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Objective: Individual differences were observed in the clinical efficacy of Botulinum toxin A (BoNT-A) in the treatment of the primary Meige syndrome. Our study aimed to explore the potential associations between the clinical efficacy of BoNT-A in the treatment of the primary Meige syndrome and variants of SNAP25, SV2C and ST3GAL2, which are involving in the translocation of the BoNT-A in vivo. Methods: Patients with the primary Meige syndrome treated with BoNT-A were enrolled. Clinical efficacy was evaluated by the maximum improvement rate of motor symptoms and the duration of efficacy. Variants of SNAP25, SV2C and ST3GAL2 were obtained by Sanger sequencing. Another cohort diagnosed with primary cervical dystonia was also enrolled in the replication stage. Results: Among the 104 primary Meige syndrome patients, 80 patients (76.9%) had a good efficacy (the maximum improvement rate of motor symptoms ≥30%) and 24 (23. 1%) had a poor (the maximum improvement rate of motor symptoms

In neurological diseases, the regulation of autophagy plays a crucial role in their pathology, particularly the relationship between autophagy and hepatic encephalopathy (HE) which merits detailed investigation. Glycosphingolipids are abundant and broadly functional in the nervous system and are closely associated with autophagy. However, the specific link and mechanisms between glycosphingolipids and autophagy in HE remain unclear. This study aims to explore the impact of glycosphingolipid changes on the autophagy in HE and its potential mechanisms. Utilizing lectin microarrays, we observed elevated expression levels of α2-3 sialylated glycosphingolipid in the brain tissue of HBV transgenic mice and ammonia-induced astrocyte models, suggesting that the increase in α2-3 sialylated glycosphingolipid is related to HE. Further research revealed that the increased expression of α2-3 sialylated glycosphingolipid, mediated by ST3GAL2, affects autophagy by regulating the autophagy initiation complex Vps34-Beclin-1. In summary, our research not only comprehensively reveals the changes in brain glycosphingolipid during HBV-related HE but also elucidates the interactions and regulatory mechanisms between α2-3 sialylated glycosphingolipid and autophagy. This study provides a new perspective on understanding the pathogenesis of HE and offers novel theories and targets for future research and treatment strategies. [ABSTRACT FROM AUTHOR]

Objective: Individual differences were observed in the clinical efficacy of Botulinum toxin A (BoNT-A) in the treatment of the primary Meige syndrome. Our study aimed to explore the potential associations between the clinical efficacy of BoNT-A in the treatment of the primary Meige syndrome and variants of SNAP25 , SV2C and ST3GAL2 , which are involving in the translocation of the BoNT-A in vivo., Methods: Patients with the primary Meige syndrome treated with BoNT-A were enrolled. Clinical efficacy was evaluated by the maximum improvement rate of motor symptoms and the duration of efficacy. Variants of SNAP25 , SV2C and ST3GAL2 were obtained by Sanger sequencing. Another cohort diagnosed with primary cervical dystonia was also enrolled in the replication stage., Results: Among the 104 primary Meige syndrome patients, 80 patients (76.9%) had a good efficacy (the maximum improvement rate of motor symptoms ≥30%) and 24 (23. 1%) had a poor (the maximum improvement rate of motor symptoms <30%). As to the duration of efficacy, 52 patients (50.0%) had a long duration of efficacy (≥4 months), and 52 (50.0%) had a short (<4 months). In terms of primary Meige syndrome, SNAP25 rs6104571 was found associating with the maximum improvement rate of motor symptoms (Genotype: P  = 0.02, OR = 0.26; Allele: P  = 0.013, OR = 0.29), and SV2C rs31244 was found associating with the duration of efficacy (Genotype: P  = 0.024, OR = 0.13; Allele: P  = 0.012, OR = 0.13). Besides, we also conducted the association analyses between the variants and BoNT-A-related adverse reactions. Although, there was no statistical difference between the allele of SV2C rs31244 and BoNT-A-related adverse reactions, there was a trend ( P  = 0.077, OR = 2.56). In the replication stage, we included 39 patients with primary cervical dystonia to further expanding the samples' size. Among the 39 primary cervical dystonia patients, 25 patients (64.1%) had a good efficacy (the maximum improvement rate of motor symptoms ≥50%) and 14 (35.9%) had a poor (the maximum improvement rate of motor symptoms <50%). As to the duration of efficacy, 32 patients (82.1%) had a long duration of efficacy (≥6 months), and 7 (17.9%) had a short (<6 months). Integrating primary Meige syndrome and primary cervical dystonia, SV2C rs31244 was still found associating with the duration of efficacy (Genotype: P  = 0.002, OR = 0. 23; Allele: P  = 0.001, OR = 0. 25)., Conclusion: In our study, SNAP25 rs6104571 was associated with the maximum improvement rate of motor symptoms in patients with primary Meige syndrome treated with BoNT-A, and patients carrying this variant had a lower improvement rate of motor symptoms. SV2C rs31244 was associated with duration of treatment in patients with primary Meige syndrome treated with BoNT-A and patients carrying this variant had a shorter duration of treatment. Patients with primary Meige syndrome carrying SV2C rs31244 G allele have an increase likelihood of BoNT-A-related adverse reactions. Involving 39 patients with primary cervical dystonia, the results further verify that SV2C rs31244 was associated with duration of treatment and patients carrying this variant had a shorter duration of treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)