Cerebellar Involvement During Attacks of Aquaporin-4-IgG Positive Neuromyelitis Optica Spectrum Disorder

ObjectiveTo describe clinical and radiological features of cerebellar involvement during and following attacks of aquaporin-4-IgG positive neuromyelitis optica spectrum disorder (AQP4+NMOSD). BackgroundCerebellar attacks are not a core clinical characteristic of 2015 AQP4+NMOSD diagnostic criteria and lack detailed characterization with a paucity of prior studies. Design/MethodsBrain MRI from AQP4+NMOSD patients were screened for cerebellar T2/FLAIR hyperintense lesions. Inclusion criteria were: 1) AQP4+NMOSD; 2) MRI with cerebellar lesion(s) ≤40 days from attack onset. ResultsFrom 432 patients, 18 (4%) were included (at onset, 9; at subsequent attack, 9). The median age at onset was 49 years (range, 7-74), 17 (94%) were female and 12 were White. Cerebellar symptoms or signs occurred in 16/18 (89%) and included: gait ataxia, 9 (56%); diplopia, 8 (50%); vertigo, 7 (44%); nystagmus, 6 (38%); dysarthria, 3 (19%), appendicular ataxia, 2 (11%); or other, 2 (11%). Sixteen had concomitant attacks in one or more other regions: brainstem, 13 (area postrema, 5); spinal cord, 4: optic nerve, 2: cerebral, 1. Median EDSS at nadir (available in 9) was 8 (range, 2-9). CSF showed: pleocytosis, 7/13 (54%); positive oligoclonal bands 1/13 (8%). Cerebellar MRI T2-lesions (14 single; 4 multiple; 10 contiguous with brainstem) involved: cerebellar peduncles,14 (78%) (unilateral, 10 [71%]; bilateral, 4 [29%]; inferior, 2 [14%]; middle, 11 [61%]; superior, 6 [33%]); dentate nucleus, 3 (17%); medial cerebellum, 3 (17%); lateral hemispheres, 2 (11%). None had vermis or tonsil lesions. Contrast enhancement was observed in 4/15 (27%). Follow-up imaging (n=12), after a median of 15 months (range:6-49) showed that the lesions persisted in 10 (83%) and resolved in 2 (17%). ConclusionsCerebellar involvement occurs in a minority of AQP4+NMOSD attacks, but is important to recognize as it may be the heralding manifestation and attacks can be severe. Future iterations of the AQP4+NMOSD criteria could incorporate cerebellar attacks.