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BACKGROUND: Multiple sclerosis is a disease continuum with an initial relapsing remitting course (RRMS) and secondary progression (SPMS) at later stages. Most of the hitherto approved treatments do not adequately control for the phase of secondary progression. Thus, early detection of SPMS conversion is a key issue to initiate SPMS-tailored treatment. In this context, assessment of cognitive functions and magnetic resonance imaging (MRI) both play an important role in the longitudinal follow-up of MS patients. OBJECTIVE: To elucidate the importance of cognitive testing and MRI for prediction and detection of SPMS conversion as well as to discuss strategies for disease monitoring and for optimizing treatment in standard clinical care, particularly in outpatient settings. MATERIAL AND METHODS: Review article based on a nonsystematic literature review. RESULTS: Standardized cognitive testing can support early diagnosis of SPMS and facilitate disease monitoring. Annual application of sensitive screening tests, such as the Symbol Digit Modalities Test (SDMT) and Brief Visual Memory Test-Revised (BVMTR) or the entire Brief International Cognitive Assessment for MS (BICAMS) test battery are recommended in this context. The MRI evidence of persistent inflammatory activity within 3 years of diagnosis as well as evidence of cortical lesions are predictive for SPMS conversion. Standardized MRI monitoring for markers of progression can substantiate clinical and neurocognitive signs of SPMS conversion. CONCLUSION: Multidisciplinary patient care involving careful clinical examination, neuropsychological testing and MRI monitoring is of great significance for the prediction of SPMS conversion and diagnostics. This enables early treatment adaptation, since pharmacological interventions in SPMS differ from those in RRMS. Continuous clinical, neuropsychological and MRI vigilance enable stringent monitoring of treatment outcomes with respect to neuroinflammatory and neurodegenerative activity as well as treatment-related complications.
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Trastornos del Conocimiento , Esclerosis Múltiple Crónica Progresiva , Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Humanos , Imagen por Resonancia Magnética , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: Recent studies have created awareness that facial features can be reconstructed from high-resolution MRI. Therefore, data sharing in neuroimaging requires special attention to protect participants' privacy. Facial features removal (FFR) could alleviate these concerns. We assessed the impact of three FFR methods on subsequent automated image analysis to obtain clinically relevant outcome measurements in three clinical groups. METHODS: FFR was performed using QuickShear, FaceMasking, and Defacing. In 110 subjects of Alzheimer's Disease Neuroimaging Initiative, normalized brain volumes (NBV) were measured by SIENAX. In 70 multiple sclerosis patients of the MAGNIMS Study Group, lesion volumes (WMLV) were measured by lesion prediction algorithm in lesion segmentation toolbox. In 84 glioblastoma patients of the PICTURE Study Group, tumor volumes (GBV) were measured by BraTumIA. Failed analyses on FFR-processed images were recorded. Only cases in which all image analyses completed successfully were analyzed. Differences between outcomes obtained from FFR-processed and full images were assessed, by quantifying the intra-class correlation coefficient (ICC) for absolute agreement and by testing for systematic differences using paired t tests. RESULTS: Automated analysis methods failed in 0-19% of cases in FFR-processed images versus 0-2% of cases in full images. ICC for absolute agreement ranged from 0.312 (GBV after FaceMasking) to 0.998 (WMLV after Defacing). FaceMasking yielded higher NBV (p = 0.003) and WMLV (p ≤ 0.001). GBV was lower after QuickShear and Defacing (both p < 0.001). CONCLUSIONS: All three outcome measures were affected differently by FFR, including failure of analysis methods and both "random" variation and systematic differences. Further study is warranted to ensure high-quality neuroimaging research while protecting participants' privacy. KEY POINTS: ⢠Protecting participants' privacy when sharing MRI data is important. ⢠Impact of three facial features removal methods on subsequent analysis was assessed in three clinical groups. ⢠Removing facial features degrades performance of image analysis methods.
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Encéfalo/diagnóstico por imagen , Confidencialidad , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Neuroimagen/métodos , Anciano , Anciano de 80 o más Años , Algoritmos , Enfermedad de Alzheimer/patología , Encéfalo/patología , Cara , Femenino , Glioblastoma/diagnóstico por imagen , Glioblastoma/patología , Humanos , Difusión de la Información , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/patología , Reproducibilidad de los Resultados , Carga TumoralRESUMEN
BACKGROUND: Natalizumab is an effective treatment for relapsing-remitting multiple sclerosis (RRMS). Data on clinical and imaging measures predictive of disease activity and progression during treatment is limited. OBJECTIVE: To determine clinical and imaging predictors of long-term inflammatory disease activity and disability progression in RRMS patients on natalizumab. METHODS: Patients (nâ¯=â¯135) were selected from our prospective observational natalizumab cohort and monitored using brain MRI and extensive clinical testing. Progression and improvement on the Expanded Disability Status Scale (EDSS), no evidence of disease activity (NEDA) and no evidence of progression or active disease (NEPAD) status were determined using measurements after the initial phase of inflammation and the early anti-inflammatory impact of natalizumab. RESULTS: EDSS progression was seen in 43.7% of patients and EDSS improvement in 17.8%. Median follow-up was 4.9 years (IQR 3.6-6.0). Patients with a longer disease duration at natalizumab initiation have a higher hazard for earlier EDSS progression (HR 1.05, CI 1.00-1.09, pâ¯=â¯0.037) and a higher pre-baseline relapse rate predicted a longer NEPAD status (HR 1.70, CI 1.06-2.72, pâ¯=â¯0.028). CONCLUSION: The results suggest that starting natalizumab early, during active inflammatory disease results in a more favourable outcome. When taking into account early inflammation and the impact of natalizumab on disease activity during the initial treatment phase, a higher than expected proportion of patients showed disability progression.
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Factores Inmunológicos/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Natalizumab/uso terapéutico , Adulto , Evaluación de la Discapacidad , Progresión de la Enfermedad , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND AND PURPOSE: To predict disability and cognition in multiple sclerosis (MS) after 6 and 12 years, using early clinical and imaging measures. METHODS: A total of 115 patients with MS were selected and followed up after 2 and 6 years, with 79 patients also being followed up after 12 years. Disability was measured using the Expanded Disability Status Scale (EDSS); cognition was measured only at follow-up using neuropsychological testing. Predictors of interest included EDSS score, baseline brain and lesion volumes and their changes over 2 years, baseline age, clinical phenotype, sex and educational level. RESULTS: Higher 6-year EDSS score was predicted by early EDSS score and whole-brain volume changes and baseline diagnosis of primary progressive MS (adjusted R2 = 0.56). Predictors for 12-year EDSS score included larger EDSS score changes and higher T1-hypointense lesion volumes (adjusted R2 = 0.38). Year 6 cognition was predicted by primary progressive MS phenotype, lower educational level, male sex and early whole-brain atrophy (adjusted R2 = 0.26); year 12 predictors included male sex, lower educational level and higher baseline T1-hypointense lesion volumes (adjusted R2 = 0.14). CONCLUSIONS: Patients with early signs of neurodegeneration and a progressive disease onset were more prone to develop both disability progression and cognitive dysfunction. Male sex and lower educational level only affected cognitive dysfunction, which remains difficult to predict and probably needs more advanced imaging measures.
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Encéfalo/patología , Trastornos del Conocimiento/etiología , Cognición/fisiología , Esclerosis Múltiple/patología , Sustancia Blanca/patología , Adulto , Atrofia/diagnóstico por imagen , Atrofia/patología , Encéfalo/diagnóstico por imagen , Trastornos del Conocimiento/psicología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/psicología , Pruebas Neuropsicológicas , Sustancia Blanca/diagnóstico por imagenRESUMEN
OBJECTIVES: Apathy, a lack of motivation, is frequently seen in older individuals, with and without depression, with substantial impact on quality of life. This prospective cohort study of patients with severe late-life depression treated with electroconvulsive therapy (ECT) aims to study the course of apathy and the predictive value of vascular burden and in particular white matter hyperintensities on apathy course. METHODS: Information on apathy (defined by a score of >13 on the Apathy Scale), depression severity, vascular burden, and other putative confounders was collected in at 2 psychiatric hospitals on patients with late-life depression (aged 55 to 87 years, N = 73). MRI data on white matter hyperintensities were available in 52 patients. Possible risk factors for apathy post-ECT were determined using regression analyses. RESULTS: After treatment with ECT, 52.0% (26/50) of the depression remitters still suffered from clinically relevant apathy symptoms. In the entire cohort, more patients remained apathetic (58.9%) than depressed (31.5%). Presence of apathy post-ECT was not associated with higher age, use of benzodiazepines, or severity of apathy and depression at baseline. Less response in depressive symptomatology after ECT predicted post-treatment apathy. The presence of vascular disease, diabetes mellitus and smoking, and white matter hyperintensities in the brain was not associated with post-treatment apathy. CONCLUSIONS: Apathy may perpetuate in individual patients, despite remission of depressive symptoms. In this cohort of patients with late-life depression, post-ECT apathy is not associated with white matter hyperintensities.
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Multiple sclerosis (MS) is the most common chronic autoimmune disorder of the central nervous system (CNS) largely affecting young adults. The diagnosis of MS is based on two pillars: 1) detection of the spatial and temporal dissemination of focal neurological deficits and 2) exclusion of important differential diagnoses. The current revision of the diagnostic criteria (McDonald 2017) also follows these principles, takes new data on magnetic resonance imaging (MRI) into account and reintroduces the role of cerebrospinal fluid (CSF) diagnostics for relapsing-remitting forms. The main priority is a reliable diagnosis as early as possible with the aim of a timely initiation of course-adapted treatment. Some of the concrete innovations are the consideration of cortical MRI lesions (equivalent to juxtacortical foci), the elimination of a distinction between asymptomatic and symptomatic MRI lesions and consideration of characteristic CSF findings for the criterion of temporal dissemination. Relapsing MS can be diagnosed at the time of the first attack by the detection of CSF-specific oligoclonal bands and the MRI detection of a typical local lesion distribution (even without simultaneous detection of a contrast-enhancing lesion). For the primary progressive course, for which a first treatment option has recently been approved, the known definition remains unaltered. With respect to the differential diagnosis there is a clear demarcation from Devic's syndrome, now known as neuromyelitis optica spectrum disorders (NMOSD), as recent insights indicate a separate disease entity caused by an autoimmune response against the astrocytic aquaporin 4 (AQP4) water channel. Finally, future studies will have to provide a definition for secondary progressive MS courses and clarify how to handle diseases characterized by antibodies against myelin oligodendrocyte glycoprotein (MOG) or patients with radiologically isolated syndrome (RIS), i.â¯e. incidental MRI-based detection of CNS lesions in the absence of any clinical event. In summary, McDonald 2017 is within the conceptual structure of its predecessor and simplifies an early diagnosis, thus paving the way to early treatment of MS.
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Esclerosis Múltiple , Acuaporina 4/metabolismo , Diagnóstico Diferencial , Humanos , Imagen por Resonancia Magnética , Esclerosis Múltiple/líquido cefalorraquídeo , Esclerosis Múltiple/diagnóstico por imagen , Glicoproteína Mielina-Oligodendrócito/metabolismo , Neuromielitis Óptica/diagnósticoRESUMEN
Imaging, in particular magnetic resonance imaging (MRI), has in recent years increasingly become a crucial tool for the diagnostics of inherited and acquired muscular diseases. The aim of imaging in neuromuscular disorders goes beyond the detection and quantification of degenerative muscular changes, such as fatty degeneration and includes recognition of very early signs of muscular pathologies presenting as muscular edema. Therefore, imaging is a valuable diagnostic method to support the clinical diagnosis and to narrow down the differential diagnoses, leading to specific additional diagnostic tests in order to establish the correct diagnosis. Although advances in MRI hardware and technology have led to a faster, more accurate and advanced image acquisition allowing whole body examination in a feasible fashion, the standardization of image acquisition and interpretation remains a challenge. The aim of this review article is to address the important and clinically relevant issues concerning the role of imaging of neuromuscular diseases in order to facilitate a good interdisciplinary management for the diagnostics and monitoring of neuromuscular diseases.
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Enfermedades Neuromusculares/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Neurólogos/psicología , RadiólogosRESUMEN
BACKGROUND AND PURPOSE: Infection with the John Cunningham virus (JCV) is required for the development of progressive multifocal leukoencephalopathy, the feared complication of natalizumab treatment in multiple sclerosis patients. The JCV seroconversion rate seems higher in natalizumab treated patients than in the normal population, with an unknown cause. METHODS: Natalizumab concentration was correlated to JCV antibody status and seroconversion in a large cohort of multiple sclerosis patients. RESULTS: One hundred and thirty-five patients were included. No correlation was found between natalizumab concentration and JCV status, JCV seroconversion or JCV index. CONCLUSIONS: Higher natalizumab concentrations do not explain the increased JCV seroconversion rate in natalizumab treated patients.
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Factores Inmunológicos/efectos adversos , Virus JC , Leucoencefalopatía Multifocal Progresiva/complicaciones , Leucoencefalopatía Multifocal Progresiva/epidemiología , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/epidemiología , Natalizumab/efectos adversos , Adulto , Anticuerpos Antivirales/sangre , Estudios de Cohortes , Femenino , Humanos , Factores Inmunológicos/sangre , Factores Inmunológicos/uso terapéutico , Masculino , Persona de Mediana Edad , Natalizumab/sangre , Natalizumab/uso terapéutico , Estudios Prospectivos , RiesgoRESUMEN
Progressive multifocal leukoencephalopathy (PML) is a disease of immunosuppressed patients caused by the JC polyomavirus (JCPyV). Due to the elevated risk in patients treated with natalizumab for multiple sclerosis (MS) and also treatment with other biologicals for different indications, the relevance of PML has increased in recent years. This article summarizes the published knowledge on the biology and pathogenesis of PML with a focus on the role of cerebrospinal fluid diagnostics in the work-up for PML and the current PML case definition. Current recommendations regarding risk management are discussed, as are possible therapies and prevention.
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Biomarcadores/líquido cefalorraquídeo , Manejo de Caso/organización & administración , Técnicas de Diagnóstico Neurológico , Leucoencefalopatía Multifocal Progresiva/líquido cefalorraquídeo , Leucoencefalopatía Multifocal Progresiva/diagnóstico , Leucoencefalopatía Multifocal Progresiva/terapia , Medicina Basada en la Evidencia , Humanos , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: John Cunningham virus (JCV) seropositivity is a risk factor for the development of natalizumab-associated progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients. When JCV seronegative patients seroconvert, their risk of developing PML increases. Limited longitudinal data exist about the seroconversion rate amongst natalizumab-treated relapsing-remitting MS (RRMS) patients. Our objective was to evaluate the seroconversion rate in a large Dutch cohort of natalizumab-treated RRMS patients. Seroconversion was defined as at least two consecutive seropositive serum samples (or cessation of therapy after a single seropositive sample because of seropositivity) after initial seronegative testing. METHODS AND RESULTS: In our study of 179 patients for whom longitudinal blood samples were available over a long period (median 4.2 years), anti-JCV antibody indices were measured in 933 available samples. Eighty-six patients (48.0%) tested seronegative initially. Of these 86 seronegative patients, 23 patients (26.7%) seroconverted during follow-up. The annualized seroconversion rate was 7.1%. Seroconversion occurred between 9 and 90 months (median 43 months) of treatment. The rate of seroconversion was independent of follow-up duration. No significant increase was seen in the anti-JCV antibody index in the non-converting patients during the follow-up. CONCLUSION: The annualized seroconversion rate of 7.1% in patients using natalizumab, cumulatively leading to more than 25% of seronegative patients becoming seropositive in 4 years, is of clinical relevance and should be taken into account in the risk assessment when considering the start of natalizumab therapy.
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Anticuerpos Antivirales/sangre , Factores Inmunológicos/efectos adversos , Virus JC/inmunología , Leucoencefalopatía Multifocal Progresiva/inmunología , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Natalizumab/efectos adversos , Adulto , Femenino , Humanos , Factores Inmunológicos/uso terapéutico , Leucoencefalopatía Multifocal Progresiva/sangre , Leucoencefalopatía Multifocal Progresiva/inducido químicamente , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/inmunología , Natalizumab/uso terapéutico , Medición de Riesgo , Factores de Riesgo , SeroconversiónRESUMEN
In this review we discuss the use of conventional (computed tomography, magnetic resonance imaging, ultrasound) and advanced muscle imaging modalities (diffusion tensor imaging, magnetic resonance spectroscopy) in hereditary and acquired myopathies. We summarize the data on specific patterns of muscle involvement in the major categories of muscle disease and provide recommendations on how to use muscle imaging in this field of neuromuscular disorders.
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Enfermedades Musculares/diagnóstico por imagen , HumanosRESUMEN
BACKGROUND AND PURPOSE: Spinal cord atrophy is a common and clinically relevant characteristic in multiple sclerosis. We aimed to perform a multicenter validation study of mean upper cervical cord area measurements in patients with multiple sclerosis and healthy controls from head MR images and to explore the effect of gadolinium administration on mean upper cervical cord area measurements. MATERIALS AND METHODS: We recruited 97 subjects from 3 centers, including 60 patients with multiple sclerosis of different disease types and 37 healthy controls. Both cervical cord and head 3D T1-weighted images were acquired. In 11 additional patients from 1 center, head images before and after gadolinium administration and cervical cord images after gadolinium administration were acquired. The mean upper cervical cord area was compared between cervical cord and head images by using intraclass correlation coefficients (ICC) for both consistency (ICCconsist) and absolute (ICCabs) agreement. RESULTS: There was excellent agreement of mean upper cervical cord area measurements from head and cervical cord images in the entire group (ICCabs = 0.987) and across centers and disease subtypes. The mean absolute difference between the mean upper cervical cord area measured from head and cervical cord images was 2 mm(2) (2.3%). Additionally, excellent agreement was found between the mean upper cervical cord area measured from head images with and without gadolinium administration (ICCabs = 0.991) and between the cervical cord and head images with gadolinium administration (ICCabs = 0.992). CONCLUSIONS: Excellent agreement between mean upper cervical cord area measurements on head and cervical cord images was observed in this multicenter study, implying that upper cervical cord atrophy can be reliably measured from head images. Postgadolinium head or cervical cord images may also be suitable for measuring mean upper cervical cord area.
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Médula Cervical/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/diagnóstico por imagen , Adulto , Anciano , Atrofia , Médula Cervical/patología , Medios de Contraste , Evaluación de la Discapacidad , Femenino , Gadolinio , Cabeza , Humanos , Procesamiento de Imagen Asistido por Computador , Imagenología Tridimensional , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/patología , Reproducibilidad de los ResultadosRESUMEN
Magnetic resonance imaging (MRI) is the most powerful tool for the early (differential) diagnosis of multiple sclerosis (MS) and has been part of the International Panel criteria (2001, 2005, 2010) for more than 10 years. The role of brain and spinal cord MRI in the diagnosis of MS is well established. New MR techniques and markers will further improve the diagnostic value in a research and clinical routine setting. In addition to diagnosis, MRI is widely used for prognostic evaluation as well as treatment efficacy and safety monitoring. This field has gained importance with the introduction of new MS therapeutics. Therefore, the scope of MRI-guided MS disease monitoring has been widened to include rigorous treatment monitoring aiming at "no evidence of disease activity (NEDA)". Next, safety monitoring of treated MS patients has become major concern to enable early detection of opportunistic infections such as progressive multifocal leukoencephalopathy (PML). Driven by these new developments, recently published expert panel guidelines stressed the need for standardized imaging protocols and targeted specialized imaging markers for MS diagnosis and disease monitoring. This review article aims to give an update on the role of MRI in the diagnosis and monitoring of MS with particular emphasis to treatment efficacy and safety, both in clinical practice and in research.
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Encéfalo/patología , Interpretación de Imagen Asistida por Computador/normas , Imagen por Resonancia Magnética/normas , Esclerosis Múltiple/patología , Guías de Práctica Clínica como Asunto , Médula Espinal/patología , Alemania , Humanos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
A multiple sclerosis (MS) patient developed progressive multifocal leukoencephalopathy (PML) after 43 months of natalizumab treatment. New clinical and magnetic resonance imaging (MRI) findings were initially misinterpreted as breakthrough MS disease activity and natalizumab treatment was replaced by rituximab treatment. The patient had a single infusion of rituximab 1000 mg before a definite PML diagnosis was confirmed. Despite undetectable levels of B-cells, JC virus DNA became undetectable in the cerebrospinal fluid by quantitative polymerase chain reaction. The patient partially recovered without any clinical or MRI signs of new MS activity. These findings suggest that B-cell depletion in a non-immune compromised individual did not prevent the patient from clearing the JC virus infection.
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Factores Inmunológicos/uso terapéutico , Leucoencefalopatías/tratamiento farmacológico , Leucoencefalopatías/etiología , Esclerosis Múltiple/complicaciones , Rituximab/uso terapéutico , Adulto , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Resultado del TratamientoRESUMEN
Progressive multifocal leukoencephalopathy (PML) is a severe complication of natalizumab treatment. Restoring immune function by plasmapheresis/immunoadsorption (PLEX/IA) is important for the outcome of PML. We report on four multiple sclerosis (MS) patients whom developed PML during natalizumab treatment, in whom we measured serum natalizumab concentrations before and during PLEX. Depending on the serum natalizumab concentration at the time of PML diagnosis, the number of PLEX treatments necessary to reach subtherapeutic serum natalizumab concentrations is variable. Measuring serum natalizumab concentrations before and during PLEX is helpful to determine the optimum number of PLEX treatments in individual MS patients with PML.
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Factores Inmunológicos/sangre , Leucoencefalopatía Multifocal Progresiva/inducido químicamente , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Natalizumab/sangre , Adulto , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Factores Inmunológicos/efectos adversos , Leucoencefalopatía Multifocal Progresiva/terapia , Masculino , Esclerosis Múltiple Recurrente-Remitente/sangre , Natalizumab/efectos adversos , Intercambio PlasmáticoRESUMEN
OBJECTIVE: To investigate the coexistence of anterograde and retrograde trans-synaptic axonal degeneration, and to explore the relationship between selective visual pathway damage and global brain involvement in longstanding multiple sclerosis (MS). METHODS: In this single-centre, cross-sectional study, patients with longstanding MS (N=222) and healthy controls (HC, N=62) were included. We analysed thickness of retinal layers (optical coherence tomography), damage within optic radiations (OR) (lesion volume and fractional anisotropy and mean diffusivity by diffusion tensor imaging) and atrophy of the visual cortex and that of grey and white matter of the whole-brain (structural MRI). Linear regression analyses were used to assess associations between the different components and for comparing patients with and without optic neuritis and HC. RESULTS: In patients with MS, an episode of optic neuritis (MSON) was significantly associated with decreased integrity of the ORs and thinning of the peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell complex (GCC). Lesion volume in the OR was negatively associated with pRNFL and GCC thickness in patients without optic neuritis (MSNON). The pRNFL and GCC showed associations with integrity of the OR, thickness of the primary visual cortex (only in patients with MSON), and also with global white and grey matter atrophy. In HCs, no such relationships were demonstrated. INTERPRETATION: This study provides evidence for presence of bidirectional (both anterograde and retrograde) trans-synaptic axonal degeneration in the visual pathway of patients with MS. Additionally, thinning of the retinal pRNFL and GCC are related to global white and grey matter atrophy in addition to pathology of the visual pathway.
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Axones/patología , Esclerosis Múltiple/patología , Degeneración Nerviosa/patología , Sinapsis/patología , Vías Visuales/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Atrofia , Encéfalo/patología , Estudios de Cohortes , Imagen de Difusión Tensora , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía de Coherencia Óptica , Adulto JovenRESUMEN
BACKGROUND: Virchow-Robin spaces (VRS) are associated with vascular and neurodegenerative disease. In multiple sclerosis (MS), VRS have been associated with neuroinflammation. Ultra-high field imaging may be used to gain insight in these contradictory findings. OBJECTIVE: The objective of this paper is to analyze VRS in MS patients using high-resolution 7 Tesla (T) MRI. Additionally, we investigated whether the widening of VRS is related to inflammatory or neurodegenerative aspects of MS. METHODS: Thirty-four MS patients and 11 healthy controls were examined at 7T. Number and size of VRS were measured on three-dimensional (3D) T1-weighted images, and 3D fluid-attenuated inversion recovery (FLAIR) images were used for MS lesion detection. Brain atrophy was quantified by computing supratentorial brain volume fraction (sBVF). VRS counts were correlated with clinical variables, lesion count and sBVF. RESULTS: MS patients displayed more VRS (median 11) than healthy controls (median four), p = 0.001. VRS size did not differ between both groups. VRS count in MS patients was associated with sBVF (rho = -0.40, p = 0.02), but not with lesion count (p = 0.22). CONCLUSIONS: The 7T MRI reveals increased numbers of VRS in MS. The finding that VRS are associated with supratentorial brain atrophy, but not with lesion count, suggests that VRS might rather serve as a neurodegenerative than an inflammatory marker in MS.
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Encéfalo/patología , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/patología , Enfermedades Neurodegenerativas/patología , Adulto , Atrofia/patología , Biomarcadores , Femenino , Humanos , Imagen por Resonancia Magnética/instrumentación , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico , Enfermedades Neurodegenerativas/diagnósticoRESUMEN
Background. Natalizumab treatment is frequently discontinued and replaced by alternative medication in multiple sclerosis (MS) patients having a high risk of progressive multifocal leukoencephalopathy (PML). Case Presentation. We report a PML case that was missed on magnetic resonance imaging (MRI) at the time Natalizumab treatment was discontinued. The patient subsequently developed a PML-immune reconstitution inflammatory syndrome after the initiation of Fingolimod treatment, suggesting that immune reconstitution may occur even during Fingolimod induced lymphopenia. Conclusion. This report highlights the need for strict drug surveillance using MRI of Natalizumab-associated MS patients at the time of drug discontinuation and beyond. This is important with respect to pharmacovigilance purposes not only for Natalizumab, but also for alternative drugs used after Natalizumab discontinuation.