Objective: To follow a cohort of stroke patients with white matter hyperintensities (WMH), using MRI, and thereby track the natural history of changes in blood-brain barrier (BBB) disruption. By establishing a better understanding of the relationship between the presence of BBB disruption and WMH progression, we hope to identify BBB permeability on MRI as a biomarker for disease pathogenesis, disease activity, and disease progression. Study Population: Stroke patients will be eligible for this study if their MRI shows evidence of confluent WMH on FLAIR imaging (Fazekas score 2 or greater), obtain a six-item screener score greater than 3, and have no other diagnosis to explain the finding (e.g. multiple sclerosis). The NIH stroke service currently evaluates 600 patients a year with MRI. Approximately 20% have confluent WMH on their FLAIR MRI and would meet the inclusion criteria for this study. Thus, the cohort for this study will be recruited from the population evaluated by the NIH stroke service. Design: Patients with a clinical or radiographic history of stroke will be eligible for enrollment. Enrolled subjects who meet the inclusion/exclusion criteria will be followed serially with MRI. Research procedures will consist of an MRI, interval history and cognitive/clinical scaling. Research procedures will occur every 3 months for the first year, every 6 months for the second year, and then yearly thereafter for a total of 6 years. Outcome measures: Using a previously described and independently validated method, BBB permeability will be assessed at each research time point as will WMH burden. The presence of BBB will be compared with progression of WMH into normal appearing white matter (NAWM). The primary outcome is the relationship between BBB disruption and WMH progression. It is postulated that BBB disruption in the NAWM will be associated with progression of the WMH. Secondary outcomes will examine the spatial relationship between BBB disruption and WMH progression and changes in cognitive scaling. Additionally, other exploratory MRI biomarkers for disease progression will be examined (e.g. susceptibility weighted imaging with 7T MRI to examine regions of known BBB disruption).
- INCLUSION CRITERIA: - Age greater than or equal to 18 - Have been evaluated for stroke-like symptoms such as difficulty moving or speaking, blurred vision, dizziness or balance issues or have radiographic evidence of a stroke on an MRI scan of the brain. This qualifying event must be attributable to a stroke or TIA with no other definitive cause identified at the time of screening. - Provides written informed consent prior to study participation OR is able to provided assent and consent is provided by a qualifying LAR. - Is willing to appoint a Durable Power of Attorney (DPA) for NIH research EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from this study: - Medical contraindications for MRI (e.g., any non-organic implant or other device such as a cardiac pacemaker or infusion pump or other metallic implants, objects, or body piercings that are not MRI-compatible or cannot be removed) - Psychological contraindications for MRI (e.g., claustrophobia), to be assessed at the time the medical history is collected - If unable to lie comfortably on their back for up to 1 hour. - Contraindication to gadolinium (pregnant or nursing, previous allergic reaction, renal insufficiency) - Known diagnosis that is thought to be the cause of their WMH (e.g. multiple sclerosis) other than chronic cerebrovascular disease, cerebral autosomal dominant arteriopathy with subcortical infarcts (CADASIL), or migraine. - Clinically significant medical or neurological disorders that might expose the patient to undue risk of harm, confound study outcomes or prevent the participant from completing the study; examples of such conditions include but are not limited to respiratory compromise, cardiovascular instability or cerebral edema. - History of an ongoing seizure disorder, structural brain abnormality or nonvascular brain injury. - Unlikely to be released from the hospital following the qualifying event or has severe disability preventing ambulation or verbal communication. - Known malignant disease or other chronic illness with poor 5-year prognosis other than dementia. - Attaining a six-item screener score less than 4, during screening.