toxins Review Botulinum Toxin for the Treatment of Hemifacial Spasm: An Update on Clinical Studies Nicola Tambasco 1,2, * , Marta Filidei 2 , Pasquale Nigro 1 , Lucilla Parnetti 2 and Simone Simoni 2   Citation: Tambasco, N.; Filidei, M.; Nigro, P.; Parnetti, L.; Simoni, S. Botulinum Toxin for the Treatment of Hemifacial Spasm: An Update on Clinical Studies. Toxins 2021, 13, 881. https://doi.org/10.3390/ toxins13120881 Received: 1 November 2021 Accepted: 2 December 2021 Published: 9 December 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Movement Disorders Center, Neurology Department, Perugia General Hospital and University of Perugia, 06129 Perugia, Italy; pasquale.nigro1987@gmail.com 2 Neurology Department, Perugia General Hospital and University of Perugia, 06129 Perugia, Italy; martafilidei91@gmail.com (M.F.); lucilla.parnetti@unipg.it (L.P.); simonesimoni84@gmail.com (S.S.) * Correspondence: n.tambasco@libero.it Abstract: Hemifacial spasm (HFS) is a movement disorder characterized by involuntary contractions of the facial muscles innervated by the seventh cranial nerve. Generally, it is associated with a poor quality of life due to social embarrassment and can lead to functional blindness. Moreover, it is a chronic condition, and spontaneous recovery is rare. Intramuscular injections of Botulinum Toxin (BoNT) are routinely used as HFS treatment. Methods: We reviewed published articles between 1991 and 2021 regarding the effectiveness and safety of BoNT in HFS as well as any reported differences among BoNT formulations. Results: The efficacy of BoNT for HFS treatment ranged from 73% to 98.4%. The mean duration of the effect was around 12 weeks. Effectiveness did not decrease over time. Adverse effects were usually mild and transient. The efficacy and tolerability of the different preparations appeared to be similar. Among the studies, dosage, injected muscles, intervals of treatment, and rating scales were variable, thus leading to challenges in comparing the results. Conclusions: BoNT was the treatment of choice for HFS due to its efficacy and safety profile. Further studies are needed to investigate the factors that influence the outcome, including the optimal timing of treatment, injection techniques, dosage, and the best selection criteria for formulations. Keywords: hemifacial spasm; botulinum toxin; BoNT; spasm; onabotulinum toxin; abobotulinum toxin Key Contribution: Botulinum toxin is reported as the most efficacious therapy for hemifacial spasm. Clinical studies regarding effectiveness and safety of botulinum toxin are presented. 1. History Presentation and Epidemiology Hemifacial spasm (HFS) is a hyperkinetic movement disorder characterized by short or persistent, intermittent synchronous twitching of the muscles innervated by the facial nerve [1], which is a chronic condition, and spontaneous recovery is rare [2,3]. Typical features include involuntary clonic and/or tonic contractions of the muscles of facial expression, usually unilaterally, initiating in the periorbital musculature, progressing to involve the perioral, platysma, and other muscles of facial expression [1,4]. HFS interferes with social life in about 90% of patients, leading to isolation and even depression, there, in turn, having a negative impact on the quality of life [5]. Therefore, early diagnosis and optimal therapy are generally necessary. HFS was described for the first time by F. Schultze, in 1875, in a 56-year-old male having involuntary movements involving the left side of his face with post-mortem exami- nation of a giant aneurysm of the left vertebral artery compressing the left facial nerve [6]. The condition received its current terminology by Babinski in 1905 [7]. Currently, HFS is classified as primary (79%) or secondary to facial nerve damage (21%) [8]. The former is attributed to the compression of the facial nerve at the root exit zone in the brainstem, usually by an ectatic or aberrant blood vessel [8,9]. Instead, the latter has been associated with a number of conditions, including cerebellopontine Toxins 2021, 13, 881. https://doi.org/10.3390/toxins13120881 https://www.mdpi.com/journal/toxins