Characterizing the Association Between Complement-Mediated Thrombotic Microangiopathy and Cognitive Dysfunction using MRI and Neurocognitive Assessment

• Complement-mediated thrombotic microangiopathy patients, despite remission, have significant white matter changes on MRI and lower scores on neurocognitive testing.

• These changes suggest more research is required to determine optimal therapy in these patients to preserve neurocognitive status.

Complement-mediated thrombotic microangiopathy (CM-TMA) is a rare, life-threatening thrombotic microangiopathy caused by a defect in the alternative complement pathway. It is associated with renal failure and acute encephalopathy, but long-term neurocognitive effects are uncertain. Using magnetic resonance imaging (MRI) and neurocognitive tests, we can further evaluate the long-term neurocognitive complications in CM-TMA and compare them to controls. In this study, we analyzed microstructural changes in the cerebral white matter and neurocognitive testing results of patients with CM-TMA. Seven adult patients with CM-TMA in remission and 6 healthy controls were included. All patients were treated with C5 complement blockade. They were followed for 12 months after study entry. All patients had consecutive MRI scans (standard-of-care and quantitative sequences) to assess for white matter changes and concurrent neurocognitive testing. Patients with CM-TMA had increased white matter signal intensity in most regions of the brain compared with controls. This was accompanied by increased depression and neurocognitive dysfunction (impaired concentration, short-term memory, and verbal memory). These findings were also present up to 12 months after the initial study visit. In summary , patients with previous CM-TMA were found to have significant albeit nonspecific cerebral white matter abnormalities with impaired memory and concentration. Larger studies with longitudinal follow-up to assess neurocognitive complications in CM-TMA are required. This trial was registered at Clinical Trials Ontario (ctontario.ca; Project ID: 1318).