Ischemia Care Biomarkers of Acute Stroke Etiology (BASE)

Acute ischemic stroke (AIS) is a leading cause of adult mortality and morbidity in the United
States, affecting over 800,000 individuals, annually, leaving many with permanent disability.
Furthermore, hundreds of thousands of Americans experience a transient ischemic attack (TIA),
a momentary episode of neurologic dysfunction, which often precedes a major stroke and serves
as a warning for future ischemic events. Despite symptoms resolving, experiencing a TIA
increases the risk of stroke by 20% within 90 days. Emergent evaluation, prompt acute
treatment, and identification of stroke etiology for secondary prevention are key to
decreasing the morbidity and mortality associated with cerebrovascular disease. Key to
treatment and prevention is the identification of stroke etiology - large vessel
atherosclerosis, cardioembolic phenomenon, or in-situ small vessel cerebrovascular disease -
since primary and secondary prevention measures differ based on stroke subtype. The diagnosis
of ischemic stroke includes a combination of patient history, clinical assessment, and brain
imaging. However, identifying the cause of cerebrovascular ischemia is challenging and
routinely assigned of cryptogenic origin.

Therefore, there is a great need to understand the pathogenesis of TIA and AIS events in
order to develop more effective preventative measures. Recent studies have identified the
differential expression of genes in whole blood that may differentiate the major ischemic
stroke types. Such differences may help identify TIA and AIS events that are more likely to
respond to therapy specifically tailored to the major stroke type. Furthermore, by
establishing a more robust standard for secondary prevention, future stroke events may be
avoided.

BASE is a multisite prospective study with a estimated enrollment of up to 1100 subjects
adult subjects and 100 age, gender and co-morbidity matched controls ("Controls") will be
recruited from patients who present to the Emergency Department (ED) or hospital with
suspected AIS or TIA. Research personnel will identify potential patients by responding to
"Brain Attacks" pages from the ED to the Stroke Team for patients who meet current Brain
Attack criteria. Following evaluation by the ED and neurology physicians, the clinical
coordinator will verify the patient had a suspected AIS or TIA and meets eligibility
criteria. The patient or their legal surrogate will be approached for study participation.
Written informed consent will be obtained for all subjects enrolled.

There are two recruitment windows related to BASE determined by time of symptom onset, time
of presentation at ED or hospital, and ability to consent:

1. "BASE" - patients that present with suspected stroke symptoms within 18 hours of symptom
onset or last known normal time OR

2. "BASE 24" - patients that present within 24 hours +/- 6 hours (i.e. 18 - 30 hour window)
of symptom onset or last known normal time and clinical evidence suggesting Acute
Ischemic Stroke.

Inclusion Criteria:

- Patients >18 years of age

- Signs and symptoms suggestive of AIS or TIA

- One of the following:

1. BASE - Arrival to the emergency department or hospital within 18 hrs of symptom
onset or last known normal time

2. BASE 24 - Arrival to the emergency department or hospital within 24 hours +/- 6
hours (i.e. 18 - 30 hour window) of symptom onset or last known normal time and
clinical evidence suggesting Acute Ischemic Stroke.

- Head CT or MRI ruling out other pathology such as vascular malformation, hemorrhage,
tumor or abscess which would likely be responsible for presenting neurologic symptoms

- Informed consent obtained

Exclusion Criteria:

- Any central nervous system infection, i.e. meningitis or encephalitis in the past 30
days

- Any form of head trauma, stroke or intracranial hemorrhage in the past 30 days

- Known primary or metastatic cancer involving the brain

- Active Cancer defined as a diagnosis of cancer, within 6 months before enrollment, any
treatment for cancer within the previous 6 months, or recurrent or metastatic cancer.

- Autoimmune diseases: such as lupus, rheumatoid arthritis, Crohn's disease, ulcerative
colitis

- Active infectious diseases (eg. HIV/AIDS, hepatitis C)

- Any underlying medical condition which in the opinion of the investigator would
prohibit the patient from providing informed consent

- Major surgery within three months prior to the index event