Current use of neurotoxins for alleviating symptoms of cervical dystonia

ABSTRACT

Introduction

Cervical dystonia (CD) causes involuntary movements and postures of the head, neck, and shoulders, as well as nonmotor symptoms including pain, mood, and sleep dysfunction, and impacts quality of life. The first-line treatment for CD is botulinum neurotoxin (BoNT) injections.

Areas covered

The clinical presentation and diagnosis of CD, as well as where BoNT resides in the treatment landscape, is reviewed first. Next, the mechanism of action and the pharmacological differences in the available preparations of BoNT products are explained. The evidence base for motor and nonmotor efficacy and safety of the available BoNT formulations is reviewed, with attention to duration of benefit as a driver of patient satisfaction. Practical determinants of BoNT efficacy are reviewed including muscle selection, accurate muscle injection, factors related to poor or deteriorating response, and immunogenicity.

Expert opinion

BoNT represents a significant advancement in the treatment of CD. More accurate diagnosis, muscle selection and targeting, and dosing can improve outcomes with existing BoNT formulations. Further refinement of BoNT potency, duration of action, safety, and immunogenicity will help reduce unmet needs in the magnitude and duration of benefit. Additional validation of DBS and MRI-guided focused ultrasound may expand options for patients with toxin nonresponse.

KEYWORDS:

• Botulinum neurotoxin
• cervical dystonia
• movement disorders
• focal dystonia
• ultrasound
• EMG

Article highlights

• Botulinum neurotoxin (BoNT) is a first line therapy for cervical dystonia.

• There are five commercially available BoNT products currently, with comparable efficacy and tolerability.

• BoNT improves both motor and nonmotor symptoms associated with cervical dystonia, including pain, disability, anxiety, and depression.

• Muscle selection and dosing is chiefly guided by physical examination, though electromyographic and ultrasound guidance may enhance accuracy, especially of deeper muscles.

• Treatment failures may be due to misdiagnosis, incorrect muscle selection, underdosing, inaccurate muscle targeting, and less commonly toxin immunoresistance.

Declaration of interest

RA Hauser has received speaking fees from Acorda, ADAMAS, Amneal Pharmaceuticals, Cerevel, Inhibikase, Kyowa Kirin, Neurocrine Biosciences, Sunovion, and Supernus. He has also received consulting fees from AbbVie, Acsel Health, ADAMAS, Alterity, Amneal Pharmaceuticals, Avanex, Biogen Idec, BlueRock Therapeutics, Cerevance, EPI-Q, Enterin, Forsee Pharmaceuticals, Global Kinetics, Inhibikase, Jazz Pharmaceuticals, KeifeRX, Kyowa Kirin, MDCE Suzhou, MedRhythms, Medsphere, Merck, Merz, Neuroderm, Neurocrine Biosciences, Orion, Ovid Therapeutics, PD Neurotechnology, Pharma Two B, Regenxbio, Revance, Sage Therapeutics, Scion NeuroStim, Sio Gene Therapies, Stoparkinson, Sunovion, Supernus Pharmaceuticals, Tolmar, Tremor Research Group, Tris Pharma, UCB, and Vivifi Biotech. He also serves on a scientific advisory board for Stoparkinson and Inhibikase Therapeutics. RA Hauser also holds stock in Revance Therapeutics and has stock options in Enterin, Inhibikase Therapeutics, and Axial Therapeutics. RA Hauser, furthermore, has received intellectual property interests from a PD Diary through his University and acknowledges a Center of Excellence grant from the Parkinson Foundation. RA Hauser’s University has received research support from Annovis Bio, Inc., Artizan Biosciences, Parkinson’s & Movement Disorder Alliance, Inhibikase Therapeutics, AbbVie, Inc., Aeon Biopharma, Biogen MA, Bukwang Pharmaceutical Co., Ltd., Cavion, Inc., Cerevance, Inc., Cerevel Therapeutics, Cynapsus Therapeutics, Enterin, Inc., Genentech, Global Kinetics Corporation, Hoffman-La Roche Inc., Impax Laboratories, Integrative Research Laboratories Sweden, Lundbeck, Inc., the Michael J. Fox Foundation for Parkinson’s Research, the National Parkinson’s Foundation, Neuraly Inc., Neurocrine Biosciences, Neuroderm, Pharma Two B Ltd, Revance Therapeutics, Sage Therapeutics, Sanofi Pharmaceuticals, Scion NeuroStim, SunPharma, and UCB BioPharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One reviewer declares that they have received honoraria for advisory boards, consultancy work, and presentations from Allergan France, AbbVie, Merz Pharma France, and Ipsen Pharma. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.