RESUMEN
BACKGROUND AND PURPOSE: dVRS have been previously associated with aging and cerebrovascular diseases. However, little is known about their prevalence and topographic distribution in the general elderly population. MATERIALS AND METHODS: dVRS were evaluated by using high-resolution 3D MR imaging in 1826 subjects enrolled in the 3C-Dijon MR imaging study. On T1-weighted MR imaging, dVRS were detected according to 3D imaging criteria and rated by using 4-level severity scores based in the BG or in the WM. The number and anatomic location of large dVRS (≥3 mm) were recorded. RESULTS: dVRS were observed in the BG or WM in every subject. The severity of dVRS was significantly associated with higher age in both the BG and WM, whereas sex was related to the severity of dVRS only in the BG. Large dVRS were detected in 33.2% of participants. Status cribrosum was found in 1.3% of participants. dVRS were also highly prevalent within the hippocampus (44.5%) and hypothalamus (11.6%). CONCLUSIONS: dVRS are always detected in the BG or WM in elderly people, and large dVRS are also prevalent. The topographic distribution of dVRS is not uniform within the brain and may depend on anatomic or pathologic characteristics interacting with aging and sex.
Asunto(s)
Envejecimiento/patología , Enfermedad Cerebrovascular de los Ganglios Basales/patología , Imagenología Tridimensional , Leucoencefalopatías/patología , Imagen por Resonancia Magnética/métodos , Anciano , Ganglios Basales/patología , Enfermedad Cerebrovascular de los Ganglios Basales/epidemiología , Femenino , Hipocampo/patología , Humanos , Hipotálamo/patología , Leucoencefalopatías/epidemiología , Imagen por Resonancia Magnética/normas , Masculino , Prevalencia , Valores de Referencia , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a dominantly inherited small artery disease that leads to dementia and disability in mid-life. The clinical presentation of CADASIL is variable between and within affected families and is characterized by symptoms including migraine with aura, subcortical ischemic events, mood disturbances, apathy, and cognitive impairment. The mean age at onset of symptoms is 45 years, with variable duration of the disease ranging from 10 to 40 years. In 1996, linkage studies mapped and identified mutations in the NOTCH3 gene on chromosome 19 as causative in CADASIL. Head magnetic resonance imaging (MRI) is always abnormal in participants with NOTCH3 mutations after age 35. Magnetic resonance imaging shows on T2-weighted images or fluid attenuation inversion recovery (FLAIR) sequence, widespread areas of increased signal in the white matter associated with focal hyperintensities in basal ganglia, thalamus, and brainstem. The pathologic hallmark of CADASIL is the presence of electron-dense granules in the media of arterioles that can be identified by electron microscopic evaluation of skin biopsies.
Asunto(s)
Encéfalo/patología , CADASIL/genética , CADASIL/patología , Receptores Notch/genética , Afecto , Factores de Edad , Edad de Inicio , Ganglios Basales/patología , Tronco Encefálico/patología , CADASIL/diagnóstico , CADASIL/fisiopatología , CADASIL/psicología , Cromosomas Humanos Par 19/genética , Cognición , Asesoramiento Genético , Humanos , Ataque Isquémico Transitorio/genética , Imagen por Resonancia Magnética , Migraña con Aura/genética , Actividad Motora , Mutación , Receptor Notch3 , Accidente Cerebrovascular/genética , Tálamo/patologíaRESUMEN
BACKGROUND: Cerebral infarcts are responsible for functional alterations and microscopic tissue damage at distance from the ischaemic area. Such remote effects have been involved in stroke recovery. Thalamic hypometabolism is related to motor recovery in middle cerebral artery (MCA) infarcts but little is known concerning the tissue changes underlying these metabolic changes. Diffusion tensor imaging (DTI) is highly sensitive to microstructural tissue alterations and can be used to quantify in vivo the longitudinal microscopic tissue changes occurring in the thalamus after MCA infarcts in humans. METHODS: Nine patients underwent DTI after an isolated MCA infarct. Mean diffusivity (MD), fractional anisotropy (FA), and thalamic region volume were measured from the first week to the sixth month after stroke onset in these patients and in 10 age matched controls. RESULTS: MD significantly increased in the ipsilateral thalamus between the first and the sixth month (0.766 x 10(-3) mm(2)/s first month; 0.792 x 10(-3) mm(2)/s third month; 0.806 x 10(-3) mm(2)/s sixth month). No significant modification of FA was detected. In six patients, the ipsilateral/contralateral index of MD was higher than the upper limit of the 95% CI calculated in 10 age matched controls. An early decrease of MD preceded the increase of ipsilateral thalamic diffusion in one patient at the first week and in two other patients at the first month. CONCLUSION: After MCA infarcts, an increase in diffusion is observed with DTI in the ipsilateral thalamus later than 1 month after the stroke onset. This is presumably because of the progressive loss of neurons and/or glial cells. In some patients, this increase is preceded by a transient decrease in diffusion possibly related to an early swelling of these cells or to microglial activation. Further studies in larger series are needed to assess the clinical correlates of these findings.
Asunto(s)
Infarto de la Arteria Cerebral Media/complicaciones , Infarto de la Arteria Cerebral Media/patología , Tálamo/patología , Adulto , Anciano , Imagen de Difusión por Resonancia Magnética , Progresión de la Enfermedad , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Neuroglía/patologíaRESUMEN
BACKGROUND AND PURPOSE: In cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), water diffusion changes suggestive of microstructural tissue alterations have been recently reported in abnormal- and normal-appearing white matter as seen on T2-weighted images. In the subcortical gray matter, typical lacunar infarcts are repeatedly observed. Whether microstructural tissue changes are also present outside these lesions within the putamen or thalamus remains unknown. METHODS: We used diffusion tensor imaging, an MRI method highly sensitive to cerebral microstructure, in 20 CADASIL patients and 12 controls. Both the trace of the diffusion tensor [Tr(D)] and an anisotropic diffusion index (volume ratio) of diffusion were measured within the putamen and thalamus outside typical lacunar infarcts as detected on both T1- and T2-weighted images. RESULTS: A significant increase in Tr(D) and a decrease in anisotropy were observed in the putamen and thalamus in patients. The right/left indices of Tr(D) in the thalamus, but not in the putamen, were strongly correlated with the corresponding indices calculated in the white matter of the centrum semiovale. In addition, the diffusion increase in the thalamus was positively correlated with Tr(D) and with the load of small deep infarcts within the white matter and negatively correlated with the Mini-Mental State Examination score. CONCLUSIONS: Our results suggest that microstructural tissue alterations are present in the putamen and thalamus, outside the typical lacunar infarcts in CADASIL. In the thalamus, these microstructural changes appear constant and are even observed in asymptomatic subjects. Some of these thalamic changes appear to result from degeneration of thalamocortical pathways secondary to ischemic white matter damage. The importance of this degenerative phenomenon in the pathophysiology of CADASIL requires further investigation.
Asunto(s)
Demencia por Múltiples Infartos/diagnóstico , Imagen por Resonancia Magnética/métodos , Putamen/patología , Receptores de Superficie Celular , Tálamo/patología , Análisis de Varianza , Anisotropía , Infarto Cerebral/complicaciones , Infarto Cerebral/diagnóstico , Demencia por Múltiples Infartos/complicaciones , Demencia por Múltiples Infartos/genética , Difusión , Humanos , Persona de Mediana Edad , Fibras Nerviosas Mielínicas/patología , Pruebas Neuropsicológicas , Proteínas Proto-Oncogénicas/genéticaRESUMEN
CADASIL, a recently identified autosomal dominant condition characterized by the recurrence of subcortical infarcts leading to dementia, was previously mapped to chromosome 19p13.1 within a 2-cM interval, D19S226-D19S199. No recombination event was observed with D19S841, a highly polymorphic microsatellite marker isolated from a cosmid mapped to this region. We recently identified within this cosmid a conserved sequence that we used to screen a fetal brain cDNA library and isolated an ubiquitous and abundantly transcribed gene. We did not detect any mutation of this gene in CADASIL patients, suggesting that it is not implicated in this disorder. Interestingly, this gene encodes a putative protein homologous to several thiamine pyrophosphate-binding proteins previously identified in bacteria, yeast, and plants. The proteins with the highest degree of similarity were the acetolactate synthase enzymes which, in prokaryotes, are involved in the branched chain amino acid biosynthetic pathway, raising fascinating questions on the yet unknown function of this gene in mammals.
Asunto(s)
Acetolactato Sintasa/genética , Enfermedades Arteriales Cerebrales/genética , Demencia por Múltiples Infartos/genética , Leucoencefalopatía Multifocal Progresiva/genética , Secuencia de Aminoácidos , Animales , Proteínas Bacterianas/genética , Secuencia de Bases , Mapeo Cromosómico , ADN Complementario , Humanos , Datos de Secuencia Molecular , Mutagénesis , Homología de Secuencia de AminoácidoRESUMEN
In 8 patients with small unilateral posterolateral thalamic (or, in one case, thalamocapsular) stroke (infarction or hemorrhage) selected on strict clinical (pure hemisomatosensory deficit without hemiparesis, visual field defect or neuropsychological impairment) and MRI criteria, we studied cortical energy metabolism using positron emission tomography with the 18F-fluorodeoxyglucose or the 15O-oxygen method. We found no significant ipsi- or contra-lateral metabolic depression either in the whole cortical mantle or in the sensorimotor cortex. These results support the hypothesis that location of thalamic stroke is a major determinant of the ipsilateral cortical hypometabolism characteristic of cognitively impaired patients with thalamic lesions and further emphasize the influence of the "non-specific" thalamocortical system on resting cortical metabolism. The lack of sensorimotor cortex hypometabolism in our patients suffering from hemidysesthesia and/or -hyperpathia also suggests that cortical metabolism is unaltered in thalamic pain.