Objective To investigate the risk factors of neutralizing antibody (NAB)–induced complete secondary treatment failure (cSTF) during long-term botulinum neurotoxin (BoNT) treatment in various neurologic indications. Methods This monocenter retrospective cohort study analyzed the data of 471 patients started on BoNT therapy between 1995 and 2015. Blood samples of 173 patients were investigated for NABs using the mouse hemidiaphragm test (93 with suspected therapy failure, 80 prospective study participants). The frequency of NAB-cSTF was assessed for various indications: hemifacial spasm, blepharospasm, cervical dystonia, other dystonia, and spasticity. A priori defined potential risk factors for NAB-cSTF were evaluated, and a stepwise binary logistic regression analysis was performed to identify independent risk factors. Results Treatment duration was 9.8 ± 6.2 years (range, 0.5–30 years; adherence, 70.6%) and number of treatment cycles 31.2 ± 22.5 (3–112). Twenty-eight of 471 patients (5.9%) had NAB-cSTF at earliest after 3 and at latest after 103 treatment cycles. None of the 49 patients treated exclusively with incobotulinumtoxinA over 8.4 ± 4.2 (1–14) years developed NAB-cSTF. Independent risk factors for NAB-cSTF were high BoNT dose per treatment, switching between onabotulinumtoxinA and other BoNT formulations (except for switching to incobotulinumtoxinA), and treatment of neck muscles. Conclusions We present a follow-up study with the longest duration to date on the incidence of NAB-cSTF in patients treated with various BoNT formulations, including incobotulinumtoxinA. Whereas the overall risk of NAB-cSTF is low across indications and BoNT formulations, our findings underpin the recommendations to use the lowest possible dose particularly in cervical dystonia, and to avoid unnecessary switching between different formulations.

Background: Sporadic degenerative ataxia patients fall into 2 major groups: multiple system atrophy with predominant cerebellar ataxia (MSA‐C) and sporadic adult‐onset ataxia (SAOA). Both groups have cerebellar volume loss, but little is known about the differential involvement of gray and white matter in MSA‐C when compared with SAOA.Objectives: The objective of this study was to identify structural differences of brain gray and white matter between both patient groups.Methods: We used magnetic resonance imaging to acquire T1‐weighted images and diffusion tensor images from 12 MSA‐C patients, 31 SAOA patients, and 55 healthy controls. Magnetic resonance imaging data were analyzed with voxel‐based‐morphometry, tract‐based spatial statistics, and tractography‐based regional diffusion tensor images analysis.Results: Whole‐brain and cerebellar‐focused voxel‐based‐morphometry analysis showed gray matter volume loss in both patient groups when compared with healthy controls, specifically in the cerebellar areas subserving sensorimotor functions. When compared with controls, the SAOA and MSA‐C patients showed white matter loss in the cerebellum, whereas brainstem white matter was reduced only in the MSA‐C patients. The tract‐based spatial statistics revealed reduced fractional anisotropy within the pons and cerebellum in the MSA‐C patients both in comparison with the SAOA patients and healthy controls. In addition, tractography‐based regional analysis showed reduced fractional anisotropy along the corticospinal tracts in MSA‐C, but not SAOA.Conclusion: Although in our cohort extent and distribution of gray and white matter loss were similar between the MSA‐C and SAOA patients, magnetic resonance imaging data showed prominent microstructural white matter involvement in the MSA‐C patients that was not present in the SAOA patients. Our findings highlight the significance of microstructural white matter changes in the differentiation between both conditions. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Background: Sporadic adult‐onset ataxias without known genetic or acquired cause are subdivided into multiple system atrophy of cerebellar type (MSA‐C) and sporadic adult‐onset ataxia of unknown etiology (SAOA).Objectives: To study the differential evolution of both conditions including plasma neurofilament light chain (NfL) levels and magnetic resonance imaging (MRI) markers.Methods: SPORTAX is a prospective registry of sporadic ataxia patients with an onset >40 years. Scale for the Assessment and Rating of Ataxia was the primary outcome measure. In subgroups, blood samples were taken and MRIs performed. Plasma NfL was measured via a single molecule assay. Regional brain volumes were automatically measured. To assess signal changes, we defined the pons and middle cerebellar peduncle abnormality score (PMAS). Using mixed‐effects models, we analyzed changes on a time scale starting with ataxia onset.Results: Of 404 patients without genetic diagnosis, 130 met criteria of probable MSA‐C at baseline and 26 during follow‐up suggesting clinical conversion to MSA‐C. The remaining 248 were classified as SAOA. At baseline, NfL, cerebellar white matter (CWM) and pons volume, and PMAS separated MSA‐C from SAOA. NfL decreased in MSA‐C and did not change in SAOA. CWM and pons volume decreased faster, whereas PMAS increased faster in MSA‐C. In MSA‐C, pons volume had highest sensitivity to change, and PMAS was a predictor of faster progression. Fulfillment of possible MSA criteria, NfL and PMAS were risk factors, CWM and pons volume protective factors for conversion to MSA‐C.Conclusions: This study provides detailed information on differential evolution and prognostic relevance of biomarkers in MSA‐C and SAOA. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.