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Vol2 No3 1 PDF
Vol2 No3 1 PDF
3 October 2015
ISSN 2374-3522 (PRINT) ISSN 2374-3530 (ONLINE) http://www.researchpub.org/journal/nc/nc.html
Invited Review
Abstract— Dystonia is the third most common movement II. HISTORY
disorder, yet remains widely under-recognized. Dystonia may be a The term dystonia was first introduced in a 1911 paper by
primary disorder or symptomatic of an additional underlying
neurological condition. Accurate diagnosis and effective
Hermann Oppenheim, a preeminent German neurologist.2 In
treatment for patients will rely on increased awareness and the paper, he described a condition in four unrelated Jewish
knowledge about dystonia. In this review, we summarize the children from Russia and Galicia, in which tone was
history, epidemiology, and pathophysiology of dystonia, followed intermittently increased or decreased. The condition was
by a focus on clinical features and the new classification system. further characterized by muscle spasms causing twisted
We then highlight evidence-based recommendations from clinical postures of the limbs and trunk, including scoliosis and
trials.
lordosis. The twisted postures worsened with walking, and at
Keywords — dystonia, dystonic disorders, movement disorders. times resembled a dromedary. The condition was progressive
and some postures became fixed over time. 2 While he initially
considered these patients to have either hysteria or bilateral
athetosis, ultimately he decided this was a new disease and
proposed the names dystonia musculorum deformans and
dysbasia lordotica progressiva.2,3
I. INTRODUCTION AND DEFINITION Oppenheim may have coined the term dystonia, but he was
not the first to describe patients with this phenomenology.
D YSTONIA is the third most common movement disorder,
yet it is still a widely under-recognized disorder,
particularly to medical practitioners outside of neurology. This
Marcus Walter Schwalbe, a psychiatry doctoral student,
described three Jewish siblings from Lithuania with similar
may be partly due to the variability in its clinical presentation. presentations in his thesis presentation. He referred to their
The definition of dystonia was recently updated by an condition as “maladie des tics and tonic cramps with hysterical
international panel of experts in a special issue of the Movement symptoms.” In 1911, Schwalbe’s professor, Theodor Ziehan,
Disorders journal to reflect this heterogeneity:1 published these cases as “torsion neurosis.”2 Also in 1911, a
third paper was published from Edward Flatau and Wladyslaw
“Dystonia is defined as a movement disorder characterized Sterling in Poland, describing a similar condition in two Jewish
by sustained or intermittent muscle contractions causing boys as “progressive torsion spasms”.2
abnormal, often repetitive movements, postures, or both. Cases of what we now recognize as dystonia were described
Dystonic movements are typically patterned, twisting, and may by the medical community as early as 1713, when a description
be tremulous. Dystonia is often initiated or worsened by of probable writer’s cramp was published.4,5 Subsequent
voluntary action and associated with overflow muscle reports include a case dubbed “Scrivener’s palsy” in 1864 6;
activation.” descriptions of writer’s cramp by the British Civil Service in
the 1830s6; cases of blepharospasm and oromandibular
This article summarizes the origins, clinical features, dystonia by Horatio Wood in 18877; publication of “wry neck”
evaluation, and management of this complex disorder for the photos in 18968; and a case of “tetanoid chorea” in Wilson’s
practicing clinician. disease by William Gowers in 18889.
In 1929, it was widely believed within the medical
community that dystonia was a symptom of an underlying
1
Submission August 28, 2015. Accepted on August 30, 2015. The authors condition, rather than a unique disease.2 This perspective was
have no relevant disclosures.
Department of Neurology, University of Pennsylvania, Philadelphia,
largely based on the growing number of cases of dystonia
Pennsylvania. Penn Neurological Institute, 330 S. 9th Street, Philadelphia, PA described as secondary to cerebral palsy, post-encephalitic
19107, USA. *Correspondence to Dr. Christine Cooper (e-mail: parkinsonism, Wilson’s disease, Parkinson’s disease, and
Christine.Cooper@uphs.upenn.edu).
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Neurological Cases Vol.2 No.3 October 2015
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Huntington’s disease. However, in 1944, Dr. Ernst Herz, a based on clinical characteristics and associated features, the
German-American neurologist, described cases of isolated second is focused on etiology.
dystonia with an electromyographic signature of co-contraction Axis 1 classification includes the key clinical aspects of age
of agonist and antagonist muscles. His cases as well as the of onset, body distribution, and temporal pattern. Categories for
unique electromyographic findings supported its existence as a age of onset include infancy (0-2 years), childhood (3-12
primary disorder.2,10 Since this time there has been considerable years), adolescence (13-20 years), early adulthood (21-40
growth in the understanding of the etiology and treatment of years), and late adulthood (over 40 years). Body distribution
dystonia as a primary disease. can be focal, segmental (two contiguous body regions),
multifocal (more than one non-contiguous body region),
generalized, or hemidystonia, the latter of which is usually
secondary to an underlying neurological insult. The temporal
III. EPIDEMIOLOGY
pattern is specified in terms of disease course, whether static or
In general, the prevalence of dystonia is likely progressive; and variability, which can be described as
underestimated due to under-diagnosis. Moreover, differences task-specific, diurnal, paroxysmal, or persistent. This axis also
in study designs and populations yield highly variable includes associated features to separate isolated (formerly
estimates. The prevalence of primary early-onset dystonia in “primary”) dystonia from dystonia combined with other
the Ashkenazi Jewish population in New York City has been movement disorders, neurological findings, or systemic
proposed to range from 50 to 111 people per million. 11 In manifestations.1
northern England, the prevalence of primary late-onset dystonia Axis 2 is designed to provide classification by etiology.1 It
is estimated to be 430 to 600 people per million. 12 The takes into account pathology, inheritance, and potential
Rochester Epidemiology Project found the United States underlying causal mechanisms. Often there is no obvious
incidence of primary early-onset dystonia to be 2 per million pathological finding in individuals with dystonia, but if present,
per year, and the incidence of late-onset dystonia to be 24 per these may include evidence of degeneration or structural
million per year.13 lesions. A structural lesion is likely to cause a static course.
Inheritance may be autosomal dominant, autosomal recessive,
X-linked, or mitochondrial. If no family history is present,
dystonia is considered sporadic. Reported cases of acquired
IV. CLINICAL FEATURES
dystonias include lesions due to brain injury, infection, toxins,
The clinical features of dystonia are highly variable between drugs, vascular abnormalities, paraneoplastic syndromes, or
individuals, and also intermittent within a single individual. To functional origin.
those unfamiliar with dystonia, the presentations can appear It is important to mention that another commonly used
bizarre and raise suspicion of a functional etiology. Accurate classification for inherited dystonias is the DYTn coding
diagnosis relies heavily on the medical provider’s familiarity system developed by the Human Genome Organization Gene
with the range of clinical characteristics of dystonia. Nomenclature Committee. Several problematic features of this
While individual presentations of dystonia vary, as a system prompted the development of the new 2013
disorder, dystonia has a number of common clinical features. classification system. These problematic features include the
Abnormal movements and postures are usually stereotyped, following: many DYTn designations were made as
involving the repeated contractions of the same muscle groups. “placeholders” before the actual gene loci abnormalities were
The postures are often sustained, though phasic movements and identified; the genes included are both risk factors and
causative mutations; some DYTn designations are limited to
tremor are common. The dystonia is activated by voluntary
single families or have later been found to have erroneous
movements, frequently worse with walking, and may even be
linkage; the list incorrectly suggests that the disorders are of the
task-specific. The presence of a sensory trick (“geste
same phenotype and primarily dystonic in nature; the
antagoniste”) is highly suggestive of dystonia. classification system is incomplete with both missing inherited
In addition to motor abnormalities, mood disorders including dystonias and missing loci.1,15 Despite these concerns with the
anxiety, social phobia, and major depression are common in DYTn coding system, the DYT descriptions are widely used in
patients with dystonia, and may precede the onset of motor dystonia nosology and we will include these in the descriptions
symptoms.14 The presence of these non-motor symptoms of selected dystonias below.
further misleads many clinicians to make the misdiagnosis of a
functional movement disorder. SELECTED DYSTONIAS AND DIAGNOSTIC EVALUATION
The four cases Oppenheim originally described in his paper
CLASSIFICATION are cases of what we now call early-onset generalized isolated
Over the last century, as knowledge of the characteristics and dystonia (Videos 1-3). The first identified genetic cause of
etiologies of dystonia has grown, classification systems have early-onset generalized dystonia is DYT1, caused by a
evolved to highlight these differences. The most recent mutation in the gene encoding Torsin 1A. The most common
classification scheme proposed in 2013 was developed to help
detect clinical syndromic patterns to aid in ascertaining the
underlying etiology.1 This scheme has two axes; the first is
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Neurological Cases Vol.2 No.3 October 2015
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mutation in this gene, TOR1 A, is a three base pair DYT6 (THAP 1) mutations, a levodopa trial to determine
deletion in the coding region. This specific mutation is presence of a DRD, copper studies to rule out Wilson’s
found in 90% of Ashkenazi Jewish cases, and in 60% of disease, brain imaging, and metabolic studies to look for
non-Jewish cases.16 Although this is a dominant other neurological or systemic diseases, particularly if
mutation, penetrance is roughly only 30%.17 Typically there are any additional findings on physical exam.
the initial onset involves a limb and occurs prior to the Adult-onset focal dystonias most often occur in early
age of 26. Over time, the dystonia generalizes, but often or late adulthood. They can be focal or segmental,
spares cranial muscles. In adults, there may be limited persistent or paroxysmal, and sporadic or familial. Of the
spread, resulting in only focal limb involvement. few known autosomal dominant genetic mutations
DYT6 dystonia is another autosomal dominant linked to adult-onset focal dystonia, the penetrance is
disorder with reduced penetrance. It is associated with a estimated to be 12-15%,18 which may cloud the
THAP1 gene mutation, first reported in inheritance pattern and thereby appear sporadic.
Amish-Mennonite families, but is now known to be Cervical dystonia is the most common manifestation of
more widespread. Typically it causes adolescent or adult-onset focal dystonia (video 4). It can appear to
adulthood onset of cranio-cervical or upper-limb have a fairly abrupt onset, and is not typically
dystonia, which occasionally goes on to generalize. progressive. Neck pain is present in 75% of patients.19
Segawa’s disease, DYT5, is one of the Dopa Sensory tricks are present in over 50% of patients. 20
Responsive Dystonias (DRDs). These dystonias are due About 10% of cases remit spontaneously, but the
to a deficiency within the dopamine synthesis pathway. majority recur.19 There is a 2:1 female to male ratio, with
The most salient clinical features of DRDs are diurnal a peak age of onset of 40-50 years. The abnormal head
fluctuations and a robust response to levodopa. Most posture may consist of lateral rotation (turn, or
often DYT5 has childhood onset, affecting females more torticollis), tilt (laterocollis), neck flexion (anterocollis)
than males. There is variable expression, as it may also or extension (retrocollis), lateral shift, sagittal shift, or
present as a gait disorder or developmental delay. In shoulder elevation. Tremulous or jerky phasic
adults, it presents as a focal or multifocal dystonia, or movements often accompany tonic abnormal posture.
parkinsonism. Typically, there is visible or palpable local muscle
Dystonia in children is commonly misdiagnosed as hypertrophy of the sternocleidomastoid and posterior
scoliosis, cerebral palsy, or a functional movement neck musculature. Common misdiagnoses in cervical
disorder. The recommended diagnostic evaluation in dystonia include osteoarthritis, disc herniation, neck
children is genetic testing for the DYT1 (TOR1A) and strain, essential tremor, and functional origin.
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Neurological Cases Vol.2 No.3 October 2015
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4
Neurological Cases Vol.2 No.3 October 2015
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dysphagia, ptosis, or impaired limb use until the effects Video 3: Patient 1. Foot inversion dystonia due to
of the botulinum toxin wear off. generalized dystonia.
Deep brain stimulation (DBS) can be effective in This video demonstrates inversion of both feet, left
decreasing dystonia symptoms and improving quality of greater than right, as well as left greater than right,
life in medication-refractory generalized dystonia.31,32 In dystonic posturing of the hands while walking. The foot
primary generalized DYT1 dystonia, shorter disease inversion is task-specific, as it is seen while walking but
duration at the time of surgery is associated with better not in the previous videos while at rest or performing
long-term DBS outcomes.33 There have been increasing rapid alternating movements.
reports of efficacy of DBS for cervical dystonia. A recent
randomized sham-controlled trial showed efficacy of Video 4: Patient 2. Cervical dystonia.
pallidal DBS in improving cervical dystonia symptoms This patient’s cervical dystonia is characterized by left
in patients with sub-optimal response to botulinum toxin torticollis, right laterocollis, and limited range of motion
injections.34 Pallidal DBS can also be of benefit in of right head turn with associated irregular, jerky
medication-refractory tardive dystonia.35 dystonic head tremor. Right sternocleidomastoid
Comprehensive reviews of DBS for dystonia have been hypertrophy is visible, best seen in this video while
recently published by Vidailhet36 et al. and Mills et al.37. patient is turning to the left. Left head turn reaches a null
Currently, there is not enough evidence of efficacy of point, at which the patient no longer has any involuntary
paramedical therapies such as physical therapy, speech muscle contraction.
therapy, sensorimotor training, or transcutaneous
electrical nerve stimulation (TENS) to recommend these Video 5: Patient 3. Blepharospasm associated with
as treatments for dystonia.38 Parkinson’s disease.
This patient has dystonia affecting her eyes and limbs
VII. CONCLUSIONS associated with Parkinson’s disease. This video features
Dystonia is a common movement disorder with blepharospasm, dystonia causing involuntary eyelid
variable presentations that is often unrecognized and closure. She demonstrates how a sensory trick of
under-diagnosed. In the past century, there have been touching and pulling on the skin below her eyes allows
tremendous advances in understanding the pathology her eyes to open.
and genetics of dystonia, which has led to improvements
in diagnosis and classification. Individuals with dystonia Video 6: Patient 3. Dromedary gait due to lower
will benefit from continued improvements in clinical extremity dystonia associated with Parkinson’s disease.
recognition, diagnosis, and treatment. This video demonstrates mild right foot plantar
flexion and inversion, with compensatory toe extension.
As the patient walks, she develops a dromedary gait,
particularly in the right leg, with right hip and knee
APPENDIX
flexion during the swing phase. Both hands are held in a
dystonic posture, fisted with thumb extension.
Video captions:
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Neurological Cases Vol.2 No.3 October 2015
ISSN 2374-3522 (PRINT) ISSN 2374-3530 (ONLINE) http://www.researchpub.org/journal/nc/nc.html
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Mov. Disord. 2013;28(7):958-967. 1. Which of the following clinical features is NOT suggestive of
[22] Jankovic J. Medical treatment of dystonia. Mov. Disord. dystonia?
2013;28(7):1001-1012.
[23] Burke RE, Marsden CD. Torsion dystonia: a double-blind, A. presence of a sensory trick
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NCBI. Neurology 1986;36:160-164. C. non-stereotyped, random movements
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M. An open trial of clozapine for dystonia. - PubMed - NCBI.
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Neurother. 2011;11(11):1509-1523. being related to ______, and Axis 2 as defining ______.
[26] Leland Albright A, Barry MJ, Shafron DH, Ferson SS.
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Efficacy, Tolerability, and Immunogenicity of D. family history; clinical features
OnabotulinumtoxinA in a Randomized, Double-Blind,
Placebo-Controlled Trial for Cervical Dystonia: Clin.
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Efficacy and safety of incobotulinumtoxinA (NT 201, found in clinical trials as a treatment for dystonia?
XEOMIN®, botulinum neurotoxin type A, without accessory
proteins) in patients with cervical dystonia. J. Neurol. Sci. A. Trihexyphenidyl
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Outcome at 10 years or more. Mov. Disord. 2011;26(4):750-753.
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[31] Volkmann J, Wolters A, Kupsch A, et al. Pallidal deep brain
stimulation in patients with primary generalised or segmental Answers: 1. C. 2. A. 3. D.