{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:16:57Z","timestamp":1785284217992,"version":"3.55.0"},"reference-count":87,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,11,24]],"date-time":"2024-11-24T00:00:00Z","timestamp":1732406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Botulinum neurotoxin type-A (BoNT\/A), which blocks quantal acetylcholine (ACh) release at the neuromuscular junction (NMJ), has demonstrated its efficacy in the symptomatic treatment of blepharospasm. In 3.89% of patients treated for blepharospasm at Tenon Hospital, BoNT\/A was no longer effective in relieving the patient\u2019s symptoms, and a partial upper myectomy of the Orbicularis oculi muscle was performed. We used surgical waste samples from 14 patients treated with repeated injections of either abobotulinumtoxinA (Dysport\u00ae) or incobotulinumtoxinA (Xeomin\u00ae). These muscle fragments were compared to others from 4 normal subjects, na\u00efve of BoNT\/A. The morphological study was performed blinded to the BoNT\/A treatment and between treated and control samples. Neuromuscular specimens analyzed by confocal laser scanning microscopy, using fluorescent staining and immune-labeling of presynaptic proteins, revealed that the pattern of innervation (e.g., polyneuronal and convergent innervation), the muscle nicotinic ACh receptors (nAChRs), and the NMJs exhibited marked differences in BoNT\/A-treated muscles (regardless of the toxin clinically used), with respect to controls. BoNT\/A-treated junctions exhibited profuse polyneuronal innervation in which 2\u20136 axons innervated 74.84% of single muscle fibers, while 99.47% of control junctions were mono-innervated. Another new finding was the stable convergent innervation, in which several motor axons end onto the same endplate. Morphological signs of synapse elimination included the presence of retraction bulbs in axons and nerve terminals and a reduced extension of postsynaptic nAChRs. These outcomes suggest that synapse elimination is altered and raise questions on the origin and factors contributing to the plasticity changes observed and the functioning of NMJs.<\/jats:p>","DOI":"10.3390\/toxins16120506","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T08:38:24Z","timestamp":1732523904000},"page":"506","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Stable Convergent Polyneuronal Innervation and Altered Synapse Elimination in Orbicularis oculi Muscles from Patients with Blepharospasm Responding Poorly to Recurrent Botulinum Type-A Neurotoxin Injections"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2324-3158","authenticated-orcid":false,"given":"Brigitte","family":"Girard","sequence":"first","affiliation":[{"name":"Service d\u2019Ophtalmologie, H\u00f4pital Tenon, Sorbonne Universit\u00e9, Universit\u00e9 Pierre et Marie Curie, 4 rue de la Chine, 75020 Paris, France"},{"name":"H\u00f4pital Priv\u00e9 Armand Brillard, 3. Avenue Watteau, 94130 Nogent sur Marne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Couesnon","sequence":"additional","affiliation":[{"name":"Institut des Neurosciences Paris-Saclay, UMR 9197, CNRS\/Universit\u00e9 Paris-Sud, 91198 Gif-sur-Yvette, Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6730-9596","authenticated-orcid":false,"given":"Emmanuelle","family":"Girard","sequence":"additional","affiliation":[{"name":"Institut NeuroMyoGene\u2014Physiopathology & Genetic of Neuron and Muscle, CNRS UMR5261, INSERM U1315, Universit\u00e9 Lyon1, 8 Avenue Rockefeller, 69008 Lyon, France"},{"name":"Plateforme Aniphy, SFR Sant\u00e9 Lyon-Est, CNRS UAR3453, INSERM US7, Universit\u00e9 Lyon1, 8 Avenue Rockefeller, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0693-8994","authenticated-orcid":false,"given":"Jordi","family":"Molg\u00f3","sequence":"additional","affiliation":[{"name":"Institut des Neurosciences Paris-Saclay, UMR 9197, CNRS\/Universit\u00e9 Paris-Sud, 91198 Gif-sur-Yvette, Cedex, France"},{"name":"Service d\u2019Ing\u00e9nierie Mol\u00e9culaire pour la Sant\u00e9 (SIMoS), EMR CNRS 9004, D\u00e9partement M\u00e9dicaments et Technologies pour la Sant\u00e9 (DMTS), Institut des Sciences du Vivant Fr\u00e9d\u00e9ric Joliot, Commissariat \u00e0 l\u2019\u00e9nergie Atomique et aux \u00c9nergies Alternatives (CEA), Universit\u00e9 Paris-Saclay, 91191 Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1007\/s00204-022-03271-9","article-title":"Toxicology and pharmacology of botulinum and tetanus neurotoxins: An update","volume":"96","author":"Pirazzini","year":"2022","journal-title":"Arch. 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