Biomarkers of CASH

We propose to recruit human subjects at three sites, with the project approved and coordinated by the University of Chicago Medicine (UCM) central institutional review board (IRB) and endorsed by respective IRBs at the other two enrolling sites. The study involves no more than minimal risks, discussed herein. The enrolling sites include UCM where the project will be led and where the data coordinating center (DCC) is located and all plasma biomarker assays and statistical analyses are planned, the University of California at San Francisco (UCSF), and Mayo Clinic, Rochester, MN (Mayo). UCSF and Mayo are participants in imaging biomarker validations in longitudinal follow-up of cavernous angioma with symptomatic hemorrhage (CASH) subjects in the TR Project. We project enrolling 1,040 cases during 4 years to address hypotheses in 3 Specific Aims (40 cases enrolled in Specific Aim 2 are also included among the 800 subjects addressing hypotheses of Specific Aim 1).

Aim 1 and 2:

Inclusion Criteria:

1. Clinical diagnosis of CA
2. age 18 or older
3. solitary or multiple
4. familial or sporadic
5. with or without prior symptoms

Exclusion Criteria:

1. Prior excision of a solitary CA lesion
2. prior stereotactic radiosurgery or any brain irradiation
3. spinal cavernoma without brain lesion
4. other brain pathology unrelated to CA (demyelinating disease, brain tumor)
5. seizures or stroke unrelated to CA in the prior year
6. current pregnancy or within 6 months postpartum
7. reluctance to undergo venipuncture or donate blood specimen, or be called for clinical follow-up for up to one year
8. homeless or incarcerated persons, or other reason a subject will be unable/unlikely to be reached for follow-up

Aim 3:

Inclusion Criteria:

1. \< 30 years of age
2. one or more seizures (with or without medical therapy) in the prior year

OR

1. > 50 years of age
2. having received an MRI of the brain with SWI (susceptibility weighted imaging) sequences for any indication in the year prior to enrollment
3. No HMA on brain MRI SWI sequences

OR

1. > 50 years of age
2. having received an MRI of the brain with SWI sequences for any indication in the year prior to enrollment
3. Two or more microbleeds on SWI brain MRI sequences, adjudicated by neuroradiologist

Exclusion Criteria:

1. concurrent brain disease or structural brain pathology
2. medical illness requiring hospitalization or surgery, seizure or stroke in the prior 12 months
3. active use of prescription medications in the prior 12 months
4. current pregnancy or within 6 months postpartum
5. reluctance to undergo venipuncture or donate blood specimen

OR

1. concurrent brain disease or structural brain pathology
2. medical illness requiring hospitalization or surgery, or stroke in the prior 12 months other than seizure disorder
3. active use of prescription medications in the prior 12 months except anticonvulsants
4. current pregnancy or within 6 months postpartum
5. reluctance to undergo venipuncture or donate blood specimen

OR

1. concurrent brain disease or structural brain pathology
2. medical illness requiring hospitalization or surgery within the prior year
3. any history of stroke or epileptic seizure within the prior year
4. current pregnancy or within 6 months postpartum
5. reluctance to undergo venipuncture or donate blood specimen

OR

1. concurrent brain disease or structural brain pathology
2. medical illness requiring hospitalization or surgery within the prior year
3. any history of stroke or epileptic seizure within the prior year
4. current pregnancy or within 6 months postpartum
5. reluctance to undergo venipuncture or donate blood specimen