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Biomedical subjects

Hugues Chabriat

Publications and source records attributed to Hugues Chabriat.

At least 19 recordsLinked to original sources
PubMed2007

Risk of rapid global functional decline in elderly patients with severe cerebral age-related white matter changes: the LADIS study.

BACKGROUND: Age-related white matter changes (ARWMCs), frequently detected on neuroimaging, are associated with motor, cognitive, urinary, and mood disorders. The LADIS (LeukoAraiosis and DISability) Study primarily aims to assess ARWMCs as a determinant of global functional decline in the elderly population. METHODS: We enrolled 639 patients (mean age, 74.1 +/- 5.0 years; 45.1% male) referred for nondisabling complaints, who had ARWMCs detected on brain magnetic resonance imaging (MRI) of mild, moderate, or severe grade according to the Fazekas scale. At the 1-year follow-up, 619 were reassessed using the Instrumental Activities of Daily Living (IADL) scale. Of these, 506 were totally independent at baseline, and 113 were impaired in only 1 item of the IADL scale. We studied the 1-year transition to 2 or more activities limited and selective functional impairments as cofactors of functional decline. RESULTS: The rate of transition was 9%, 15%, and 26%, in the mild, moderate, and severe ARWMC group, respectively. Comparing the severe with the mild ARWMC groups and adjusting for age and for other predictors of decline, the risk was more than 2-fold higher (odds ratio; 2.38; 95% confidence interval, 1.29-4.38) in patients with 0 or 1 activity limited, and 3-fold higher (odds ratio, 3.02; 95% confidence interval, 1.34-6.78) among patients fully independent at baseline. Both motor and cognitive deterioration predominantly explained the effect of ARWMCs on global functional decline. CONCLUSION: Elderly patients who are functionally independent and who have severe ARWMCs are at considerable risk of becoming more dependent in a short period, mostly owing to motor and cognitive deterioration.

Aged↗
PubMed2006

Cortical neuronal apoptosis in CADASIL.

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations of the NOTCH3 gene and is a model of pure vascular dementia. Cortical atrophy has been reported to be associated with cognitive decline in the disease, although the underlying mechanism is unknown. We postulated that apoptosis may be involved in this process. METHODS: We report the clinical history, magnetic resonance imaging findings, and pathologic examinations of 4 patients (2 of whom were demented) who died from complications of the disease. Apoptosis was evaluated in brain tissue using antibodies against activated caspase3 and in situ end labeling assays for DNA fragmentation. RESULTS: Widespread neuronal apoptosis in the cerebral cortex (predominantly in layers 3 and 5) was observed in all patients. This was not seen in 3 non-CADASIL controls. Semiquantitative analysis suggested that apoptosis was more extensive in the presence of larger load of subcortical ischemic lesions and smaller brain volumes. CONCLUSIONS: Neuronal apoptosis may be involved in cortical atrophy in CADASIL and appears related to the burden of subcortical ischemic lesions. These findings may have important implications in other small vessel diseases and may provide a potential target for future therapeutic interventions.

Adult↗
PubMed2006

Blood pressure and haemoglobin A1c are associated with microhaemorrhage in CADASIL: a two-centre cohort study.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a hereditary arteriopathy caused by mutations of the Notch3 gene. The risk factors for cerebral microhaemorrhages (CM), their relationship to other MRI lesions in the disease and their potential clinical impact have not been previously defined. Our purpose was to examine the frequency, number and location of microhaemorrhages in a multicentre cohort study, defining predisposing factors and associated radiographic markers in CADASIL patients. We collected clinical data from 147 consecutive patients enrolled in an ongoing prospective cohort study. Degree of neurological disability and cognitive impairment were assessed by standardized scales. T(1)-weighted, FLAIR and T2*-weighted gradient-echo (GE) MRI sequences were performed. Volume and location of lacunar infarcts and white matter hyperintensity (WMH) were assessed. Number and location of CM were recorded. CM were present in 35% patients, most commonly occurring in the thalamus, brainstem and basal ganglia. The location of CM qualitatively differed from areas of lacunar infarction and WMH. There was a significant association between the presence of CM and a history of hypertension (P = 0.005), systolic blood pressure (SBP) (P = 0.014), haemoglobin A1c (HbA1c) (P = 0.004) and the volume of lacunar infarcts (P = 0.010) and WMHs (P = 0.046). The number of CM was independently associated with SBP (P = 0.005), the diagnosis of hypertension (P = 0.0004), volume of WMH (P = 0.0005) and lacunar infarcts (P = 0.004). In contrast, no association was found between blood pressure or HbA1c and the load of WMH or lacunar infarcts. The presence of CM was independently associated with increased modified Rankin scores. CM are independently associated with blood pressure and HbA1c as well as with lacunar infarct and WMH volume in CADASIL. Both the vascular risk factors and regional distribution of CM appear distinct from those associated with other MRI markers, suggesting a distinct pathological process. These lesions have a potential clinical impact in CADASIL. These findings further suggest that modulation of blood pressure and glucose levels might influence the course of the disease.

Adult↗
PubMed2006

Characteristic features of in vivo skin microvascular reactivity in CADASIL.

CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is caused by mutations in the Notch3 receptor expressed at the surface of vascular smooth muscle cells. The functional consequences of the disease at the peripheral microcirculation level are incompletely elucidated. In this study, we aimed to assess, in vivo, the endothelium-dependent and independent vasodilation of the skin microvasculature in CADASIL patients. Twenty-three affected subjects were compared with 23 gender and age-matched controls. The brachial artery endothelium-dependent and endothelium-independent vasodilation were assessed after forearm cuff occlusion and nitroglycerin administration. Skin vasoreactivity to transcutaneous administration of acetylcholine and sodium nitroprussiate, and after postocclusive hyperemia were measured by Laser Doppler flowmetry. The maximum changes in the diameter of the brachial artery after the cuff release or after nitroglycerin administration did not differ between patients and controls. With iontopheresis, only the peak value of the dose response was found decreased in normocholesterolemic patients after nitroprussiate administration. The postocclusive test revealed a large increase of the time to peak value and whole duration of the hyperemic response in CADASIL patients. The results of this study show that the skin vasoreactivity is altered in CADASIL. Particularly, the kinetics of reactive hyperemia after cuff occlusion is dramatically changed with a lengthened and delayed response. This characteristic pattern may be related to the specific ultrastructural modifications related to Notch3 gene mutations involving smooth muscle cells in the microvasculature.

Adult↗
PubMed2006

Electrocardiogram in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy patients without any clinical evidence of coronary artery disease: a case-control study.

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited systemic arteriopathy caused by highly stereotyped mutations in NOTCH3. The clinical expression of CADASIL is confined to the central nervous system with characteristic recurrent subcortical infarcts and vascular dementia. However, cases have been reported with associated circulatory small vessel abnormalities in the retina or the myocardium and with myocardial infarction. Classical cardiovascular risk factors may influence such circulatory abnormalities. Thus, we conducted a case control study to determine the frequency of electrical abnormalities on a 12-lead resting ECG in CADASIL patients without classical atherosclerotic risk factors. METHODS: Twenty-three CADASIL patients (mean age+/-SD; 55.1+/-11 years) free of any classical cardiovascular risk factors except for hypercholesterolemia were recruited from 1 neurology department and compared with 23 sex- and age-matched healthy controls (mean age+/-SD; 54.7+/-9.5 years). A resting supine 12-lead ECG was recorded at inclusion and analyzed later by 2 reviewers. Signs of myocardial infarction or ischemia, conduction, and rhythm disturbances were looked for. RESULTS: We found no ECG sign evoking myocardial infarction or myocardial ischemia. CADASIL patients had, compared with healthy controls, a significantly higher heart rate and a significantly lower Sokolow index, but these values remained in the normal ranges. CONCLUSIONS: In this case-control study, we found no ECG evidence for myocardial infarction or ischemia, conduction disturbances, or arrhythmias in CADASIL patients compared with healthy controls.

Adult↗
PubMed2006

MRI of clot in cerebral venous thrombosis: high diagnostic value of susceptibility-weighted images.

BACKGROUND AND PURPOSE: In cerebral venous thrombosis (CVT), the sensitivity of conventional MRI sequences to detect clot in the sinuses or veins is incomplete and largely depends on the time elapsed since thrombus formation. Little is known concerning the corresponding diagnostic value of fluid-attenuated inversion recovery (FLAIR), echo-planar T2* susceptibility-weighted imaging (T2*SW) or diffusion-weighted images (DWI). METHODS: We performed a retrospective analysis of 114 MRI examinations from 39 patients with CVT using a structured assessment. The time course of sensitivity in the detection of clot (n=166 clots) was analyzed for different MR sequences using a multilevel logistic model. The sensitivity of different MR sequences for diagnosis of cortical venous thrombosis was tested separately (n=38 clots). RESULTS: The sensitivity of T2*SW and T1-weighted spin echo image (T1SE) sequences to detect clot in the sinuses or veins was estimated at 90% and 71% between day 1 and day 3, which was much higher than that of T2SE, FLAIR or DWI during the first week of clinical onset. The sensitivity of T2*SW was stable in the first week. After this period, the sensitivity of T2*SW decreased less than that of T1SE. Thrombosed cortical veins, even in the absence of visible occlusion on magnetic resonance venography, were detected more frequently with T2*SW (97%) and T1SE (78%) than with FLAIR or DWI (<40%). CONCLUSIONS: T2*SW imaging appears to be of additional diagnostic value in CVT. The T2*SW sequence may be particularly useful during the acute phase of CVT when the sensitivity of the other sequences is incomplete and for the diagnosis of isolated cortical venous thrombosis.

Adolescent↗
PubMed2006

Age, hypertension, and lacunar stroke are the major determinants of the severity of age-related white matter changes. The LADIS (Leukoaraiosis and Disability in the Elderly) Study.

BACKGROUND: Age-related white matter changes (ARWMC), seen on neuroimaging with high frequency in older people, are thought to be consequent to the effect of vascular risk factors and vascular diseases including hypertension and stroke. Among the proofs conventionally required for a factor to be considered a risk factor for a definite pathology, there is the demonstration of a trend in risk exposure related to disease severity. We sought whether such a trend existed in the association of vascular risk factors or comorbidities with the severity of ARWMC aiming particularly at further elucidating the relative roles of hypertension and stroke in this regard. METHODS: The LADIS (Leukoaraiosis and Disability) Study is evaluating the role of ARWMC as an independent determinant of the transition to disability in the elderly. Six hundred and thirty-nine nondisabled subjects (mean age 74.1+/-5.0, M/F: 288/351) with ARWMC of different severity grades on MRI (mild, moderate, or severe according to the Fazekas scale) were assessed at baseline for demographics, vascular risk factors, and comorbidities, and are being followed up for 3 years. RESULTS: Age, frequency of hypertension and history of stroke increased along with increasing ARWMC severity independently of other factors. For hypertension, however, this occurred only in subjects without a stroke history, while for stroke history, it mainly depended on lacunar stroke. The amount of cigarettes smoked and the interaction between hypercholesterolemia and smoking predicted only the most severe ARWMC grade. CONCLUSIONS: The LADIS Study confirms that age, hypertension and lacunar strokes are the major determinants of ARWMC. Smoking and hypercholesterolemia provide additional risk.

Age Factors↗
PubMed2006

Cerebral microhemorrhage.

BACKGROUND AND PURPOSE: With the advent of modern MRI imaging techniques, cerebral microhemorrhages have been increasingly recognized on gradient-echo (GE) or T2*-weighted MRI sequences in different populations. However, in clinical practice, their diagnostic value, associated risk, and prognostic significance are often unclear. This review summarizes the pathophysiology, differential diagnosis, epidemiology, and clinical significance of cerebral microhemorrhages. SUMMARY OF REVIEW: Focal areas of signal loss on GE MRI imaging pathologically represent focal hemosiderin deposition associated with previous hemorrhagic events. Cerebral microhemorrhages have been noted in healthy elderly, ischemic cerebrovascular disease, intracerebral hemorrhage (ICH), cerebral amyloid angiopathy (CAA), and in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Microhemorrhages have been associated with older age, hypertension, smoking, white matter disease, lacunar infarcts, previous ischemic stroke, or ICH. In CAA, microhemorrhages predict both the risk of recurrent lobar ICH and future clinical decline. In patients with ischemic cerebrovascular disease, microhemorrhage number and location may be associated with executive dysfunction and may predict the occurrence of ICH and lacunar infarction. CONCLUSIONS: When cerebral microhemorrhages are diagnosed on MRI, conclusions regarding their significance and associated risks should be made based on the population examined. Further studies to characterize the associated risks of cerebral microhemorrhages in different stroke populations are needed to use this new imaging marker in therapeutic decisions.

Aged↗
PubMed2006

A novel hereditary small vessel disease of the brain.

OBJECTIVE: Only few hereditary ischemic small vessel diseases of the brain (SVDB) have been reported so far. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most frequent of them. Herein, we report a family affected by a SVDB distinct from CADASIL. METHODS: After the occurrence of a small deep infarct associated with white matter lesions both in a 46-year-old man and in his 52-year-old sister, clinical and neuroimaging investigations were conducted in 13 of their relatives originating from Portugal. Other investigations included (1) skin biopsy immunostaining with a Notch3 monoclonal antibody, (2) sequencing of the 23 exons encoding the epidermal growth factor-like domains of the NOTCH3 gene, and (3) a NOTCH3 locus haplotype analysis. RESULTS: Diffuse white matter hyperintensities were observed on T2-weighted magnetic resonance imaging (MRI) in six individuals. In contrast with MRI results in the father and paternal uncle of the proband who were hypertensive, white matter lesions were extensive in the mother who had no vascular risk factor. MRI data in four asymptomatic family members together with the results in the two initial cases were suggestive of an underlying hereditary small vessel disease of the brain. Skin biopsy and NOTCH3 gene mutation screening were negative. Haplotype analysis excluded the NOTCH3 locus. INTERPRETATION: These data strongly suggest that this family is affected by a novel hereditary small vessel disease of the brain and that the mutated gene is distinct from NOTCH3.

Brain Ischemia↗
PubMed2006

Leukoaraiosis predicts hidden global functioning impairment in nondisabled older people: the LADIS (Leukoaraiosis and Disability in the Elderly) Study.

OBJECTIVES: To determine whether leukoaraiosis severity is independently associated with differences in global functioning in nondisabled elderly patients. DESIGN: Cross-sectional data analysis from an ongoing longitudinal multicenter and multinational study. SETTING: The Leukoaraiosis and Disability Study, a collaboration aimed at assessing leukoaraiosis as an independent predictor of the transition to disability in older people. PARTICIPANTS: Six hundred thirty-nine nondisabled subjects (288 men, 351 women, mean age+/-standard deviation 74.1+/-5.0) with magnetic resonance imaging-detected leukoaraiosis of different severity and presenting with one of the following: mild cognitive or motor disturbances, minor cerebrovascular events, or mood alterations or in whom leukoaraiosis was incidentally identified. MEASUREMENTS: Centralized assessment of leukoaraiosis severity according to the three severity degrees of the Fazekas scale; Disability Assessment for Dementia (DAD) Scale for measurement of global functioning. RESULTS: At baseline, 44% of participants had a mild, 31% a moderate, and 25% a severe degree of leukoaraiosis. A significant trend toward declining performance on the DAD Scale was apparent with increasing leukoaraiosis score severity (total score=98.8, 98.6, 97.5, respectively, in the three leukoaraiosis categories, analysis of variance P=.002). Similar trends were obtained for basic (P=.01) and instrumental (P<.001) function items. The statistical significance of these differences was confirmed in a multiple linear regression analysis correcting for numerous factors known to influence disability in older people. Executive function test performance declined along with increasing leukoaraiosis severity and was significantly related to DAD total score. CONCLUSION: Even in nondisabled elderly patients, levels of functional ability are related to white matter lesion severity. Executive dysfunction may mediate this relationship.

Activities of Daily Living↗
PubMed2006

Development of a neuropsychological battery for the Leukoaraiosis and Disability in the Elderly Study (LADIS): experience and baseline data.

The relationship between age-related white matter changes and cognitive performance in independent elderly people is still not clear. The Leukoaraiosis and Disability in the Elderly study (LADIS) involves 11 European centers. It aims to assess the role of the age-related white matter changes as an independent factor in the transition to disability, and in cognitive performance of an independent elderly population. A comprehensive neuropsychological battery was constructed in order to harmonize the cognitive assessment across countries. Patients were evaluated at baseline and during the 3-year follow-up with the Mini-Mental State Examination, a modified version of the VADAS-Cog (Alzheimer's Dementia Assessment Scale plus tests of Delayed recall, Symbol digit, Digit span, Maze, Digit cancellation and Verbal fluency), Trail making and Stroop test. Six hundred thirty-eight patients (mean age 74 +/- 5 years; mean educational level 10 +/- 4, F/M: 351/287) were included in this study. Neuropsychological data were analyzed test by test and also grouped in three compound measures (executive, memory and speed/motor control domains). Older subjects (>74 years) performed significantly worse than younger subjects on the ADAS-Mod and on the tests of memory (t(631) = 3.25; p = 0.001), executive functions (t(581) = 4.68; p = 0.001) and speed/motor control (t(587) = 4.01; p = 0.001). Participants with higher educational level (>8 years of school) showed better performances on the compound measures for memory (t(631) = 3.25; p = 0.001), executive functions (t(581) = 4.68; p = 0.001) and speed/motor control (t(587) = 4.01; p = 0.001). Using multiple regression analysis models to study the influence of demographic variables on cognitive performance, age and education remained important variables influencing test performance. In the LADIS population baseline data, older age and lower educational levels negatively influence neuropsychological performance.

Aged↗
PubMed2005

Shape and volume of lacunar infarcts: a 3D MRI study in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

BACKGROUND AND PURPOSE: The shape and exact size of lacunar infarcts have been investigated only postmortem. Recent imaging techniques based on triangulation and connectivity can now be used for 3D segmentation of cerebral lesions. The shape and size of lacunar infarcts was investigated using these techniques in 10 cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients. METHODS: We segmented 102 lacunar infarcts on T1-weighted images. The surface of the corresponding set of voxels was computed as a mesh of triangles. Thereafter, the shape of each lesion in 3D was visually analyzed by 2 investigators. RESULTS: The volume of lesions ranged from 10.5 to 1146 mm, with 93% of them having a volume <500 mm; 83% lacunar infarcts had a spheroid or ovoid shape, but 17% presented as sticks, slabs, or with a complex shape. Lesions with multiple components appeared larger than the others, and a tail extension was noticed in 13 of 102 lesions. CONCLUSIONS: These results suggest the following: (1) most lacunar infarcts in CADASIL have a volume far below one third of that of a sphere of 15 mm in diameter, the upper limit currently used for their identification on 2D imaging; (2) a significant proportion of lacunar infarcts have a shape distinct from the spheroid-ovoid morphology; and (3) lesions with a complex shape may result from the involvement of the largest small arteries, confluence of ischemic lesions, or secondary tissue degeneration. The segmentation of lacunar infarcts appears promising to better understand the pathophysiology of tissue lesions secondary to small vessel diseases.

Aged↗
PubMed2005

Longitudinal diffusion changes in cerebral hemispheres after MCA infarcts.

Diffusion tensor imaging can be used in vivo to assess the longitudinal and regional microstructural changes occurring after middle cerebral artery (MCA) infarcts in humans. Nine patients were investigated 1 week (D7), 1 (M1), 3 (M3), and 6 months (M6) after the occurrence of an isolated MCA infarction. First, an overall analysis was performed using histograms of mean diffusivity (MD) and fractional anisotropy (FA) in each hemisphere. Thereafter, the regional pattern of diffusion changes was investigated voxel by voxel with statistical parametric mapping 99. In the hemisphere ipsilateral to the infarction, histogram analysis revealed a significant decrease in FA between D7 and M6 associated with a progressive increase in MD from D7 to M3. Remote from the MCA territory, the voxel by voxel analyses detected a significant increase in MD within the thalamus at M3 and M6 and a reduction in FA along the pyramidal tract at M6. In the contralateral hemisphere, between D7 and M6, a significant hemispheric atrophy was observed in association with a global reduction in anisotropy, in the absence of distinctive regional diffusion changes. These results suggest that micro- and macrostructural tissue modifications can be detected with diffusion tensor imaging in regions remote from the ischemic area in both hemispheres.

Adult↗
PubMed2005

Impact of age-related cerebral white matter changes on the transition to disability -- the LADIS study: rationale, design and methodology.

Age-related white matter changes (ARWMC) on brain MRI have been associated with cognitive, motor, mood and urinary disturbances. These factors are known to contribute to disability in elderly people, but the impact of ARWMC and of their progression on the transition to disability is not determined. The LADIS (Leukoaraiosis and Disability in the Elderly) study aims at assessing the role of ARWMC as an independent predictor of the transition to disability in initially nondisabled elderly (65-84 years). Subjects who are not impaired or impaired on only 1 item of the Instrumental Activity of Daily Living (IADL) scale, presenting with different grades of ARWMC severity, were enrolled. Eleven European centers are involved. All the patients were assessed at baseline using an extensive set of clinical and functional tests including global functioning, cognitive, motor, psychiatric and quality of life measures. MRI studies were performed at baseline and will be repeated at the end of the follow-up period to evaluate changes of ARWMC and other lesions. ARWMC were categorized into mild, moderate or severe using the scale of Fazekas et al. For each ARWMC severity class, the primary study outcome is the transition to disability defined as an impairment on 2 or more IADL scale items. Secondary outcomes are the occurrence of dementia, depression, vascular events or death. Six-hundred and thirty-nine subjects (mean age 74.13 +/- 5.0 years, M/F: 288/351) were enrolled in a hospital-based setting and are being followed up for up to 3 years. The large and comprehensive set of measures in LADIS enables a comprehensive description of their functional and clinical features to be examined in relation to different morphological patterns and severity of ARWMC. The longitudinal design will give insight into the possible role of ARWMC and their progression as an independent contributor to disability in the elderly, eventually helping to develop preventive strategies to reduce the burden of disability in late life. The study results may also help to standardize, on an international basis, tools and criteria to identify early stages of disability.

Activities of Daily Living↗
PubMed2004

Migraine with aura and brain magnetic resonance imaging abnormalities in patients with CADASIL.

BACKGROUND: Migraine with aura (MA) is one of the clinical hallmarks of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a small vessel disease of the brain caused by mutations in the NOTCH3 gene, but its exact mechanisms are unknown. OBJECTIVES: To describe the patterns of MA in CADASIL and to compare brain magnetic resonance signal abnormalities between CADASIL patients with and without MA. DESIGN: Comparison of brain magnetic resonance signal abnormalities between cases and controls. SETTING: Patients with CADASIL seen at Lariboisière Hospital. PATIENTS: Forty-one CADASIL patients with MA and 31 age-matched CADASIL controls without MA. RESULTS: The mean age at onset of MA was significantly younger in women compared with men and occurred a mean of 15 years prior to stroke onset. A majority of patients (56%) reported at least 1 migraine attack with atypical aura. All CADASIL patients either with or without MA had white matter signal abnormalities on T2-weighted imaging. There was no difference in the frequency and distribution of brain signal abnormalities between CADASIL patients with and without MA. CONCLUSIONS: In CADASIL, MA is characterized by an unusually high frequency of attacks of migraine with atypical aura. The distribution and extent of magnetic resonance signal abnormalities did not differ according to migraine phenotype.

Adult↗