on behalf of the DECIMAL InvestigatorsBackground and Purpose-There is no effective medical treatment of malignant middle cerebral artery (MCA) infarction.The purpose of this clinical trial was to assess the efficacy of early decompressive craniectomy in patients with malignant MCA infarction. Methods-We conducted in France a multicenter, randomized trial involving patients between 18 and 55 years of age with malignant MCA infarction to compare functional outcomes with or without decompressive craniectomy. A sequential, single-blind, triangular design was used to compare the rate of development of moderate disability (modified Rankin scale score Յ3) at 6 months' follow-up (primary outcome) between the 2 treatment groups. Results-After randomization of 38 patients, the data safety monitoring committee recommended stopping the trial because of slow recruitment and organizing a pooled analysis of individual data from this trial and the 2 other ongoing European trials of decompressive craniectomy in malignant MCA infarction. Among the 38 patients randomized, the proportion of patients with a modified Rankin scale score Յ3 at the 6-month and 1-year follow-up was 25% and 50%, respectively, in the surgery group compared with 5.6% and 22.2%, respectively, in the no-surgery group (Pϭ0.18 and Pϭ0.10, respectively). There was a 52.8% absolute reduction of death after craniectomy compared with medical therapy only (PϽ0.0001). Conclusions-In this trial, early decompressive craniectomy increased by more than half the number of patients with moderate disability and very significantly reduced (by more than half) the mortality rate compared with that after medical therapy.
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.
Background and Purpose-Cerebral atrophy has been recently recognized as a key marker of disease progression in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The contribution of subcortical cerebral lesions in this process remains undetermined. The aim of this study was to investigate the relationships between cerebral volume and different types of subcortical MRI lesions in CADASIL. Methods-Demographic, clinical, and laboratory data from 147 patients with CADASIL recruited from a prospective cohort study were analyzed. Validated methods were used to determine the ratio of brain volume to intracranial cavity volume (brain parenchymal fraction [BPF]), volume of white matter hyperintensities, volume of lacunar lesions, number of cerebral microhemorrhages, and mean apparent diffusion coefficient. Associations between BPF, clinical scales, and the different subcortical MRI markers were tested. Results-BPF obtained in 129 patients was significantly associated with the Mattis dementia rating scale (PϽ0.0001), Mini-Mental State Examination (Pϭ0.002), and modified Rankin scale (PϽ0.0001) after adjustment for age and sex. Multiple linear regression modeling showed that BPF was independently associated with mean apparent diffusion coefficient (PϽ0.0001), volume of lacunar lesions (Pϭ0.004), and age (PϽ0.0001), accounting for 46% of the observed variance in BPF but not with volume of white matter hyperintensities or number of microhemorrhages. Conclusions-In association with age, mean apparent diffusion coefficient and volume of lacunar lesions are strong and independent MRI predictors of BPF, a key marker of cognitive and motor disability in CADASIL. These results suggest brain atrophy is related to remote and/or diffuse consequences of both lacunar lesions and widespread microstructural alterations within the brain outside lacunar lesions.
The results of this study support the role of a conservative "wait-and-scan" policy of management for small-sized VSs because most have a slow growth rate. Long-term neuroimaging follow-up is needed even with non-growing tumors.
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