Brain volume changes in CADASIL

Peters, Nils; Holtmannspötter, Markus; Opherk, Christian; Gschwendtner, Andreas; Herzog, Jürgen; Sämann, Philipp G.; Dichgans, Martin

doi:10.1212/01.wnl.0000216271.96364.50

Cited by 123 publications

(129 citation statements)

References 31 publications

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“…In contrast, age, male sex, and the volume of lacunar infarcts were found to be predictors of brain atrophy in line with results previously obtained in smaller samples of patients. 12,13 In the multivariate analysis, removing of confounders one by one showed that the positive association between brain parenchymal fraction and WMH remained unchanged as long as age was maintained in the model. This association is modest but highly significant and probably hidden at the crosssectional level by the strong but inverse effect of age on brain volume.…”

Section: Discussionmentioning

confidence: 98%

Extensive White Matter Hyperintensities May Increase Brain Volume in Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

Yao

Jouvent

Düring

et al. 2012

Stroke

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The main clinical manifestations of the disease include attacks of migraine with aura, mood disturbances, recurrent ischemic stroke, apathy, and progressive cognitive decline. 2 MRI features in CADASIL include confluent white matter hyperintensities (WMH), lacunar infarctions, and cerebral microbleeds. [3][4][5] Patients with CADASIL can also present with a large number of dilated Virchow-Robin spaces, mostly located in the lentiform nuclei and within the subcortical white matter. 6 Extensive WMH are observed in the centrum semiovale and periventricular areas in all symptomatic patients. They are also detected in more than two thirds of patients with CADASIL in the anterior part of the temporal lobes. It is noteworthy that WMH in this region are associated with punctiform hypointensities on fluid-attenuated inversion recovery images mainly at the frontiers between the cortical ribbon and the underlying white-matter. 5 This highly specific aspect is presumably related to the accumulation of dilated Virchow-Robin spaces. 7 Postmortem data recently showed that dilated Virchow-Robin spaces and degeneration of myelin are the 2 main pathological lesions underlying WMH in the temporal lobes. 7 These lesions are possibly related to insufficient drainage of the interstitial fluid accumulating in the cerebral tissue secondary to blood-brain barrier dysfunction and vessel wall changes. In other cerebral regions where focal ischemic lesions are detected, axonal loss with demyelination is the most prominent feature within WMH and is associated Background and Purpose-The extent of white matter hyperintensities (WMH) is associated with cerebral atrophy in elderly people. WMH is a radiological hallmark of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), but their relationship with brain volume remains poorly understood. The association between WMH and brain volume was analyzed in a large population of patients with CADASIL. Methods-Demographic and MRI data of 278 patients recruited from a prospective cohort study were analyzed. Volumes of WMH and lacunar infarcts, number of cerebral microbleeds, and brain parenchymal fraction were measured. Multivariate analysis was used to study the impact of WMH on brain volume at baseline. Results-In univariate analyses, brain parenchymal fraction was negatively associated with age, male sex, and all MRI markers. Multiple regression modeling showed that brain parenchymal fraction was inversely related to age, number of cerebral microbleeds, and normalized volume of lacunar infarcts but positively related to normalized volume of WMH (P<0.001). This positive relationship was independent of the presence/absence of lacunar infarcts or of cerebral microbleeds. Subgroup analysis showed that this association was significant in subjects having normalized volume of WMH ≥6.13 or brain parenchymal fraction ≥86.37% (median values, both P≤0.001). At the macroscopic level, these different pathophysiological mechanisms may have opposite consequences on t...

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Section: Discussionmentioning

confidence: 98%

Extensive White Matter Hyperintensities May Increase Brain Volume in Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

Yao

Jouvent

Düring

et al. 2012

Stroke

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“…2,11 Brain parenchymal fraction (BPF), defined as the ratio of brain volume to the intracranial cavity volume, and the volume of lacunes were determined from the 3D-T1 sequence in all subjects. 12 Masks of lacunes were obtained manually by a trained rater. Hypointense lesions with a signal identical to that of CSF, sharp delineation, and a diameter of Ͼ2 mm were selected for this segmentation.…”

Section: Neuropsychological Assessmentmentioning

confidence: 99%

Reaction Time Is Negatively Associated with Corpus Callosum Area in the Early Stages of CADASIL

Delorme

Guio

Reyes

et al. 2017

AJNR Am J Neuroradiol

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BACKGROUND AND PURPOSE:Reaction time was recently recognized as a marker of subtle cognitive and behavioral alterations in the early clinical stages of CADASIL, a monogenic cerebral small-vessel disease. In unselected patients with CADASIL, brain atrophy and lacunes are the main imaging correlates of disease severity, but MR imaging correlates of reaction time in mildly affected patients are unknown. We hypothesized that reaction time is independently associated with the corpus callosum area in the early clinical stages of CADASIL.

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“…In the future, neurobiological markers of early injury will probably be used in studies trying to influence the onset and progression of clinical changes; this should help reducing the number of patients needed in therapeutic studies. The search for these markers in MR studies involving analysis of the patterns of appearance and progression of atrophy and accumulation of white matter lesions and other typical structural changes is under way, as well as analyses of diffusion histograms and metabolic relations as assessed by spectroscopy 89,[132][133][134][135] . The main marker of disease progression is, unfortunately, increasing age, which can be seen as a non modifiable risk factor.…”

Section: Treatment Of Cadasilmentioning

confidence: 99%

CADASIL: pathogenesis, clinical and radiological findings and treatment

André

2010

Arq. Neuro-Psiquiatr.

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Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common genetic cause of ischemic strokes and a most important model for the study of subcortical vascular dementia. This unrelentlessly progressive disease affects many hundreds of families all over the world but is not well studied in Brazil. This manuscript reviews pathogenetic, clinical, radiological and therapeutic features of CADASIL. The causal mutations are now very well known, but the same can not be said about its intimate pathogenetic mechanisms. The variable clinical presentation should lead physicians to actively pursue the diagnosis in many settings and to more thouroughly investigate family history in first degree relatives. A rational approach to genetic testing is however needed. Treatment of CADASIL is still largely empiric. Highquality therapeutic studies involving medications and cognitive interventions are strongly needed in CADASIL. Key words: CADASIL, etiology, genetics, diagnosis, therapeutics.cADAsIL: patogênese, achados clínicos e radiológicos e tratamento resumo CADASIL é a causa genética mais freqüente de infartos cerebrais e constitui modelo importante de estudo de demências vasculares subcorticais. De natureza inexoravelmente progressiva, afeta milhares de pessoas em todo o mundo. Sua importância é pouco reconhecida entre nós, o que nos levou à presente revisão dos principais aspectos patogenéticos, clínicos, neuroradiológicos e terapêuticos da doença. As mutações causais são hoje bem conhecidas, mas os mecanismos patogenéticos íntimos ainda permanecem misteriosos. A apresentação clínica variável deve fazer com que os médicos considerem o diagnóstico em vários contextos clínicos e investiguem de forma mais extensa que o usual a história familial deparentes de primeiro grau. Além disso, uma abordagem racional é necessária para reduzir custos e aumentar a eficiência do diagnóstico genético. O tratamento atual de pacientes com CADASIL é basicamente empírico. Estudos clínicos sobre medicamentos e intervenções cognitivas de alto nível metodológico constituem uma necessidade urgente.

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Brain volume changes in CADASIL

Cited by 123 publications

References 31 publications

Extensive White Matter Hyperintensities May Increase Brain Volume in Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

Extensive White Matter Hyperintensities May Increase Brain Volume in Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

Reaction Time Is Negatively Associated with Corpus Callosum Area in the Early Stages of CADASIL

CADASIL: pathogenesis, clinical and radiological findings and treatment

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