcortical structures. This novel method for the analysis of subcortical volume and shape allows depicting specific contributions of DGM abnormalities to neurological deficits in MS patients. The results stress the importance of ventral thalamic nuclei in this respect.
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Encéfalo/patología , Sustancia Gris/patología , Esclerosis Múltiple Recurrente-Remitente/patología , Adulto , Anciano , Atlas como Asunto , Estudios Transversales , Evaluación de la Discapacidad , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagenología Tridimensional , Modelos Lineales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Estudios Retrospectivos , Núcleos Talámicos/patología , Sustancia Blanca/patología , Adulto JovenRESUMEN
OBJECTIVE: To investigate the entire spinal cord (SC) of multiple sclerosis (MS) patients with biplanar MRI and to relate these MRI findings to clinical functional scores. METHODS: Two hundred and two patients (140 women, 62 men 24-74 years, Expanded Disability Status Scale (EDSS) scores 0-7.5) were investigated clinically and with biplanar MRI. Sagittal and axial proton density weighted (PDw) and T2 weighted (T2w) images of the whole SC were obtained employing parallel imaging. Data were analyzed by consensus reading using a standardized reporting scheme. Different combinations of findings were compared to EDSS scores with Spearman's rank correlation coefficient (ρ). RESULTS: The combined analysis of sagittal and axial planes demonstrated slightly differing results in 97/202 (48%) patients. There were 9% additional lesions identified, leading to a higher lesion count in 28% of these patients, but also rejection of equivocal abnormality leading to a lower lesion count in 11% of patients. Considering both sagittal and axial images, SC abnormalities were found in 167/202 (83%) patients. When compared with EDSS scores, the combination of focal lesions, signs of atrophy and diffuse abnormalities showed a moderate correlation (ρ=0.52), that precludes its use for individual patient assessment. CONCLUSION: Biplanar MRI facilitates a comprehensive identification, localization, and grading of pathological SC findings in MS patients. This improves the confidence and utility of SC imaging.
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Imagen por Resonancia Magnética , Esclerosis Múltiple/diagnóstico , Médula Espinal/patología , Adulto , Anciano , Atrofia , Encéfalo/patología , Evaluación de la Discapacidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/patología , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
BACKGROUND: We hypothesized that in multiple sclerosis (MS) patients, reduced cortical perfusion is associated with chronic white matter injury. OBJECTIVE: To investigate the influence of different clinical and magnetic resonance imaging characteristics on cortical perfusion. METHODS: Cerebral blood flow (CBF) was assessed by applying a pulsed arterial spin labelling (ASL) technique combined with single-shot 3D-GRASE (gradient-spin echo) in a cohort of 165 MS patients with a relapsing-remitting (n=123) or secondary progressive disease course (n=42). Mean age was 45.4 years (20-68 years), mean disease duration was 14.2 years (1-48 years). RESULTS: Mean cortical CBF was 45.6 ml/100g per min (SD: 7.8 ml/100g per min). Stepwise multiple linear regression models were calculated to investigate the relationship between different factor sets and mean CBF. The model with the highest adjusted coefficient of determination included T2 lesion load, age, gender and disease duration as significant factors. Post-hoc Spearman rank correlation revealed significant correlation of adjusted CBF with T2 lesion load (ρ=-0.35, p=1*10(-6)), with age (ρ=-0.34, p=4*10(-6)), and with disease duration (ρ=0.16, p=0.03), while Expanded Disability Status Scale (EDSS) did not reach significance in either model. CONCLUSION: This study suggests that the amount of white matter lesions indicates a reduced metabolic demand and reduced perfusion at a cortical level.
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Corteza Cerebral/irrigación sanguínea , Circulación Cerebrovascular , Leucoencefalopatías/diagnóstico , Imagen por Resonancia Magnética , Esclerosis Múltiple Crónica Progresiva/diagnóstico , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Imagen de Perfusión/métodos , Marcadores de Spin , Adulto , Anciano , Atrofia , Velocidad del Flujo Sanguíneo , Corteza Cerebral/patología , Evaluación de la Discapacidad , Femenino , Humanos , Leucoencefalopatías/patología , Leucoencefalopatías/fisiopatología , Modelos Lineales , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Crónica Progresiva/patología , Esclerosis Múltiple Crónica Progresiva/fisiopatología , Esclerosis Múltiple Recurrente-Remitente/patología , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Análisis Multivariante , Valor Predictivo de las Pruebas , Flujo Sanguíneo Regional , Adulto JovenRESUMEN
As attention, processing speed, and working memory seem to be fundamental for a broad range of cognitive performance, the present study on patients with mild forms of relapsing-remitting multiple sclerosis (RR-MS) focused on these domains. To explore subtle neuropsychological changes in either the clinical or fMRI domain, we applied a multistep experimental design with increasing task complexity to investigate global brain activity, functional adaptation, and behavioral responses to typical cognitive processes related to attention and working memory. Fifteen patients with RR-MS (mean age 38 years, 22-49 years, 9 females, mean disease duration 5.9 years (SD = 3.6 years), mean Expanded Disability Status Scale score, 2.3 (SD = 1.3) but without reported cognitive impairment), and 15 age-matched healthy controls (HC; mean age, 34 years, 23-50 years, 6 women) participated. After a comprehensive neuropsychological assessment, participants performed different fMRI experiments testing attention and working memory. In the neuropsychological assessment, patients showed only subtle reduction in learning and memory abilities. In the fMRI experiments, both groups activated the brain areas typically involved in attention and working memory. HC showed a linear in- or decrease in activation paralleling the changing task complexity. Patients showed stronger activation change at the level of the simple tasks and a subsequent saturation effect of (de-)activation at the highest task load. These group/task interaction differences were found in the right parahippocampal cortex and in the middle and medial frontal regions. Our results indicate that, in MS, functional adaptation patterns can be found which precede clinical evidence of apparent cognitive decline.
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Adaptación Fisiológica/fisiología , Atención/fisiología , Encéfalo/fisiopatología , Memoria a Corto Plazo/fisiología , Esclerosis Múltiple Recurrente-Remitente/patología , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Adulto , Análisis de Varianza , Encéfalo/irrigación sanguínea , Mapeo Encefálico , Estudios de Casos y Controles , Evaluación de la Discapacidad , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Oxígeno/sangre , Tiempo de Reacción/fisiología , Adulto JovenRESUMEN
In patients with multiple sclerosis (MS) non-communicating syringomyelia (NCS) has been described as an incidental finding in case studies and small case series. NCS in MS patients commonly leads to uncertainty particularly as the clinical picture of NCS is variable and surgical therapy may be considered. Up to date little is known about the prevalence and clinical importance of NCS in MS. We report the imaging and clinical characteristics of NCS formations in nine MS patients from a 1 year follow-up study in a representative group of 202 MS (4.5%) patients. Brain and spinal cord MRI was performed as part of a genetic study. NCS did commonly extend the central canal and the cord was slightly distended at the level of the syrinx. The cord and syrinx showed no tendency to change in size or shape over 1 year. Despite thorough search into the clinical history and current clinical status no definite but only minimal indications of symptoms potentially related to the NCS were found. We confirm that NCS may occur in MS patients with spinal cord pathology. It can be a subtle finding without clinical correlates. Syrinx formations are more likely to be a consequence of MS cord pathology than a coincidental finding.
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Esclerosis Múltiple/complicaciones , Siringomielia/etiología , Adulto , Anciano , Encéfalo/patología , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/patología , Médula Espinal/patología , Siringomielia/patologíaRESUMEN
OBJECTIVE: To investigate how monophasic acquired demyelinating syndromes (ADS) affect age-expected brain growth over time. METHODS: We analyzed 83 pediatric patients imaged serially from initial demyelinating attack: 18 with acute disseminated encephalomyelitis (ADEM) and 65 with other monophasic ADS presentations (monoADS). We further subdivided the monoADS group by the presence (n = 33; monoADSlesion) or absence (n = 32; monoADSnolesion) of T2 lesions involving the brain at onset. We used normative data to compare brain volumes and calculate age- and sex-specific z scores, and used mixed-effect models to investigate their relationship with time from demyelinating illness. RESULTS: Children with monophasic demyelination (ADEM, non-ADEM with brain lesions, and those without brain involvement) demonstrated reduced age-expected brain growth on serial images, driven by reduced age-expected white matter growth. Cortical gray matter volumes were not reduced at onset but demonstrated reduced age-expected growth afterwards in all groups. Brain volumes differed from age- and sex-expected values to the greatest extent in children with ADEM. All patient groups failed to recover age-expected brain growth trajectories. CONCLUSIONS: Brain volume, and more importantly age-expected brain growth, is negatively affected by acquired demyelination, even in the absence of chronicity, implicating factors other than active inflammation as operative in this process.
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Encéfalo/diagnóstico por imagen , Encéfalo/crecimiento & desarrollo , Enfermedades Autoinmunes Desmielinizantes SNC/diagnóstico por imagen , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/crecimiento & desarrollo , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Tamaño de los Órganos , Estudios Prospectivos , Adulto JovenRESUMEN
Spinal cord (SC) atrophy is an important contributor to the development of disability in many neurological disorders including multiple sclerosis (MS). To assess the spinal cord atrophy in clinical trials and clinical practice, largely automated methods are needed due to the sheer amount of data. Moreover, using these methods in longitudinal trials requires them to deliver highly reliable measurements, enabling comparisons of multiple data sets of the same subject over time. We present a method for SC volumetry using 3D MRI data providing volume measurements for SC sections of fixed length and location. The segmentation combines a continuous max flow approach with SC surface reconstruction that locates the SC boundary based on image voxel intensities. Two cutting planes perpendicular to the SC centerline are determined based on predefined distances to an anatomical landmark, and the cervical SC volume (CSCV) is then calculated in-between these boundaries. The development of the method focused on its application in MRI follow-up studies; the method provides a high scan-rescan reliability, which was tested on healthy subject data. Scan-rescan reliability coefficients of variation (COV) were below 1 %, intra- and interrater COV were even lower (0.1-0.2 %). To show the applicability in longitudinal trials, 3-year follow-up data of 48 patients with a progressive course of MS were assessed. In this cohort, CSCV loss was the only significant predictor of disability progression (p = 0.02). We are, therefore, confident that our method provides a reliable tool for SC volumetry in longitudinal clinical trials.
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Médula Cervical/patología , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Esclerosis Múltiple/patología , Adulto , Anciano , Médula Cervical/diagnóstico por imagen , Evaluación de la Discapacidad , Progresión de la Enfermedad , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico por imagen , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
BACKGROUND: Cognitive decline in multiple sclerosis (MS) negatively impacts patients' everyday functioning and quality of life. Since symptomatic pharmacological treatment is not yet available alternative treatment strategies such as cognitive rehabilitation are of particular interest. OBJECTIVES: To analyse the ways in which MS patients respond to cognitive training, by combining behavioral and fMRI data in a case-based triangulation approach. METHODS: Ten relapsing-remitting (RR) MS patients aged between 39 and 58 years and between 1 and 8 years post MS diagnosis were included. EDSS ranged from 1 to 3.5. Participants had normal to high intelligence levels. Six patients were assigned to the training group (TG) and four to the control group (CG) without intervention. The TG received a 4-week computerized working memory (WM) training, consisting of 16 training sessions of 45 min duration each. Before and after the training a neuropsychological examination and fMRI investigation by using an N-back task of different complexity was applied. RESULTS: Patients in the TG responded differently to cognitive training. Four participants did not meet the triangulation criteria for being treatment responders. The two responders showed two distinct changes regarding activation patterns after training: (I) decreased brain activation associated with increased processing speed and (II) increased brain activation associated with higher processing speed and WM performance. CONCLUSION: The occurrence of different and opposed response patterns after the same training indicates a risk in applying classical group statistics. Different and especially opposed patterns within the same sample may distort results of classical statistical comparisons. Thus, underlying processes may not be discovered and lead to misinterpretation of results.
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BACKGROUND: In multiple sclerosis (MS), periaqueductal lesions (PAL) have been described histopathologically. OBJECTIVES: We sought to investigate the frequency and characteristics of PAL on magnetic resonance images (MRIs) in patients with MS or clinically isolated syndrome (CIS). METHODS: We analyzed proton density (PD)-weighted MRIs of 247 MS and 10 CIS patients. PAL were identified based on their abnormal hyperintensity and lesion shape on at least two consecutive slices. Patients with and without PAL were compared for clinical characteristics in a propensity score weighted analysis. RESULTS: We identified PAL in 48/257 patients (18.7%), 34 of which had CIS or relapsing-remitting MS and 14 a progressive disease course. The shape of PAL was often circular (65%), or/and wedge-like (42%). Multi-planar image analysis in a subgroup of patients with double inversion recovery sequences revealed that 36% of PAL were periventricular lesions of the third ventricle extending towards the aqueduct. We found an association of PAL and brainstem functional system. CONCLUSIONS: Although PAL may be underreported in MS, they are relatively frequent and found at all clinical stages and in CIS. They could be considered as a variant of periventricular lesions in the supratentorial midbrain and thus be useful in the diagnosis of MS.
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The cerebellum is known to be involved not only in motor but also cognitive and affective processes. Structural changes in the cerebellum in relation to cognitive dysfunction are an emerging topic in the field of neuro-psychiatric disorders. In Multiple Sclerosis (MS) cerebellar motor and cognitive dysfunction occur in parallel, early in the onset of the disease, and the cerebellum is one of the predilection sites of atrophy. This study is aimed at determining the relationship between cerebellar volumes, clinical cerebellar signs, cognitive functioning and fatigue in MS. Cerebellar volumetry was conducted using T1-weighted MPRAGE magnetic resonance imaging of 172 MS patients. All patients underwent a clinical and brief neuropsychological assessment (information processing speed, working memory), including fatigue testing. Patients with and without cerebellar signs differed significantly regarding normalized cerebellar total volume (nTCV), normalized brain volume (nBV) and whole brain T2 lesion volume (LV). Patients with cerebellar dysfunction likewise performed worse in cognitive tests. A regression analysis indicated that age and nTCV explained 26.3% of the variance in SDMT (symbol digit modalities test) performance. However, only age, T2 LV and nBV remained predictors in the full model (r(2)â=â0.36). The full model for the prediction of PASAT (Paced Auditory Serial Addition Test) scores (r(2)â=â0.23) included age, cerebellar and T2 LV. In the case of fatigue, only age and nBV (r(2)â=â0.17) emerged as significant predictors. These data support the view that cerebellar abnormalities contribute to disability, including cognitive impairment in MS. However, this contribution does not seem to be independent of, and may even be dominated by wider spread MS pathology as reflected by nBV and T2 LV.
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Cerebelo/patología , Trastornos del Conocimiento/patología , Fatiga/fisiopatología , Esclerosis Múltiple/patología , Esclerosis Múltiple/fisiopatología , Adulto , Factores de Edad , Anciano , Trastornos del Conocimiento/etiología , Fatiga/etiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Modelos Biológicos , Esclerosis Múltiple/complicaciones , Pruebas Neuropsicológicas , Tamaño de los Órganos/fisiología , Análisis de RegresiónRESUMEN
Cerebellar dysfunction is an important contributor to disability in patients with multiple sclerosis (MS), however, few in vivo studies focused on cerebellar volume loss so far. This relates to technical challenges regarding the segmentation of the cerebellum. In this study, we evaluated the semi-automatic ECCET software for performing cerebellar volumetry using high-resolution 3D T1-MR scans in patients with MS and healthy volunteers. We performed test-retest as well as inter-observer reliability testing of cerebellar segmentation and compared the ECCET results with a fully automatic cerebellar segmentation using the FreeSurfer software pipeline in 15 MS patients. In a pilot matched-pair analysis with another data set from 15 relapsing-remitting MS patients and 15 age- and sex-matched healthy controls (HC), we assessed the feasibility of the ECCET approach to detect MS-related cerebellar volume differences. For total normalized cerebellar volume as well as grey and white matter volumes, intrarater (intraclass correlation coefficient (ICC) = 0.99, 95 % CI = 0.98-0.99) and interobserver agreement (ICC = 0.98, 95 % CI = 0.74-0.99) were strong. Comparison between ECCET and FreeSurfer results likewise yielded a good intraclass correlation (ICC = 0.86, 95 % CI = 0.58-0.95). Compared to HC, MS patients had significantly reduced normalized total brain, total cerebellar, and grey matter volumes (p ≤ 0.05). ECCET is a suitable tool for cerebellar segmentation showing excellent test-retest and inter-observer reliability. Our matched-pair analysis between MS patients and healthy volunteers suggests that the method is sensitive and reliable in detecting cerebellar atrophy in MS.