Dystonias (except torticollis)

Disease/Disorder

Definition

Dystonia is a movement disorder characterized by involuntary muscle contractions, either sustained or intermittent, resulting in repetitive movements and/or abnormal postures. Dystonic movements are typically twisting and patterned. Symptoms vary with body position, emotions, attempts to perform tasks or voluntary movements, and with levels of consciousness.¹

Etiology

The etiology of pediatric dystonia is quite heterogeneous. Based on the revised classification scheme from 2013, there are two descriptors of etiology¹ 

• Nervous system pathology
  • Evidence of degeneration
  • Evidence of structural lesions
  • No evidence of degeneration or structural lesion
• Pattern of inheritance
  • Inherited, including isolated inherited dystonias (e.g., DYT1 or DYT6), combined inherited dystonias (e.g., myoclonus dystonia syndrome, dopa-responsive dystonia), or complex inherited dystonia due to hereditary neurodegenerative and metabolic disorders.
  • Acquired, such as cerebral palsy, medications, autoimmune disorders
  • Idiopathic, which have an unknown cause

Epidemiology including risk factors and primary prevention

Prevalence estimates range between 2 to 50 cases per million for early-onset dystonia (<26 years) and 30 to 7320 cases per million for late-onset dystonia (>26 years).² This large variability is likely due to the heterogeneity of dystonia, so determining the true frequency is difficult. 

Family history is the most important known risk factor of dystonia. Mutations in the DYT1 gene are the most common hereditary form of early-onset dystonia.² Most likely, dystonic syndromes develop due to genetic and environmental causes. Conditions such as perinatal brain injury, infections, reactions to drugs, or vascular abnormalities can predispose to dystonia. 

Patho-anatomy/physiology

Evidence suggests that the pathophysiology of dystonic syndromes involves the complex dopaminergic system. In a simple model, the physiological role of dopamine can be described as regulating the balance between the direct and indirect striatal pathways, which respectively select agonist muscles and inhibit antagonists to allow for movement execution.³ A failure of this mechanism can lead to muscular co-contractions and overflow of muscular activity, two hallmarks of dystonia.

However, this model of dystonia may be an oversimplification. Other circuits such as the cerebello-thalamic network involving the cholinergic system are likely to play a role. Another issue is delineating the mechanism underlying focal versus generalized dystonia. Finally, despite patients having the same genotype, significant phenotypic variability has been observed.³ Thus, we are far from understanding all the mechanisms underlying dystonia and dystonic syndromes.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

The phenomenology of dystonia varies with temporal disease progression, as well as with momentary triggers such as attempting voluntary action, changes in body posture, and psychological state. Characterizing the temporal pattern is clinically important in regards to diagnosis and treatment. Dystonia can be characterized as having either a static or progressive disease course with 4 different patterns of variability^1,4

• Persistent: Occurs approximately the same extent throughout the day. 
• Action-specific: Occurs only during a particular activity or task. 
• Diurnal fluctuations: Fluctuates during the day, with recognizable circadian variations in occurrence, severity, and phenomenology. 
• Paroxysmal: Sudden, self-limited episodes usually induced by a trigger with return to pre-existing neurological state.

Specific secondary or associated conditions and complications

Because of the diverse etiologies of dystonia and dystonic syndromes, there is potential for a large range of secondary or associated conditions and complications. These include but are not limited to^4,5

• Additional movement disorders: tremor, myoclonus, parkinsonism
• Dysmorphisms secondary to genetic mutations: facial dysmorphism, microcephaly, short stature
• Neurological conditions/symptoms: seizures, developmental delay, hypotonia or spasticity, ataxia
• Pain syndromes as a result of abnormal postures and sustained muscle contractions
• Contractures, skin breakdown, or wounds secondary to poor positioning

Essentials of Assessment

History

History and physical examination can be focused on classification developed by an international consensus committee based on Axis I (clinical characterization) and Axis II (etiology).⁴

• Axis I: Clinical characterization
  • Age of onset
    • Infancy < 2y
    • Childhood 3-12y
    • Adolescence 13-20y
    • Early adulthood 21-40y
    • Later adulthood >40y
  • Body distribution
    • Focal
    • Segmental – two or more contiguous body regions
    • Multifocal – two or more noncontiguous regions
    • Generalized – trunk with at least two other body regions
    • Hemidystonia
  • Temporal pattern
    • Persistent
    • Paroxysmal
      • Triggered by physical or emotional stress
      • Task specific (e.g., writer’s cramp, musicians)
    • Diurnal
    • Static vs progressive disease course
  • Clinical syndrome
    • Isolated pure dystonia
    • Combined or complex syndromes
      • Dystonia-parkinsonism
      • Myoclonus-dystonia
      • Other neurologic and systemic abnormalities (Kayser-Fleischer rings, retinitis pigmentosa, optic atrophy, tremor, facial dysmorphism)
• Axis II: Etiology
  • “Inherited” with genetic predisposition: Family history of movement disorders
    • Most severe form ‘generalized dystonia’ is more prevalent in Ashkenazi Jewish population (11.1/100,000)⁴
  • Acquired
    • Brain injury – cerebral palsy, stroke, neoplasm, medications (tardive syndrome), autoimmune encephalopathies
    • Intrauterine crowding
    • Nasopharyngeal infections, posterior fossa/cervical spinal cord lesions
    • Compensation for visual disturbances (diplopia/nystagmus) or Sandifer’s syndrome
    • Psychogenic causes

Physical examination

Dystonia describes abnormal movements or postures caused by sustained or intermittent muscle contraction. It is more prominent with action and sometimes completely absent when the patient is at rest or asleep, which makes it important to assess both active and passive movements. It is not velocity-dependent, which is a key feature of spasticity, but they are not mutually exclusive. It is not uncommon for both dystonia and spasticity to be present at the same time. The dynamic feature may often progress, and the postures may progress to be fixed.⁴

Other interesting features include “overflow” posturing, which is involuntary muscle contractions of unaffected body parts when the dystonic limb performs a task, and “Geste antagoniste” or “sensory trick” in focal dystonia when a gesture or touch may transiently alleviate the symptoms of dystonia.⁵

Clinical functional assessment: mobility, self-care, cognition/behavior/affective state

There are multiple clinical scales reported to measure dystonia, particularly assessing severity, duration, amplitude/range impacted, provoking factors, and activity/participation level.⁶ Barry-Albright Dystonia Scale (BADS) is the most well-established and commonly used clinical tool. Others include Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), Dyskinesia Impairment Scale (DIS), Movement Disorder-Childhood Rating Scale (MD-CRS), and Unified Dystonia Rating Scale (UDRS). 

The Hypertonia Assessment Tool (HAT) for children was developed to differentiate the subtypes of hypertonia: dystonia, spasticity, and rigidity.⁷ The HAT is a 7-item clinical assessment tool designed for children aged 4 to 19 years applied to each limb separately. It consists of 2 spasticity items, 2 rigidity items, and 3 dystonia items, each scored as either present or absent. If 1 subitem is scored as present, then some form of hypertonia is present. If 2 or more subitems from different categories are scored as present then the child has mixed hypertonia.

Kinematic measures are most familiar in the clinical evaluation of children with dystonia in the form of gait analyses.

Laboratory studies

Due to the remarkable heterogeneity of clinical manifestations and causes, universal workup is challenging and often incomplete.⁸ Blood tests may not reveal any abnormality, such as in isolated idiopathic dystonia, but remain an important piece of the diagnostic work-up to identify treatable conditions.⁹

• Metabolic screening is important in infants or young children who present with encephalopathy.
• Additional workup should be based on careful history and physical examination but is essential for Wilson’s disease, glutaric aciduria, vitamin E deficiency, GLUT1 deficiency, and autoimmune disease.

Imaging

Brain MRI may either exclude or identify structural, degenerative, and metabolic lesions.^4,9

Supplemental assessment tools

Genetic testing can be targeted to single gene, targeted gene panel, broad gene panel, or whole exome sequencing depending on suspected syndromic etiologies. Identifying a genetic cause of dystonia is important, as some forms can inform prognosis and predict treatment response.⁹

Early prediction of outcomes

Sometimes isolated dystonia is the sole initial presentation of inherited neurologic syndrome. Early discovery and treatment may prevent permanent neurologic sequelae.

Environmental

A subset of dystonia is triggered by emotional and physical stress at the molecular level.⁴

Social role and social support system

Counseling and social support systems are essential since correct diagnosis may take several years. It may also take an extended period of time to achieve the optimal benefit from treatment. Since there are no available cures, empiric therapy focuses on symptom management.¹⁰ A list of patient advocacy groups is available at: www.rdcrn.org/cms/dystonia/Get-Involved/Patient-Advocacy.

Professional issues

Serial genetic testing with targeting a single or small number of potential diagnoses may be frustrating and financially burdensome. The dystonia gene panel is not standardized across the laboratories and may cost as much as brain MRI.⁸ 

Since a major approach to treat dystonia is symptom management, a strategy to do a focused investigation only on disorders with existing treatment may not be beneficial for families who have been struggling in search for diagnostic answers. It also may limit information for prognostic counseling and opportunity to discuss potential risk for family members. 

Rehabilitation Management and Treatments

Available or current treatment guidelines

• Targeted therapy for treatable secondary dystonia
• Physical therapy, stretching, strengthening exercises, yoga, chiropractic therapy, and other non-invasive conservative modalities have shown variable results without consistent benefits.
• Physical and occupational therapy can mobilize frozen joints, limit contractures, and provide appropriate assistive devices. Experienced therapists can utilize geste antagoniste to reduce dystonic symptoms. 
• All oral medications for dystonia are off-label use, and there are no medications which have undergone rigorous trials for efficacy.
  • As a subset of patients have dopa-responsive dystonia (DRD), it is common practice to administer a trial of levodopa for several weeks to any child with isolated dystonia of unknown cause. 
  • Anticholinergic (trihexyphenidyl, benztropine)
  • GABAergic (clonazepam, baclofen)
  • Anticonvulsants (carbamazepine, valproic acid)
• Botulinum toxins are first line therapy for focal and segmental dystonia. 
• Surgical procedures are available when conservative measures fail.
  • Selective peripheral denervation in select group of cervical dystonia
  • Intrathecal baclofen
  • Deep brain stimulation (DBS) is the most commonly offered surgical treatment
    • DYT1 dystonia has a robust response to pallidal deep brain stimulation (GPi DBS)
  • Central nervous system ablation with focused ultrasound

At different disease stages¹¹

Coordination of care

• Counseling to help patients understand the diagnosis, available treatments, set realistic expectations, and to provide additional resources for support
• Adjunctive services with physical, occupational, and speech therapies
• Adequate psychological support as living with dystonia can impact emotional and psychological well-being

Patient & family education

• Keep track of triggers that either exacerbate or alleviate symptoms
• Adequate sleep, nutrition, and exercise as able can improve symptoms
• Maintaining bowel and bladder health can improve comfort and thereby have a positive impact on motor symptoms
• Depression and anxiety can worsen motor symptoms, while stress reduction and relaxation can improve symptoms and quality of life

Measurement of Treatment Outcomes including those that are impairment-based, activity participation-based and environmentally-based

The goal of treatment of dystonia is largely to provide symptomatic relief of abnormal movement, posture, pain, discomfort, and associated comorbidities. Therapy is individualized and tailored to patients based on age, anatomic distribution of dystonia, and potential risk of adverse effects. Selection of therapeutic agent or procedure is often guided by personal experience, case reports, or anecdotal evidence because robust clinical trials are lacking. The previously mentioned clinical scales (i.e. BADS, BFMDRS, DIS, MD-CRS, and UDRS) may be used to qualitatively assess dystonia and response to treatment. However, the assessment of various therapeutic interventions in dystonia is problematic due to the heterogeneity of etiology and clinical manifestations, as well as difficulty translating and measuring the effect of dystonia on function.¹²

Translation into Practice:  practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Medications

• Trihexyphenidyl – Efficacy limited and side effects common due to dosing. Seems more effective and better tolerated in childhood onset dystonia.
• Carbidopa-Levodopa – Effective in some with focal dystonias, but less so with craniofacial and cervical dystonia. Adequate trial in children and adults = reaching daily dose of 20 mg/kg x 1 month.
• Tetrabenazine – May be effective in idiopathic primary dystonia and more so in those with tardive dystonia.
• Dopamine receptor antagonists – Not commonly used due to potential side effects of tardive dyskinesia. 
• Enteral Baclofen – Typically not effective in the adult population, with benzodiazepines and anticholinergic agents favored in this population.¹³ However, enteral baclofen is recommended as first-line pharmacotherapy for pediatric patients with cerebral palsy and generalized dystonia interfering with either activities of daily living or ease of caregiving.¹⁴
• Benzodiazepines – Commonly used especially in blepharospasm and tremulous or jerky quality type dystonias.⁶

Cutting Edge/Emerging and Unique Concepts and Practice

Promising experimental pharmacotherapeutics are dipraglurant and sodium oxybate. Dipraglurant modulates the metabolic glutamate receptor type 5 (mGluR5), which is involved in the development of dystonia in DYT1 rodent models. Sodium oxybate is a GABA analog and is being studied in alcohol-responsive spasmodic dysphonia patients.¹⁵

DBS has been shown to be an effective surgical option for medication refractory dystonia, with the Globus Pallidus interna (GPi) being the most regularly targeted area in dystonia. An alternative emerging target is the subthalamic nucleus (STN). In terms of efficacy, a meta-analysis discovered no difference between the two targets, though each target is associated with its own stimulation-related side effects. Both targets are associated with side effects such as paresthesias, dysarthria, dysphagia, balance problems, and gait disturbances, but mood symptoms (dysphoria, depression, and anxiety), weight gain, and dyskinesias are linked to the STN, while bradykinesia and coordination problems are linked to the GPi.¹⁶

MRI-guided focused ultrasound (MRgFUS) is an emerging modality that uses high-intensity ultrasound to precisely ablate targets in the brain. This technique is incisionless, potentially avoiding the surgical risks of a burr hole and transcortical tract to reach the anatomical target. There is some evidence of efficacy in essential tremor and Parkinson’s disease, but to date, there is no study aggregating the evidence of MRgFUS in dystonia.¹⁷

Gaps in the Evidence-Based Knowledge

A better understanding of pathophysiology will be important in developing disease-modifying therapies as opposed to symptom control. At the same time, studies in the pediatric population will help establish dosing guidelines. Further studies on safety and effectiveness of agents for symptom management such as anticonvulsants, mexilitine, amphetamines, cannabidiol, cyproheptadine, and others are also needed to guide treatment.^6,10,15

References

1. Albanese A, Bhatia K, Bressman SB, et al. Phenomenology and classification of dystonia: A consensus update. Movement disorders. 2013;28(7):863-873. doi: 10.1002/mds.25475.
2. Defazio G. The epidemiology of primary dystonia: Current evidence and perspectives. European journal of neurology. 2010;17:9-14. doi: 10.1111/j.1468-1331.2010.03053.x.
3. Ribot B, Aupy J, Vidailhet M, et al. Dystonia and dopamine: From phenomenology to pathophysiology. Progress in neurobiology. 2019;182:101678. doi: 10.1016/j.pneurobio.2019.101678.
4. Meijer IA, Pearson TS. The twists of pediatric dystonia: Phenomenology, classification, and genetics. Seminars in pediatric neurology. 2018;25:65-74. doi: 10.1016/j.spen.2018.02.001.
5. Jankovic J. Dystonia. 1st ed. New York: Springer Publishing Company; 2005. https://ebookcentral.proquest.com/lib/[SITE_ID]/detail.action?docID=289755.
6. Stewart K, Harvey A, Johnston LM. A systematic review of scales to measure dystonia and choreoathetosis in children with dyskinetic cerebral palsy. Developmental medicine and child neurology. 2017;59(8):786-795. doi: 10.1111/dmcn.13452.
7. Pavone L, Burton J, Gaebler-Spira D. Dystonia in childhood: clinical and objective measures and functional implications. Journal of child neurology. 2012;28(3):340-350. doi: 10.1177/0883073812444312.
8. Jinnah H. The dystonias. Continuum (Minneapolis, Minn.). 2019;25(4):976-1000. doi: 10.1212/CON.0000000000000747.
9. Balint B, Mencacci NE, Valente EM et al. Dystonia. Nature review disease primers. 2018;4(25). doi: 10.1038/s41572-018-0023-6.
10. Jinnah H. “Treatment Strategies for Dystonia: Medical and Surgical.” Dystonia Coalition, Rare Diseases Clinical Research Network, www.rarediseasesnetwork.org/cms/dystonia/Healthcare-Professionals/Treatment
11. Cloud LJ, Jinnah H. Treatment strategies for dystonia. Expert opinion on pharmacotherapy. 2010;11(1):5-15. doi: 10.1517/14656560903426171.
12. Jankovic J. Medical treatment of dystonia. Movement disorders. 2013;28(7);1001-1012. doi: 10.1002/mds.25552.
13. Lizarraga K, Al-Shorafat D, Fox S. Update on current and emerging therapies for dystonia. Neurodener Dis Manag. 2019;9(3):135-147. doi: 10.2217/nmt-2018-0047.
14. AACPDM Dystonia Care Pathway Team. “Cerebral Palsy and Dystonia.” American Academy for Cerebral Palsy and Developmental Medicine, https://www.aacpdm.org/publications/care-pathways/dystonia-in-cerebral-palsy.
15. Abu-hadid O, Jimenez-Shahed J. An overview of the pharmacotherapeutics for dystonia: advances over the past decade. Expert opinion on pharmacotherapy. 2022;23(17):1927-1940. doi: 10.1080/14656566.2022.2147823.
16. Centen L, van Egmond M, Tijssen M. New developments in diagnostics and treatment of adult-onset focal dystonia.  Current opinion in neurology. 2023;36(4):317-323. doi: 10.1097/WCO.0000000000001165.
17. Momin S, Aquilina K, Bulstrode H, Taira T, Kalia S, Natalwala A. MRI-Guided focused ultrasound for the treatment of dystonia: a narrative review. Cureus. 2024;16(2):e54284. doi: 10.7759/cureus.54284.

Original Version of the Topic

Kavita Nadendla, MD, Ohmin Kwon, MD, Nancy Yeh, MD. Dystonias (except torticollis). 4/29/2021

Author Disclosures

Kavita Nadendla, MD
Nothing to Disclose

Ohmin Kwon, MD
Nothing to Disclose

Nancy Yeh, MD
Nothing to Disclose