eMedicine Specialties > Neurology > Movement and Neurodegenerative Diseases

Primary Torsion Dystonia

Author: Rowena Emilia Tabamo, MD, Associate Director for Clinical Research, Institute for Neurodegenerative Disorders
Coauthor(s): Michele Tagliati, MD, Division Chief of Movement Disorders, Associate Professor, Department of Neurology, Mount Sinai School of Medicine; Susan B Bressman, MD, Chairperson, Department of Neurology,, Department of Neurology, St. Luke's-Roosevelt Hospitals; Professor, Beth Israel Deaconess Medical Center; Chairperson, Department of Neurology, Albert Einstein College of Medicine
Contributor Information and Disclosures

Updated: Mar 30, 2007

Introduction

Background

Dystonia is a syndrome of sustained muscle contractions, usually producing twisting and repetitive movements or abnormal postures (Fahn, 1987).

In 1908, Schwalbe first described primary, or idiopathic, torsion dystonia in a Jewish family, and in 1911, Oppenheim termed this dystonia musculorum deformans (DMD). Initially believed to be a manifestation of hysteria, idiopathic torsion dystonia gradually became established as a neurologic entity with a genetic basis. DMD and Oppenheim disease are terms now used for childhood- and adolescent-onset dystonia due to the DYT1 gene.

With the recent mapping of genes for idiopathic torsion dystonia and identification of a gene for early onset dystonia, the description primary, or idiopathic, dystonia has evolved; it now may be viewed as secondary to or symptomatic of an identified cause. However, continuing to use primary torsion dystonia to classify a group of dystonias as a clinically and genetically heterogeneous group of movement disorders is justifiable because dystonia is the primary and sole abnormality attributable to the condition, and degeneration on pathologic examination is not clearly established.

Primary torsion dystonia may be focal, segmental, multifocal, or generalized, depending on which anatomic sites are involved (see Table 1).

Table 1. Anatomic Distribution of Primary Torsion Dystonia

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Pathophysiology

Although secondary forms of dystonia are frequently associated with structural lesions of the basal ganglia and thalamus, no consistent histologic or biochemical findings are noted in primary torsion dystonia. However, perinuclear inclusion bodies have been described in the midbrain reticular formation and in the periaqueductal gray matter in 4 patients in whom DYT1 was clinically documented and genetically confirmed (McNaught, 2004).

No discernible abnormalities are seen on current structural neuroimaging studies. Abnormal brain networks have been described in different functional imaging studies; this is substantial evidence implicating dysfunction in dopaminergic pathways in the pathophysiology of primary torsion dystonia (Eidelberg, 1998; Perlmutter, 2004).

Besides motor control difficulties, defective sensory processing is described (Kaji, 2004).

Current models of basal ganglia circuitry have been adapted and suggesting dysfunction at the basal ganglia level. These aberrations involve the direct and indirect pathways and result in impaired inhibition at the cortical level with consequent loss of normal inhibitory reflexes at the level of the brainstem and spinal levels.

See Image 1 for a diagram of the basal ganglia circuitry dysfunction in dystonia.

Frequency

United States

The relative frequencies of primary and secondary forms of dystonia are not known.

In the Movement Disorder Center at Columbia Presbyterian Medical Center, 71% of more than 3000 patients with the disorder had primary torsion dystonia; the remaining 29% had secondary etiologies, with tardive dystonia being the leading acquired cause (unpublished data).

The prevalence of primary torsion dystonia is difficult to estimate because of the variation in its expression and the tendency for mild cases to go undiagnosed. In Rochester, Minnesota, the prevalence was calculated to be approximately 330 cases per million population. Late-onset focal primary dystonia was 10 times more common than early-onset generalized primary torsion dystonia (Nutt, 1998). Several large studies showed that early-onset primary torsion dystonia is 5-10 times more common in Ashkenazi Jews than in people who were not Jewish or in Jewish individuals not of Ashkenazi heritage (Zibler, 1984).

International

In a recent European collaborative study (the Epidemiological Study of Dystonia in Europe [ESDE]), investigators found a crude annual prevalence of 15.2 cases per 100,000 individuals, the majority of whom had focal dystonia at a rate of 11.7 cases per 100,000 individuals (ESDE Collaborative Group, 1999).

Race

Childhood- and adolescent-onset primary dystonia is more common in Jews of Eastern European or Ashkenazi ancestry than in other groups.

• Many cases of early primary torsion dystonia, especially those among non-Jewish populations, are not due to the TOR1A GAG deletion in DYT1. The DYT6 locus was identified by means of linkage analysis in 15 affected members from 2 Swiss Mennonite families (Almasy, 1997).
• A genomewide search for primary torsion dystonia in a large family from central Italy in whom 11 members were definitely affected revealed a novel locus, namely, DYT13 (Valente, 2001).

Sex

In a large study of 957 cases of primary dystonia from Europe, segmental and focal dystonias had notable female predilections. This finding suggested that patients with focal dystonia should not be treated as a homogenous group and that sex-linked factors may play a role (ESDE Collaborative Group, 1999).

Clinical

History

The following history should be elicited:

• Age of onset
• Initial site of involvement and progression to other body sites and time course of progression
• Occurrence of dystonia at rest, with any specific voluntary action or, posture maintenance
• Presence or absence of tremor or other movement disorders.
• Presence or absence of a sensory trick, or geste antagoniste
• A family history of similar symptoms or other involuntary movements, the age of onset of similar symptoms, and body part predominantly affected
• Inquiry about other imaging or laboratory abnormalities (ie, MRI findings, serum ceruloplasmin concentrations) that suggest another cause of dystonia
• Previous therapeutic trial and response to low-dose levodopa to exclude dopamine-responsive dystonia
• Any secondary etiologies, such as trauma, infectious process, birth injury, or developmental delay
• Use of any medications reported to cause dystonia, such as levodopa, dopamine agonists, antipsychotics, neuroleptics, dopamine-blocking agents, metoclopramide, fenfluramine, flecainide, ergot agents, anticonvulsive agents, and certain calcium channel blockers
• Other neurologic complaints associated with the dystonic symptoms
• Pain, which is not usually a prominent feature except in some cases of cervical dystonia and other forms of secondary dystonia (eg, reflex sympathetic dystrophy and foot dystonia occurring with Parkinson disease)
• Aggravating or attenuating factors
• Degree of functional impairment resulting from the dystonia
• Medication trials, benefits, and adverse effects
• Additional questions about the following may help in determining if dystonia is affecting other body parts (Such involvement might not be otherwise volunteered.):
  • Increased blinking
  • Intermittent puckering of the mouth
  • Chewing movements
  • Tongue popping
  • Stuttering
  • Difficulty speaking
  • Becoming breathless when speaking with a soft voice
  • Turning, tilting, or shifting of the head in any direction
  • Jerking of the head
  • Twisting of the body
  • Tremors of the hands or feet, arms, or legs
  • Twisting or moving involuntarily when using hands or walking
  • Difficulty with writing
  • History of clumsiness
  • Cramps when using the hands or legs
  • Toes going up or down involuntarily or being pigeon toed

Physical

It is important to note the distribution of body parts affected. Although classification of the distribution is arbitrary, it may serve as a useful guide in clinical practice and may help in grouping families and patients for clinical trials and genetic studies.

• Distributions are classified as follows:
  • Focal (single body region)
  • Segmental (contiguous regions)
  • Multifocal (noncontiguous regions)
  • Hemidystonia (a type of multifocal distribution involving an ipsilateral arm and leg)
  • Generalized (leg, trunk, and 1 other region or both legs with or without trunk involvement plus 1 other region)
• The central features that distinguish dystonia from other involuntary movement disorders are the posture-assuming features or directional quality and patterned predictable involvement of a specific set of muscles involved.
• Although the pattern of muscle contractions in dystonia is consistent and predictable, involuntary movements vary with changing postures or tasks.
• The site of involvement may remain focal or progress to involve other parts of the body over time.
• The speed of dystonic contractions may be rapid or slow.
• Various sensory tricks may be performed that diminish the dystonic movements, termed geste antagoniste.
• Dystonic movements intensify with voluntary action. Movements of primary dystonia commonly occur with specific actions and are not present at rest. As the dystonic condition progresses, relatively nonspecific voluntary actions can bring out the dystonic movements. With still further worsening, the affected limb can develop dystonic movements while at rest, and the patient eventually develops sustained posturing.
• Irregular, rhythmic contractions termed dystonia tremors may be observed. The tremor is less regular than essential tremor.
• Facial muscles are affected, as manifested by patterned and sustained contractions of the forehead, eyelids, and lower face. Limbs may be affected as well, and specific voluntary tasks may intensify such contractions. Examples are writing when the upper extremities are affected and walking forward but not backward when lower extremities are affected.
• It is important to note other physical and abnormal neurologic findings in addition to the dystonia.

Causes

Causes of dystonia have historically consisted of 2 main groups: idiopathic (or primary) and symptomatic (or secondary) (Fahn, 1998). Idiopathic dystonia was distinguished from the symptomatic dystonias both by its lack of known cause and the absence of consistent brain pathology. However, it has become clearer that idiopathic dystonia consists of a group of clinical syndromes that are likely to have a genetic basis.

Table 2 summarizes the clinical characteristics of primary torsion dystonia associated with different genes. Table 3 lists the genetic loci for dystonia.

Table 2. Clinical Characteristics of Primary Torsion Dystonia Associated with Different Genes

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Table 3. Genetic Loci for Dystonia

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Note.—Although the etiologies for these dystonic syndromes are attributed mainly to genetic causes and to no other secondary causes, only some these conditions have dystonia as the sole clinical finding to fulfill the criteria for a diagnosis of primary torsion dystonia.

^* Adapted from Bressman et al, 1989.

• Types of dystonia
  • Idiopathic or primary torsion dystonia: Despite a negative family history, a genetic basis for dystonia is not ruled out completely, as its mode of inheritance usually is autosomal dominant with reduced penetrance.
  • Sporadic and familial torsion dystonia
  • Inherited (ie, hereditary) dystonia
• Secondary etiologies of dystonia
  • Vascular
    • Cerebrovascular, or ischemic injury
    • Arteriovenous malformation
    • Perinatal cerebral injury
  • Infectious
    • Viral encephalitis
    • Subacute sclerosing panencephalitis
    • AIDS
    • Creutzfeldt-Jakob disease
  • Trauma
    • Head trauma
    • Peripheral trauma
  • Brain tumor
  • Toxins - Manganese, carbon monoxide, carbon disulfide, methanol, disulfiram, wasp sting
• Drugs - Levodopa, dopamine agonists, antipsychotics, metoclopramide, fenfluramine, flecainide, ergot agents, anticonvulsant agents, certain calcium channel blockers
• Metabolic conditions
  • Kernicterus
  • Wilson disease
  • Amino acid disorders
  • Glutaric acidemia
  • Methylmalonic acidemia
  • Homocystinuria
  • Hartnup disease
  • Tyrosinosis
  • Lipid disorders
  • Metachromatic leukodystrophy
  • Neuronal ceroid lipofuscinosis
  • Dystonic lipidoses - Niemann-Pick disease, type C (ie, sea blue histiocytosis)
  • Primary antiphospholipid antibody syndrome
  • Gangliosidoses (ie, GM1, GM2)
  • Mitochondrial encephalopathies (eg, Leigh disease, Leber disease)
  • Lesch-Nyhan syndrome
  • Triosephosphate isomerase deficiency
  • Vitamin E deficiency
  • Biopterin deficiency
• Genetic factors
  • Dystonia plus syndromes
  • Myoclonus dystonia
  • Dopa-responsive dystonia (DRD)
  • Rapid-onset dystonia parkinsonism
  • Lubag or X-linked dystonia parkinsonism
• Neurodegenerative conditions
  • Progressive supranuclear palsy
  • Multiple systems atrophy
  • Corticobasal-ganglionic degeneration
  • Hallervorden-Spatz disease
  • Hypobetalipoproteinemia, acanthocytosis, retinitis pigmentosa, pallidal degeneration (HARP) syndrome
  • Neuroacanthocytosis
  • Spinocerebellar ataxia (SCA), types 1, 2, or 3
  • Ataxia telangiectasia
  • Huntington disease
  • Dentatorubropalidoluysian atrophy
• Demyelination - Multiple sclerosis
• Structural conditions
  • Atlantoaxial subluxation
  • Syringomyelia
  • Arnold-Chiari malformation
  • Congenital Klippel-Feil syndrome

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