Treatment of Dystonia: Medications, Neurotoxins, Neuromodulation, and Rehabilitation

Dystonia is a complex disorder with numerous presentations occurring in isolation or in combination with other neurologic symptoms. Its treatment has been significantly improved with the advent of botulinum toxin and deep brain stimulation in recent years, though additional investigation is needed to further refine these interventions. Medications are of critical importance in forms of dopa-responsive dystonia but can be beneficial in other forms of dystonia as well. Many different rehabilitative paradigms have been studied with variable benefit. There is growing interest in noninvasive stimulation as a potential treatment, but with limited long-term benefit shown to date, and additional research is needed. This article reviews existing evidence for treatments from each of these categories. To date, there are many examples of incomplete response to available treatments, and improved therapies are needed

FDA Approvals and Consensus Guidelines for Botulinum Toxins in the Treatment of Dystonia.

In 2016, the American Academy of Neurology (AAN) published practice guidelines for botulinum toxin (BoNT) in the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache. This article, focusing on dystonia, provides context for these guidelines through literature review. Studies that led to Food and Drug Administration (FDA) approval of each toxin for dystonia indications are reviewed, in addition to several studies highlighted by the AAN guidelines. The AAN guidelines for the use of BoNT in dystonia are compared with those of the European Federation of the Neurological Societies (EFNS), and common off-label uses for BoNT in dystonia are discussed. Toxins not currently FDA-approved for the treatment of dystonia are additionally reviewed. In the future, additional toxins may become FDA-approved for the treatment of dystonia given expanding research in this area

FDA Approvals and Consensus Guidelines for Botulinum Toxins in the Treatment of Dystonia.

In 2016, the American Academy of Neurology (AAN) published practice guidelines for botulinum toxin (BoNT) in the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache. This article, focusing on dystonia, provides context for these guidelines through literature review. Studies that led to Food and Drug Administration (FDA) approval of each toxin for dystonia indications are reviewed, in addition to several studies highlighted by the AAN guidelines. The AAN guidelines for the use of BoNT in dystonia are compared with those of the European Federation of the Neurological Societies (EFNS), and common off-label uses for BoNT in dystonia are discussed. Toxins not currently FDA-approved for the treatment of dystonia are additionally reviewed. In the future, additional toxins may become FDA-approved for the treatment of dystonia given expanding research in this area

Cerebellar Deep Brain Stimulation for Acquired Hemidystonia

BackgroundThe cerebellum's role in dystonia is increasingly recognized. Dystonia can be a disabling and refractory condition; deep brain stimulation can help many patients, but it is traditionally less effective in acquired dystonia. New surgical targets would be instrumental in providing treatment options and understanding dystonia further.ObjectiveTo evaluate the efficacy of deep brain stimulation of the cerebellum in acquired dystonia.MethodsWe report our management of a 37-year-old woman with severe left arm and leg dystonia, a complication of an ischemic stroke in childhood. She had already had 2 thalamotomies with only transient benefit. These procedures, in addition to her initial stroke that had damaged the basal ganglia, left traditional deep brain stimulation targets unavailable.ResultsAfter implantation of bilateral deep cerebellar nuclei, dystonia improved with a 40% reduction in severity on scales and subjective reports of improved posturing, gait, and pain. This improvement has been maintained for almost 2 years after implantation.ConclusionCerebellar stimulation has potential for therapeutic benefit in acquired dystonia and should be further explored

Phenomenology and Management of Subthalamic Stimulation‐Induced Dyskinesia in Patients With Isolated Dystonia

BackgroundThe pallidum has been the preferred DBS target for dystonia, but recent studies have shown equal or greater improvement in patients implanted in the STN.1 Transient stimulation-induced dyskinesia (SID) is frequently observed when stimulating this novel target, and there are no previously published video case reports of this phenomenon.CasesWe describe in detail the SID phenomenology experienced by 4 patients who had been implanted with STN DBS for isolated dystonia.ConclusionsSID can occur in focal, segmental, axial, or generalized distribution, can resemble levodopa-induced dyskinesia choreiform or dystonic movements observed in Parkinson's disease, and is generally transient and resolves with customized DBS programming. Providers should be aware that SID can occur after STN DBS when treating isolated dystonia and not assume movements are the result of worsening or spread of the underlying dystonia

Embedded adaptive deep brain stimulation for cervical dystonia controlled by motor cortex theta oscillations

Dystonia is a disabling movement disorder characterized by excessive muscle contraction for which the underlying pathophysiology is incompletely understood and treatment interventions limited in efficacy. Here we utilize a novel, sensing-enabled, deep brain stimulator device, implanted in a patient with cervical dystonia, to record local field potentials from chronically implanted electrodes in the sensorimotor cortex and subthalamic nuclei bilaterally. This rechargeable device was able to record large volumes of neural data at home, in the naturalistic environment, during unconstrained activity. We confirmed the presence of theta (3–7 Hz) oscillatory activity, which was coherent throughout the cortico-subthalamic circuit and specifically suppressed by high-frequency stimulation. Stimulation also reduced the duration, rate and height of theta bursts. These findings motivated a proof-of-principle trial of a new form of adaptive deep brain stimulation - triggered by theta-burst activity recorded from the motor cortex. This facilitated increased peak stimulation amplitudes without induction of dyskinesias and demonstrated improved blinded clinical ratings compared to continuous DBS, despite reduced total electrical energy delivered. These results further strengthen the pathophysiological role of low frequency (theta) oscillations in dystonia and demonstrate the potential for novel adaptive stimulation strategies linked to cortico-basal theta bursts

Enhancing Clinical Information Display to Improve Patient Encounters: Human-Centered Design and Evaluation of the Parkinson Disease-BRIDGE Platform

BackgroundPeople with Parkinson disease (PD) have a variety of complex medical problems that require detailed review at each clinical encounter for appropriate management. Care of other complex conditions has benefited from digital health solutions that efficiently integrate disparate clinical information. Although various digital approaches have been developed for research and care in PD, no digital solution to personalize and improve communication in a clinical encounter is readily available. ObjectiveWe intend to improve the efficacy and efficiency of clinical encounters with people with PD through the development of a platform (PD-BRIDGE) with personalized clinical information from the electronic health record (EHR) and patient-reported outcome (PRO) data. MethodsUsing human-centered design (HCD) processes, we engaged clinician and patient stakeholders in developing PD-BRIDGE through three phases: an inspiration phase involving focus groups and discussions with people having PD, an ideation phase generating preliminary mock-ups for feedback, and an implementation phase testing the platform. To qualitatively evaluate the platform, movement disorders neurologists and people with PD were sent questionnaires asking about the technical validity, usability, and clinical relevance of PD-BRIDGE after their encounter. ResultsThe HCD process led to a platform with 4 modules. Among these, 3 modules that pulled data from the EHR include a longitudinal module showing motor ratings over time, a display module showing the most recently collected clinical rating scales, and another display module showing relevant laboratory values and diagnoses; the fourth module displays motor symptom fluctuation based on an at-home diary. In the implementation phase, PD-BRIDGE was used in 17 clinical encounters for patients cared for by 1 of 11 movement disorders neurologists. Most patients felt that PD-BRIDGE facilitated communication with their clinician (n=14, 83%) and helped them understand their disease trajectory (n=11, 65%) and their clinician’s recommendations (n=11, 65%). Neurologists felt that PD-BRIDGE improved their ability to understand the patients’ disease course (n=13, 75% of encounters), supported clinical care recommendations (n=15, 87%), and helped them communicate with their patients (n=14, 81%). In terms of improvements, neurologists noted that data in PD-BRIDGE were not exhaustive in 62% (n=11) of the encounters. ConclusionsIntegrating clinically relevant information from EHR and PRO data into a visually efficient platform (PD-BRIDGE) can facilitate clinical encounters with people with PD. Developing new modules with more disparate information could improve these complex encounters even further

Thalamic deep brain stimulation for acquired dystonia in children and young adults: a phase 1 clinical trial

OBJECTIVE: To evaluate feasibility, preliminary efficacy and safety of bilateral ventralis oralis posterior/ventralis intermedius (Vop/Vim) deep brain stimulation (DBS) for the treatment of acquired dystonia in children and young adults. Pallidal DBS is efficacious for severe, medication refractory isolated dystonia, providing 50–60% long-term improvement. Unfortunately, pallidal stimulation response rates in acquired dystonia are modest and unpredictable with frequent non-responders. Acquired dystonia, most commonly caused by cerebral palsy, is more common in pediatric populations than isolated dystonia and more recalcitrant to standard treatments. Given the limitations of pallidal DBS in acquired dystonia, there is a need to explore alternative brain targets. Preliminary evidence suggests that thalamic stimulation may be efficacious for acquired dystonia. MATERIALS AND METHODS: Four participants, three with perinatal brain injuries and one with postencephalitic symptomatic dystonia, underwent bilateral Vop/Vim DBS and bimonthly evaluations for 12 months. The primary efficacy outcome was the change in Burke-Fahn-Marsden (BFMDRS) and Barry-Albright (BADS) Dystonia Rating Scales at 12 months. Video documentation was used for blinded ratings. Secondary outcomes included evaluation of spasticity (Modified Ashworth Scale), quality of life (PedsQL™, Modified Unified Parkinson Disease Rating Scale Part II, UPDRS-II) and neuropsychological assessments. Adverse events were monitored for safety. RESULTS: All participants tolerated the procedure well and there were no safety concerns or serious adverse events. There was an average improvement of 21.5% in BFMDRS motor subscale, but only 1.6% in BADS. Following blinded video review, dystonia severity ratings were even more modest. Secondary outcomes were however more encouraging, with the BFMDRS disability subscale improving by 15.7%, the PedsQL™ total score by 27%, and the modified UPDRS part II by 19.3%. Neuropsychological assessments were unchanged one year after surgery. DISCUSSION: Bilateral thalamic neuromodulation by DBS for severe, refractory acquired dystonia was well tolerated. Primary and secondary outcomes showed highly variable treatment effect sizes comparable to pallidal stimulation in this population. As previously described, improvements in quality of life and disability were not reflected in dystonia severity scales, suggesting a need for the development of scales specifically for acquired dystonia. (Clinical trial number: NCT03078816