Time to consider health services dedicated for adults living with cerebral small vessel disease: Report of a ESO scientific seminar.

Purpose: Cerebral small vessel disease (cSVD) is a highly prevalent disorder leading to physical, cognitive and functional decline. We report key barriers in the management of individuals with cSVD, the potential benefit of cSVD-dedicated health services, and evidence from existing models of care for adults with cSVD.

Methods: We examined information from a scientific seminar developed between seven experts in cSVD during the eighth European Stroke Organisation Conference that discussed the optimal health care for adults with cSVD and what health services dedicated to cSVD should include.

Determining Clinical Disease Progression in Symptomatic Patients With CADASIL.

Background And Objectives: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most frequent small artery brain disease caused by pathogenic variants of the NOTCH3 gene. During the disease, we still do not know how the various deficits progress and develop with each other at different stages of the disease. We aim to model disease progression and identify possible progressive subgroups and the effects of different covariates on clinical worsening.

Moyamoya Angiopathy and Antiphospholipid Antibodies: A Coincidental Association?

Background: The presence of antiphospholipid antibodies (aPL) has been suggested as a potential cause of moyamoya angiopathy (MMA), but this remains uncertain. In this case-control study, we aimed to compare the prevalence of circulating aPL in patients with MMA and in non-MMA cerebrovascular controls.

Methods: For comparison, we included 95 patients with MMA from the French National Referral Centre for this condition and 182 age- and sex-matched non-MMA controls with a different cerebrovascular disease, all younger than 55 years.

Diagnosis and management of adult Moyamoya angiopathy: An overview of guideline recommendations and identification of future research directions.

Despite the progress made in understanding the management and outcomes of Moyamoya angiopathy (MMA), several aspects of the disease remain largely unknown. In particular, evidence on the disease history and management of MMA is lacking, mainly due to methodological and selection biases in the available studies and the lack of large, randomized prospective studies. Therefore, the care of MMA patients remains limited to a few expert centers worldwide, and management is often based on local expertise and available resources.

CADA-PRO: A Patient Questionnaire Measuring Key Cognitive, Motor, Emotional, and Behavioral Outcomes in CADASIL.

Background: Cerebral small vessel disease (cSVD) of ischemic type, either sporadic or genetic, as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), can impact the quality of daily life on various cognitive, motor, emotional, or behavioral aspects. No instrument has been developed to measure these outcomes from the patient's perspective. We thus aimed to develop and validate a patient-reported questionnaire.

Prevalence and characteristics of vascular cognitive impairment in a European cohort of adult patients with Moyamoya angiopathy.

Introduction: Moyamoya angiopathy (MMA) is associated with a high risk of stroke, but it is also increasingly recognized as leading to cognitive impairment. The aim of this study was to determine the prevalence, nature, and severity of vascular cognitive impairment no dementia (VCIND) in adults with MMA and to identify clinical and imaging factors associated with VCIND.

Methods: We conducted a retrospective study of consecutive adult patients with MMA followed in two tertiary hospitals (Toulouse and Paris Lariboisiere).

An AluYa5 Insertion in the 3'UTR of COL4A1 and Cerebral Small Vessel Disease.

Importance: Cerebral small vessel diseases (CSVDs) account for one-fifth of stroke cases. Numerous familial cases remain unresolved after routine screening of known CSVD genes.

Objective: To identify novel genes and mechanisms associated with familial CSVD.

MRI hypoperfusion as a determinant of cognitive impairment in adults with Moyamoya angiopathy.

Introduction: In Moyamoya angiopathy (MMA), mechanisms underlying cognitive impairment remain debated. We aimed to assess the association of cognitive impairment with the degree and the topography of cerebral hypoperfusion in MMA.

Methods: A retrospective analysis of neuropsychological and perfusion MRI data from adults with MMA was performed.

Early remodeling and loss of light-induced dilation of retinal small arteries in CADASIL.

A major hurdle to therapeutic development in cerebral small vessel diseases is the lack of in-vivo method that can be used repeatedly for evaluating directly cerebral microvessels. We hypothesised that Adaptive Optics (AO), which allows resolution images up to 1-2 μm/pixel at retinal level, could provide a biomarker for monitoring vascular changes in CADASIL, a genetic form of such condition. In 98 patients and 35 healthy individuals, the wall to lumen ratio (WLR), outer and inner diameter, wall thickness and wall cross-sectional area were measured in a parapapillary and/or paramacular retinal artery.

Border-Zone Cerebral Infarcts Associated with COVID-19 in CADASIL: A Report of 3 Cases and Literature Review.

Introduction: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common inherited cerebral small vessel disease and is a cause of early onset ischemic lacunar stroke. COVID-19 infection may lead, in addition to acute respiratory syndrome, to vascular complications including stroke. Herein, we report three CADASIL patients presenting with cerebral border-zone infarcts concomitant to COVID-19 infection and summarize similar cases previously published in literature.

Operant Training for Highly Palatable Food Alters Translating Messenger RNA in Nucleus Accumbens D Neurons and Reveals a Modulatory Role of Ncdn.

Background: Highly palatable food triggers behavioral responses including strong motivation. These effects involve the reward system and dopamine neurons, which modulate neurons in the nucleus accumbens (NAc). The molecular mechanisms underlying the long-lasting effects of highly palatable food on feeding behavior are poorly understood.

BDNF/TrkB pathway activation in D1 receptor-expressing striatal projection neurons plays a protective role against L-DOPA-induced dyskinesia.

L-DOPA-induced dyskinesia (LID) is a frequent adverse side effect of L-DOPA treatment in Parkinson's disease (PD). Understanding the mechanisms underlying the development of these motor disorders is needed to reduce or prevent them. We investigated the role of TrkB receptor in LID, in hemiparkinsonian mice treated by chronic L-DOPA administration.

Retinal vascular density in CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy).

Background And Objective: Retinal vascular density (VD) measured using optical coherence tomography with angiography (OCTA) has been suggested as a potential marker of intracerebral vascular changes in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). We aimed to determine whether VD is related to the clinical and imaging manifestations of the disease.

Methods: OCTA was performed in 104 CADASIL patients (parallel to their clinical and imaging assessment) and in 83 healthy individuals.

Extension of the Clinicoradiologic Spectrum of Newly Described End-Truncating Variations.

Objectives: To refine the clinical spectrum of a very recently identified phenotype associated with end-truncating pathogenic variations.

Methods: Detailed clinical, neuropsychological, and MRI investigation of 6 patients from 2 unrelated families segregating end-truncating variations.

Results: All patients harbored end-truncating pathogenic variation.

Biallelic variants in NOS3 and GUCY1A3, the two major genes of the nitric oxide pathway, cause moyamoya cerebral angiopathy.

Background: Moyamoya angiopathy (MMA) is a rare cerebrovascular condition leading to stroke. Mutations in 15 genes have been identified in Mendelian forms of MMA, but they explain only a very small proportion of cases. Our aim was to investigate the genetic basis of MMA in consanguineous patients having unaffected parents in order to identify genes involved in autosomal recessive MMA.

Psychological impact of COVID-19 containment on CADASIL patients.

Introduction: COVID-19 restrictive containment was responsible for major psychological distress and alteration of quality of life (QoL) in the general population. Their impact in a group of patients having cerebral small vessel disease (SVD) and at high risk of stroke and disability was unknown.

Objective: We aimed to determine the potential psychological impact of strict containment during the COVID-19 pandemic in a sample of CADASIL patients, a rare SVD caused by NOTCH3 gene mutations.

White Matter Hyperintensities of the Corpus Callosum Are Associated With Clinical Severity in CADASIL.

Background: In CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy), clinical severity is not related to the total burden of white matter hyperintensities (WMHs), presumably because of heterogeneous underlying tissue alterations. We aimed to investigate whether WMHs in the corpus callosum (WMH) are due to secondary degeneration and related to clinical severity.

Methods: We evaluated data from 228 CADASIL patients included in an ongoing prospective cohort with available 3-dimensional fluid-attenuated inversion recovery magnetic resonance imaging sequences.

Psychostimulant Drugs Activate Cell-type Specific and Topographic cFos Expression in the Lumbar Spinal Cord.

Psychostimulant drugs, such as cocaine, d-amphetamine and methylphenidate, alter a wide range of behaviors including locomotor activity and somatosensory perception. These altered behaviors are accompanied by the activation of specific neuronal populations within reward-, emotion- and locomotion-related circuits. However, whether such regulation occurs at the level of the spinal cord, a key node for neural circuits integrating and coordinating sensory and motor functions has never been addressed.

DNA methylation and hydroxymethylation characterize the identity of D1 and D2 striatal projection neurons.

Neuronal DNA modifications differ from those in other cells, including methylation outside CpG context and abundant 5-hydroxymethylation whose relevance for neuronal identities are unclear. Striatal projection neurons expressing D1 or D2 dopamine receptors allow addressing this question, as they share many characteristics but differ in their gene expression profiles, connections, and functional roles. We compare translating mRNAs and DNA modifications in these two populations.

Main features of related cerebral microangiopathies.

and genes encode the alpha1 and the alpha2 chains of type IV collagen, a key component of basement membranes. Mutations located in the coding sequence of genes are responsible for an autosomal dominant (AD) cerebral angiopathy that manifest in either adults, children or fetuses. The most typical among such mutations are missense glycine mutations in the triple helix.

Phenotypic variability in 446 CADASIL patients: Impact of NOTCH3 gene mutation location in addition to the effects of age, sex and vascular risk factors.

The recent discovery that the prevalence of cysteine mutations in the NOTCH3 gene responsible for CADASIL was more than 100 times higher in the general population than that estimated in patients highlighted that the mutation location in EGFr-like-domains of the NOTCH3 receptor could have a major effect on the phenotype of the disease. The exact impact of such mutations locations on the multiple facets of the disease has not been fully evaluated. We aimed to describe the phenotypic spectrum of a large population of CADASIL patients and to investigate how this mutation location influenced various clinical and imaging features of the disease.

Natural history of Myhre syndrome.

Background: Myhre syndrome (MS) is a rare genetic disease characterized by skeletal disorders, facial features and joint limitation, caused by a gain of function mutation in SMAD4 gene. The natural history of MS remains incompletely understood.

Methods: We recruited in a longitudinal retrospective study patients with molecular confirmed MS from the French reference center for rare skeletal dysplasia.

Trajectory Pattern of Cognitive Decline in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy.

Background And Objectives: The course and pattern of cognitive decline in ischemic cerebral small vessel disease remain poorly characterized. We analyzed the trajectory pattern of cognitive decline from age 25 to 75 years in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

Methods: We applied latent process mixed models to data obtained from patients with CADASIL who were repeatedly scored during their follow-up using 16 selected clinical scales or cognitive tests.