Therapeutic strategies in dystonia have evolved considerably in the past few decades. Three major treatment modalities include oral medications, botulinum toxin injections and surgical therapies, particularly deep brain stimulation. Although there has been a tremendous interest in the later two modalities, there are relatively few recent reviews of oral treatment. We review the medical treatment of dystonia, focusing on three major neurotransmitter systems: cholinergic, GABAergic and dopaminergic. We also provide a practical guide to medication selection, therapeutic strategy and unmet needs.

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Medical treatment of dystonia

Objective: To determine the frequency of medication use in patients with dystonia enrolled in an international biorepository study. Methods: In a cross-sectional analysis, we included 2,026 participants enrolled at 37 sites in the United States, Canada, Europe, and Australia through Project 1 of the Dystonia Coalition, an international biorepository study. The primary aim was to assess the frequency of medication classes recommended for treating patients with dystonia, and the secondary aim was to compare characteristics (disease type, age, sex, duration of disease, comorbid conditions, severity). Results: Querying the database for the presence of any medication for dystonia used (includes both injectable and oral therapy), we found 73% using medications (n = 1,488) and 27% using no dystonia medications (n = 538). Furthermore, 61% of the total sample used botulinum toxin (BoNT) therapy alone or in combination. Differences were found in medication use patterns by dystonia type, with the lowest oral medication use in focal dystonia and highest use in generalized dystonia; by region, with highest BoNT therapy rate reported in Italy and the lowest in the Northeast region of the United States; and by focal dystonia subtype, with highest BoNT therapy alone in blepharospasm and spasmodic dysphonia (49%) and lowest in other cranial dystonia (32%). Conclusions: The majority of patients with dystonia enrolled in the Dystonia Coalition Project 1 were using medications to treat their dystonia. Overall, a complex picture of medication use patterns emerged, with factors such as region, disease duration, type of dystonia, disease severity, and psychiatric comorbidities all playing a significant role.

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Dystonia treatment: Patterns of medication use in an international cohort

Introduction: Botulinum toxin (BT) is used in many medical specialties to treat muscle hyperactivity, exocrine gland hyperactivity and pain disorders. BT drugs consist of botulinum neurotoxin (BNT), complexing proteins (CP) and excipients. Antibodies can be formed against BNT and CP. When they are formed against BNT (BTAB) they can block BT’s therapeutic efficacy thus producing antibody induced therapy failure (ABTF).Areas covered: BT applied and BTAB are in a functional balance within the body. ABTF is rare, but influences the treatment algorithms of BT therapy considerably. ABTF risk factors include BT doses given, interinjection intervals, booster injections and immunological quality of the BT drug. Testing for BTAB and interpretation of ABTF is complicated. As management of ABTF is frustrating, prevention of ABTF is of major importance. Improved antigenicity of new BT drugs may improve treatment algorithms of BT therapy, substandard antigenicity may very likely be their end.Expert commentary: ...

Immunological aspects of botulinum toxin therapy

This consensus paper is derived from a meeting of an international group of 19 neurological rehabilitation specialists with a combined experience of more than 250 years (range 4-25 years; mean 14.1 years) in treating post-stroke spasticity with botulinum toxin A. The group undertook critical assessments of some recurring practical challenges, not yet addressed in guidelines, through an exten-sive literature search. They then discussed the results in the light of their individual clinical experience and developed consensus statements to present to the wider community who treat such patients. The analysis provides a comprehensive overview of treatment with botulinum toxin A, including the use of adjunctive therapies, within a multidisciplinary context, and is aimed at practicing clinicians who treat patients with post-stroke spasticity and require further practical guidance on the use of botulinum toxin A. This paper does not replicate information published elsewhere, but instead aims to provide practical advice to help optimize the use of botulinum toxin A and maximize clinical outcomes. The recommendations for each topic are summarized in a series of statements. Where published high-quality evidence exists, the recommendations reflect this. However, where evidence is not yet conclusive, the group members issued statements and, in some cas-es, made recommendations based on their clinical experience.

A practical guide to optimizing the benefits of post-stroke spasticity interventions with botulinum toxin A: An international group consensus.

Background Dystonia may have different neuroanatomical substrates and pathophysiology. This is supported by studies on the motor system showing, for instance, that plasticity is abnormal in idiopathic dystonia, but not in dystonia secondary to basal ganglia lesions. Objective The aim of this study was to test whether somatosensory inhibition and plasticity abnormalities reported in patients with idiopathic dystonia also occur in patients with dystonia caused by basal ganglia damage. Methods Ten patients with acquired dystonia as a result of basal ganglia lesions and 12 healthy control subjects were recruited. They underwent electrophysiological testing at baseline and after a single 45-minute session of high-frequency repetitive somatosensory stimulation. Electrophysiological testing consisted of somatosensory temporal discrimination, somatosensory-evoked potentials (including measurement of early and late high-frequency oscillations and the spatial inhibition ratio of N20/25 and P14 components), the recovery cycle of paired-pulse somatosensory-evoked potentials, and primary motor cortex short-interval intracortical inhibition. Results Unlike previous reports of patients with idiopathic dystonia, patients with acquired dystonia did not differ from healthy control subjects in any of the electrophysiological measures either before or after high-frequency repetitive somatosensory stimulation, except for short-interval intracortical inhibition, which was reduced at baseline in patients compared to control subjects. Conclusions The data show that reduced somatosensory inhibition and enhanced cortical plasticity are not required for the clinical expression of dystonia, and that the abnormalities reported in idiopathic dystonia are not necessarily linked to basal ganglia damage. © 2020 International Parkinson and Movement Disorder Society.

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Defective Somatosensory Inhibition and Plasticity Are Not Required to Develop Dystonia

Treatment of dystonias is generally symptomatic. To produce sufficient therapy effects, therefore, frequently a multimodal and interdisciplinary therapeutic approach becomes necessary, combining botulinum toxin therapy, deep brain stimulation, oral antidystonic drugs, adjuvant drugs and rehabilitation therapy including physiotherapy, occupational therapy, re-training, speech therapy, psychotherapy and sociotherapy. This review presents the recommendations of the IAB-Interdisciplinary Working Group for Movement Disorders Special Task Force on Interdisciplinary Treatment of Dystonia. It reviews the different therapeutic modalities and outlines a strategy to adapt them to the dystonia localisation and severity of the individual patient. Hints to emerging and future therapies will be given.

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Strategies for treatment of dystonia

Botulinum toxin (BT) therapy is a complex and highly individualised therapy defined by treatment algorithms and injection schemes describing its target muscles and their dosing. Various consensus guidelines have tried to standardise and to improve BT therapy. We wanted to update and improve consensus guidelines by: (1) Acknowledging recent advances of treatment algorithms. (2) Basing dosing tables on statistical analyses of real-life treatment data of 1831 BT injections in 36 different target muscles in 420 dystonia patients and 1593 BT injections in 31 different target muscles in 240 spasticity patients. (3) Providing more detailed dosing data including typical doses, dose variabilities, and dosing limits. (4) Including total doses and target muscle selections for typical clinical entities thus adapting dosing to different aetiologies and pathophysiologies. (5) In addition, providing a brief and concise review of the clinical entity treated together with general principles of its BT therapy. For this, we collaborated with IAB-Interdisciplinary Working Group for Movement Disorders which invited an international panel of experts for the support.

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Eckart Altenmueller

Papers

Strategies for treatment of dystonia

Consensus guidelines for botulinum toxin therapy: general algorithms and dosing tables for dystonia and spasticity