Pediatric Opsoclonus-Myoclonus-Ataxia Syndrome can Lead to Long-Term Neurological, Neuropsychological, and Cognitive Sequelae Associated with Cerebellar Atrophy.

Abstract

To outline the long-term neuropsychological profile of a pediatric cohort with Opsoclonus-Myoclonus-Ataxia Syndrome (OMAS), and evaluate whether volumetric brain abnormalities correlate with clinical findings years after onset. Twelve patients diagnosed with OMAS between 2008 and 2020 (6 males, mean age 9.6 years, median follow-up 5.4 years) underwent a videorecorded neurological examination and a standardized cognitive and neuropsychological assessment. Patients and 12 age-matched controls underwent advanced 3-Tesla brain MRI studies. Voxel-Based Morphometry (VBM) and targeted cerebellar evaluation using ACAPULCO and ENIGMA pipelines were performed. The results were correlated with neuropsychological scores. Nine subjects (75%) had abnormal neurological findings (dysmetria n = 7, balance deficit n = 7, and speech impairment n = 6). The mean Full-Scale IQ was 76, with borderline IQ in 2 cases, intellectual disability in 5, visuospatial processing impairments in 6, and affective and internalizing issues in 7. Brain MRI and VBM showed mild cerebellar atrophy (41.6%), especially in Crus I-II, IV, VIIIa and VIIb lobules. Reduced gray matter volumes were noted in the precentral, inferior-occipital and middle orbitofrontal gyrus, while larger volumes were found in the ventral diencephalon fusiform and inferior temporal gyri. Lower white matter volumes were found in the cerebellum, superior frontal gyrus, midbrain, postcentral and precentral gyri. Patients with lower cognitive scores, especially in Working Memory and Processing Speed, had smaller volumes in several cerebellar lobules (p = 0.001). Smaller cerebellar volumes correlate with lower cognitive scores at long-term follow-up, confirming not only the role of the cerebellum in the pathogenesis of OMAS, but also its role in cognitive functioning.