Citation: Newland, D.P.; Novakovic, D.; Richards, A.L. Voice Tremor and Botulinum Neurotoxin Therapy: A Contemporary Review. Toxins 2022, 14, 773. https://doi.org/10.3390/ toxins14110773 Received: 6 September 2022 Accepted: 7 November 2022 Published: 9 November 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 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/). toxins Review Voice Tremor and Botulinum Neurotoxin Therapy: A Contemporary Review David P. Newland 1 , Daniel Novakovic 2,3 and Amanda L. Richards 1, * 1 Department of Otolaryngology, The Royal Melbourne Hospital, Parkville, VIC 3050, Australia 2 Voice Research Laboratory, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW 2050, Australia 3 Department of Otolaryngology, The Canterbury Hospital, Campsie, NSW 2194, Australia * Correspondence: amanda.richards@pinnaclesurgery.com.au Abstract: Voice tremor is a common, yet debilitating symptom for patients suffering from a number of tremor-associated disorders. The key to targeting effective treatments for voice tremor requires a fundamental understanding of the pathophysiology that underpins the tremor mechanism and accurate identification of the disease in affected patients. An updated review of the literature detailing the current understanding of voice tremor (with or without essential tremor), its accurate diagnosis and targeted treatment options was conducted, with a specific focus on the role of botulinum neurotoxin. Judicious patient selection, following detailed characterisation of voice tremor qualities, is essential to optimising treatment outcomes for botulinum neurotoxin therapy, as well as other targeted therapies. Further focused investigation is required to characterise the response to targeted treatment in voice tremor patients and to guide the development of innovative treatment options. Keywords: voice tremor; essential tremor; botulinum neurotoxin Key Contribution: Botulinum neurotoxin therapy plays a central role in the treatment of essential voice tremor, but optimising patient selection and ensuring detailed assessment of treatment response remain paramount to achieving optimal treatment outcomes. 1. Introduction Affecting 1–5% of the general population, essential tremor (ET) is the most common movement disorder [1]. Despite being so common, because ET is a clinical diagnosis and the spectrum of tremor-associated disorders frequently overlap [2–4], this poses challenges for the treating clinician and therefore typically makes ET a diagnosis of exclusion. In 2018, the International Parkinson and Movement Disorder Society (IPMDS) proposed updated diagnostic criteria for ET, including the following four features—isolated tremor consisting of bilateral upper limb action tremor without other motor abnormalities; present for at least three years; with or without head, voice or lower limb tremor; absence of other neurologic signs such as dystonia, ataxia or parkinsonism. Isolated voice tremor is now removed from the essential tremor classification [5]. As such, studies pre-reclassification will be herewith referred to with nomenclature that is appropriate to the period in which they were classified. Essential voice tremor (EVT), previously described as the laryngological manifestation of ET, is present in 18–30% of ET patients [6], as the third most common tremor site after the hands and head [7]. EVT typically presents with tremor associated with increased phonatory effort [8]. Prior to reclassification, studies report that EVT may be present in the absence of any other manifestations of ET [9]; however, a more recent consensus statement proposed updated diagnostic criteria which state that isolated voice or head tremor are not sufficient for a diagnosis of ET [5]. ET is independently associated with the female gender [10,11]. The disease may be familial—showing an autosomal-dominant inheritance Toxins 2022, 14, 773. https://doi.org/10.3390/toxins14110773 https://www.mdpi.com/journal/toxins