Dystonia

Dystonia is a neurologic movement disorder dominated by involuntary, sustained or repetitive, patterned muscle contractions or spasms, frequently causing squeezing, twisting, and other movements or abnormal postures.

Diagnosis

The diagnosis of dystonia is based on clinical evaluation. Depending on the evaluation, additional testing such as brain MRI and genetic testing may be required. Typically, dystonia begins in a single body part (focal dystonia), such as the hand, neck or eyelids, and may subsequently spread to adjacent body parts (segmental dystonia). Blepharospasm, a focal dystonia manifested by an involuntary eye closure produced by sporadic contractions of the eyelids and eyebrows, is often associated with dystonic movements of facial, jaw, laryngeal, and neck muscles. This combination is referred to as cranial dystonia. Oromandibular or cranial dystonia can present as involuntary jaw opening or closing associated with clenching (trismus) and grinding of the teeth (bruxism), which may lead to secondary dental wear and temporal-mandibular joint (TMJ) syndrome.

Cervical dystonia is the most frequent form of dystonia. This form of focal dystonia is characterized by patterned, repetitive, head movements or more sustained abnormal postures of the head. In addition to torticollis (turning of the head), cervical dystonia may be manifested by neck flexion (anterocollis), extension (retrocollis), or head tilt (laterocollis). In approximately one-third of all patients, cervical dystonia progresses to involve connecting body parts such as the skull region, shoulder, trunk, and arm.

Cervical dystonia is associated with pain in about 75% of patients and most patients have discovered certain alleviating maneuvers such as touching the chin or neck, to correct the abnormal postures. Segmental dystonia involving eyelids (blepharospasm) and other facial, jaw (oromandibular) and neck (cervical) muscles is referred to "cranial-cervical dystonia." Spasmodic dysphonia, focal dystonia of the vocal cords and larynx, is characterized by strained, effortful voice interrupted by uncontrollable pitch breaks or voiceless pauses (adductor spasmodic dysphonia) or whispering, breathy voice (abductor spasmodic dysphonia).

While cervical dystonia is the most common form of dystonia encountered in a specialized clinic, writer's cramp is probably more common form of dystonia in general population. In addition to this "task-specific" dystonia, there are many other examples of occupational dystonias affecting the performance of musicians, sportsmen, and others whose skills depend on finely coordinated movements. Dystonia, particularly experienced in childhood, may spread to involve the legs, trunk and other body parts (generalized dystonia).

Unilateral dystonia, confined to only one half of the body, is referred to as hemidystonia. In contrast to focal and segmental dystonia, which is usually "idiopathic" or "primary" (no other neurological abnormality and no specific cause except possibly genetic), the majority of patients with hemidystonia have an identifiable cause such as head trauma, stroke, arteriovenous malformation, tumor, encephalitis or other pathology affecting the opposite basal ganglia.

Cause

The cause of primary dystonias is not always apparent, but most are probably due to some genetic abnormalities (inherited). Although in most patients with dystonia (particularly focal dystonias) no specific abnormality or lesion can be identified by neuroimaging or even autopsy studies, there is evidence that this movement disorder is due to abnormal function of the deep portion of the brain, called basal ganglia. Currently, dystonia is considered the result of a combination of impaired modulation of the centers that control the movements and an abnormal flexibility of the neurons in that circuitry.

There are many genetic forms of dystonia, and new gene abnormalities are being added to the growing list every year. Mutation of the DYT1 gene on chromosome 9 is the most studied genetic mutation among the inherited forms.

Not all dystonias, however, are of genetic origin. Some dystonias are secondary to specific causes such as metabolic and neurodegenerative disorders (e.g. Wilson's disease), brain injury or other lesions (e.g. cerebral palsy), certain drugs that block dopamine receptors, and many other causes. In addition, injuries to the nerves can result in peripherally-induced dystonia caused by an injury to the affected body part is being increasingly recognized as an important cause of focal and segmental dystonia. Dystonia may often be seen as part of other neurologic conditions, such as Parkinson’s disease, other neurodegenerative disease, and  autoimmune disorders.

Finally, physical or emotional stress and a variety of other psychological factors may be associated with abnormal movements resembling dystonia, also known as "functional dystonia." 

Treatment

Despite the lack of knowledge about causes of dystonia, the treatment of this condition has improved as a result of application of botulinum toxin (BTX). Before contemplating BTX therapy, potentially curable causes of dystonia, such as certain drug-induced dystonias or Wilson's disease, should be considered. The treatment of dystonia should be individualized. Involvement of a rehabilitation team, such as a physical therapist, and addressing potential depression or anxiety can improve the response to treatment. For those patients with focal or segmental dystonia, BTX is the treatment of choice. Several types of BTX are clinically available, including some newly approved for treating cervical dystonia. However, the cases of generalized dystonia may benefit from pharmacologic therapy using medications such as trihexyphenidyl, baclofen, tetrabenazine, and levodopa.

Surgical techniques, such as local nerve or muscle excision and ablation or high frequency deep brain stimulation (DBS) have been used successfully in patients who continue to have disabling dystonia despite optimal medical or BTX therapies. DBS may be particularly helpful in certain genetic dystonias. 

References

• Anandan C, Jankovic J. Use of botulinum toxin in the management of dystonia in Parkinson's disease. Front Neurosci. 2024 Apr 8;18:1371601. 
• Balint B, Mencacci NE, Valente EM, Pisani A, Rothwell J, Jankovic J, Vidailhet M, Bhatia KP. Dystonia. Nat Rev Dis Primers. 2018;4(1):25.
• Cif L, Demailly D, Lin JP, et al. KMT2B-related disorders: expansion of the phenotypic spectrum and long-term efficacy of deep brain stimulation. Brain. 2020 Dec 5;143(11):3242-3261.
• Cisneros E, Stebbins GT, Chen Q, et al. It's tricky: Rating alleviating maneuvers in cervical dystonia. J Neurol Sci. 2020;419:117205.
• Comella CL, Jankovic J, Hauser RA, Patel AT, Banach MD, Ehler E, Vitarella D, Rubio RG, Gross TM; ASPEN-1 Study Group. Efficacy and Safety of DaxibotulinumtoxinA for Injection in Cervical Dystonia: ASPEN-1 Phase 3 Randomized Controlled Trial. Neurology. 2024 Feb 27;102(4):e208091. 
• Cotton AC, Scorr L, McDonald W, Comella C, Perlmutter JS, Goetz CG, Jankovic J, Marsh L, Factor S, Jinnah HA. Assessing the Severity of Cervical Dystonia: Ask the Doctor or Ask the Patient? Mov Disord Clin Pract. 2023 Aug 3;10(9):1399-1403. 
• Fearon C, Peall KJ, Vidailhet M, Fasano A. Medical management of myoclonus-dystonia and implications for underlying pathophysiology. Parkinsonism Relat Disord. 2020;77:48-56.
• Jankovic J. An update on new and unique uses of botulinum toxin in movement disorders. Toxicon. 2018;147:84-88.
• Jankovic J, Hallett M, Okun M, Comella C, Fahn S. Principles and Practice of Movement Disorders, Elsevier, Philadelphia, PA, 2022.
• Jankovic J. Parkinson’s Disease and Other Movement disorders. Chapter 96; In: Jankovic J, Maziotta J, Newman N, Pomeroy S, eds. Bradley and Daroff’’s Neurology in Clinical Practice, 8th Edition, Elsevier, Philadelphia, PA, 2022.
• Jankovic J, Tsui J, Brin MF. Treatment of cervical dystonia with Botox (onabotulinumtoxinA): Development, insights, and impact. Medicine (Baltimore). 2023 Jul 1;102(S1):e32403. 
• Jankovic J. Is Dystonia an Immunologic Disorder? Parkinsonism Relat Disord. 2024 May;122:106084. 
• Lenka A, Jankovic J. Sports-Related Dystonia. Tremor Other Hyperkinet Mov (N Y). 2021 Dec 21;11:54. 
• Lenka A, Jankovic J. Peripherally-induced Movement Disorders: An Update. Tremor Other Hyperkinet Mov (N Y). 2023 Mar 28;13:8. 
• Rodrigues FB, Duarte GS, Prescott D, Ferreira J, Costa J. Deep brain stimulation for dystonia. Cochrane Database Syst Rev. 2019;1:CD012405.
• Schirinzi T, Garone G, Travaglini L, et al. Phenomenology and clinical course of movement disorder in GNAO1 variants: Results from an analytical review. Parkinsonism Relat Disord. 2019;61:19-25. 
• Younce JR, Cascella RH, Berman BD, Jinnah HA, Bellows S, et al. Anatomical categorization of isolated non-focal dystonia: novel and existing patterns using a data-driven approach. Dystonia. 2023;2:11305

Dystonia Medical Research Foundation (DMRF)
https://www.dystonia-foundation.org/