Characterizing the association between complement-mediated TMA and cognitive dysfunction using MRI and neurocognitive...

Area of Science:

• Neuroscience
• Hematology
• Complement System Biology

Background:

• Complement-mediated thrombotic microangiopathy (CM-TMA) is a severe condition linked to complement pathway defects, often causing kidney and brain issues.
• Long-term neurocognitive consequences of CM-TMA remain unclear, necessitating further investigation.

Purpose of the Study:

• To evaluate long-term neurocognitive complications in CM-TMA patients using MRI and neurocognitive tests.
• To compare cerebral white matter changes and cognitive function in CM-TMA patients versus healthy controls.

Main Methods:

• Included seven adult CM-TMA patients in remission (treated with C5 complement blockade) and six healthy controls.
• Utilized serial MRI scans (standard-of-care and quantitative) and neurocognitive testing over 12 months.
• Assessed microstructural changes in cerebral white matter and cognitive performance.

Main Results:

• CM-TMA patients exhibited increased white matter signal intensity compared to controls.
• Patients reported higher rates of depression and demonstrated neurocognitive dysfunction, including impaired concentration, short-term memory, and verbal memory.
• These neurological and cognitive impairments persisted up to 12 months post-initial assessment.

Conclusions:

• Previous CM-TMA is associated with significant, non-specific cerebral white matter abnormalities.
• Impaired memory and concentration are notable long-term neurocognitive complications in CM-TMA survivors.
• Larger longitudinal studies are required to fully elucidate the neurocognitive sequelae of CM-TMA.