Dystonia’s Hidden Burden: What Treatments Actually Do for the Mind, Pain, and Sleep

Dystonia has long been defined by what it does to the body: muscles pulling involuntarily, postures twisting into unnatural shapes, eyelids clamping shut, a voice breaking under spasms. But a growing body of evidence suggests that the most disabling features of this neurological disorder may not be visible at all. Anxiety, depression, chronic pain, sleep disruption, and subtle cognitive changes now appear to be independent features of the disease itself, sometimes out of proportion to motor severity and sometimes predating the onset of any movement symptoms. A new systematic review published in the journal Dystonia on 30 June 2025 by Dana Sugar and Sarah Pirio Richardson of the University of New Mexico Health Sciences Center and the New Mexico VA Healthcare System takes the first comprehensive look at what happens to these non-motor symptoms when dystonia patients receive treatment, and the answer is sobering: in most cases, the treatments were primarily aimed at motor symptoms, and their effects on the mind, pain, and sleep were inconsistent at best.

The review is notable for its scope and its candor. Sugar and Pirio Richardson searched PubMed, Embase, Web of Science, and Cochrane databases for studies published between 2019 and 2025 that described non-motor symptoms in dystonia and changes after treatment. From 408 records identified after removal of duplicates, 89 met the criteria for full-text review, and ultimately 22 reports plus 10 additional studies found through reference screening were included. The authors stratified the evidence by treatment type, including deep brain stimulation, ablative surgery, botulinum toxin injection, and non-invasive therapies such as physical therapy and psychotherapy, and by dystonia body distribution, distinguishing generalized from focal and segmental forms. The picture that emerges is one of a field still in its infancy, where non-motor outcomes are almost always secondary endpoints, scales are heterogeneous, and meta-analysis is precluded by the sheer variety of assessment tools used across studies.

The neuroimaging literature offers a unifying explanation for why dystonia patients suffer so much beyond their movements. Dystonia is increasingly understood as a network disorder, and resting-state functional imaging studies have documented abnormal activity in brain structures involved in both motor and non-motor networks. The cerebellum, which modulates input related to sensorimotor, salience, and default mode networks, has been implicated across non-motor symptoms including pain perception, depression, and anxiety. In cervical dystonia, social phobia is common and appears to arise from a sense of body deformation and anticipation of negative perception by others, a self-conscious hypervigilance in public spaces that is out of proportion to motor severity and leads to self-stigmatization, isolation, and depression. This perception is thought to reflect erroneous assignment of salience to unimportant stimuli, involving salience network structures like the amygdala and cerebellar structures that interact with the salience network. The severity of the neuropsychiatric burden is stark: 32.3 percent of patients with isolated dystonia report a history of suicidal behavior, a rate significantly higher than that of the general population.

Sleep and wake symptoms are equally prevalent and equally neglected. Fatigue and excessive daytime sleepiness significantly impact quality of life in dystonia patients, influencing their perceptions of the disease and their satisfaction with treatment. Compared to healthy controls, patients with dystonia exhibit reduced daytime activity as measured by both self-report and accelerometry data. Sleep disturbances are present in up to 70 percent of patients with cervical dystonia, and across various dystonia subtypes patients experience higher rates of insomnia, poorer sleep quality, reduced sleep duration, and lower sleep efficiency. Dysregulation of circadian rhythm networks, particularly cerebellar hyperactivity, has been proposed as a potential contributing factor to these sleep-wake disturbances. In Meige syndrome, a segmental form of dystonia affecting the face and neck, sleep disorders were observed in 23 percent of participants in one study, typically developing three to fifteen years before the onset of motor symptoms, highlighting sleep dysfunction as a primary non-motor feature of the disorder rather than a consequence of it.

Pain, perhaps the most tangible of the non-motor symptoms, has the most consistent treatment response. In cervical dystonia, pain arises from complex mechanisms including increased muscle contraction affecting muscle spindles and their associated pain receptors, alterations in peripheral sensitivity due to neuropeptide activity, abnormal processing of pain pathways, and impaired inhibitory signalling. Patients with blepharospasm frequently experience eye pain and photophobia. Across four studies involving 141 patients with cervical dystonia, botulinum toxin consistently relieved pain as measured by the McGill Pain Questionnaire, the Toronto Western Spasmodic Torticollis Rating Scale pain subscale, and the Pain Numeric Rating Scale. In a large case series of 408 patients with oromandibular dystonia treated with botulinum toxin injections, significant improvements were found in pain, sleep, mood, and psychosocial functioning as assessed by the Oromandibular Dystonia Questionnaire-25, with idiopathic patients demonstrating greater improvements than those with tardive dystonia. However, pain may recur between injection cycles, and its persistence is associated with lower patient satisfaction with treatment.

The surgical evidence is far more mixed. Deep brain stimulation of the globus pallidus internus, the subthalamic nucleus, and the ventral intermediate nucleus of the thalamus has been investigated over the past five years in thirteen publications, including one randomized controlled trial, six case series, five prospective non-controlled studies, and one prospective crossover double-blind study. In a randomized double-blind crossover trial of six patients with laryngeal dystonia, thalamic deep brain stimulation improved mood as assessed with the Beck Depression Inventory, while cognition as measured by the Montreal Cognitive Assessment was not impacted. In a study of 37 patients with cervical dystonia, pallidal deep brain stimulation significantly improved pain as measured after five years of stimulation, but did not find an impact on mood as measured by the Hospital Anxiety and Depression Scale despite significant motor improvement. In direct comparisons of subthalamic versus pallidal stimulation in 71 patients with isolated dystonia, both targets produced equivalent long-term benefits for mood and pain, though the subthalamic group experienced improvements in motor and mood symptoms within one month while similar benefits in the pallidal group were not observed until six months. Neither target had an impact on cognitive function as assessed by the Mini Mental Status Exam and the Montreal Cognitive Assessment.

Ablative therapies, including radiofrequency and focused ultrasound ablation of the pallidothalamic tracts, show promise in targeting both motor and non-motor symptoms including mood and pain, but come with inherent risks. In 2022, a group reported on 35 patients with cervical dystonia who underwent unilateral radiofrequency ablation of Forel’s Field H1, finding that pain scores improved by 40 percent as measured by the Toronto Western Spasmodic Torticollis Rating Scale pain subscale, but with a high incidence of adverse events in 50 percent of patients. Expanding upon this work, the same group reported on ten patients with cervical dystonia in 2024 who underwent focused ultrasound pallidothalamic tractotomy, demonstrating modest improvement at six months in depression, anxiety, and apathy as assessed by the Beck Depression Inventory, the Beck Anxiety Inventory, and the Apathy Evaluating Scale. Adverse events included prolonged loss of hand dexterity in 30 percent of participants, thought to be related to associated hypotonia. Both studies were limited by short-term follow-up ranging from six to eighteen months, leaving the important question of long-term benefits to future study.

Botulinum toxin, the mainstay of focal dystonia treatment, consistently improved mood and pain across multiple dystonia populations, though the mood benefit appears transient. Over the past five years, six studies examined the impact of botulinum toxin injection on mood symptoms in cervical dystonia. Four studies found improvements in mood at the peak of botulinum toxin effect, four to six weeks post-injection, in a combined total of 121 patients, measured using various scales including the Beck Anxiety Inventory, the Beck Depression Inventory, the Hamilton Anxiety and Depression Rating Scales, the State-Trait Anxiety Inventory, and the Toronto Western Spasmodic Torticollis Rating Scale psych subscale. In contrast, two studies with follow-up intervals ranging from three months to two years reported no sustained impact on mood symptoms in a combined 105 patients. These findings suggest that botulinum toxin has an immediate impact on mood symptoms but may not produce sustained modifications. Notably, changes in non-motor symptoms including mood, pain, and sleep did not correlate with changes in motor severity, supporting non-motor symptoms as primary features of cervical dystonia independent of motor symptom severity and suggesting a direct effect of botulinum toxin on these symptoms.

Non-invasive therapies, including physical therapy, psychotherapy, and behavioral interventions, produced mixed results but offer important insights into the patient experience. In one randomized controlled trial, 40 patients with cervical dystonia received specialized physical therapy while 32 patients followed a standard physical therapy protocol, and both groups showed significant improvements in pain and mood as measured by the Toronto Western Spasmodic Torticollis Rating Scale pain scale, the Pain Numeric Rating Scale, the Beck Anxiety Inventory, and the Beck Depression Inventory, though no between-group differences were observed at twelve-month follow-up. Another negative crossover randomized controlled trial involving 17 patients with cervical dystonia compared botulinum toxin treatment alone, botulinum toxin with kinesiotaping, and botulinum toxin with sham taping, finding no differences between groups in non-motor symptoms as measured by the Dystonia Non-Motor Symptoms Questionnaire, the Hospital Anxiety and Depression Scale, and the Pittsburgh Sleep Quality Index. An internet-based cognitive behavioral therapy program compared to routine care in a small randomized controlled study of 20 patients with cervical dystonia over a six-month period showed trends toward improved anxiety and depression scores, and participants reported that the treatment was beneficial, but no significant differences were observed between the two groups. A survey of 118 participants with cervical dystonia found that illness perception and coping strategies accounted for 59 percent of the variance in anxiety and 61 percent of the variance in depression and health-related quality of life, highlighting the importance of these psychological factors in adjustment to the disease.

The authors of the review are careful to acknowledge the limitations of the evidence base. The review protocol was not published and was expanded after the initial PubMed review to include the other databases, introducing the possibility of reporting bias. Within the primary studies, common biases included performance bias given the lack of a control arm in most reports, and outcome reporting bias, especially as non-motor symptoms were mostly secondary outcomes and non-significant findings were less likely to be included for publication. The overall quality of the studies reviewed was limited by small sample sizes and the absence of control groups. Meta-analysis of the reviewed data is precluded by the heterogeneous use of scales in non-motor symptom assessment, a well-documented challenge in dystonia research. Several validated scales have been developed for distinct dystonia subgroups, but these generally focus on motor symptoms, limiting their capacity to comprehensively assess non-motor outcomes. Progress has been made in the past five years, including the development of a digital patient-centered outcome tool to measure non-motor symptoms in cervical dystonia, the Pain Scale for Adult-Onset Idiopathic Dystonia and its validation in cervical dystonia, the Dystonia Pain Classification System, and the Oromandibular Dystonia Rating Scale, which includes non-motor domains.

Perhaps the most provocative finding of the review is the emerging evidence that dystonia patients can be phenotyped into distinct subgroups based on non-motor symptom severity rather than motor symptom severity. Recent studies have identified two phenotypes within the cervical dystonia population: one motor-predominant, with fewer non-motor symptoms, lower disability, and better quality of life, and another non-motor-predominant, with higher rates of depression, anxiety, sleep dysfunction, cognitive complaints, and pain. These subgroups did not differ in sex, motor severity, duration of dystonia, or the presence of tremor or alleviating maneuvers, though a potential age difference was noted, with the non-motor-predominant group being older. Regarding sex differences, other research has shown that women with blepharospasm have a higher frequency of non-motor symptoms and are more likely to have multiple comorbid non-motor symptoms, and women with cervical dystonia report worse health-related quality of life compared to men. The impact of sex on dystonia and non-motor symptoms warrants further investigation, especially given the increased penetrance of cervical dystonia in women, who are affected at least twice as often as men.

The theories of overlapping motor and non-motor network dysfunction suggest that motor treatments could potentially influence non-motor symptoms, and while this hypothesis is plausible and offers practical benefits, evidence supporting a sustained and clinically significant non-motor response to motor treatments remains inconclusive. The findings of this systematic review do not clarify whether the non-motor symptoms of dystonia are primary features of the disease or secondary to motor symptoms, and it remains likely that both factors contribute to the patient experience. Similar to Parkinson’s disease, a tailored approach addressing each patient’s specific combination of non-motor features, with symptom-specific interventions, may be necessary for optimal management. The authors conclude that better detection and treatment of non-motor symptoms in dystonia are needed to wholly treat patients with this disorder, and that future research must focus on high-quality studies with non-motor improvement as a primary outcome, standardized rating scales across studies, and refined phenotyping of dystonia subgroups to facilitate meta-analyses and improve the reproducibility of treatment outcomes.

Subject of Research: Neuroscience

Article Title: Treating non-motor symptoms in dystonia: a systematic review

Article References: Sugar, D., & Pirio Richardson, S. (2025). Treating non-motor symptoms in dystonia: a systematic review. Dystonia, 4, Article 14545. https://doi.org/10.3389/dyst.2025.14545

Image Credits: AI Generated

DOI: 10.3389/dyst.2025.14545

Keywords: dystonia, non-motor symptoms, botulinum toxin, deep brain stimulation, systematic review, neurology, pain, quality of life, Treating, non-motor, symptoms, systematic