Active clinical trials for "CADASIL"

Researchers are trying to find out more about the side effects of fremanezumab when treating patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) for migraine headaches.

This study is a Phase II, randomized, crossover trial designed to compare one fixed dose of dabigatran with open-label use of ASA in patients affected by CADASIL; the study is a safety trial, and the primary objective is to assess that dabigatran is not less safe than ASA in subjects with CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarct (CADASIL) is a lethal disease caused by a gene mutation that affects arteries in the brain. Symptoms include migraines, strokes, memory loss, and dementia. There are no treatments. Researchers want to study people who have CADASIL to learn more about it. Objectives: To learn more about CADASIL by studying people who have it. Eligibility: People ages 18-100 who were diagnosed with CADASIL in the past 5 years and can make their own decisions Design: Participants will be screened in another NIH protocol. Participants will have 3 visits over 2 years. These may include: Physical exam Thinking and concentration tests Blood tests Skin biopsy: A small skin punch is removed from the arm or leg Eye exam and eye imaging tests Fluorescein angiogram: A catheter is placed in an arm vein. Dye is given through the catheter and travels to the eyes. EndoPAT: A small clamp on the fingertip measures blood volume. Cardio-ankle vascular index (CAVI): Artery stiffness is tested with blood pressure cuffs on the arms and legs. Soft electrodes on the skin measure heart signals. Brain MRI or MRA: They lie on a table that slides in and out of a tube that takes pictures. They may get a contrast agent in their vein. It brightens the brain so researchers can see where blood flows. CT scan of the heart: They lie on a table that slides in and out of a machine that takes pictures. They get contrast dye injected through a catheter. They may get a medicine that makes their blood vessels bigger or slows their heart rate.

The aim of the study is to investigate whether there is a polarity-specific influence of tDCS on cerebral vasomotor reactivity monitored by transcranial doppler sonography.

The purpose of this study is to delineate early neurological features and their progression in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in order to facilitate early diagnosis, prevent erroneous diagnosis and mistreatment and improve physician education about this relatively common yet under-recognized dementing disorder. Patients with CADASIL suffer from a variant from migraine that differs from wild type migraine in terms of its severity, progressive nature and underlying pathophysiology. Recurrent stereotypic acute confusional state associated with the headache episodes in patients with CADASIL is a distinctive phenomenon, which if recognized will lead to an earlier and accurate diagnosis of this condition. Specific Aims: Characterize the nature, frequency and severity of migraine in patients with CADASIL. Delineate the phenomenon of acute confusional migraine as a distinct subgroup of migraine and establish its prevalence in patients with CADASIL. Determine the latency between the onset of neurological symptoms including migraine, and diagnosis of CADASIL and the prevalence of misdiagnosis.

The Cerebral Amyloid angiopathy (CAA) is the leading cause of cortical hemorrhage after 65 years. The presence of cerebral infarction is also reported anatomically in the AAC. MRI studies of these infarcts are rare. They are described as punctate, cortical silent. Frequency and pathophysiology is poorly understood. The investigators put the question of a link with hemorrhagic lesions of the AAC.

The aim of this study is to investigate using fMRI methods, EEG and dedicated mathematical models, the potential alterations of neurovascular coupling in CADASIL.

CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is an cerebral microangiopathy secondary to mutations in the NOTCH3 gene located on chromosome 19. This disease is the most frequent of the hereditary vascular leukoencephalopathies. CADASIL begins between the ages of 20 and 40 with the appearance of hyper-signs of brain white matter visible on T2 sequences in magnetic resonance imaging (MRI). Before the age of 30, patients are most often asymptomatic. The disease is then responsible for different neurological manifestations: Migraine attacks with aura occur on average in one in three patients, most often at the beginning of the course of the disease, sometimes even before the appearance of MRI abnormalities; Transient ischemic strokes or strokes associated with small cerebral infarcts occur most frequently after the age of 50-60 years in more than two out of three patients; Mood disorders are reported by one in three patients in the same age group; Cognitive disorders that affect executive functions, especially after the age of 60, until the stage of severe dementia associated with walking disorders are observed during the course of the disease. To date, there is no treatment whose efficacy has been proven in CADASIL. Various studies have shown that the accumulation of the most destructive brain tissue lesions at the subcortical level was closely correlated in CADASIL with the clinical severity of patients (motor and cognitive disability). It is now possible to measure microstructural changes in brain tissue in diffusion imaging during the course of the disease, even before significant clinical changes are detected.

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy (CADASIL) is an archetypal small vessel disease of the brain caused by dominant mutations in the NOTCH3 receptor. Cardinal vascular lesions include deposition of granular osmiophilic material (GOM) within the basal lamina of smooth muscle cells, progressive smooth muscle cell loss, and fibrosis of the media. Pathogenic mutations alter the number of cysteine residues in the extracellular domain of NOTCH3 (Notch3 ECD), leading to its abnormal accumulation in the GOM deposits. Vascular smooth muscle cell has been identified as the primary target cell in this disease. Pathophysiological processes leading from NOTCH3 mutations to smooth muscle cell loss remain poorly understood. The investigators propose to study these mechanisms by reprogramming skin cells to become stem cells and then differentiating them to vascular smooth muscle cells. The hypothesis of this study is that the differentiated smooth muscle cells will display the characteristic features of CADASIL, ie, Notch3 ECD accumulation and GOM deposits.