Spasmodic dysphonia (SD) is a chronic voice disorder of unknown origin that is characterized by excessive or inappropriate contraction of laryngeal muscles during speech. Spasmodic dysphonia (SD) manifests as excessive glottic closure (adductor dysphonia) or prolonged lateralization of the vocal folds (abductor dysphonia). Strained or strangled phonation and irregular voice stoppages (the form originally described and most commonly observed clinically) characterize adductor dysphonia. Abductor spasmodic dysphonia (SD) presents with a breathy or absent voice or brief vocal loss.
Spasmodic dysphonia (SD) remains one of the most inveterate dysphonias despite various attempts to treat the disease. Because the cause of spasmodic dysphonia (SD) is still undetermined, management of this disorder continues to be directed at relief of symptomatic vocal spasm rather than cure.
Traube, who believed the condition to be a form of nervous hoarseness, first described spasmodic dysphonia (SD) in 1871.[1] For many years, the disorder was referred to as spastic dysphonia, but the term spasmodic dysphonia is more widely accepted today.
Dedo first introduced recurrent laryngeal nerve section for the treatment of spasmodic dysphonia (SD) in 1976.[2] Other investigators modified this approach by crushing the recurrent laryngeal nerve.[3] However, the use of these techniques gradually declined because of a high late recurrence rate and the inherent disability that occurred.[4]
In 1980, Isshiki et al introduced a laryngeal framework surgery (laryngoplasty) for patients with adductor spasmodic dysphonia (SD).[5] This technique permits adjustment of the position and tension in the vocal folds. This surgical approach is still experimental, and further investigation is required.
Blitzer et al applied the botulinum toxin injection technique in 1984.[6] This procedure has become the treatment of choice for spasmodic dysphonia (SD). Advantages of this technique include a high success rate in restoring or improving the voice. However, botulinum toxin injections provide only temporary symptomatic relief, and repeated intramuscular injections are required.
Recent surgical advances include recurrent laryngeal nerve denervation and reinnervation, as well as thyroarytenoid (TA) and lateral cricoarytenoid myectomy. These procedures have not yet been widely accepted as a primary treatment for spasmodic dysphonia (SD), and their long-term efficacy is controversial.[7, 8]
Early textbooks reported that spasmodic dysphonia (SD) was a relatively rare voice disorder, although recent reports suggest that it is not rare but rather frequently goes undiagnosed. Most studies show that this disorder affects females more commonly than males, with a female-to-male ratio as high as 4:1.[9]
Reports of the mean age of patients with spasmodic dysphonia (SD) typically indicate a range of 39-45 years; however, the condition may occur as early as the second decade of life in rare exceptions and as late as the ninth decade of life.[9, 10]
Although a genetic basis of spasmodic dysphonia (SD) has not been established, some patients (12%) report relatives with similar voice problems or other dystonias.[10]
The origin of spasmodic dysphonia (SD) is currently unknown. Primary generalized dystonia is clearly a genetic disorder and has been attributed to a defect on bands 9q32-34.[11] The location of the genetic defect in patients with primary focal dystonias is unknown.
Hall et al described a case in which spasmodic dysphonia (SD) was associated with hereditary spastic paraplegia type 7 (SPG7 mutation).[12]
Spasmodic dysphonia (SD) is currently understood to be a focal dystonia that affects laryngeal muscle control during speech. Dystonia refers to a syndrome of sustained muscle contractions. Focal dystonias involve abnormal activity in only a few muscles. Dystonic movements are aggravated or become manifest during voluntary movement and worsen with fatigue or physical and emotional stress. Dystonia may be focal, segmental, multifocal, or generalized. Although spasmodic dysphonia (SD) is considered a focal dystonia, it may present as a segmental or multifocal dystonia.
Spasmodic dysphonia (SD), as with other neuromotor disorders, is frequently associated with tremor. Essential tremor causes 6- to 8-Hz shaking, primarily of the hands, head, and voice. In spasmodic dysphonia (SD), the tremor may be isolated to the larynx or may involve the pharynx, head, or even hands.
The preponderance of evidence suggests that idiopathic dystonias are due to an abnormality of neurotransmitters in the basal ganglia (putamen, head of caudate, and upper brainstem). Zweig et al suggested that the putamen and the striatopallidothalamocortical circuit are disrupted in patients with focal dystonias.[13]
A study by Khosravani et al using electroencephalographic analysis indicated that compared with healthy controls, persons with spasmodic dysphonia (SD) demonstrate, during voice production, “a reduced movement-related desynchronization of motor cortical networks” and “an excessively large synchronization between left somatosensory and premotor cortical areas.”[14]
A study by Simonyan et al suggests that the pathophysiology of spasmodic dysphonia (SD) may be related to specific brain abnormalities.[15] Evidence from both diffusion tensing imaging and neuropathological data show specific white matter changes along the corticobulbar and corticospinal tracts and in the brain regions contributing to them. Specifically, the genu of the internal capsule was found to have decreased quality and density of axonal tracts.
Postmortem histopathology also confirmed reduced axonal course and myelin content in the right genu of the internal capsule. An increase in microglial activation in these regions suggests a slow demyelination process. The changes in the CBT/CST suggest deficiency in connection between the cortical and subcortical regions, which are essential for voluntary voice production. Diffusion tensor imaging found changes in the common areas sited for focal dystonias namely the basal ganglia, cerebellum, and thalamus. Postmortem clusters of mineral accumulations in these areas may suggest a pathological process that is common to focal dystonias.[15]
Similarly, Ali et al used H215 O PET to examine speech-related changes in regional cerebral blood flow to assess patients both before and after botulinum toxin injection.[16] Their data demonstrate definitive patterns of cerebral activity in patients with ADSD and neurologically normal controls. Their results suggest that the pathophysiology of spasmodic dysphonia (SD) is related to sensory cortical areas as well as motor areas.
Using PET imaging, activity in the postcentral gyrus, inferior parietal lobule, and middle temporal gyrus are found to be significantly reduced in patients with ADSD. Afferent (proprioceptive/tactile) feedback mechanisms that are controlled in these sensory areas are known to play a crucial role in coordinated oral-laryngeal movements. Hypoactivity suggests that this sensory feedback is not being processed appropriately in ADSD. Without sensory feedback, intracortical inhibitory mechanisms are deficient.
Interestingly, botulinum toxin therapy resulted in a reversal of sensory hypoactivity 3-4 weeks after injection. The authors suggest that this process of renewed sensory feedback can lead to reorganization in both sensory and motor areas. Motor regions as well as the lateral premotor system (responsible for organizing and executing movements in response to afferent signals) are found to have an increase in cerebral blood flow. This suggests more efficient processing of sensory signals and possibly a return of normal inhibition. This may translate to clinical improvement in speech and voice after botulinum toxin injection.[16]
The etiology of spasmodic dysphonia (SD) is unclear. Approximately half the patients can associate the onset if their symptoms with either an upper respiratory infection (30%) or a major life stressor (21%).[9] A study of 350 patients with spasmodic dysphonia showed that 35% of them could identify inciting events that caused the onset of their disorder, with 45% of these noting a sudden onset of dysphonia. The most commonly cited behavioral and environmental factors surrounding the onset of this disorder were stress, upper respiratory tract infections, and pregnancy/parturition.[17]
Speech is characterized by strained or strangled phonation with intermittent voice offsets on voicing of vowels. Patients report that symptoms are worse when they are under emotional stress, when they talk on the telephone, or when they speak publically. The symptoms are often better upon awakening in the morning or after a drink of alcohol. Patients are generally able to whisper or sing without strain or vocal breaks; this is often not the case with muscle tension dysphonia and helps to clinically distinguish between the 2 disorders. Voicing is effortful, with strain and occasional hoarseness, but the essential symptom is voice breaks. The voice breaks are due to spasmodic hyperadductions of the folds that interrupt phonation. Upon fiberoptic laryngoscopy examination, the vocal folds of patients with adductor spasmodic dysphonia (SD) have intermittent rapid shortening and squeezing, which results in a quick glottic closure that shuts the glottis and interrupts airflow through the glottis.
Abductor spasmodic dysphonia (SD) is rarer than the adductor type (17% of all patients with spasmodic dysphonia).[10] Patients have prolonged voiceless consonants because of difficulties with voice onset following voiceless sounds such as /h/, /s/, /f/, /p/, /t/, and /k/. Additional symptoms in some patients with abductor spasmodic dysphonia (SD) include pitch changes, phonatory breaks during vowels, uncontrolled rises in vowels' fundamental frequency, or a breathy voice quality. Upon fiberoptic laryngoscopy, patients with abductor spasmodic dysphonia (SD) have wide-ranging abduction movements for voiceless consonants that are prolonged and interfere with following vowels.
A careful evaluation of the patient by a multidisciplinary team is needed before the best treatment for that patient can be selected. The primary treatment modality as endorsed by the American Academy of Otolaryngology- Head and Neck Surgery is currently botulinum toxin injection into the laryngeal musculature. The patient should be counseled about the advantages and disadvantages of each management approach and their expected results.
The following treatment options are currently available:
Contraindications and relative contraindications to botulinum toxin therapy are as follows:
CT scanning with gadolinium or MRI: Reserve brain imaging for patients with focal findings upon neurologic examination that are beyond the distribution of spasmodic dysphonia (SD).
A study by Creighton et al indicated that the diagnosis of spasmodic dysphonia can be delayed by years owing to a lack of physician awareness of the condition and the need for well-defined diagnostic criteria. The study, in which 107 patients with spasmodic dysphonia answered questionnaires concerning diagnosis and treatment, found that diagnosis of the condition took an average of 4.43 years after patients first saw a physician for vocal symptoms. Patients also required visits to an average of 3.95 physicians before receiving the correct diagnosis.[18]
The occurrence of other neurologic signs not associated with other dystonias or tremor suggests that spasmodic dysphonia (SD) is secondary to another disease process. The neurologic examination may also reveal signs of other neurologic disorders that may be misconstrued as spasmodic dysphonia (SD).
Grade, roughness, breathiness, atonicity, and strain (GRBAS) is the evaluation system currently used to evaluate perceptual judgment. GRBAS involves a scale of 0-3 (0 = normal or absence of deviance; 1 = slight deviance; 2 = moderate deviance; 3 = severe deviance).
Conversational speech or the reading of a passage is rated. The classic perceptual sign of spasmodic dysphonia (SD) is abnormal voice quality that is heard in contextual speech but not necessarily in singing, whispering, laughing, falsetto voice, or crying.
Sentences that elicit adductor breaks when spoken include the following:
Sentences that elicit abductor breaks when spoken include the following:
Acoustic measures reflect the status of vocal function. Standard deviation of the fundamental frequency or jitter (measured in ms) and amplitude modulation or shimmer are significantly higher in patients with spasmodic dysphonia (SD). The signal-to-noise ratio is generally lower in patients with spasmodic dysphonia (SD) than in healthy control subjects.
Aerodynamic analysis of voice production includes the measurement of airflow and air pressure and their relationships during phonation.
In adductor spasmodic dysphonia (SD), mean airflow rates range from normal to extremely low.
In abductor spasmodic dysphonia (SD), mean phonatory airflow rate is generally above normal, with bursts of airflow occurring with the abductor spasm.
Subglottic pressure measures were estimated to be higher than normal in patients with adductor spasmodic dysphonia (SD).
In 2001, Hillel demonstrated that all the laryngeal muscles are involved in spasmodic dysphonia using examination with hooked wired electrodes.[19]
Either abductor or adductor muscle spasms are believed to predominate, resulting in the corresponding symptoms. EMG is generally not used in diagnosing spasmodic dysphonia (SD). In experienced hands, EMG guidance may not be necessary.[20]
The purpose of a subjective self-evaluation is to determine the deviance of voice quality and the severity of disability or handicap in daily professional and social life and to determine the possible emotional repercussions of the dysphonia.
Videolaryngostroboscopy is the main clinical tool used in determining the origin of voice disorders. Abductor and adductor spasms can be visualized during voice breaks. This procedure can also be used to assess the quality of vocal fold vibration to evaluate treatment effectiveness.
The symptoms of spasmodic dysphonia often include worsening of voice during periods of stress and relative improvement on sedatives such as alcohol and benzodiazepines. Despite these effects, no clear pharmacological agent provides even marginal relief of spasmodic dysphonia (SD). Typical agents used include benzodiazepines, anticholinergics, and dopamine antagonists. Even when success is noticed with these agents, their use is often precluded due to the well-documented peripheral and CNS side effects.[21]
Clinicians have found that voice therapy in patients with spasmodic dysphonia (SD) generally has limited benefit, although it may help them gain greater insight into their voice production and reduce hyperfunctional compensatory behaviors.[22] As such, voice therapy can be a useful as an adjunctive therapy.
At present, voice therapy is recommended for the following types of patients with spasmodic dysphonia (SD):
Voice therapy usually lasts for 6-8 sessions over 8-10 weeks. The key element in this treatment is the reduction of excessive pressure; the maintenance of a nonspasmodic phonation gives patients a sense of control over their treatment.
Focus on reducing the effort associated with voice onset by using gliding phonation with fricatives or vowels.
The program includes replacing short shallow inspirations with slow smooth inspirations, first without phonation and then with phonation. Conscious awareness of lower thoracic breath control and the rhythm of breathing are initiated. Patients are taught to use only the amount of breath needed for a particular phrase. Emphasis is placed on coordinating the lower thoracic exhalation phase of breathing with the onset of phonation.
Phrasing of 3-6 syllables is emphasized. Voiceless phonemes are added to the voiced phonemes to develop awareness in the patient that voicing is now produced more easily than in the past. Exercises to improve resonance are added after treatment for airflow control and breathing is established.
The ideal treatment for spasmodic dysphonia (SD) has not been identified. Currently, the American Academy of Otolaryngology- Head and Neck Surgery endorses the injection of minute quantities of botulinum toxin into laryngeal muscles as the primary treatment modality. Botulinum toxin causes a chemical denervation of muscle fibers by blocking the release of acetylcholine at neuromuscular junctions.
The clinical effect of botulinum toxin is classically thought to result from its peripheral effect, but some research suggests otherwise. The toxin is found to not only affect extrafusal muscle fibers but also the afferent muscle spindle output. Muscle activity is known to be regulated by afferent feedback, so a decrease in muscle spindle output can lead to decreased muscle effectiveness. In addition, because spasmodic dysphonia is by definition a focal dystonia, a deficient level of CNS inhibition is inherent. This lack of inhibition can lead to increased activity of the muscle fibers leading to spasms.
Some suggest that the selective denervation and deafferentation of botulinum toxin may cause an increase in inhibition, causing an improvement in the involuntary muscle spasms.[23] For more information, see the Pathophysiology section.
Botulinum toxin injection is accomplished with a monopolar hollow polytetrafluoroethylene (Teflon)–coated EMG needle connected to an EMG recorder.
Typically, the commercially available botulinum toxin is reconstituted with preservative-free 0.9% sodium chloride before injection. Traditionally, this reconstituted solution is injected within 4 hours. A recent study, however, shows no significant difference in efficacy or side effects between this freshly reconstituted BOTOX® and reconstituted BOTOX®, which is stored frozen for 4-8 weeks. This cost-effective measure allows the otolaryngologist a longer period of use without sacrificing quality.[24] The patient is placed in either a nearly supine position with a pillow underneath the upper back and with the neck extended or a seated position in an examination chair with the neck extended. The thyroid and cricoid cartilages are palpated, and the midline of the CT membrane is identified.
Dosage
Percutaneous injection of botulinum toxin into the thyroarytenoid (TA) muscle in adductor spasmodic dysphonia (SD) is usually performed with a starting dose of 1.25 U into each TA muscle.
For patients with abductor spasmodic dysphonia (SD), the dose is 5 U for unilateral posterior cricoarytenoid (PCA) injection. The patient returns 2 weeks later for a second contralateral injection if symptoms are not sufficiently abated. Prior to injection, flexible laryngoscopy is performed to confirm that weakened but adequate abduction of the injected vocal fold is present. If abduction is minimal, airway compromise due to contralateral injection is a significant risk. As a result, this injection is postponed.[25]
Alternatively, 1.25 U can be administered on one side, while 5-7 U are administered in the other side during the same visit. Botulinum toxin treatment for abductor spasmodic dysphonia (SD) is more difficult than for adductor spasmodic dysphonia (SD) and is associated with greater risk, including mild-to-severe stridor caused by PCA paralysis.
In a case review by Stong et al, patients with abductor spasmodic dysphonia (SD) simultaneously injected with least 2.0-2.5 U in each PCA muscle were found to have no major complications such as intubations, tracheotomies, or admissions for airway observation. Importantly, their review did report a 5% rate of dyspnea on exertion and a 2% rate of dysphagia, which resolved after 2-3 weeks.[26]
Procedure
In adductor spasmodic dysphonia (SD), the needle is passed through the skin that lies over the superior edge of the cricoid, just lateral to midline. The needle is then advanced through the CT membrane and superiorly and laterally directed into the right or left vocal fold to reach the TA muscle as seen in the image below.
View Image | Thyroarytenoid injection for adductor spasmodic dysphonia. Needle is advanced through the cricothyroid membrane. |
By entering slightly off the midline, the injection can be accomplished totally submucosally, without entering the airway. The oscilloscope and auditory output of the EMG apparatus are monitored to detect muscle activity. When crisp action potentials are obtained with phonation, needle position in a TA muscle is confirmed. Once the position is confirmed, the toxin is slowly injected.
Injection of botulinum toxin for abductor spasmodic dysphonia (SD) is more technically demanding. The larynx must be grasped and rotated away from the site of the planned injection. The needle is advanced through the inferior constrictor muscle at the posterior border of the thyroid cartilage at the junction of the lower third and upper two thirds of the cartilage. The needle is advanced to the cricoid cartilage and then slightly moved out (under EMG guidance) to the optimal position in the PCA muscle as seen in the image below.
View Image | Posterior cricoarytenoid (PCA) injection for abductor spasmodic dysphonia. Needle is advanced through the inferior constrictor muscle to the PCA muscl.... |
The patient is asked to sniff—an action that yields maximal abduction of vocal folds and activation of the PCA. The EMG signal is observed for correct placement, and the toxin is injected in the area of brisk activity.
Evaluation and rating criteria
Patients are re-evaluated in the second week after injection. Typically, the toxin's effect occurs within the first 48-72 hours. Adductor patients' voices initially become hoarse or breathy. Some patients develop mild aspiration when drinking liquids. Accordingly, advise patients to sip through a straw, to avoid gulping liquids, or to use a supraglottic swallow technique. As noted above, abductor patients may experience stridor or dysphagia.
Patients are given a diary so they can rate themselves before injection, then every day for 2 weeks after injection, and then weekly until the next injection. This rating aids assessment of botulinum toxin treatment effectiveness and indicates the optimal timing and dosage for the next injection.
Treatment regimen
Because of differing sensitivity to botulinum toxin, the injection protocol and dosage must be established for every patient on an individual basis. Each patient is started with a standard dose. This is then increased or decreased based on the patient's side effects, symptom response, and individual needs.
In a recent study by Holden et al, patients reviewed over a 14-year period were evaluated for changes in dose and interval. Their data showed that over time, doses remained consistent and intervals between injections were found to be relatively stable.[27]
Some patients are very sensitive to toxin. They may not have adequate relief with small bilateral doses and too much breathiness at larger doses. For those patients, injections can be initiated with a larger dose unilaterally, with or without a contralateral injection 2 weeks later. A delay allows some recovery before the second dose is administered. Alternatively, patients often do well with only a unilateral injection.
Another approach to prevent breathiness is more frequent administration of bilateral minidose injections (0.1-0.5 U), although the duration of benefit in these patients is only 6-8 weeks.
If results are still suboptimal and the diagnosis of spasmodic dysphonia (SD) is clear, then injection of multiple muscles within the affected group may be helpful. Interarytenoid injections may be helpful in adductor spasmodic dysphonia (SD), while cricothyroid injections maybe be helpful in abductor spasmodic dysphonia (SD).[28, 29]
In addition to botulinum toxin injections, which have become the standard of care in the treatment of spasmodic dysphonia (SD), several surgical treatments are currently in practice.
Isshiki et al proposed type 2 thyroplasty techniques for adductor spasmodic dysphonia (SD). These techniques were successful in 5 of 6 patients. The concept of these techniques is to change the thyroid cartilage shape to relax and slightly lateralize the vocal folds. The advantages of the surgery include (1) the ability to adjust optimal glottal closure for phonation, (2) unlikely recurrence, (3) no damage to the physiological function of phonation, (4) intraoperative reversibility if ineffective, and (5) the ability to perform readjustments when needed.[5]
Conflicting results were presented in a subsequent study by Chan et al, who could not replicate the success of Isshiki and colleagues.[30] However, a retrospective study by Sanuki and Isshiki details the success of type 2 thyroplasty with a titanium bridge (to maintain separation of incised thyroid cartilage) in a larger subset of patients. Although limited by length of follow up, significant improvement in comparative perceptual analysis such as degree of strangulation, interruption, and tremor were observed in the patients, who had adductor spasmodic dysphonia (SD), less than a year after surgery.[21]
Another study by Sanuki, with Yumoto, indicated that in adductor spasmodic dysphonia (SD), type 2 thyroplasty using implanted titanium bridges can provide long-term symptom relief. At an average follow-up of 41.3 months after surgery, almost all of the 31 patients surveyed reported satisfaction with their postoperative voice, with scores on the Voice Handicap Index-10 (n=17) improving from 26.3 to 9.4.[31]
A retrospective study by Nomoto et al indicated that bilateral thyroarytenoid muscle myectomy (TAM) and type 2 thyroplasty are each effective in treating adductor spasmodic dysphonia, with both resulting in comparable improvements on the voice handicap index-10. The study, in which 30 patients underwent TAM and 35 were treated with type 2 thyroplasty, also found that TAM was better than type 2 thyroplasty in improving strangulation, interruption, and tremor but that it tended to worsen breathiness.[32]
Recurrent laryngeal nerve denervation and reinnervation was first described in 1999.[33] The adductor branch of the recurrent laryngeal nerve (to TA and LCA) is bilaterally denervated and the distal nerve TA is reanastomosed to the ansa cervicalis. In addition, a lateral cricoarytenoid myectomy is performed. The ansa cervicalis reinnervation results in tone of the TA and LCA muscles and prevents reinnervation by the laryngeal nerves affected by spasmodic dysphonia (SD). Most voices improved in the judgment of both professionals and patients, and 83% of patients would recommend or strongly recommend the surgery to others with spasmodic dysphonia (SD). Twenty percent of patients had complications of moderate-to-severe breathiness, with one patient suffering from aspiration.
A follow-up retrospective study by Chhetri et al showed long-term (mean 49 months) improvement in both patient satisfaction and expert perceptual voice evaluation. Again, postoperative breathiness was significant in 30% of patients.[7] A Canadian group has been able to reproduce similar results in a small series of patients. Six patients were treated without complication and with favorable results based on subjective evaluation of expert and untrained listeners. One patient required continued botulinum toxin therapy.[34]
A final surgical option for adductor spasmodic dysphonia is a bilateral TA and lateral cricoarytenoid myectomy staged a minimum of 6 months apart. This weakens the vocal folds bilaterally to prevent spasms. It is performed under local anesthesia and is titrated to breathiness to eliminate the risk of overresection. Short-term results in 5 patients revealed improved fluency in all patients.[8] Long-term studies are needed, especially considering the history of blepharospasm treatment using a similar procedure. Many patients with blepharospasm treated with myectomy had either recurrence of symptoms or dysfunction due to muscular fibrosis or scarring.
These surgical techniques are in their infancy and require wider evaluation and long-term follow-up data before being considered as a standard treatment for spasmodic dysphonia (SD).
For excellent patient education resources, see eMedicineHealth's patient education article BOTOX® Injections.
See the list below:
Most patients experience toxin effect within the first 48-72 hours after injection, with a variable amount of breathy dysphonia and slight aspiration. These adverse effects disappear within the first week, but voice improvement persists for approximately 12 weeks.
Treatment of adductor spasmodic dysphonia (SD) with botulinum toxin achieves good results, with an average benefit of 90% of normal voice function.[6]
Treatment of abductor spasmodic dysphonia (SD) is more difficult. The abductor muscle (the PCA) is located between the larynx and pharynx and is more difficult to inject. Most patients require bilateral PCA injections. Botulinum toxin treatment achieves an average benefit of 70% of normal voice function.[35]
Surgical therapy for spasmodic dysphonia (SD) is still controversial because the side effects can be severe, and wide evaluation with long-term follow-up data is not available.
To date, botulinum toxin injection is the standard therapy for spasmodic dysphonia (SD). Unfortunately, this is just a treatment at the end organ and is not a cure. The key to understanding this disorder is to understand its pathophysiology and that of other spasmodic movement disorders.
Current research, especially gene research, is progressing in the elucidation of the cause of focal dystonia. Advances in the understanding of genetically determined early-onset primary torsion dystonia are offering insight into the pathophysiology of dystonia. An amino acid deletion in the DYT1 gene has been found to be responsible for familial primary torsion dystonia. This defect results in an abnormality in the protein torsinA, which is widely distributed in the CNS.[36] Further investigation of the of this gene and its protein products will hopefully spur advances in our understanding of dystonia and improve our treatment of the disorder.