View clinical trials related to Leukoencephalopathies.
Filter by:Inherited leukoencephalopathies are a broad spectrum of genetically determined disorders, characterized by specific involvement of the white matter of the central nervous system. These pathologies are almost as common as other acquired white matter disorders, such as acute disseminated encephalomyelitis and multiple sclerosis. The onset can occur at any age, from prenatal life to adulthood, and the clinical picture is mostly progressive, but can also be non-evolving or, rarely, improve over time. Thanks to new diagnostic approaches, including next-generation genetic sequencing and recognition of magnetic resonance imaging patterns, in recent years the investigators have witnessed a significant increase in the number of genetically defined leukoencephalopathies. However, despite advances in genetic studies, inherited leukoencephalopathies include a large number of inherited white matter diseases in children and adults and remain of unknown cause in many patients (about 40%). This significant percentage of cases of unknown etiology represents a major challenge for public health, both in prognostic terms and, consequently, economically. However, even in leukoencephalopathies of genetically determined cause, the absence of specific biomarkers can be a limiting factor in the design and execution of clinical studies in search of promising therapies. As in other fields of neurology, the integration of clinical and genetic data with brain MRI data plays a fundamental role in the diagnostics of subjects affected by these pathologies. Currently, the methodologies commonly used in magnetic resonance imaging are qualitative, and evaluate brain lesions through the contrast between white and gray matter. The lack of specific biomarkers is therefore a limiting factor in the design of therapeutic challenges. In this regard, the development of new multiparametric quantitative magnetic resonance imaging (qMRI) methods could allow the investigators to identify new biomarkers to assess the etiology behind leukodystrophies, increasing diagnostic power and understanding the progression or improvement of leukoencephalopathy for both future trials and existing therapies. In this perspective, recent rapid "transient-state" magnetic resonance imaging methods, such as MR Fingerprinting (MRF), have proven effective in efficiently separating different components of brain tissue. These techniques consist of rapid and highly undersampled acquisitions performed by continuously changing the MR sequence parameters, thus obtaining a signal evolution that is unique for each combination of underlying tissue properties. Furthermore, if these techniques have already shown their validity at 3 Tesla, they could be even more informative in 7T MRI where the use of qMRI could provide more details thanks to the high image resolution. The project's objective is to evaluate and validate new and innovative quantitative magnetic resonance imaging (qMRI) methodologies at both clinical and ultra-high fields in inherited leukodystrophies and those of unknown etiology. This is a national, multi-institutional, multicenter exploratory study on the potential identification and predictability of early structural and metabolic markers in quantitative MRI at 3T and 7T in the diagnosis and follow-up of leukodystrophy and leukoencephalopathy in adults and during development. The study will include multiple sub-studies: 1. A cross-sectional study in leukoencephalopathies at clinical fields. 2. A longitudinal study in leukoencephalopathies at 3T: natural history and therapy outcomes. 3. A cross-sectional and longitudinal study at 7T: The added value of ultra-high-field Magnetic Resonance Imaging in leukoencephalopathies.
Background: Multiple sclerosis (MS) and progressive multifocal leukoencephalopathy (PML) are disorders that affect the central nervous system (CNS). The CNS includes the brain, spinal cord, and optic nerves. Both diseases can cause muscle weakness and impair vision, speech, and coordination. Researchers are working to better understand how MS and PML affect the CNS. Objective: To test whether an experimental radioactive tracer (minibody) can help positron emission tomography (PET) scans detect certain immune cells in the CNS of people with MS and PML. Eligibility: People aged 18 years and older with MS or PML. Design: Participants will come to the clinic for at least 3 visits over 4 to 6 weeks. Participants will undergo testing. They will have a physical and neurological exam. They will have blood tests and tests of their heart function. They will have a magnetic resonance imaging (MRI) scan of the brain. They may have a spinal tap: Their lower back will be numbed, and a needle will be inserted between the bones of the spine to withdraw fluid from around the spinal cord. Minibody is given through a tube with a needle placed in a vein in the arm. This takes 5 to 10 minutes. Participants will have heart function tests before and after receiving the minibody. Participants will return the next day for the PET scan. They will lie on a table that moves through a doughnut-shaped machine. This scan will take about 1 hour. Participants with PML may opt to repeat the minibody infusion and the PET scan within 6 months.
This study uses medical records that allow retrospective data extraction of clinical manifestation to assess the natural history of HPDL mutations
ABBV-CLS-7262 is an investigational drug being researched for the treatment of Vanishing White Matter disease in adult and pediatric subjects. This is a 96-week, open-label, multiple cohort study enrolling adults and pediatric subjects with Vanishing White Matter disease who are 6 years or older. Subjects will attend regular visits during the course of the study and complete medical assessments, blood tests, checking for side effects, and completing questionnaires.
Leukoencephalopathy with brain stem involvement and lactate elevation (LBSL) is a genetic disorder caused by biallelic mutations in the DARS2 gene that encodes mitochondrial aspartyl tRNA synthase.(1, 2) It is characterized by typical abnormalities on MRI of the brain and spinal cord.(3) Clinically, the disorder is heterogeneous and can present in the neonatal period, later in childhood or even in adults.(3) In general it can be stated that the earlier presentations are characterized by rapid progression leading to severe disability and death. Presentation at a later age is typically characterized by a more benign disease course, although considerable disability is common. Clinically, the disease presents as a slowly progressive myelopathy with mainly involvement of the corticospinal tracts and the dorsal columns. Although the natural history has been studied in large cohorts, the rate of progression has not been systematically studied with clinimetric outcome scales or potential surrogate outcomes for spinal cord disease.
This is an observational study to better understand the risk factors and progression of CADASIL, a leading cause of vascular cognitive impairment and dementia (VCID). 500 participants will be enrolled and can expect to be on study for up to 5 years.
This study is being done in order to create a registry (list) of people interested in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) research. It may be that you have a family member or other loved one with CADASIL, or that you may have CADASIL or are at risk. Participation means that your name will be added to a list of people who will be invited to participate in future research studies on CADASIL. Participants must be 18 years or older, and will remain on the registry until they request to be removed.
The primary goal of this study is to address the need for targeted therapeutic interventions for impairments that impact walking in related neurodegenerative diseases.
The primary objective of the study is to estimate the incidence of progressive multifocal leukoencephalopathy (PML) and serious adverse events (SAEs) of other opportunistic infections (OIs) among all participants taking natalizumab. The secondary objectives of the study are to estimate the incidence of SAEs, to estimate the incidence of SAEs among participant subgroups defined by demographic and clinical factors (age, gender, duration of treatment, pregnancy, breastfeeding), to characterize and estimate incidences of malignancies, hypersensitivity reactions and John Cunningham Virus (JCV) positivity among all participants taking natalizumab, and to count and describe pregnancies and breastfeeding among participants previously exposed to natalizumab.
Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare, rapidly progressing, genetic, neurodegenerative disease for which no definitive treatment options and limited information on the natural history of the disease are available. The structural, genetic, and neuropathophysiological abnormalities of ALSP lead to the onset of neurologic symptoms, such as moderate to severe motor and neuropsychiatric impairments. This natural history study will collect data to contribute to the development of future novel therapies that focus on the neuropathophysiological features that underlie ALSP and that are essential to reverse, delay, or stop progression of this debilitating disorder.