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BACKGROUND: Neurological inherited disorders are rare in domestic animals. Cerebellar cortical degeneration remains amongst the most common of these disorders. The condition is defined as the premature loss of fully differentiated cerebellar components due to genetic or metabolic defects. It has been studied in dogs and cats, and various genetic defects and diagnostic tests (including magnetic resonance imaging (MRI)) have been refined in these species. Cases in cats remain rare and mostly individual, and few diagnostic criteria, other than post-mortem exam, have been evaluated in reports with multiple cases. Here, we report three feline cases of cerebellar cortical degeneration with detailed clinical, diagnostic imaging and post-mortem findings. CASE PRESENTATION: The three cases were directly (siblings, case #1 and #2) or indirectly related (same farm, case #3) and showed early-onset of the disease, with clinical signs including cerebellar ataxia and tremors. Brain MRI was highly suggestive of cerebellar cortical degeneration on all three cases. The relative cerebrospinal fluid (CSF) space, relative cerebellum size, brainstem: cerebellum area ratio, and cerebellum: total brain area ratio, were measured and compared to a control group of cats and reference cut-offs for dogs in the literature. For the relative cerebellum size and cerebellum: total brain area ratio, all affected cases had a lower value than the control group. For the relative CSF space and brainstem: cerebellum area ratio, the more affected cases (#2 and #3) had higher values than the control group, while the least affected case (#3) had values within the ranges of the control group, but a progression was visible over time. Post-mortem examination confirmed the diagnosis of cerebellar cortical degeneration, with marked to complete loss of Purkinje cells and associated granular layer depletion and proliferation of Bergmann glia. One case also had Wallerian-like degeneration in the spinal cord, suggestive of spinocerebellar degeneration. CONCLUSION: Our report further supports a potential genetic component for the disease in cats. For the MRI examination, the relative cerebellum size and cerebellum: total brain area ratio seem promising, but further studies are needed to establish specific feline cut-offs. Post-mortem evaluation of the cerebellum remains the gold standard for the final diagnosis.
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Enfermedades de los Gatos , Imagen por Resonancia Magnética , Animales , Gatos , Enfermedades de los Gatos/patología , Enfermedades de los Gatos/diagnóstico por imagen , Masculino , Imagen por Resonancia Magnética/veterinaria , Femenino , Corteza Cerebelosa/patología , Corteza Cerebelosa/diagnóstico por imagen , Cerebelo/patología , Cerebelo/diagnóstico por imagenRESUMEN
The cerebellum is essential for motor control and cognitive functioning, engaging in bidirectional communication with the cerebral cortex. The common marmoset, a small non-human primate, offers unique advantages for studying cerebello-cerebral circuits. However, the marmoset cerebellum is not well described in published resources. In this study, we present a comprehensive atlas of the marmoset cerebellum comprising (1) fine-detailed anatomical atlases and surface-analysis tools of the cerebellar cortex based on ultra-high-resolution ex vivo MRI, (2) functional connectivity and gradient patterns of the cerebellar cortex revealed by awake resting-state fMRI, and (3) structural-connectivity mapping of cerebellar nuclei using high-resolution diffusion MRI tractography. The atlas elucidates the anatomical details of the marmoset cerebellum, reveals distinct gradient patterns of intra-cerebellar and cerebello-cerebral functional connectivity, and maps the topological relationship of cerebellar nuclei in cerebello-cerebral circuits. As version 5 of the Marmoset Brain Mapping project, this atlas is publicly available at https://marmosetbrainmapping.org/MBMv5.html.
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Callithrix , Cerebelo , Animales , Imagen por Resonancia Magnética , Mapeo Encefálico , Corteza Cerebelosa/diagnóstico por imagenRESUMEN
Understanding cerebellar alterations due to healthy aging provides a reference point against which pathological findings in late-onset disease, for example spinocerebellar ataxia type 6 (SCA6), can be contrasted. In the present study, we investigated the impact of aging on the cerebellar nuclei and cerebellar cortex in 109 healthy controls (age range: 16 - 78 years) using 3 Tesla magnetic resonance imaging (MRI). Findings were compared with 25 SCA6 patients (age range: 38 - 78 years). A subset of 16 SCA6 (included: 14) patients and 50 controls (included: 45) received an additional MRI scan at 7 Tesla and were re-scanned after one year. MRI included T1-weighted, T2-weighted FLAIR, and multi-echo T2*-weighted imaging. The T2*-weighted phase images were converted to quantitative susceptibility maps (QSM). Since the cerebellar nuclei are characterized by elevated iron content with respect to their surroundings, two independent raters manually outlined them on the susceptibility maps. T1-weighted images acquired at 3T were utilized to automatically identify the cerebellar gray matter (GM) volume. Linear correlations revealed significant atrophy of the cerebellum due to tissue loss of cerebellar cortical GM in healthy controls with increasing age. Reduction of the cerebellar GM was substantially stronger in SCA6 patients. The volume of the dentate nuclei did not exhibit a significant relationship with age, at least in the age range between 18 and 78 years, whereas mean susceptibilities of the dentate nuclei increased with age. As previously shown, the dentate nuclei volumes were smaller and magnetic susceptibilities were lower in SCA6 patients compared to age- and sex-matched controls. The significant dentate volume loss in SCA6 patients could also be confirmed with 7T MRI. Linear mixed effects models and individual paired t-tests accounting for multiple comparisons revealed no statistical significant change in volume and susceptibility of the dentate nuclei after one year in neither patients nor controls. Importantly, dentate volumes were more sensitive to differentiate between SCA6 (Cohen's d = 3.02) and matched controls than the cerebellar cortex volume (d = 2.04). In addition to age-related decline of the cerebellar cortex and atrophy in SCA6 patients, age-related increase of susceptibility of the dentate nuclei was found in controls, whereas dentate volume and susceptibility was significantly decreased in SCA6 patients. Because no significant changes of any of these parameters was found at follow-up, these measures do not allow to monitor disease progression at short intervals.
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Ataxias Espinocerebelosas , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Ataxias Espinocerebelosas/diagnóstico por imagen , Ataxias Espinocerebelosas/patología , Cerebelo/patología , Corteza Cerebelosa/diagnóstico por imagen , Corteza Cerebelosa/patología , Núcleos Cerebelosos/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Atrofia/patologíaRESUMEN
The hallmark of Multiple Sclerosis (MS) pathophysiology is the damage to the myelin sheath around axons. The cerebellum is a predilection site for demyelination with a well-recognized role in motor and a rather understudied contribution to cognitive functions. The aim of this study is to investigate patterns of cerebellar grey and white matter pathology, expressed as reduced volume, as well as cortical thickness and their potential contribution to cognitive performance and disability status of patients with MS. 24 patients with MS underwent extensive neuropsychological assessment using paper and pencil tests and the Brain Health Assessment (BHA) tablet-based battery. Cerebellar lobular volumes and thickness were calculated using a volumetric analysis with automated segmentation of the cerebellum and its lobules. The main findings are a reduction of cerebellar grey matter (CGMV) and white matter volumes (CWMV) in lobule X and a widespread cerebellar cortical thinning in patients. Overall disease severity and neurological disability, assessed with the Expanded Disability Status Severity Scale, was correlated with fatigue and information processing speed tasks, but not with CGMV and CWMV. CWMV and CGMV of lobule I-II was negatively correlated with information processing speed, as well as visuospatial memory tests and, finally, inverse cortical thinning associations were noted between the whole cerebellum, lobule I-II, lobule III, lobule VI, Crus I, lobule VIIIA and information processing speed and verbal fluency tasks. The inverse associations observed may represent a compensatory mechanism activated in MS engaging additional high-level cortical areas functionally interconnected with the damaged cerebellum, in order to cope with the cognitive demands of a task.
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Cerebelo/patología , Disfunción Cognitiva/patología , Disfunción Cognitiva/fisiopatología , Sustancia Gris/patología , Esclerosis Múltiple/patología , Esclerosis Múltiple/fisiopatología , Sustancia Blanca/patología , Adulto , Corteza Cerebelosa/diagnóstico por imagen , Corteza Cerebelosa/patología , Cerebelo/diagnóstico por imagen , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiología , Femenino , Sustancia Gris/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagenRESUMEN
BACKGROUND AND PURPOSE: Although evidence accumulates that the cerebellum is involved in cerebral amyloid angiopathy (CAA), cerebellar superficial siderosis is not considered to be a disease marker. The objective of this study is to investigate cerebellar superficial siderosis frequency and its relation to hemorrhagic magnetic resonance imaging markers in patients with sporadic and Dutch-type hereditary CAA and patients with deep perforating arteriopathy-related intracerebral hemorrhage. METHODS: We recruited patients from 3 prospective 3 Tesla magnetic resonance imaging studies and scored siderosis and hemorrhages. Cerebellar siderosis was identified as hypointense linear signal loss (black) on susceptibility-weighted or T2*-weighted magnetic resonance imaging which follows at least one folia of the cerebellar cortex (including the vermis). RESULTS: We included 50 subjects with Dutch-type hereditary CAA, (mean age 50 years), 45 with sporadic CAA (mean age 72 years), and 43 patients with deep perforating arteriopathy-related intracerebral hemorrhage (mean age 54 years). Cerebellar superficial siderosis was present in 5 out of 50 (10% [95% CI, 2-18]) patients with Dutch-type hereditary CAA, 4/45 (9% [95% CI, 1-17]) patients with sporadic CAA, and 0 out of 43 (0% [95% CI, 0-8]) patients with deep perforating arteriopathy-related intracerebral hemorrhage. Patients with cerebellar superficial siderosis had more supratentorial lobar (median number 9 versus 2, relative risk, 2.9 [95% CI, 2.5-3.4]) and superficial cerebellar macrobleeds (median number 2 versus 0, relative risk, 20.3 [95% CI, 8.6-47.6]) compared with patients without the marker. The frequency of cortical superficial siderosis and superficial cerebellar microbleeds was comparable. CONCLUSIONS: We conclude that cerebellar superficial siderosis might be a novel marker for CAA.
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Enfermedades Cerebelosas/etiología , Angiopatía Amiloide Cerebral/complicaciones , Hemosiderosis/etiología , Adulto , Anciano , Anciano de 80 o más Años , Corteza Cerebelosa/diagnóstico por imagen , Enfermedades Cerebelosas/diagnóstico por imagen , Enfermedades Cerebelosas/genética , Angiopatía Amiloide Cerebral/diagnóstico por imagen , Angiopatía Amiloide Cerebral/genética , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/diagnóstico por imagen , Femenino , Hemosiderosis/diagnóstico por imagen , Hemosiderosis/genética , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Siderosis , Adulto JovenRESUMEN
Falls are the second most frequent cause of injury in the elderly. Physiological processes associated with aging affect the elderly's ability to respond to unexpected balance perturbations, leading to increased fall risk. Every year, approximately 30% of adults, 65 years and older, experiences at least one fall. Investigating the neurophysiological mechanisms underlying the control of static and dynamic balance in the elderly is an emerging research area. The study aimed to identify cortical and muscular correlates during static and dynamic balance tests in a cohort of young and old healthy adults. We recorded cortical and muscular activity in nine elderly and eight younger healthy participants during an upright stance task in static and dynamic (core board) conditions. To simulate real-life dual-task postural control conditions, the second set of experiments incorporated an oddball visual task. We observed higher electroencephalographic (EEG) delta rhythm over the anterior cortex in the elderly and more diffused fast rhythms (i.e., alpha, beta, gamma) in younger participants during the static balance tests. When adding a visual oddball, the elderly displayed an increase in theta activation over the sensorimotor and occipital cortices. During the dynamic balance tests, the elderly showed the recruitment of sensorimotor areas and increased muscle activity level, suggesting a preferential motor strategy for postural control. This strategy was even more prominent during the oddball task. Younger participants showed reduced cortical and muscular activity compared to the elderly, with the noteworthy difference of a preferential activation of occipital areas that increased during the oddball task. These results support the hypothesis that different strategies are used by the elderly compared to younger adults during postural tasks, particularly when postural and cognitive tasks are combined. The knowledge gained in this study could inform the development of age-specific rehabilitative and assistive interventions.
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Envejecimiento/fisiología , Corteza Cerebelosa/diagnóstico por imagen , Corteza Sensoriomotora/diagnóstico por imagen , Heridas y Lesiones/fisiopatología , Accidentes por Caídas/prevención & control , Adulto , Anciano , Envejecimiento/patología , Mapeo Encefálico , Corteza Cerebelosa/fisiopatología , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Equilibrio Postural/fisiología , Desempeño Psicomotor/fisiología , Corteza Sensoriomotora/fisiopatología , Posición de Pie , Adulto JovenRESUMEN
We present an exploratory cross-sectional analysis of the effect of season and weather on Freesurfer-derived brain volumes from a sample of 3,279 healthy individuals collected on two MRI scanners in Hartford, CT, USA over a 15 year period. Weather and seasonal effects were analyzed using a single linear regression model with age, sex, motion, scan sequence, time-of-day, month of the year, and the deviation from average barometric pressure, air temperature, and humidity, as covariates. FDR correction for multiple comparisons was applied to groups of non-overlapping ROIs. Significant negative relationships were found between the left- and right- cerebellum cortex and pressure (t = -2.25, p = 0.049; t = -2.771, p = 0.017). Significant positive relationships were found between left- and right- cerebellum cortex and white matter between the comparisons of January/June and January/September. Significant negative relationships were found between several subcortical ROIs for the summer months compared to January. An opposing effect was observed between the supra- and infra-tentorium, with opposite effect directions in winter and summer. Cohen's d effect sizes from monthly comparisons were similar to those reported in recent psychiatric big-data publications, raising the possibility that seasonal changes and weather may be confounds in large cohort studies. Additionally, changes in brain volume due to natural environmental variation have not been reported before and may have implications for weather-related and seasonal ailments.
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Encéfalo/fisiología , Estaciones del Año , Tiempo (Meteorología) , Adulto , Encéfalo/diagnóstico por imagen , Corteza Cerebelosa/diagnóstico por imagen , Corteza Cerebelosa/fisiología , Estudios Transversales , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/fisiología , Adulto JovenRESUMEN
Neurodegeneration of the cerebellum progresses over years and primarily affects cerebellar cortex. It leads to a progressive loss of control and coordination of gait, posture, speech, fine motor, and oculomotor function. Yet, little is known how the cerebro-cerebellar network compensates for the loss in cerebellar cortical neurons. To address this knowledge gap, we examined 30 people with cerebellar cortical degeneration and a group of 30 healthy controls. We assessed visuomotor performance during a forearm-pointing task to 10°, 25°, and 50° targets. In addition, using MRI imaging, we determined neurodegenerative-induced changes in gray matter volume (GMV) in the cerebro-cerebellar network and correlated them to markers of motor performance. The main results are as follows: first, the relative joint position error (RJPE) during pointing was significantly greater in the ataxia group for all targets confirming the expected motor control deficit. Second, in the ataxia group, GMV was significantly reduced in cerebellar cortex but increased in the deep cerebellar nuclei. Motor error (RJPE) correlated negatively with decreased cerebellar GMV but positively with increased GMV in supplementary motor area (SMA) and premotor cortex. GMV of the deep cerebellar nuclei did not correlate significantly with markers of motor performance. We discuss whether the GMV changes in the cerebellar output nuclei and the extracerebellar efferent targets in secondary motor cortex can be understood as a central compensatory response to the neurodegeneration of the cerebellar cortex.NEW & NOTEWORTHY Neurodegeneration of the cerebellum progresses over years and primarily affects cerebellar cortex. It leads to a progressive loss of control and coordination of movement. We here show that the neurodegenerative process not only leads to cells loss in cerebellar cortex but also induces neurostructural changes in the form of increased gray matter in the efferent targets of the cerebellar cortex, namely, the cerebellar output nuclei, the SMA, and premotor cortex.
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Ataxia Cerebelosa , Corteza Cerebelosa , Núcleos Cerebelosos , Sustancia Gris , Actividad Motora/fisiología , Corteza Motora/fisiopatología , Desempeño Psicomotor/fisiología , Adulto , Anciano , Ataxia Cerebelosa/diagnóstico por imagen , Ataxia Cerebelosa/patología , Ataxia Cerebelosa/fisiopatología , Corteza Cerebelosa/diagnóstico por imagen , Corteza Cerebelosa/patología , Corteza Cerebelosa/fisiopatología , Núcleos Cerebelosos/diagnóstico por imagen , Núcleos Cerebelosos/patología , Núcleos Cerebelosos/fisiopatología , Femenino , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Sustancia Gris/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: It has been proposed that amyloid-ß (Aß) plays a causal role in Alzheimer's disease (AD) by triggering a series of pathologic events-possibly including neuroinflammation-which culminate in progressive brain atrophy. However, the interplay between the two pathological molecular events and how both are associated with neurodegeneration is still unclear. OBJECTIVE: We aimed to estimate the spatial inter-relationship between neurodegeneration, neuroinflammation and Aß deposition in a cohort of 20 mild AD patients and 17 healthy controls (HC). METHODS: We resorted to magnetic resonance imaging to measure cortical atrophy, using the radiotracer 11C-PK11195 PET to measure neuroinflammation levels and 11C-PiB PET to assess Aß levels. Between-group comparisons were computed to explore AD-related changes in the three types of markers. To examine the effects of each one of the molecular pathologic mechanisms on neurodegeneration we computed: 1) ANCOVAs with the anatomic data, controlling for radiotracer uptake differences between groups and 2) voxel-based multiple regression analysis between-modalities. In addition, associations in anatomically defined regions of interests were also investigated. RESULTS: We found significant differences between AD and controls in the levels of atrophy, neuroinflammation, and Aß deposition. Associations between Aß aggregation and brain atrophy were detected in AD in a widely distributed pattern, whereas associations between microglia activation and structural measures of neurodegeneration were restricted to few anatomically regions. CONCLUSION: In summary, Aß deposition, as opposed to neuroinflammation, was more associated with cortical atrophy, suggesting a prominent role of Aß in neurodegeneration at a mild stage of the AD.
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Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Encefalitis/metabolismo , Sustancia Gris/metabolismo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/patología , Atrofia , Corteza Cerebelosa/diagnóstico por imagen , Corteza Cerebelosa/metabolismo , Corteza Cerebelosa/patología , Estudios de Cohortes , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Encefalitis/diagnóstico por imagen , Encefalitis/patología , Femenino , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Voluntarios Sanos , Humanos , Imagen por Resonancia Magnética , Masculino , Pruebas de Estado Mental y Demencia , Persona de Mediana Edad , Enfermedades Neurodegenerativas/diagnóstico por imagen , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/patología , Tomografía de Emisión de PositronesRESUMEN
ABSTRACT: Using voxel-based morphometry (VBM), we studied cortical gray matter volume changes in patients with cervical spondylotic myelopathy (CSM) before and after cervical cord surgical decompression. We then discussed the structural damage mechanisms and the neural plasticity mechanisms involved in postsurgical CSM.Forty-five presurgical CSM patients, 41 of the same group followed-up 6âmonths after decompression surgery and 45 normal controls (NC) matched for age, sex and level of education underwent high-resolution 3-dimensional T1-weighted scans by 3.0âT MR. Then, VBM measurements were compared and cortical gray matter volume alterations were assessed among pre- or postsurgical CSM patients and NC, as well as correlations with clinical indexes by Pearson correlation.Compared with NC, presurgical CSM patients showed reduced gray matter volume in the left caudate nucleus and the right thalamus. After 6âmonths, postsurgical CSM patients had lower gray matter volume in the bilateral cerebellar posterior lobes but had higher gray matter volume in the brain-stem than did presurgical CSM patients. Postsurgical CSM patients had significantly lower gray matter volume in the left caudate nucleus but greater regional gray matter volume in the right inferior temporal gyrus, the right middle orbitofrontal cortex (OFC) and the bilateral lingual gyrus / precuneus /posterior cingulate cortex than did NC. Abnormal areas gray volume in presurgical CSM and postsurgical CSM patients showed no significant correlation with clinical data (Pâ>â.05).Myelopathy in the cervical cord may cause chronic cerebral structural damage before and after the decompression stage, markedly in outlier brain regions involving motor execution/control, vision processing and the default mode network and in areas associated with brain compensatory plasticity to reverse downstream spinal cord compression and respond to spinal cord surgical decompression.
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Corteza Cerebelosa/patología , Vértebras Cervicales/cirugía , Descompresión Quirúrgica/métodos , Sustancia Gris/patología , Plasticidad Neuronal/fisiología , Espondilosis/cirugía , Adulto , Corteza Cerebelosa/diagnóstico por imagen , Femenino , Sustancia Gris/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
INTRODUCTION: Adults with Parkinson's disease (PD) experience gait disturbances that can sometimes be improved with rhythmic auditory stimulation (RAS); however, the underlying physiological mechanism for this improvement is not well understood. We investigated brain activation patterns in adults with PD and healthy controls (HC) using functional magnetic resonance imaging (fMRI) while participants imagined gait with or without RAS. METHODS: Twenty-seven adults with PD who could walk independently and walked more smoothly with rhythmic auditory cueing than without it, and 25 age-matched HC participated in this study. Participants imagined gait in the presence of RAS or white noise (WN) during fMRI. RESULTS: In the PD group, gait imagery with RAS activated cortical motor areas, including supplementary motor areas and the cerebellum, while gait imagery with WN additionally recruited the left parietal operculum. In HC, the induced activation was limited to cortical motor areas and the cerebellum for both the RAS and WN conditions. Within- and between-group analyses demonstrated that RAS reduced the activity of the left parietal operculum in the PD group but not in the HC group (condition-by-group interaction by repeated measures analysis of variance, p < 0.05). CONCLUSION: During gait imagery in adults with PD, the left parietal operculum was less activated by RAS than by WN, while no change was observed in HC, suggesting that rhythmic auditory stimulation may support the sensory-motor networks involved in gait, thus alleviating the overload of the parietal operculum and compensating for its dysfunction in these patients.
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Estimulación Acústica , Corteza Cerebelosa/fisiopatología , Señales (Psicología) , Trastornos Neurológicos de la Marcha/fisiopatología , Trastornos Neurológicos de la Marcha/rehabilitación , Corteza Motora/fisiopatología , Rehabilitación Neurológica , Lóbulo Parietal/fisiopatología , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/rehabilitación , Estimulación Acústica/métodos , Anciano , Anciano de 80 o más Años , Animales , Corteza Cerebelosa/diagnóstico por imagen , Femenino , Trastornos Neurológicos de la Marcha/diagnóstico por imagen , Trastornos Neurológicos de la Marcha/etiología , Humanos , Imaginación/fisiología , Imagen por Resonancia Magnética , Masculino , Corteza Motora/diagnóstico por imagen , Rehabilitación Neurológica/métodos , Evaluación de Resultado en la Atención de Salud , Lóbulo Parietal/diagnóstico por imagen , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagenRESUMEN
PET hypoxia imaging can assess tissue viability in acute ischemic stroke (AIS). [18F]FMISO is an established tracer but requires substantial accumulation time, limiting its use in hyperacute AIS. [64Cu]CuATSM requires less accumulation time and has shown promise as a hypoxia tracer. We compared these tracers in a M2-occlusion model (M2CAO) with preserved collateral blood flow. Rats underwent M2CAO and [18F]FMISO (n = 12) or [64Cu]CuATSM (n = 6) examinations. [64Cu]CuATSM animals were also examined with MRI. Pimonidazole was used as a surrogate for [18F]FMISO in an immunofluorescence analysis employed to profile levels of hypoxia in neurons (NeuN) and astrocytes (GFAP). There was increased [18F]FMISO uptake in the M2CAO cortex. No increase in [64Cu]CuATSM activity was found. The pimonidazole intensity of neurons and astrocytes was increased in hypoxic regions. The pimonidazole intensity ratio was higher in neurons than in astrocytes. In the majority of animals, immunofluorescence revealed a loss of astrocytes within the core of regions with increased pimonidazole uptake. We conclude that [18F]FMISO is superior to [64Cu]CuATSM in detecting hypoxia in AIS, consistent with an earlier study. [18F]FMISO may provide efficient diagnostic imaging beyond the hyperacute phase. Results do not provide encouragement for the use of [64Cu]CuATSM in experimental AIS.
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Isquemia Encefálica/patología , Misonidazol/análogos & derivados , Compuestos Organometálicos/química , Radiofármacos/química , Tiosemicarbazonas/química , Animales , Astrocitos/química , Astrocitos/metabolismo , Autorradiografía , Encéfalo/diagnóstico por imagen , Isquemia Encefálica/metabolismo , Corteza Cerebelosa/química , Corteza Cerebelosa/diagnóstico por imagen , Corteza Cerebelosa/patología , Complejos de Coordinación , Radioisótopos de Cobre/química , Modelos Animales de Enfermedad , Radioisótopos de Flúor/química , Hipoxia , Masculino , Misonidazol/síntesis química , Misonidazol/química , Neuronas/química , Neuronas/metabolismo , Compuestos Organometálicos/síntesis química , Tomografía de Emisión de Positrones , Radiofármacos/síntesis química , Ratas , Ratas Sprague-Dawley , Tiosemicarbazonas/síntesis químicaRESUMEN
A heterogeneous spectrum of clinical manifestations caused by mutations in ATP1A3 have been previously described. Here we report two cases of infantile-onset cerebellar ataxia, due to two different ATP1A3 variants. Both patients showed slowly progressive cerebellar ataxia without paroxysmal or episodic symptoms. Brain magnetic resonance imaging revealed mild cerebellar cortical atrophy in both patients. Whole exome sequencing revealed a de novo heterozygous variant in ATP1A3 in both patients. One patient had the c.460A>G (p.Met154Val) variant, while the other carried the c.1050C>A (p.Asp350Lys) variant. This phenotype was characterized by a slowly progressive cerebellar ataxia since the infantile period, which has not been previously described in association with ATP1A3 variants or in ATP1A3-related clinical conditions. Our report contributes to extend the phenotypic spectrum of ATP1A3 mutations, showing paediatric slowly progressive cerebellar ataxia with mild cerebellar atrophy alone as an additional clinical presentation of ATP1A3-related neurological disorders.
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Ataxia Cerebelosa/genética , ATPasa Intercambiadora de Sodio-Potasio/genética , Adolescente , Atrofia/patología , Ataxia Cerebelosa/patología , Ataxia Cerebelosa/fisiopatología , Corteza Cerebelosa/diagnóstico por imagen , Corteza Cerebelosa/patología , Niño , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Fenotipo , Secuenciación del ExomaRESUMEN
Down Syndrome is a chromosomal disorder that affects the development of cerebellar cortical lobules. Impaired neurogenesis in the cerebellum varies among different types of neuronal cells and neuronal layers. In this study, we developed an imaging analysis framework that utilizes gadolinium-enhanced ex vivo mouse brain MRI. We extracted the middle Purkinje layer of the mouse cerebellar cortex, enabling the estimation of the volume, thickness, and surface area of the entire cerebellar cortex, the internal granular layer, and the molecular layer in the Tc1 mouse model of Down Syndrome. The morphometric analysis of our method revealed that a larger proportion of the cerebellar thinning in this model of Down Syndrome resided in the inner granule cell layer, while a larger proportion of the surface area shrinkage was in the molecular layer.
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Corteza Cerebelosa/diagnóstico por imagen , Corteza Cerebelosa/patología , Síndrome de Down/diagnóstico por imagen , Síndrome de Down/patología , Imagen por Resonancia Magnética/métodos , Neuronas/patología , Animales , Medios de Contraste , Modelos Animales de Enfermedad , Gadolinio/administración & dosificación , Aumento de la Imagen/métodos , Masculino , Ratones Endogámicos C57BL , Coloración y Etiquetado/métodosRESUMEN
Visualization and characterization of [Formula: see text]-amyloid deposits is a fundamental task in pre-clinical study of Alzheimer's disease (AD) to assess its evolution and monitor the efficiency of new therapeutic strategies. While the cerebellum is one of the brain areas most underestimated in the context of AD, renewed interest in cerebellar lesions has recently arisen as they may link to motor and cognitive alterations. Thus, we quantitatively investigated three-dimensional plaque morphology in the cerebellum in APP/PS1 transgenic mouse, as a model of AD. In order to obtain a complete high-resolution three-dimensional view of the investigated tissue, we exploited synchrotron X-ray phase contrast tomography (XPCT), providing virtual slices with histology-matching resolution. We found the formation of plaques elongated in shape, and with a specific orientation in space depending on the investigated region of the cerebellar cortex. Remarkably, a similar shape is observed in human cerebellum from demented patients. Our findings demonstrate the capability of XPCT in volumetric quantification, supporting the current knowledge about plaque morphology in the cerebellum and the fundamental role of the surrounding tissue in driving their evolution. A good correlation with the human neuropathology is also reported.
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Enfermedad de Alzheimer/diagnóstico , Corteza Cerebelosa/patología , Imagenología Tridimensional , Placa Amiloide/diagnóstico , Anciano de 80 o más Años , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Precursor de Proteína beta-Amiloide/genética , Animales , Corteza Cerebelosa/diagnóstico por imagen , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Ratones , Ratones Transgénicos , Placa Amiloide/genética , Placa Amiloide/patología , Presenilina-1/genética , Radiografía , Sincrotrones , Tomografía Computarizada por Rayos X/instrumentación , Tomografía Computarizada por Rayos X/métodosRESUMEN
The surface of the human cerebellar cortex is much more tightly folded than the cerebral cortex. It was computationally reconstructed for the first time to the level of all individual folia from multicontrast high-resolution postmortem MRI scans. Its total shrinkage-corrected surface area (1,590 cm2) was larger than expected or previously reported, equal to 78% of the total surface area of the human neocortex. The unfolded and flattened surface comprised a narrow strip 10 cm wide but almost 1 m long. By applying the same methods to the neocortex and cerebellum of the macaque monkey, we found that its cerebellum was relatively much smaller, approximately 33% of the total surface area of its neocortex. This suggests a prominent role for the cerebellum in the evolution of distinctively human behaviors and cognition.
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Cerebelo/anatomía & histología , Neocórtex/anatomía & histología , Animales , Corteza Cerebelosa/anatomía & histología , Corteza Cerebelosa/diagnóstico por imagen , Cerebelo/diagnóstico por imagen , Humanos , Procesamiento de Imagen Asistido por Computador , Macaca , Imagen por Resonancia Magnética , Neocórtex/diagnóstico por imagenRESUMEN
Niemann-Pick Type C (NPC) is a rare genetic disorder characterized by progressive cell death in various tissues, particularly in the cerebellar Purkinje cells, with no known cure. Mouse models for human NPC have been generated and characterized histologically, behaviorally, and using longitudinal magnetic resonance imaging (MRI). Previous imaging studies revealed significant brain volume differences between mutant and wild-type animals, but stopped short of making volumetric comparisons of the cerebellar sub-regions. In this study, we present longitudinal manganese-enhanced MRI (MEMRI) data from cohorts of wild-type, heterozygote carrier, and homozygote mutant NPC mice, as well as deformation-based morphometry (DBM) driven brain volume comparisons across genotypes, including the cerebellar cortex, white matter, and nuclei. We also present the first comparisons of MEMRI signal intensities, reflecting brain and cerebellum sub-regional Mn2+-uptake over time and across genotypes.
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Encéfalo/diagnóstico por imagen , Medios de Contraste , Imagen por Resonancia Magnética/métodos , Manganeso , Enfermedad de Niemann-Pick Tipo C/diagnóstico por imagen , Algoritmos , Animales , Corteza Cerebelosa/diagnóstico por imagen , Núcleos Cerebelosos/diagnóstico por imagen , Genotipo , Heterocigoto , Manganeso/farmacocinética , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Enfermedad de Niemann-Pick Tipo C/genética , Sustancia Blanca/diagnóstico por imagenRESUMEN
Most of the studies employing neuroimaging have focused on cortical and subcortical signals individually to obtain neurophysiological signatures of cognitive functions. However, understanding the dynamic communication between the cortex and subcortical structures is essential for unraveling the neural correlates of cognition. In this quest, magnetoencephalography (MEG) and electroencephalography (EEG) are the methods of choice because they are noninvasive electrophysiological recording techniques with high temporal resolution. Sophisticated MEG/EEG source estimation techniques and network analysis methods, developed recently, can provide a more comprehensive understanding of the neurophysiological mechanisms of fundamental cognitive processes. Used together with noninvasive modulation of cortical-subcortical communication, these approaches may open up new possibilities for expanding the repertoire of noninvasive cognitive neurotechnology.
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Mapeo Encefálico , Encéfalo/fisiología , Corteza Cerebelosa/fisiología , Cognición/fisiología , Encéfalo/diagnóstico por imagen , Corteza Cerebelosa/diagnóstico por imagen , Electroencefalografía , Humanos , MagnetoencefalografíaRESUMEN
Electrophysiological signals from the cerebellum have traditionally been viewed as inaccessible to magnetoencephalography (MEG) and electroencephalography (EEG). Here, we challenge this position by investigating the ability of MEG and EEG to detect cerebellar activity using a model that employs a high-resolution tessellation of the cerebellar cortex. The tessellation was constructed from repetitive high-field (9.4T) structural magnetic resonance imaging (MRI) of an ex vivo human cerebellum. A boundary-element forward model was then used to simulate the M/EEG signals resulting from neural activity in the cerebellar cortex. Despite significant signal cancelation due to the highly convoluted cerebellar cortex, we found that the cerebellar signal was on average only 30-60% weaker than the cortical signal. We also made detailed M/EEG sensitivity maps and found that MEG and EEG have highly complementary sensitivity distributions over the cerebellar cortex. Based on previous fMRI studies combined with our M/EEG sensitivity maps, we discuss experimental paradigms that are likely to offer high M/EEG sensitivity to cerebellar activity. Taken together, these results show that cerebellar activity should be clearly detectable by current M/EEG systems with an appropriate experimental setup.
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Corteza Cerebelosa/fisiología , Electroencefalografía/métodos , Magnetoencefalografía/métodos , Modelos Teóricos , Corteza Cerebelosa/anatomía & histología , Corteza Cerebelosa/diagnóstico por imagen , Simulación por Computador , Electroencefalografía/normas , Humanos , Imagen por Resonancia Magnética , Magnetoencefalografía/normas , Estimulación Magnética TranscranealRESUMEN
Angelman syndrome (AS) is an incurable neurodevelopmental disease caused by loss of function of the maternally inherited UBE3A gene. AS is characterized by a defined set of symptoms, namely severe developmental delay, speech impairment, uncontrolled laughter, and ataxia. Current understanding of the pathophysiology of AS relies mostly on studies using the murine model of the disease, although alternative models based on patient-derived stem cells are now emerging. Here, we summarize the literature of the last decade concerning the three major brain areas that have been the subject of study in the context of AS: hippocampus, cortex, and the cerebellum. Our comprehensive analysis highlights the major phenotypes ascribed to the different brain areas. Moreover, we also discuss the major drawbacks of current models and point out future directions for research in the context of AS, which will hopefully lead us to an effective treatment of this condition in humans.