Diagnosis

The diagnostic evaluation of dystonia may include the following:

• General physical and neurologic examinations
• Evaluation of the nature of the dystonia, including...
  • Apparent age at symptom onset
  • Bodily distribution
  • Disease progression
  • Whether dystonia occurs with specific actions
  • If it is characterized by "overflow"
  • If it is present at rest
  • Whether certain "sensory tricks" temporarily suppress dystonic movements

For example, the presence of hemidystonia—or rest dystonia rather than action dystonia at symptom onset—is strongly suggestive of secondary dystonia. Identification of certain features may suggest that symptoms have an emotional rather than an organic origin [psychogenic disease], such as abrupt onset, changing characteristics over time, spontaneous remissions, etc. And early limb-onset dystonia in the absence of other findings may suggest primary dystonia possibly due to DYT1 gene mutation [Oppenheim dystonia].) During clinical evaluation to assess the nature of the dystonia, patients may be examined and videotaped while performing various actions, such as sitting, standing, lying down, or walking.

In addition, if the dystonia is not always present, the examiner may use various methods to help "trigger" dystonic spasms to aid in diagnosis, such as requesting that a patient with suspected blepharospasm repeatedly open and shut his or her eyes. The examiner may also conduct passive movements of the affected bodily region, carefully feel (palpate) contracting muscles, and/or request that a patient adapt various positions or postures with the affected area. Such methods may be necessary for accurate diagnosis, appropriate assessment of the nature of dystonia, and localization of involved muscles (e.g., for those who may be appropriate candidates for therapy with botulinum toxin). Such evaluation may be documented by videotaped recordings. For those patients with suspected laryngeal dystonia, voice assessment is typically documented on voice recordings.

Additional evaluations may include assessment by a speech-language pathologists, when appropriate, physical or occupational therapists, or genetic counselors.

• A thorough patient history to help determine or exclude causative factors potentially associated with secondary dystonia, such as exposure to certain medications, particularly dopamine antagonists; exposure to certain toxins; peripheral, head, or spinal trauma; certain infections or inflammatory conditions of the brain; etc.
• A careful family history
• Laboratory studies, such as blood and urine tests, analysis of cerebrospinal fluid (CSF), and/or other studies. Blood tests may include erythrocyte sedimentation rate (ESR), antinuclear antibodies (ANA) studies, tests to detect the presence of acanthocytes or abnormal red blood cells that have spur-like projections (i.e., a finding that may be suggestive of neuroacanthocytosis), and/or other studies. (ESR measures the rate at which red blood cells settle in a tube of unclotted blood, potentially serving as a nonspecific indicator of inflammation. ANAs, which are antibodies that act against certain of the body's own cells [autoantibodies], are commonly seen in patients with certain autoimmune disorders.) If diagnosing physicians suspect certain heredodegenerative dystonias due to specific metabolic defects, laboratory studies may also be conducted to detect the levels of certain enzymes (e.g., lysosomal enzymes, etc.). In addition, particularly for children, adolescents, and adults younger than approximately age 40, studies may be recommended to measure levels of the enzyme ceruloplasmin in the fluid portion of the blood (serum). Abnormally low ceruloplasmin serum levels may suggest a diagnosis of Wilson's disease. For some patients, other laboratory studies may also be appropriate.
• Electrical recording techniques, such as electromyography (EMG); nerve conduction velocity tests; or other methods (e.g., reflex studies). In addition, in some instances, diagnostic evaluation may include electroretinography, which measures the retina's electrical response to light stimulation; electroencephalography (EEG) to detect or rule out potential seizure activity (such as in some individuals with paroxysmal dyskinesias); or other techniques.
• Biopsies. In selected patients, diagnostic assessment may include surgical removal and microscopic evaluation (biopsy) of small samples of skin, muscle, and/or nerve tissue.
• Ophthalmologic examination, including examination of internal structures at the front of the eyes with an illuminated microscope (slit lamp examination). Such examination may be recommended for children, adolescents, and adults under approximately age 40 to help confirm or rule out the presence of Kayser-Fleischer rings. As mentioned earlier, these are gold-like, brownishrings around the corneas of the eyes that are present in many patients with Wilson disease. They are typically present in patients who manifest neurologic and psychiatric abnormalities associated with this heredodegenerative disease.
• Thorough neurologic evaluations to help confirm or exclude the presence of other neurologic signs that may suggest secondary dystonias, dystonia-plus syndromes, or heredodegenerative disorders. Such neurologic signs may include certain eye (ocular) abnormalities (e.g., optic atrophy, retinal abnormalities); parkinsonism; myoclonus; impaired coordination of voluntary movements (ataxia); spasticity; muscle weakness; dementia; seizures; and/or other findings.
• Neuroimaging studies, such as computerized tomography (CT) scanning or magnetic resonance imaging (MRI), to create detailed, cross-sectional images of the brain and spinal cord. Such studies may be recommended for those in whom patient history and clinical examination suggest the possibility of structural lesions that may be responsible for secondary or heredodegenerative dystonias.

According to experts, individuals with early-onset apparently isolated dystonia should undergo specific tests to help exclude Wilson disease (e.g., slit lamp examination, serum ceruloplasmin). If patient and family history and physical examination reveal certain symptoms, signs, and physical findings suggestive of secondary or heredodegenerative dystonias, more extensive diagnostic testing may be recommended, such as enzymatic studies (assays), neuroimaging studies, etc. For those with primary dystonias, dystonia is typically the only sign upon examination (i.e., with the possible exception of tremor or brief myoclonic jerks). In such cases, most diagnostic studies may not provide any revealing findings.

However, for individuals with early-onset or limb-onset dystonia, regardless of their family history or ancestry (i.e., whether of Ashkenazi Jewish or non-Jewish descent), DNA testing is now available to help confirm or exclude primary dystonia due to mutation of the DYT1 gene. During such testing, blood samples are taken from patients and DNA is directly analyzed for the presence of the GAG (guanine, adenine, guanine) deletion in the DYT1 gene's coded instructions. In addition to confirming or ruling out DYT1 dystonia in patients with symptoms, such testing may also help to detect or exclude the DYT1 gene mutation in family members of diagnosed individuals and may be conducted prenatally. As mentioned earlier, however, evidence indicates that only 30 to 40 percent of those who carry a mutated DYT1 gene for the disease manifest symptoms (reduced penetrance). Therefore, a majority of those with the mutated gene do not develop the disorder. There currently is no way to predict whether an individual with the disease gene will develop dystonia. Because the disorder has reduced penetrance as well as variable expressivity among those who do develop symptoms, experts recommend that genetic counseling should be provided for individuals who are considering diagnostic, carrier, or prenatal DYT1 DNA testing.

For patients with early-onset generalized or segmental limb dystonia who test negative for the DYT1 gene mutation, physicians may recommend a diagnostic trial with the agent levodopa (L-dopa). The dystonia-plus syndrome known as dopamine-responsive dystonia (DRD) is suggested in young patients with dystonia who have significant improvement with low-dose L-dopa therapy. In contrast, most dystonia patients who do not have DRD do not have a response to treatment with L-dopa or dopamine agonists. Thus, if no improvement is noted after approximately 3 months of L-dopa therapy, a diagnosis of DRD is considered unlikely and such treatment may be stopped.

For some patients with adult-onset focal dystonias that are presumed to be primary—e.g., based upon thorough clinical examination, a complete patient and family history, nature of the dystonia, absence of certain signs upon examination, etc.—experts indicate that extensive laboratory or neuroimaging studies may not be necessary. As discussed above, if patients are under 40 years of age, they should receive specific tests to help exclude Wilson disease. In addition, the presence of certain unusual (atypical) signs may suggest the need for additional testing. For example, as mentioned previously, adult-onset lower limb dystonia is extremely rare; therefore, such patients should receive diagnostic evaluations to determine whether the condition has occurred secondary to Parkinson's disease or other parkinsonism syndromes. However, individuals with typical adult-onset focal dystonias, particularly those who have been affected for several months or more, may not require further diagnostic evaluations unless new signs or unusual symptoms develop.

It is possible that DNA analysis may assist in diagnosing other forms of dystonia caused by known mutations of specific genes in certain families. However, such testing may be considered investigational and/or may not be widely available. As more is learned about the genetic causes of the different forms of dystonia, it is hoped that such information will lead to additional laboratory studies and greater availability of such testing to help confirm the diagnoses.

	Approaches to Treatment