DP061 | BRAIN MRI FINDINGS IN UNTREATED PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disease characterized by intravascular hemolysis, thrombosis, and bone marrow failure. By brain MRI, we previously demonstrated a high frequency and severity of pathological findings of the white matter (WM) with periventricular vascular degeneration and vascular abnormalities suspicious for prior partial venous thrombosis, in neurologically asymptomatic patients. Brain MRI was performed in 13 untreated PNH patients and 29 age/sex matched controls (1:2 ratio) by innovative technologies. Briefly, it included quantitative susceptibility mapping (QSM), diffusion tensor imaging (DTI) that analyses the microstructure of the brain WM, and 2D and 3D fluid attenuated inversion recovery (FLAIR) images. Finally, we correlated brain MRI findings with clinical and hematological parameters of PNH patients. At MRI assessment PNH patients had a median Hb of 11.4 g/dL (IQR 9.9-12.8), LDH 1.7 x ULN (IQR 1.2 -3.3), PMN clone size 77% (IQR 51-88) and disease duration of 7 years (IQR 9.9-12.89). Most of the patients started Complement inhibitors after brain MRI assessment. By comparing patients and controls, no significant differences were observed in number/ percentages and severity of the different MRI scores, except for a reduction of temporal age-related white matter changes in the former. Moreover, microbleed anatomical rating scale scores and small vessel disease burden scale scores were comparable between patients and controls. Interestingly, patients displayed a significantly higher total scores of enlarged perivascular spaces (EPVS) versus healthy controls. Likewise,diffusion tensor imaging along the perivascular space (DTI-ALPS) index showed a tendency towards increased values in patients versus controls. Both EPVS and DTI-ALPS are markers of the glymphatic system, which is a highly organized fluid transport system of perivascular tunnels involved in maintaining brain homeostasis and immune surveillance. Correlations between MRI scores and clinical/hematological findings were weak overall, probably due to the low number of patients investigated. Of note, both Hb values and disease duration had a negative correlation with EPVS, suggesting that anemia, as a marker of disease severity, may affect glymphatic function. Consistently, LDH values showed a positive correlation with EPVS, suggesting that a more hemolytic disease may also impact on glymphatic function. PNH clone, WBC, PLT and reticulocytes values showed no significant association with MRI findings. Finally, ALPS index showed a strong positive correlation with platelets, and a moderate for WBC and reticulocytes, suggesting that a non-aplastic/myelodysplastic PNH (i.e. a hemolytic disease) is associated with a glymphatic dysfunction. This is the first study demonstrating dysfunction of the glymphatic system and its relationship with disease severity and hemolytic features in untreated PNH patients. The glymphatic dysfunction is involved in aging-associated neurodegenerative and neurologic-related diseases, including Alzheimer's disease, Parkinson's disease, traumatic brain injury, and cognitive impairment.