View clinical trials related to Leukoencephalopathies.
Filter by:JC virus is a benign virus which infects approximately up to 90% of the normal adult population. However, it may be reactivated in people who have a decreased immune function as in HIV infection, cancer, chemotherapy, transplant recipients, or in MS patients treated with natalizumab (Tysabri). In these patients, JC virus can cause a severe brain disease called Progressive Multifocal Leukoencephalopathy (PML), for which there is no cure. As of September 2013, 400 MS patients in the world, who have been treated with natalizumab, have developed PML. The risk of PML is approximately 5 patients in 1000 after 24 months on the drug. Researchers do not know exactly in which cells of the body the virus lives but it has been isolated from the blood, urine, cerebrospinal fluid (CSF), and from the brains of patients with immunosuppression. In this study, the investigators wish to determine precisely where the virus lives, and how the body prevents it from causing brain disease. Because of the association of PML with natalizumab, the investigators would like to see if there is a difference in the amounts of virus in blood, urine, and CSF found in MS patients treated with natalizumab or those treated with different medications for MS, or those not treated at all. The investigators hope that this knowledge will allow us to find better ways of preventing the development of PML as well as treatments for patients with PML.
Stroke is a leading cause of disability; most strokes (80%) are subcortical, with ischemic damage due to occlusion in penetrating arteries. Although ischemic white matter disease (iWMD) may lack gross clinical manifestation, it causes significant cognitive impairment, particularly on measures of executive function, attention, and memory. This impairment is attributable to diffuse damage affecting network connections. While there are many studies concerning rehabilitation of motor function and language in patients with large focal strokes, few studies have addressed attentional and executive functions. To our knowledge, there are no such studies on iWMD. In this study, patients will be randomized to a novel intervention for improving executive function and a control condition matched for therapist exposure. Patients will be assessed pre-intervention, post-intervention, and at long-term follow-up using a battery of behavioural and neuroimaging tasks. We predict that the novel intervention will be associated with improved executive function, as assessed behaviourally, and improved frontal network function, as assessed through neuroimaging markers.
CoRDS, or the Coordination of Rare Diseases at Sanford, is based at Sanford Research in Sioux Falls, South Dakota. It provides researchers with a centralized, international patient registry for all rare diseases. This program allows patients and researchers to connect as easily as possible to help advance treatments and cures for rare diseases. The CoRDS team works with patient advocacy groups, individuals and researchers to help in the advancement of research in over 7,000 rare diseases. The registry is free for patients to enroll and researchers to access. Visit sanfordresearch.org/CoRDS to enroll.
Background: - Progressive multifocal leukoencephalopathy (PML) is a severe viral infection of the brain. It is caused by JC virus. Many people have this virus in their bodies all their life, but it is usually kept in check by their immune system. If the immune system does not work right because of a disease or medication, the virus becomes active and can damage cells in the brain. Not much is known about PML or how it affects the immune system. Researchers want to study people with PML to better understand the natural history of the disease. Objectives: - To study the natural history of PML. Eligibility: - Individuals at least 2 years of age who have PML. Design: - Participants will be screened with a physical exam, medical history, and imaging studies. - Participants will have several visits to the National Institutes of Health Clinical Center. There will be an initial visit, monthly visits for the next 6 months, a 12-month visit, and possible visits afterward. - At the initial visit, participants will give blood, urine, and spinal fluid samples. They will also have neurological tests and imaging studies of the brain. - For the next five visits, participants will give blood and urine samples. They will also have neurological tests and imaging studies of the brain. - The 6-month and 12-month visits will repeat the tests from the initial visit. - Other optional procedures include bone marrow samples and skin biopsies. Additional blood tests and imaging studies may be performed. - Treatment will not be provided as part of this study.
The investigators hypothesize that inflammation in carotid plaque is predictive of the extent of ischemic lesion burden on the brain and will add to risk stratification for individuals with carotid disease.
The objectives of this study are to explore the effects of administering high-dose corticosteroids to participants who developed progressive multifocal leukoencephalopathy (PML) while on natalizumab as measured by time-course change in functional status based on Karnofsky Performance Status Index through 6 months following the completion of plasma exchange (PLEX; or equivalent), survival at 6 months following the completion of PLEX (or equivalent), and incidence and severity of adverse events (AEs) and serious adverse events (SAEs); to characterize the evolution of immune reconstitution inflammatory syndrome (IRIS) as measured by time course changes in Global Clinical Impression of Improvement (GCI-I), Symbol Digit Modalities Test (SDMT), brain magnetic resonance imaging (MRI), magnetoencephalography (MEG), chemokines, cytokines, C-reactive protein (CRP), John Cunningham virus (JCV) load and cell count in cerebrospinal fluid (CSF); and to characterize the time course elimination of serum natalizumab concentrations in the study population following the last PLEX (or equivalent) procedure.
The purpose of this study is to explore host genetic mutations which may render individual subjects more susceptible (or resistant) to developing Progressive Multifocal Leukoencephalopathy (PML). Samples will also be collected to determine Deoxyribonucleic Acid (DNA) sequence of JC Virus (JCV). Analysis of the JC Virus (JCV) genome may provide information about viral genotypes that may be associated with higher pathogenicity, and help to identify individuals who may be at higher risk of developing Progressive Multifocal Leukoencephalopathy (PML) due to chronic infection with a more pathogenic variant of JC Virus (JCV).
This is a continuation of our previous studies on Progressive Multifocal Leukoencephalopathy (PML). We will focus on the role of inflammation in PML, and define prognostic markers of disease evolution.
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.
Background: - A leukodystrophy is a disease affecting the white matter of the brain. The white matter conducts electricity from one part of the brain to the other. If the insulation, or myelin, is damaged, the brain s electrical pathways will not work properly. Researchers are trying to identify what causes leukodystrophy. Objectives: - To collect detailed clinical characterizations, including histories, physical examinations, biochemical tests, genetic studies, and neurophysiologic and neuroimaging studies in patients with unclassified leukodystrophies to comprehensively characterize such patients and obtain comparative clinical profiles. - To collect detailed clinical characterizations, including histories, physical examinations, biochemical tests, genomic and proteomic tissue, and neurophysiologic and neuroimaging studies in patients with known leukodystrophies to investigate the underlying pathogenesis of these disorders. - To better understand leukodystrophies of unknown cause and to identify the part of the DNA of the patient with leukodystrophy that is causing the problem. Eligibility: - Any individual with a known or suspected leukodystrophy is eligible to participate in this protocol, including - Patients with white matter disease that is unclassified or of unknown cause, including but not limited to leukoencephalopathies with calcifications, leukoencephalopathies with cysts, leukoencephalopathies with hypomyelination, and leukoencephalopathies with brainstem involvement. - Parents or siblings of these subjects. - Exclusion criteria include patients too ill to travel to the Clinical Center and patients for whom the leukoencephalopathy is felt to be secondary to an acquired cause (for example, traumatic or infectious). Design: - Patients will be seen either as an inpatient or outpatient depending on the tests that are planned. Patients may need to stay at the Clinical Center for 3 to 5 days. - The following tests will be conducted as part of standard clinical care: - Physical and neurological examinations, including blood and urine tests. - Magnetic resonance based studies to produce a picture of the patient s brain (under general anesthesia). - Spinal tap to measure chemicals in the spinal fluid (under general anesthesia in young children). - Nerve biopsy, if the peripheral nerves are affected, or muscle biopsy, if the cells called the mitochondria or the muscles are involved (both under general anesthesia). - The following studies may be performed as part of participation in the research: - Blood, urine, spinal fluid, or muscle to understand the proteins, DNA, and molecules in these tissues. - Skin biopsy to grow (in culture) skin cells and to analyze the skin microscopically. - DNA studies to find new genes responsible for leukodystrophies and to better understand these diseases. - Participation should be based on an interest to help further the research on leukodystrophies. Specific information about a patient s present or future health risks may not be gained.