Cathepsin-A Related Arteriopathy with Strokes And Leukoencephalopathy (CARASAL)
https://www.neurology.org/doi/10.1212/NXG.0000000000200358
CARASAL is an extremely rare inherited disease that affects the brain’s small blood vessels. It is caused by a single change in the CTSA gene and can resemble the more common condition CADASIL, making diagnosis difficult. This study examined 21 people with CARASAL from three Dutch families and compared their symptoms and MRI brain scans with those of patients who have CADASIL. The researchers found that stroke patterns in CARASAL are unusually varied. Patients experienced deep (subcortical) strokes, outer‑brain (cortical) strokes, and even intracerebral haemorrhages, some of which were fatal. This contrasts with CADASIL, where deep ischemic strokes are typical, and brain bleeds are rare. MRI scans showed very extensive white‑matter damage, especially in the pons, a part of the brainstem. Despite this severe damage, CARASAL patients had fewer lacunes (blank space as a result of tissue damage from stroke) and less brain shrinkage than CADASIL patients with similar MRI severity. A distinctive feature was also identified, most CARASAL patients had deep‑set eyes with reduced eye‑muscle and orbital‑fat volume, producing an “orbital check‑mark sign” on MRI. These findings highlight that CARASAL has a unique clinical and radiologic profile, supporting the need for CARASAL‑specific diagnostic and stroke‑management guidelines.