Background: Only a few longitudinal studies, with follow-up duration up to 3.6 years, have assessed the substrates of relapses and disability in aquaporin-4 (AQP4) IgG-positive neuromyelitis optica spectrum disorders (NMOSD), primarily focusing on clinical and conventional MRI variables. Objective: We evaluated the association of clinical and MRI measures, including a comprehensive multimodal advanced MRI protocol, with key long-term clinical outcomes in AQP4 IgG-positive NMOSD patients over a median follow-up of 8.5 years (interquartile range [IQR] = 3.5; 13.3). Methods: Forty-six NMOSD patients and 77 healthy controls underwent 3T brain MRI. In patients, neurological evaluations were collected at baseline and every six months. Time to first relapse and 6-month confirmed disability worsening (6m-CDW) were recorded. Lesion volume and topography, global and regional brain volumes, normal-appearing white matter and gray matter fractional anisotropy and mean diffusivity, choroid plexus volume, enlarged perivascular spaces number and glymphatic system function were assessed. Results: During the follow-up, 30% patients experienced at least one clinical relapse, while 22% had 6m-CDW. Higher number of previous attacks (hazard ratio [HR] = 1.17, 95%-confidence interval [CI] = 1.04; 1.32) and presence of anterior optic pathway lesions (HR = 4.92, 95%-CI = 1.12; 21.852) were risk factors independently associated with a shorter time to a first clinical relapse; lower thalamic volume was marginally associated (HR = 0.93, 95%-CI = 0.87; 1.00). Presence of cervical cord lesions (HR = 3.93, 95%-CI = 1.16; 13.31) and lower normalized cortical volume (HR = 0.94, 95%-CI = 0.89;0.99) were risk factors independently associated with a shorter time to 6m-CDW; higher number of previous attacks contributed marginally (HR = 1.19, 95% = 0.99; 1.43). High efficacy treatments (HETs) delayed time to first relapse and 6m-CDW. Conclusions: Previous attacks, optic nerve/spinal cord involvement, cortical/thalamic atrophy and the use of HETs associate with long-term outcomes in NMOSD.
Substrates of 8.5-year clinical outcomes in aquaporin-4 IgG-positive neuromyelitis optica spectrum disorders / Margoni, M.; Gueye, M.; Meani, A.; Pagani, E.; Valsasina, P.; Storelli, L.; Preziosa, P.; Moiola, L.; Rocca, M. A.; Filippi, M.. - In: JOURNAL OF NEUROLOGY. - ISSN 0340-5354. - 273:2(2026). [10.1007/s00415-026-13647-x]
Substrates of 8.5-year clinical outcomes in aquaporin-4 IgG-positive neuromyelitis optica spectrum disorders
Gueye M.Secondo
;Storelli L.;Preziosa P.;Rocca M. A.Penultimo
;Filippi M.
Ultimo
2026-01-01
Abstract
Background: Only a few longitudinal studies, with follow-up duration up to 3.6 years, have assessed the substrates of relapses and disability in aquaporin-4 (AQP4) IgG-positive neuromyelitis optica spectrum disorders (NMOSD), primarily focusing on clinical and conventional MRI variables. Objective: We evaluated the association of clinical and MRI measures, including a comprehensive multimodal advanced MRI protocol, with key long-term clinical outcomes in AQP4 IgG-positive NMOSD patients over a median follow-up of 8.5 years (interquartile range [IQR] = 3.5; 13.3). Methods: Forty-six NMOSD patients and 77 healthy controls underwent 3T brain MRI. In patients, neurological evaluations were collected at baseline and every six months. Time to first relapse and 6-month confirmed disability worsening (6m-CDW) were recorded. Lesion volume and topography, global and regional brain volumes, normal-appearing white matter and gray matter fractional anisotropy and mean diffusivity, choroid plexus volume, enlarged perivascular spaces number and glymphatic system function were assessed. Results: During the follow-up, 30% patients experienced at least one clinical relapse, while 22% had 6m-CDW. Higher number of previous attacks (hazard ratio [HR] = 1.17, 95%-confidence interval [CI] = 1.04; 1.32) and presence of anterior optic pathway lesions (HR = 4.92, 95%-CI = 1.12; 21.852) were risk factors independently associated with a shorter time to a first clinical relapse; lower thalamic volume was marginally associated (HR = 0.93, 95%-CI = 0.87; 1.00). Presence of cervical cord lesions (HR = 3.93, 95%-CI = 1.16; 13.31) and lower normalized cortical volume (HR = 0.94, 95%-CI = 0.89;0.99) were risk factors independently associated with a shorter time to 6m-CDW; higher number of previous attacks contributed marginally (HR = 1.19, 95% = 0.99; 1.43). High efficacy treatments (HETs) delayed time to first relapse and 6m-CDW. Conclusions: Previous attacks, optic nerve/spinal cord involvement, cortical/thalamic atrophy and the use of HETs associate with long-term outcomes in NMOSD.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
