CASH (Cavernous Angiomas With Symptomatic Hemorrhage) Trial Readiness

Brain Cavernous Angiomas with Symptomatic Hemorrhage (CASH) are rare, but they exact a heavy burden of neurologic disability from recurrent bleeding, for which there is no proven therapy. This trial readiness project aims to address current critical obstacles in identifying cases at multiple sites, characterizing their relevant features, and measuring their outcome. The timing cannot be more opportune, with therapeutic targets already identified, exceptional collaboration among researchers and with the patient community, and several drugs ready to benefit from a track to clinical testing in the next five years.

Sex

All

Minimum age

18 Years

Inclusion Criteria

1. 18 years of age and older
2. Diagnosed with a brain CA (single or multiple)
3. Had a SH within the past year (with demonstrated new lesional bleeding or hemorrhagic growth on diagnostic studies AND attributable new symptoms)
4. Subject is able to provide informed consent

Exclusion Criteria

1. Spinal CA as source of SH
2. Prior brain irradiation
3. Cases where verification of SH with clinical and imaging review cannot be accomplished
4. Prior or planned treatment of the symptomatic lesion (after neurosurgical consultation)

To be eligible for Aims 2 and 3, CASH cases enrolled in Aim 1 will be further excluded from follow-up and baseline validation (FUBV) for the following reasons:

1. Contraindication for administration of contrast agent or otherwise unwilling or unable to undergo research MRI studies
2. Pregnant or breastfeeding women
3. Homeless or incarcerated persons, or other reason a subject will be unable/unlikely to return for follow-up visits

• DERIVEDKinkade S, Li H, Hage S, Koskimaki J, Stadnik A, Lee J, Shenkar R, Papaioannou J, Flemming KD, Kim H, Torbey M, Huang J, Carroll TJ, Girard R, Giger ML, Awad IA. Identifying features of prior hemorrhage in cerebral cavernous malformations on quantitative susceptibility maps: a machine learning pilot study. J Neurosurg. 2025 Jul 4;143(6):1567-1574. doi: 10.3171/2025.3.JNS243051. Print 2025 Dec 1. PMID 40614265
• DERIVEDFlemming KD, Kim H, Hage S, Mandrekar J, Kinkade S, Girard R, Torbey M, Huang J, Huston J 3rd, Shu Y, Lanzino G, Selwyn R, Hart B, Mabray M, Feghali J, Sair HI, Narvid J, Lupo JM, Lee J, Stadnik A, Alcazar-Felix RJ, Shenkar R, Lane K, McBee N, Treine K, Ostapkovich N, Wang Y, Thompson R, Koenig JI, Carroll T, Hanley D, Awad I. Trial Readiness of Cavernous Malformations With Symptomatic Hemorrhage, Part I: Event Rates and Clinical Outcome. Stroke. 2024 Jan;55(1):22-30. doi: 10.1161/STROKEAHA.123.044068. Epub 2023 Dec 22. PMID 38134268
• DERIVEDHage S, Kinkade S, Girard R, Flemming KD, Kim H, Torbey MT, Huang J, Huston J 3rd, Shu Y, Selwyn RG, Hart BL, Mabray MC, Feghali J, Sair HI, Narvid J, Lupo JM, Lee J, Stadnik A, Alcazar-Felix RJ, Shenkar R, Hobson N, DeBiasse D, Lane K, McBee NA, Treine K, Ostapkovich N, Wang Y, Thompson RE, Koenig JI, Carroll T, Hanley DF Jr, Awad IA. Trial Readiness of Cavernous Malformations With Symptomatic Hemorrhage, Part II: Biomarkers and Trial Modeling. Stroke. 2024 Jan;55(1):31-39. doi: 10.1161/STROKEAHA.123.044083. Epub 2023 Dec 22. PMID 38134265
• DERIVEDHage S, Kinkade S, Girard R, Flemming KD, Kim H, Torbey MT, Huang J, Huston J, Shu Y, Selwyn RG, Hart BL, Mabray MC, Feghali J, Sair HI, Narvid J, Lupo JM, Lee J, Stadnik A, Alcazar R, Shenkar R, Hobson N, DeBiasse D, Lane K, McBee N, Treine K, Ostapkovich N, Wang Y, Thompson RE, Mendoza-Puccini C, Koenig J, Carroll T, Hanley DF, Awad IA. Cavernous Angioma Symptomatic Hemorrhage (CASH) Trial Readiness II: Imaging Biomarkers and Trial Modeling. medRxiv [Preprint]. 2023 Jun 5:2023.06.01.23290854. doi: 10.1101/2023.06.01.23290854. PMID 37333396