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1.
Neuroimage ; 222: 117216, 2020 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-32745677

RESUMEN

Susceptibility weighted magnetic resonance imaging (MRI) is sensitive to the local concentration of iron and myelin. Here, we describe a robust image processing pipeline for quantitative susceptibility mapping (QSM) and R2* mapping of fixed post-mortem, whole-brain data. Using this pipeline, we compare the resulting quantitative maps in brains from patients with amyotrophic lateral sclerosis (ALS) and controls, with validation against iron and myelin histology. Twelve post-mortem brains were scanned with a multi-echo gradient echo sequence at 7T, from which susceptibility and R2* maps were generated. Semi-quantitative histological analysis for ferritin (the principal iron storage protein) and myelin proteolipid protein was performed in the primary motor, anterior cingulate and visual cortices. Magnetic susceptibility and R2* values in primary motor cortex were higher in ALS compared to control brains. Magnetic susceptibility and R2* showed positive correlations with both myelin and ferritin estimates from histology. Four out of nine ALS brains exhibited clearly visible hyperintense susceptibility and R2* values in the primary motor cortex. Our results demonstrate the potential for MRI-histology studies in whole, fixed post-mortem brains to investigate the biophysical source of susceptibility weighted MRI signals in neurodegenerative diseases like ALS.


Asunto(s)
Esclerosis Amiotrófica Lateral/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Ferritinas , Imagen por Resonancia Magnética/métodos , Vaina de Mielina , Anciano , Esclerosis Amiotrófica Lateral/metabolismo , Esclerosis Amiotrófica Lateral/patología , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Diagnóstico , Femenino , Ferritinas/metabolismo , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/metabolismo , Giro del Cíngulo/patología , Humanos , Masculino , Persona de Mediana Edad , Corteza Motora/diagnóstico por imagen , Corteza Motora/metabolismo , Corteza Motora/patología , Vaina de Mielina/metabolismo , Corteza Visual/diagnóstico por imagen , Corteza Visual/metabolismo , Corteza Visual/patología
2.
J Neurol Neurosurg Psychiatry ; 89(12): 1250-1258, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30049750

RESUMEN

BACKGROUND: The thalamus is a major neural hub, with selective connections to virtually all cortical regions of the brain. The multisystem neurodegenerative syndrome amyotrophic lateral sclerosis (ALS) has pathogenic overlap with frontotemporal dementia, and objective in vivo markers of extra-motor pathological spread are lacking. To better consider the role of the thalamus in neurodegeneration, the present study assessed the integrity of the thalamus and its connectivity to major cortical regions of the brain in a longitudinal manner. METHODS: Diffusion-based MRI tractography was used to parcellate the thalamus into distinct regions based on structural thalamo-cortical connectivity in 20 patients with ALS, half of whom were scanned at two time points, and 31 matched controls scanned on a single occasion. RESULTS: At baseline, widespread diffusivity alterations in motor- and extramotor-associated thalamic parcellations were detectable. Longitudinal decline selectively affected thalamic regions associated with frontal and temporal lobe connectivity. Diffusivity measures were significantly correlated with clinical measures of disease burden. Progression of functional disability, as indicated by change on the ALS functional rating scale, was associated with longitudinal change in mean diffusivity of the right frontal lobe thalamic parcellation (r=0.59, p=0.05). CONCLUSIONS: Regional thalamic connectivity changes mirror the progressive frontotemporal cortical involvement associated with the motor functional decline in ALS. Longitudinal MRI thalamic parcellation has potential as a non-invasive surrogate marker of cortical dysfunction in ALS.


Asunto(s)
Esclerosis Amiotrófica Lateral/patología , Lóbulo Frontal/patología , Lóbulo Temporal/patología , Tálamo/patología , Biomarcadores , Estudios de Casos y Controles , Imagen de Difusión Tensora , Evaluación de la Discapacidad , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Vías Nerviosas/patología
3.
Artículo en Inglés | MEDLINE | ID: mdl-28719997

RESUMEN

BACKGROUND: Care for people with amyotrophic lateral sclerosis (ALS) has altered at King's College Hospital over the last 20 years. The clinic has been a multidisciplinary, specialist, tertiary referral centre since 1995 with a large team with integrated palliative and respiratory care since 2006. We hypothesised that these changes would improve survival. METHODS: In this retrospective observational study, patients diagnosed with El Escorial definite, probable and possible ALS between 1995-1998 and 2008-2011 were followed up. The primary outcome measure was a chi-square test for the proportion of each cohort surviving. Kaplan-Meier survival analysis and Cox multivariate regression were secondary analyses. RESULTS: There was low reporting of some interventions. Five hundred and forty-seven people were included. Survival between the cohorts was significantly different (p = 0.022) with a higher proportion surviving during 2008-2011. Survival time was 21.6 (95% CI 19.2-24.0) months in the 2008-2011 cohort compared to 19.2 years (15.6-21.6) in the 1995-1998 cohort (log rank p = 0.018). Four hundred and ninety-three cases were included in the Cox regression. Diagnostic cohort was a significant predictor variable (HR 0.79 (0.64-0.97) p = 0.023). CONCLUSIONS: These results support the hypothesis that integrated specialist clinics with multidisciplinary input improve survival in ALS.


Asunto(s)
Esclerosis Amiotrófica Lateral/mortalidad , Esclerosis Amiotrófica Lateral/enfermería , Prestación Integrada de Atención de Salud/estadística & datos numéricos , Grupo de Atención al Paciente/estadística & datos numéricos , Modelos de Riesgos Proporcionales , Sistema de Registros , Estudios de Cohortes , Femenino , Humanos , Londres/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Análisis de Supervivencia
4.
J Neurol Neurosurg Psychiatry ; 87(6): 580-8, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26733601

RESUMEN

OBJECTIVE: To discern presymptomatic changes in brain structure or function using advanced MRI in carriers of mutations predisposing to amyotrophic lateral sclerosis (ALS). METHODS: T1-weighted, diffusion weighted and resting state functional MRI data were acquired at 3 T for 12 asymptomatic mutation carriers (psALS), 12 age-matched controls and affected patients with ALS. Cortical thickness analysis, voxel-based morphometry, volumetric and shape analyses of subcortical structures, tract-based spatial statistics of metrics derived from the diffusion tensor, and resting state functional connectivity (FC) analyses were performed. RESULTS: Grey matter cortical thickness and shape analysis revealed significant atrophy in patients with ALS (but not psALS) compared with controls in the right primary motor cortex and right caudate. Comparison of diffusion tensor metrics showed widespread fractional anisotropy and radial diffusivity differences in patients with ALS compared to controls and the psALS group, encompassing parts of the corpus callosum, corticospinal tracts and superior longitudinal fasciculus. While FC in the resting-state sensorimotor network was similar in psALS and controls, FC between the cerebellum and a network comprising the precuneus, cingulate & middle frontal lobe was significantly higher in psALS and affected ALS compared to controls. CONCLUSIONS: Rather than structural brain changes, increased FC may be among the earliest detectable brain abnormalities in asymptomatic carriers of ALS-causing gene mutations. With replication and significant refinement, this technique has potential in the future assessment of neuroprotective strategies.


Asunto(s)
Esclerosis Amiotrófica Lateral/diagnóstico por imagen , Esclerosis Amiotrófica Lateral/genética , Encéfalo/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética , Predisposición Genética a la Enfermedad/genética , Interpretación de Imagen Asistida por Computador , Imagen por Resonancia Magnética , Red Nerviosa/diagnóstico por imagen , Adulto , Anciano , Esclerosis Amiotrófica Lateral/fisiopatología , Encéfalo/fisiopatología , Proteína C9orf72 , Cerebelo/diagnóstico por imagen , Cerebelo/fisiopatología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/fisiopatología , Estudios de Cohortes , Tomografía Computarizada de Haz Cónico , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/fisiopatología , Femenino , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/fisiopatología , Tamización de Portadores Genéticos , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Red Nerviosa/fisiopatología , Lóbulo Parietal/diagnóstico por imagen , Lóbulo Parietal/fisiopatología , Proteínas/genética , Tractos Piramidales/diagnóstico por imagen , Tractos Piramidales/fisiopatología , Superóxido Dismutasa-1/genética , Adulto Joven
5.
Pract Neurol ; 9(1): 37-41, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19151237

RESUMEN

We describe a case of functional vitamin B12 deficiency where the repeated measurement of a serum B12 level within the normal range led to delay in the diagnosis of subacute combined degeneration of the spinal cord, and possibly permanent neurological damage as a result. Failure of intracellular transport of B12 by transcobalamin-2 can lead to functional B12 deficiency but with apparently normal serum levels, and is suggested by raised levels of either serum methylmalonic acid or homocysteine, associated with low levels of transcobalamin-2. Such patients may respond to repeated high-dose injections of B12.


Asunto(s)
Deficiencia de Vitamina B 12/fisiopatología , Anciano , Femenino , Historia del Siglo XIX , Historia del Siglo XX , Humanos , Imagen por Resonancia Magnética/métodos , Retratos como Asunto , Vitamina B 12/química , Deficiencia de Vitamina B 12/historia , Deficiencia de Vitamina B 12/patología
6.
Amyotroph Lateral Scler ; 8(6): 343-7, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18033592

RESUMEN

Patients homozygous for the D90A mutation of the SOD1 gene (homD90A) demonstrate markedly slower progression of disease than those patients with sporadic ALS (SALS). PET studies have demonstrated a different cortical vulnerability in the two groups, reflected also in neurophysiological studies showing reduced cortical excitability in homD90A. Voxel-based morphometric analysis of magnetic resonance images (MRIs) enables the detection of regional differences in grey matter volume, and can be used to localize cortical atrophy in vivo. In this study, segmented, spatially normalized, modulated and smoothed grey matter portions of the MRIs from 23 SALS and seven homD90A patients with similar disability, were compared with those from 28 healthy control subjects. The SALS group showed bilateral areas of atrophy mainly confined to motor and pre-motor cortices. Cortical changes in the homD90A group were more pronounced within the frontal lobes when both were compared with healthy controls. This study provides further evidence for a different pattern of cortical neuronal vulnerability in homD90A versus SALS patients that may provide insight as to their slower rate of disease progression.


Asunto(s)
Esclerosis Amiotrófica Lateral/diagnóstico , Esclerosis Amiotrófica Lateral/genética , Corteza Cerebral/patología , Imagen por Resonancia Magnética , Mutación , Superóxido Dismutasa/genética , Adulto , Anciano , Esclerosis Amiotrófica Lateral/fisiopatología , Atrofia , Femenino , Lóbulo Frontal/patología , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , Superóxido Dismutasa-1
7.
J Peripher Nerv Syst ; 8(2): 100-7, 2003 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12795714

RESUMEN

Microvasculitis may play a greater part in the pathogenesis of paraproteinaemic neuropathies than is generally recognised, producing tissue destruction by convergent immune and physical mechanisms. We present a patient with a clinical syndrome of mononeuritis multiplex and a circulating IgM lambda paraprotein, in whom bone marrow aspiration revealed a lymphoplasmacytoid lymphoma. Microvasculitic changes were present in the first nerve biopsy, and the second showed extensive destruction of neural architecture and deposition of IgM-related material. A 2-stage pathogenic cascade is postulated and explored with a review of the relevant literature.


Asunto(s)
Linfoma de Células B/complicaciones , Paraproteinemias/complicaciones , Polineuropatías/complicaciones , Vasculitis/etiología , Anciano , Complejo CD3/metabolismo , Técnicas Electrofisiológicas Cardíacas/métodos , Endotelio/ultraestructura , Fascia , Humanos , Inmunoglobulina M/metabolismo , Linfoma de Células B/metabolismo , Masculino , Microcirculación/ultraestructura , Microscopía Electrónica , Mononeuropatías/etiología , Conducción Nerviosa , Paraproteinemias/metabolismo , Paraproteínas/metabolismo , Polineuropatías/metabolismo , Literatura de Revisión como Asunto
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