Natural History of Stroke: Cause and Development

The purpose of this study is to learn more about stroke and obtain information that may serve as the basis for future investigations. It will 1) establish a registry of patients with cerebrovascular disease (stroke); 2) characterize the natural history of acute stroke and transient ischemic attacks (TIA)-an interruption of blood flow to the brain that causes stroke symptoms for a short period of time); and 3) evaluate the data to generate ideas for future studies.

Patients 18 years of age or older with suspected acute stroke or TIA may be eligible for this study. Subjects will be recruited from patients who present with stroke at the emergency department of Suburban Hospital in Bethesda, Maryland.

The study will gather data collected from diagnostic and laboratory tests the patient undergoes as part of standard medical care, including findings of medical and neurological examinations and other tests. In addition, studies will be done for research purposes only to gather data about stroke and TIA. These may include the following:

* Blood and urine tests not more than 2 tablespoons of blood will be drawn for various tests.
* Electrocardiogram (EKG) (heart tracing)-electrodes placed on the chest wall detect the heartbeat and heart rhythm.
* Computed tomography (CT) scan of the head-specialized X-rays are used to obtain images of the brain.
* Magnetic resonance imaging (MRI) of the brain-a strong magnetic field and radio waves are used to produce images that provide information about the brain tissue and blood vessels.
* Transcranial Doppler (TCD)-sound waves are used to image the arteries of the brain and neck.
* Echocardiogram-sound waves are used to image the heart and evaluate heart function.

Patients may be asked to return to Suburban Hospital for follow-up testing in 1, 3, and/or 12 months, when some of these tests may be repeated to assess changes over time

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Study Description:

This is a natural history/disease pathogenesis protocol for evaluation of patients with or at risk of acute stroke, transient ischemic attack (TIA), or other disturbances of cerebrovascular circulation. The purpose of this protocol is to generate natural history data to serve as the basis for future hypothesis-driven protocols as well as to contribute to the clinical and physiological understanding of cerebrovascular disease through the description of disease manifestation and the relationship among clinical, hematologic, and radiologic variables, as well as identifying potential subjects for future studies on stroke and other cerebrovascular diseases.

Objectives:

* To establish a registry of subjects with cerebrovascular disease including clinical, laboratory, and radiological variables associated with hemorrhagic and ischemic stroke, TIA, and other disturbances of cerebrovascular circulation.
* To characterize the natural history of acute stroke, TIA, and other disturbances of cerebrovascular circulation on these variables.
* To evaluate the relationship among these variables by exploratory analyses and to generate hypotheses for future testing.
* To identify potential subjects for research studies on stroke and other cerebrovascular diseases.

Endpoints:

A primary purpose of this observational protocol is to discover and study new imaging biomarkers that are i) relevant to the acute presentation and severity, ii) predictive of clinical outcome, and iii) are useful for stratifying the biological response as reflected in blood-biomarker and gene expression studies. As such, the primary outcome is the results from the imaging studies.

Primary Outcome Measures

Prevalence and type of abnormalities seen on neuroimaging as a function of time from acute insult such as:

* Imaging positive for acute ischemic cerebral vascular syndrome ( AICS positive )\[1\]
* Presence of a lesion on diffusion, perfusion, and mismatch between the two
* Evidence of a vascular occlusion on MR angiography
* Evidence of a thrombus or hemorrhage on T2\* GRE imaging
* Blood-brain barrier disruption as evidence by HARM \[2\]
* The evolution of these markers with time and treatment

Secondary Outcome Measures

* Stroke severity as measured by NIHSS as a function of time since index event.
* Clinical outcome measured using modified Rankin Scale and Barthel Index
* Gene expression profiles and biomarker levels obtained from blood samples.

Eligibility Criteria:
* INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Aged \>=18
2. Presented to participating study site (ED, ICU, or inpatient unit) with or at risk of acute stroke, TIA, or other disturbances of cerebrovascular circulation

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Subjects with contraindication to MRI scanning will be excluded from any testing which involves the use of MRI. The contraindications include subjects with the following devices or conditions:

   * Central nervous system aneurysm clips
   * Implanted neural stimulator
   * Implanted cardiac pacemaker or defibrillator
   * Cochlear implant
   * Ocular foreign body (e.g. metal shavings)
   * Insulin pump
   * Metal shrapnel or bullet
   * Any implanted device that is incompatible with MRI

   Subjects with a condition precluding entry in the scanner (e.g. morbid obesity, Claustrophobia, etc.) will not be included in the MRI portion of this study.
2. Pregnancy