Search

We investigated whether MCI patients with hippocampal atrophy or multiple subcortical infarcts demonstrate neuropsychological patterns and markers considered typical of Alzheimer's disease (AD) and of vascular dementia (VD), respectively. An extensive neuropsychological battery, including tests of memory, visual-spatial and executive functions, language, attention, praxis and psychomotor speed, was administered to 36 mild cognitive impairment (MCI) patients with hippocampal atrophy and 41 MCI patients with multiple subcortical infarcts. Both groups of MCI patients were very mildly impaired and well matched in terms of MMSE scores. A clear, disproportionately severe, episodic memory disorder was observed in MCI patients with hippocampal atrophy. A less specific neuropsychological profile, consisting of impairment on an Action Naming task that is sensitive to frontal lobe lesions, was observed in MCI patients with multiple subcortical infarcts. In MCI patients, a disproportionately severe episodic memory impairment strongly points to an Alzheimer's type brain pathology, whereas the prevalence of executive deficits and other frontal lobe symptoms are a much weaker diagnostic marker of small vessel subcortical disease.

Background: Although cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is considered a cerebrovascular disorder with almost exclusively neurological symptoms, arteriopathy is generalized and also involves the choroid and retina. Objective. To study optic nerve head microvascular function in CADASIL by assessing blood flow, volume, and velocity with a retina flowmeter. Patients and Methods: Scanning laser Doppler flowmetry permits the noninvasive assessment of relative blood velocity, volume, and flow in a sample volume of either retina or anterior optic nerve head. Measurements were performed in a first group of 9 eyes of 5 patients with CADASIL and a second group of 8 eyes of 4 healthy subjects. Hemodynamic parameters were computed in 4 quadrants of the optic disc (superior nasal, superior temporal, inferior nasal, and inferior temporal). The Wilcoxon rank sum test was used to assess differences in relative flow, volume, and velocity in each quadrant and between the 2 groups and differences in overall optic nerve head blood flow, volume, and velocity. Results. Patients with CADASIL had a significant decrease in overall blood flow and volume compared with healthy subjects (P <.05). The reduction in blood flow and volume was particularly significant in the superior and inferior temporal quadrants. No significant differences were found nasally between the patients and the control groups. Conclusion. Our results suggest that hemodynamic parameters are abnormal in the superficial nerve fiber layer of the optic nerve head of patients with CADASIL, especially in the temporal quadrants of the neuroretinal rim.

We report the anaesthetic management of a patient suffering from an ischaemic arteriopathy of the CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy) type. The anaesthetic implications of this pathology are discussed. By analogy with other cerebral arteriopathies, the aim of our management was to keep mean arterial blood pressure and end-tidal carbon dioxide so as to prevent any cerebral ischaemic or vasospastic phenomenon. We preserved the cerebral venous return by avoiding excessive head-down position. We used a balanced anaesthetic technique because it allows easier titration of the depth of anaesthesia with regard to mean arterial pressure. There is no contraindication to the use of loco-regional anaesthesia.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a systemic vascular disease caused by Notch 3 gene mutations. On electron microscopy a specific granular osmiophilic material (GOM) is found surrounding the vascular smooth muscle cells. In 1993, we first proposed the use of skin biopsy to diagnose patients and to identify relatives of patients with CADASIL. We analyze here our experience with skin biopsies from 50 patients with CADASIL and compare the findings with those of 20 normal skin biopsy specimens. A morphometric analysis of skin vessel morphology on electron microscopy was performed by systematic measurements of several blood vessel diameters, as well as of areas of lumen, endothelial cell and smooth muscle cell cross-sectional areas, vessel wall area, arterial media and extracellular matrix areas. We found relative absence of stenosis but marked destruction of smooth muscle cells, resulting in decrease of vessel wall thickness and loss of extracellular matrix area, producing vessel wall weakness. Similar changes were also observed in brain arterioles from 5 patients with CADASIL. Our results suggest that hypotonicity of the arteriolar tree may constitute an important pathogenetic mechanism in CADASIL. Other than hypotonicity, the early and severe destruction of smooth muscle cells may potentially result in decreased secretion of vascular endothelial growth factor, loss of vascular permeability and damaging hemodynamic consequences. Blood vessel morphology of skin vessels correlated well with changes in brain arterioles. Vascular morphology in skin biopsy samples contributes to our understanding of the pathogenesis of CADASIL. It could be important to perform skin biopsies in future therapeutic trials of CADASIL as a direct measure of therapeutic effectiveness.

Early diagnosis of dementia is critical, but there is usually a time lag between onset of symptoms and referral for neuropsychological testing and dementia diagnosis. We aimed to identify factors correlated with this delayed referral.