Hyperkinetic Movement Disorders

Disease/Disorder

Definition

Movements can be divided into four categories: voluntary, semi voluntary, involuntary, and automatic (Table 1). Hyperkinetic movement disorders (HMDs), or dyskinesias, refer to a group of excessive semi voluntary and involuntary movements. There are five major types of HMDs: dystonia, myoclonus, tremor, chorea, and tics (Table 2).¹ Other HMDs include athetosis, akathitic movements, stereotypies, synkinesis, and restless legs.

Etiology

HMDs can be itself a disease entity or a sign of another underlying neurologic condition. HMDs can result from genetic abnormalities, neurodegenerative diseases, structural lesions, infection, drugs, toxins, or psychogenic causes (Table 3).^1-5 However, in many cases, HMDs have no clear cause and are thus identified as idiopathic.

Epidemiology including risk factors and primary prevention

Tremor, especially essential tremor (ET), is the most frequent type of HMD seen in clinical practice. The prevalence increases with age, with estimates that up to 10% of individuals over the age of 60 experience ET Huntington’s Disease is the most frequent cause of chorea with an estimated worldwide prevalence of 10/100,000 people.⁵ Dystonia is rare in childhood and becomes more prevalent with increasing age. Isolated focal dystonia has been estimated as occurring in 16.4 per 100,000 individuals, whereas generalized dystonia is less common. The most common type of focal dystonia is cervical dystonia.

Psychiatric illnesses and associated neuroleptic medications have been associated with HMD. Therefore, close monitoring of patients on psychiatric medications is warranted for early detection and prevention.

Patho-anatomy/physiology

• Dystonia is primarily associated with dysfunction of the putamen or globus pallidus.
• Myoclonus can be caused by irritation or destruction of gray matter and can result from insult to the cortex, brainstem, spinal cord, or peripheral nerves.
• Tremors are associated with brainstem, cerebellum, or thalamic lesions.
• Chorea and ballism have been linked to lesions in the subthalamic nucleus.
• Tics are thought to involve basal ganglia circuitry, and studies have shown that tics are not mediated through the typical motor pathways seen in normal voluntary movements.

Among all HMDs, there appears to be decreased neural firing rates in the inhibitory output nuclei of the basal ganglia leading to a subsequent disinhibition of thalamocortical activity. Patients with HMDs also tend to have notable abnormalities in sensory processing, indicating a possible link between sensory alterations and dyskinetic motor activity.⁸

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

Disease progression amongst HMDs can be highly variable. Adult-onset primary HMDs are usually non-progressive. Primary dystonia that begins in childhood can start in a single limb but will eventually spread to other body regions.⁷ Huntington’s disease will gradually progress to include dementia, psychiatric disturbance, dysphagia and falls. Tremors associated with Parkinson’s disease usually worsen. Tics generally begin in the head and neck but can progress to the trunk and extremities. Peak tic severity is usually experienced before mid-teens. Tics decrease in severity and may even disappear in adult life in a large proportion of patients.  HMDs due to stroke or brain injury are usually static and do not progress if the precipitating factor is no longer active.

Specific secondary or associated conditions and complications 

Many patients with HMD suffer from social phobias, depression, and anxiety.^9,10 Cervical dystonia has been associated with premorbid psychiatric disorders.¹⁰ Dementia and dysphagia can develop with Huntington’s disease.  People who have HD, are at greater risk for suicide than the general population. Growing and aging with a generalized dystonia can result in joint contractures, chronic pain, nerve compression, spondylosis, vascular compromise, and dysphagia.

Essentials of Assessment

History

Distinguish, based on description of the abnormal movement, if the HMD consists of tremors, jerky or shock like movements, tics or abnormal postures.  History of distribution of the movements will help determine if the disorder is focal, multifocal, unilateral or generalized. Finally focus on identification of etiology by assessing age at onset, childhood development, prior infections, exposures, trauma, progression, symptoms, co-morbidities, family history and psychosocial history.

Physical examination

The examiner should pay attention to the character of the movements, pattern of involvement, speed, rhythmicity, duration, suppressibility and triggers.

• Dystonia is characterized by focal or generalized sustained muscle contractions resulting in abnormal postures. Cervical dystonia is the most common type of focal dystonia. Focal dystonia may also present in one limb or in the abdomen. Dystonia can be seen during specific tasks, such as writer’s cramp or when playing instruments. On physical exam, the primary characteristic that distinguishes dystonia from other HMDs is the twisting quality of the movements. Other unique features include longer duration of contraction than other HMDs, and simultaneous contraction of two antagonistic muscle groups. Another exam finding may be “geste antagoniste”, which is described as an alleviating maneuver. For example, the patient may touch their chin to relieve cervical dystonia.
• Myoclonus is characterized by sudden muscle contraction. Myoclonus can be characterized as “positive”, meaning active muscle contractions, or “negative”, meaning brief lapses of muscle contraction. Unlike tics, myoclonus cannot be willfully controlled or dampened.
• Tremors are classified in two major categories: rest tremors and action tremors. Rest tremor occurs when the affected body part is not active and is fully supported against gravity, this type of tremor is common in Parkinsonism. Action tremor is seen with voluntary action. Noting whether the tremor occurs at rest or with action can help to delineate the underlying etiology of the tremor.
• Chorea appears as an involuntary, continual, and irregular movement that flows from one body part to the next. These movements are distributed randomly over the body, and at irregular intervals. A feature of chorea is the inability to maintain a voluntary contraction which gives the appearance of clumsiness.
• Tics are brief and intermittent movements or sounds that can be classified as semi voluntary and involuntary. They can occasionally be suppressed with an effort of will. Motor tics present as sudden, abrupt, coordinated movements that may resemble normal behavior. In Tourette’s syndrome, patients may display verbal tics such as echolalia (repetition of the words of others) or coprolalia (utterances of obscenities).

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

Patients should have their gait and balance assessed by clinician and/or therapist with focus on safety and fall prevention. Certain HMDs are best observed during attempts at functional tasks as these disorders may interfere with (instrumented) activities of daily living. Some neurodegenerative HMDs can affect speech, cognition, and cause dysphagia. Mental health assessment can identify associated depression, anxiety, or social phobias.

Laboratory studies

Dyskinesias are typically diagnosed clinically. However, underlying metabolic, endocrine, immunologic, infectious, and toxic etiologies may be excluded with blood work including thyroid function panel and ceruloplasmin and analysis of cerebrospinal fluid to rule out infectious or autoimmune causes. Paraneoplastic panels and genetic testing may also be pursued in certain cases.

Imaging

Computerized axial tomography (CAT) scan or magnetic resonance imaging (MRI) may assist with ruling out structural abnormalities. Radiographs, CAT scans or MRI are indicated in cases of suspected cervical or truncal dystonia to rule out structural derangements. Dopamine transporter single-photon emission computed tomography (SPECT) scan also known as DaTscan^TM may be useful in discriminating between tremor due ET versus Parkinson’s disease or other Parkinsonian syndromes. DaTscan^TM may also be helpful in helping identify dopamine responsive dystonia. Diffusion tensor imaging is emerging as a powerful tool for understanding pathway alterations in movement disorders but is not widely available yet.

Supplemental assessment tools

Electroencephalogram may be used for the work up of chorea and myoclonus to help differentiate whether the abnormal movements are due to abnormal cortical, subcortical, or spinal activity. If available, gait or motion analysis with dynamic surface polyelectromyography recordings can help identify antagonistic muscles to assist with treatment planning, especially if planning to perform targeted chemodenervation with botulinum toxin.

Early prediction of outcomes

Huntington’s disease, a trinucleotide repeat disorder, are often more severe and earlier in onset with increased repeat lengths. Onset of primary dystonia in the leg before the age of 26 increases the risk of developing severe generalized dystonia.¹⁴

Environmental

Tremors can be caused by nicotine, alcohol (and withdrawal), carbon monoxide, lead, mercury, toluene, Dichlorodiphenyltrichloroethane (DDT), naphthalene, manganese, lindane, arsenic, kepone, cyanide and dioxins.² Psychological stressors can also exacerbate HMDs stressing the importance of a social support system.

Social role and social support system

A social worker can provide patient with information regarding outside resources such as home nursing, home health aide and therapy services when appropriate. Patients should also be given information regarding national and local support groups to help provide education, access to participate in clinical research studies and life management tips.

Professional issues

For certain psychiatric disorders such as schizophrenia, the treatment itself has resulted in the HMD and the question arises whether to continue treatment. Some of these patients are cognitively impaired and institutionalized, therefore informed consent is sometimes not possible. Another ethical consideration is if patients with severe neurodegenerative disorders should have the right to physician assisted suicide.

Rehabilitation Management and Treatments

Available or current treatment guidelines

• Oral medications: Childhood onset dystonia is often considered dopamine responsive and thus can be treated to levodopa. Other forms of HMDs can be treated with medications such as anti-epileptics, anticholinergics, dopamine depleters, beta blockers, GABA agonists. These agents primarily act via inhibitory pathways in attempt to suppress abnormal movement. Tetrabenazine is FDA approved for the treatment of Huntington’s chorea and has shown good effect in the treatment of dystonia, tardive dyskinesia, and Tourette syndrome¹⁹. Pramipexole and primidone have been used to treat tremors and myoclonus with mixed success. Perampanel has been shown to be effective in myoclonus. Pimozide can be used to treat motor and verbal tics in Tourette’s syndrome. Fluphenazine is an antipsychotic that can be used to treat tics. Sodium oxybate is a medication that is FDA approved for the treatment of narcolepsy and has shown some efficacy in the treatment of posthypoxic myoclonus (Lance Adams Syndrome) in several case reports, however its use is limited to experimental use only. Table 4 outlines various medications that clinicians may prescribe for HMDs.
• Chemodenervation: Certain focal or multifocal movement disorders can be targeted with botulinum toxin injections to reduce activity in antagonist muscles with some success.
• Surgical Intervention: More severe or generalized HMDs may require neuromodulation with intrathecal baclofen or deep brain stimulation (DBS). Surgical intervention for HMDs includes thalamotomy and peripheral nerve denervation. For some, relaxation therapies (e.g., yoga, biofeedback) and avoidance of aggravating stimuli (e.g., caffeine, stressors) will also decrease the frequency and severity of tremor, tics and dystonia.

At different disease stages

Early- Sub-acute
The potential benefits of exercise in HMDs is well documented not only with improving patients’ strength and endurance but also with improving psychological wellbeing.¹¹ However, no definitive rehabilitation guidelines are available for addressing HMDs though these patients are commonly referred to therapy. Strategies (i.e., use of sensory tricks with dystonia) and adaptive equipment (i.e., weighted utensils and garments for tremor) may be beneficial. Regular stretching may prevent contractures in dystonia. Use of orthotics, assistive devices and wheelchairs may be indicated to enhance mobility and safety.

Chronic
Oral medications are of variable benefit.  Trihexyphenidyl can be used to treat tremor and dystonia but is poorly tolerated. Botulinum toxin injections are useful for focal and multifocal dystonia. Generalized dystonia may benefit from intrathecal baclofen therapy. DBS has shown benefit for multiple HMDs especially essential tremor, tremor due to Parkinson’s disease and primary generalized dystonia.

Preterminal
Secondary prevention of falls, aspiration, infections, malnutrition, and pressure sores becomes the primary focus of management. Behavioral interventions may be required. In some severe cases, hospice care should be considered.

Table 4: Medications consideration for management of HMDs

Coordination of care

Patients with HMDs may benefit from a coordinated team approach including a neurologist, a physiatrist, therapists and a social worker for ongoing management.  In some cases, this team should also include a psychiatrist and/or psychologist to assist with mood and behavioral issues, especially considering some psychiatric medications can exacerbate the HMD.

Patient & family education

Patient and family education is important for identifying symptoms, monitoring treatment response, secondary prevention efforts, goal setting and management of expectations. Decisions regarding genetic testing (whether for diagnosis or family planning) may be emotionally challenging and can have financial implications. Therefore, inclusion of a genetic counselor in these discussions is advisable.

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

The Unified Huntington’s Disease Rating Scale assesses motor function, cognitive function, behavioral abnormalities and functional capacity associated with Huntington’s disease.¹²  The Fahn-Tolosa-Marin tremor rating scale was developed to assess essential upper extremity tremor.¹³ The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) has been used for assessment of cervical dystonia and to demonstrate the benefits of botulinum toxin in clinical trials.¹⁴ Several other scales to measure dystonia are available including the Fahn-Marsden Scale, Unified Dystonia Rating Scale and the Global Dystonia Rating Scale.^15,16 For practical purposes, patient testimony, clinical assessment and collecting video recordings remain the mainstay of evaluation and assessing treatment.

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

Management of HMDs requires a multidisciplinary and multifaceted approach.  Initial treatment initially involves trials with medications to reduce HMD as well as optimization of psychiatric comorbidities sometimes in coordination with psychiatry. In some cases, focal HMDs can be treated with chemodenervation. Assistive devices such as weighted utensils and orthotics should also be considered. Cases unresponsive to conservative treatment may be amenable to neuromodulation with DBS or intrathecal baclofen therapy. Areas for practice improvement involve earlier diagnosis and intervention as oftentimes these patients are often misunderstood and misdiagnosed and therefore can go without formal diagnosis and treatment for years after onset.

Cutting Edge/Emerging and Unique Concepts and Practice

Diagnosis of HMDs is primarily accomplished through clinical exam, however there are some useful technologies that may contribute to their diagnosis or may be used to monitor progression. Some of these tools include electromyography (EMG), electroencephalography (EEG), magnetoencephalogram (MEG), functional magnetic resonance imaging (fMRI), evoked potentials, accelerometry, posturography, and sleep studies.²⁰

Advances in neuromodulation and neurosurgery for the treatment of movement disorders continue to evolve.^17,18 DBS is being offered as a treatment option for other HMDs such as cerebellar outflow tremor, Holmes tremor, tics due to Tourette syndrome, cervical dystonia, Huntington’s chorea, tardive dyskinesia, myoclonus, and hemiballismus with variable outcomes. Intraventricular baclofen therapy is also being investigated in the treatment of generalized dystonia. Magnetic resonance imaging guided focused ultrasound thalamotomy has been shown to reduce tremor. Transcranial magnetic stimulation to enhance intracortical inhibition and gene therapy are other approaches to the treatment of HMDs being investigated.

Gaps in the Evidence-Based Knowledge

Psychiatric illness and HMD are commonly associated suggesting the underlying pathophysiology is potentially intertwined. Studies of genetic and biochemical abnormalities and advanced neuroimaging (e.g., DaTscan^TM, functional MRI and diffusion tensor imaging) on these patients may help elucidate the underlying abnormalities to yield more effective treatment strategies for both.

References

1. Jankovic, Joseph, et al. Principles and Practice of Movement Disorders. Edited by Joseph Jankovic, et al., Elsevier, 2021.
2. Sanger TD, Chen D, Fehlings DL, et al. Definition and classification of hyperkinetic movements in childhood.  Movement Disorders 2010:25(11):1538-1549.
3. Morgante F, Klein C. Dystonia. Continuum 2013;19(5):1225-1241.
4. Kumar H, Jog M. Peripheral trauma-induced dystonia or post-traumatic syndrome? Canadian Journal of Neurological Science 2011;38(1):22-29.
5. Cardosa F, Seppi K, Mait, KJ, Wenning GK, Poewe W. Seminar on choreas. Lancet Neurology. 2006:5:589-602.
6. deLau LML, Breteler MMB. Epidemiology of Parkinson’s disease. Lancet Neurology. 2006; 5:525-535.
7. Defazio G, Abbruzzese G, Livera P, Berardelli A. Epidemiology of primary dystonia. Lancet Neurology 2004:3:673-678.
8. Conte A, Defazio G, Hallett M, Fabbrini G, Berardelli A. The role of sensory information in the pathophysiology of focal dystonias. Nat Rev Neurol. 2019;15(4):224-233.
9. Ozel-Kizil ET, Akbostanci MC, Ozguven HD, Atbasoglu EC. Secondary social anxiety in hyperkinesias. Movement Disorders 2008;23(5):641-645.
10. Zurowski M, McDonald WM, Fox S, Marsh L.  Psychiatric Comorbidities in Dystonia: Emerging Concepts. Movement Disorders 2013;28(7):914-20.  
11. Bilney B, Morris M, Denisenko S. Physiotherapy for People with Movement Disorders Arising from Basal ganglia Dysfunction. NZ Journal of Physiotherapy 2003;31:94-100.
12. Huntington Study Group. Unified Huntington’s Disease Rating Scale: reliability and consistency. Movement Disorders 1996;11(2):136-142.
13. Stacy MA, Elble RJ, Ondo WG, Wu SC, Hulihan J; TRS study group. Assessment of interrater and intrarater reliability of the Fahn-Tolosa-Marin Tremor Rating Scale in essential tremor. Movement Disorders 2007;22(6):833-8.
14. Consky ES, Lang AE. Clinical assessments of patients with cervical dystonia. In: Jankovic J, Hallett M, eds. Therapy with Botulinum Toxin. New York, NY: Marcel Dekker; 1994:211-237.
15. Burke RE, Fahn S, Marsden CD, Bressman SB, Moskowitz C, Friedman J. Validity and reliability of a rating scale for the primary torsion dystonias. Neurology 1985;35:73-77.
16. Comella CL, Leurgans S, Wuu J, Stebbins GT, Chmura T. Rating scales for dystonia: a multicenter assessment. Movement Disorders 2003;18:303-312.
17. Dietz N, Neimat J. Neuromodulation: Deep Brain Stimulation for Treatment of Dystonia. Neurosurg Clin N Am. 2019 Apr;30(2):161-168.
18. Obeso I, Cerasa A, Quattrone A. The Effectiveness of Transcranial Brain Stimulation in Improving Clinical Signs of Hyperkinetic Movement Disorders. Front Neurosci. 2016 Jan 7;9:486.
19. Nikkhah A. A Brief Review on the Role of Vesicular Monoamine Transporter2 Inhibitors in Hyperkinetic Movement Disorders. Iran J Child Neurol. 2021;15(3):29-33. doi:10.22037/ijcn.v15i3.33144
20. Hallett M, DelRosso LM, Elble R, et al. Evaluation of movement and brain activity. Clin Neurophysiol. 2021;132(10):2608-2638.

Original Version of the Topic

Heather R. Ene, MD. Hyperkinetic movement disorders (including dystonias, choreas). 9/20/2014

Previous Revision(s) of the Topic

Heather R. Ene, MD. Hyperkinetic Movement Disorders. 5/20/2020

Author Disclosure

Juliet Zakel, MD
Nothing to Disclose

Rebecca Greenspan, DO
Nothing to Disclose