1492
K.P. FREI ET AL.
45. Ghika J, Villemure JG, Fankhauser H, Favre J, Assal G, GhikaSchmid F. Efficiency and safety of bilateral contemporaneous pallidal stimulation (deep brain stimulation) in levodopa-responsive patients with Parkinson’s disease with severe motor fluctuations: a 2-year follow-up review. J Neurosurg 1998;89:713–718. 46. Volkmann J, Sturm V, Weiss P, et al. Bilateral high-frequency stimulation of the internal globus pallidus in advanced Parkinson’s disease. Ann Neurol 1998;44:953–961. 47. Pinter MM, Alesch F, Murg M, Helscher RJ, Binder H. Apomorphine test: a predictor for motor responsiveness to deep brain stimulation of the subthalamic nucleus. J Neurol 1999;246:907– 913. 48. Berciano J, Valldeoriola F, Ferrer I, Rumia J, Pascual J, Marin C, Rey MJ, Tolosa E. Presynaptic parkinsonism in multiple system atrophy mimicking Parkinson’s disease: a clinicopathological case study. Mov Disord 2002;17:812– 816. 49. Tarsy D, Apetauerova D, Ryan P, Norregaard T. Adverse effects of subthalamic nucleus DBS in a patient with multiple system atrophy. Neurology 2003;61:247–249. 50. Visser-Vandewalle V, Temel Y, Colle H, van der Linden C. Bilateral high-frequency stimulation of the subthalamic nucleus in patients with multiple system atrophy—parkinsonism. Report of four cases. J Neurosurg 2003;98:882– 887. 51. Anderson ME, Postupna N, Ruffo M. Effects of high-frequency stimulation in the internal globus pallidus on the activity of thalamic neurons in the awake monkey. J Neurophysiol 2003;89: 1150 –1160. 52. Hashimoto T, Elder CM, Okun MS, Patrick SK, Vitek JL. Stimulation of the subthalamic nucleus changes the firing pattern of pallidal neurons. J Neurosci 2003;23:1916 –1923. 53. Ni Z, Bouali-Benazzouz R, Gao D, Benabid AL, Benazzouz A. Changes in the firing pattern of globus pallidus neurons after the degeneration of nigrostriatal pathway are mediated by the subthalamic nucleus in the rat. Eur J Neurosci 2000;12:4338 – 4344.
Natural History of Posttraumatic Cervical Dystonia Karen P. Frei, MD, Mayank Pathak, MD, Stephen Jenkins, MD, and Daniel D. Truong, MD* The Parkinson’s and Movement Disorder Institute, Fountain Valley, California, USA Abstract: We studied a case series of 9 patients with posttraumatic cervical dystonia, in whom involuntary muscle spasms and abnormal head postures occurred within 7 days after cervical injury. Patients were examined, treated with botulinum toxin as necessary, and were followed up to 5 years. Based on our observations of these cases, we propose that complex regional pain syndrome (CRPS) could repre-
*Correspondence to: Dr. Daniel D. Truong, The Parkinson’s and Movement Disorder Institute, 9940 Talbert Ave., Ste. 204, Fountain Valley, CA 92708. E-mail:
[email protected] Received 25 September 2003; Revised 28 March 2004, 20 April 2004; Accepted 23 April 2004 Published online 15 July 2004 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.20239
Movement Disorders, Vol. 19, No. 12, 2004
sent a variant of posttraumatic cervical dystonia that may develop over time after the initiation of dystonia. © 2004 Movement Disorder Society Key words: posttraumatic torticollis; complex regional pain syndrome
The most common form of focal dystonia is torticollis or rotation of the neck to one side. Most cases of torticollis are idiopathic, although some may result from a number of identified causes including brain injury, brain tumor, stroke, cervical cord injury or lesion, drugs including levodopa (L-dopa) and neuroleptics, multiple sclerosis and, in some cases, genetic abnormalities. A small number of patients report a history of trauma before onset of dystonia. Severe head trauma associated with brain injury that produces identifiable lesions, particularly in the putamen, has been known to cause hemidystonia.1 Peripheral trauma as a precipitating cause of dystonia is not accepted universally,2– 4 although one of the earliest reported cases of torticollis, the Birmingham mummy, is thought to have been caused by an arrow in the neck.5 Posttraumatic cervical dystonia is thought to be a unique syndrome, distinct from idiopathic torticollis. Some of its unusual features include a limitation in cervical range of motion, fixed posture, absence of “geste antagoniste,” persistence of symptoms during sleep, lack of improvement after sleep (the “morning honeymoon” effect), dominant laterocollis, and poor response to botulinum toxin injections.6,7 Complex regional pain syndrome I (CRPS-I) has been known to occur in posttraumatic cervical dystonia, and dystonia has been seen in CRPS.8 –10 CRPS-I is defined as a pain syndrome that usually develops after an initiating noxious event, is not limited to the distribution of a single peripheral nerve, and is disproportional to the inciting event.11 It is associated with edema, changes in blood flow, abnormal sudomotor activity in the region of pain, and allodynia or hyperalgesia. Schott12 first proposed a possible relationship between peripheral traumainduced movement disorders and causalgia or reflex sympathetic dystrophy in 1986. We describe 9 additional patients, 3 of whom exhibit CRPS, with posttraumatic cervical dystonia after apparent peripheral trauma, who share characteristics unique to the syndrome. PATIENTS AND METHODS Patients with dystonia of the cervical musculature who presented to the Parkinson’s and Movement Disorder Clinic in Fountain Valley, CA were systematically asked for history of trauma at their first interview. Inclusion criteria2 were as follows: (1) onset of dystonia within 3
Weakness right arm Mild weakness right arm No Mild weakness left arm No Weakness, tremor left arm No No No Yes Yes No No No Yes No No No Yes Yes Yes Yes Yes Yes No Yes Yes No No No No No No Yes No No No No No No Yes No No No Yes CRPS, complex regional pain syndrome; M, male; F, female.
No No No No No No No No Yes No No No No No No Possible No No 32/M 50/F 38/M 46/F 36/F 45/F 31/F 45/M 51/M 1 2 3 4 5 6 7 8 9
Laterocollis Laterocollis Laterocollis, torticollis Laterocollis Laterocollis Mild torticollis Laterocollis Laterocollis, torticollis Laterocollis, torticollis
Other neurological symptoms CRPS Tonic contractions Geste antagoniste Improves with rest Worsens with action Family history Head position
This 32-year-old, right-handed, Caucasian male was hit on the back of the neck by the descending door of a freight elevator. He noticed a sensation running down his right arm at the moment of injury, although he continued to work, but that evening he noticed that his head was being pulled toward the right. Initial X-rays of the cervical spine and shoulder were normal; a cervical magnetic resonance imaging (MRI) scan carried out shortly after the accident revealed mild disk bulges at several levels without any cord impingement. His pain progressively worsened and he noted a progressive reduction in range of motion in his neck. After a few months, he also
Age (yr)/Gender
Case 1
Case no.
Of 892 patients in our database, 9 met the inclusion criteria. They ranged in age from 31 to 56 years and all noted onset of dystonia within hours after injury. Two patients were receiving worker’s compensation, one was applying for worker’s compensation and none were involved in litigation at the time of evaluation. Of the 9 patients, 8 exhibited characteristics reported previously in posttraumatic cervical dystonia, including lack of exacerbation with activity, no geste antagoniste effect, and tonic contractions of the neck (Table 1). None of the patients reported the morning honeymoon effect and all tended to turn en bloc. Laterocollis was exhibited in 8 patients (Fig. 1); the ninth patient had mild torticollis alone. Three patients had a combination of laterocollis and torticollis. CRPS was seen in 3 of 9 patients and involved the upper extremity ipsilateral to the site of injury. None of the patients exhibited any other form of dystonia, nor did they tend to develop any spread of dystonia. Treatment response to botulinum toxin was variable, with 3 patients responding well to treatment. There did not seem to be any dystonia progression or spread throughout the follow-up period in any of the 9 cases. The following 2 case reports are representative of the 9 cases included in this study.
TABLE 1. Characteristics of patients in our series with trauma-induced cervical dystonia
RESULTS
Follow up duration (yr)
months of the trauma; (2) no history of pyramidal, cerebellar, sensory, or intellectual deficits; (3) no history of perinatal encephalopathy or kernicterus; (4) normal childhood developmental milestones; (5) no improvement with L-dopa as seen with dopa-responsive dystonia and no history of paroxysmal dystonia; (6) no abnormality on an imaging study that could be construed as a cause of torticollis; and (7) no significant laboratory abnormalities. Treatment with botulinum toxin was provided according to patient need and patients were followed for up to 5 years.
1493
5 3 3 1 3 1 3 3 2
POSTTRAUMATIC CERVICAL DYSTONIA
Movement Disorders, Vol. 19, No. 12, 2004
1494
K.P. FREI ET AL. forearm. His right arm was swollen substantially. Treatment with stellate ganglion block was not successful due to the extreme head position. He underwent selective denervation, right thoracic sympathectomy, and right brachial plexus decompression surgeries. However, the results were unsatisfactory. During the third year, hypersensitivity spread to involve the entire right arm, hand, and shoulder, the right side of the head (including face), and right side of the upper trunk. Discoloration of the right arm also was noted. He received cervical epidural infusions of bupivacaine and duramorphin but pain continued to be a major factor. Five years after the accident he developed hypersensitivity to pinprick in the left arm.
FIG. 1. Posttraumatic cervical dystonia patient with predominant laterocollis and left shoulder elevation. (Photo is digitally processed.)
noticed restricted movement in his right shoulder and a tendency for involuntary flexion of his right arm. Before coming to our clinic, this patient had been treated with a variety of medications including cortisone injections and physical therapy. He was also treated with botulinum toxin, but the results were not satisfactory; pain continued in his right arm despite botulinum toxin injections. He came to our clinic with his head tilted 45 degrees to the right and the right shoulder elevated. There was marked tenderness of the right trapezius, right levator scapulae, and scalene muscle group. There also was moderate hypertrophy of the right sternocleidomastoid. He was unable to turn his head in any direction and held his right arm pressed to his body and flexed at the elbow and wrist; his fingers were flexed at the metaphalangeal phalangeal and interphalangeal joints. Sensory testing showed paresthesiae in the right arm and right hand as well as hypoesthesia for pinprick. Deep tendon reflexes were ⫹2 throughout but ⫹3 at the right wrist. The patient refused to lie down during our examination and most of his history was taken as he walked around. Standing actually relaxed him; lying and sitting made his condition worsen. His head position did not change during sleep. When the pain was unbearable, this patient pushed his head further toward the right with his hand and let his head rebound. He denied any trick that would improve his condition and he had no family history of dystonia. Over the next year, he developed complete contracture of his fingers and had only minimal movement in his right elbow. He developed significant allodynia with hypersensitivity to light touch and hypoesthesia to pin prick in the elbow and to a lesser degree in the right
Movement Disorders, Vol. 19, No. 12, 2004
Case 8 This 45-year-old, left-handed, Hispanic male was working on a railroad track trying to remove a spike when it suddenly gave way and he jumped back, quickly twisting his head to the left. He immediately developed pain and stiffness of the neck and was unable to straighten out his neck. The pulling of his head to the left was continuous and interfered with sleep. He had no family history of dystonia and no response to sensory tricks. Electromyography (EMG) revealed heightened activity in the left splenius capitis, left levator scapuli, and left trapezius. He was seen in our clinic approximately 6 years after the initial injury. On examination, his head was turned fully to the left and tilted to the right and backwards, with elevation of the left shoulder. There was hypertrophy of the right sternocleidomastoid and left splenius capitis and trapezius muscles. He had little mobility, being able only to turn his head about 10 degrees. He was treated with several medications including anticholinergics, neuroleptics, and baclofen, with no relief of symptoms; botulinum toxin injections resulted in minimal improvement. He underwent selective peripheral denervation surgery twice: the first surgery involved selected posterior ramisectomy of C1, C2, C3, C4, and C5 with myectomy of the levator scapular muscle; the second surgery also involved resection of the levator scapulae and splenius capitis. His head maintained the fixed posture with his head tilting to the left during the second surgery while under general anesthesia (Figs. 2 and 3). He improved after surgery but still had some degree of laterocollis and limited improvement with botulinum toxin. DISCUSSION It has been proposed that posttraumatic cervical dystonia represents a unique syndrome that is distinct from
POSTTRAUMATIC CERVICAL DYSTONIA
FIG. 2. Under general anesthesia, left laterocollis persists. (Photo is digitally processed.)
the idiopathic variant (Table 2). Truong and colleagues6 reported on 6 cases of torticollis after neck injury with clinically distinct features, Goldman and Ahlskog7 confirmed these findings and reported on an additional 5 cases, Krauss and associates13 also reported on 1 of 9 central trauma cases that may represent posttraumatic cervical dystonia, and Tarsy14 reported on 9 patients with similar features. Schott12 described 6 of 10 cases of dystonia after peripheral trauma, and cervical dystonia was reported in 1 of the 6 patients. Recently, Sa and coworkers15 reported on 16 patients with a similar presentation. The 9 patients described in the present study exhibit characteristics similar to those reported on previously and provide additional support for classification of posttraumatic cervical dystonia as a distinct syndrome. A review of posttraumatic cervical dystonia cases in the literature is shown in Table 3. Arguments contrary to the association of peripheral trauma as a causative factor in dystonia include patient recall bias, the time factor to development of this disorder, the vast amount of minor peripheral trauma compared with the rarity of this disorder, and the difficulty in identifying a possible physiological mechanism. Many times patients will attribute a disorder to a certain event, most often a form of trauma, regardless of the severity; this has been seen with other disorders such as multiple sclerosis and is thus not unique to dystonia.16 To minimize wrongly associating a traumatic event with the coincidental development of torticollis, a time limit of 3 months was instituted arbitrarily in this study so that a possible uniform syndrome might emerge. With the establishment of the clinical features, the diagnosis of posttraumatic cervical dystonia may be based on clinical features with less reliance on the time relationship. The time lag between trauma and the development of torti-
1495
collis seems important. The shorter the time lag, the greater the association between the trauma and torticollis. Tarsy14 found a distinction between those with acute onset of torticollis developing within 4 weeks of precipitating trauma and those with the time lag from 3 months to 1 year. Those with the acute onset of posttraumatic cervical dystonia seemed similar to the previously reported cases of the syndrome, whereas those with delayed onset were similar to idiopathic torticollis. However, Samii and colleagues3 did not confirm this distinction in their report of 14 cases of posttraumatic cervical dystonia. The difference may be caused by case selection; 3 of the 14 cases described by Samii and coworkers3 could be considered as acute onset of posttraumatic cervical dystonia and differed from those reported by Tarsy14 only with respect to botulinum toxin injection response. This agrees with our cases having a variable response to botulinum toxin injections. Also consistent with previously reported cases of posttraumatic cervical dystonia, the patients in our cohort showed a strikingly high incidence of laterocollis, which may occur in these cases because of unilateral neck muscle spasm. Most of our posttraumatic cervical dystonia patients also have tonic contraction of the involved neck musculature. This tonic feature was also observed by Jankovic and van der Linden.17 Shoulder elevation and cervical muscle hypertrophy was also observed in 8 of the 9 cases with laterocollis, consistent with previous reports. Diagnostic criteria for posttraumatic dystonia have been proposed by Jankovic2: (1) trauma severe enough to cause local symptoms for at least 2 weeks or requires medical evaluation within 2 weeks after trauma; (2) the initial manifestation of the movement disorder is
FIG. 3. Patient is under general anesthesia. The arrow points to contracture of the trapezius muscle. Notice the contracture persists despite adjustsment of head position using a frame. (Photo is digitally processed.)
Movement Disorders, Vol. 19, No. 12, 2004
1496
K.P. FREI ET AL. TABLE 2. Comparison of posttraumatic and idiopathic cervical dystonia Type of cervical dystonia Symptoms
Idiopathic
Posttraumatic
Range of motion Fixed posture Sleep Geste antagoniste Worsening with action Improvement with rest or support Morning honeymoon effect Presentation CRPS Response to botulinum toxin Associated pain
Decreased in direction of/opposite to dystonia No Improvement Improvement Yes Yes Yes Often torticollis No Good Variable
Decreased in all directions Yes No change No change No No No Often laterocollis May develop Poor Severe
CRPS, complex regional pain syndrome.
anatomically related to the site of injury; and (3) the onset of the movement disorder is within days or months (up to 1 year) after the injury. These criteria were followed in our study, which actually incorporated stricter inclusion criteria. The disorder of posttraumatic cervical dystonia, however, may be more variable than described. Dewey and colleagues18 and Hollinger and Burgunder19 reported on isolated cervical and shoulder muscle dystonia in response to peripheral trauma, which may represent a milder form of posttraumatic cervical dystonia. Analogous to posttraumatic cervical dystonia, oromandibular dystonia has been reported to occur after trauma including dental work and orodental surgery.20,21 Features of causalgia– dystonia syndrome and spread to include cervical musculature have also been described.20,21 Because the incidence of peripheral trauma far outnumbers posttraumatic cervical dystonia cases, predisposing factors may account for its development.22 Fletcher and associates23 proposed that peripheral injury may precipitate dystonia in idiopathic dystonia gene carriers; however, Bressman and coworkers24 did not find any relationship between trauma and the DYT1 mutation. Patients in the series described by Bressman and colleagues24 had family history of dystonia, thus differing from our cases. Other possible predisposing factors that may be implicated include the use of neuroleptics or stimulants, perinatal insults to the brain or developmental delays, family history of dystonia or tremor, coexistent essential tremor, and clinical features of acquired immunodeficiency syndrome (AIDS)-related complex.17 Of 9 patients described in the present study, 8 did not share any of these predisposing factors; only 1 patient had a possible family history of dystonia or tremor, which could not be verified. Structural lesions such as atlantoaxial subluxation produce nondystonic torticollis. Characteristics that help
Movement Disorders, Vol. 19, No. 12, 2004
distinguish a nondystonic torticollis include subacute or sudden onset of an abnormal head posture, pain, inability to passively move the head, persistence of the abnormal posture during sleep, and tenderness to palpation in the neck region4; many of these characteristics are shared by posttraumatic torticollis patients. It is indeed possible that this form of torticollis represents a nondystonic torticollis, but the structural mechanism involved remains to be determined. Psychological issues have been implied recently as potential contributing factors to the development of posttraumatic cervical dystonia. Sa and coworkers15 reported on 16 patients with features of posttraumatic cervical dystonia comparable to those reported previously. Alleviation of the dystonic posture with sodium amytal and return of range of motion during general anesthesia in addition to psychological profile suggestive of somatization were reported as substantiation of a psychological manifestation of this disorder.15 All 16 of their patients were involved in litigation and 14 of 16 patients displayed nonanatomical sensory disturbances. In contrast, none of our patients were involved in litigation, nor did they report any sensory abnormalities. Although a possibility, it is difficult to accept the concept of posttraumatic cervical dystonia as occurring solely on a psychological basis. These patients seem to share the same abnormality in posture for many years without fluctuation in symptoms. We do not want to ignore or discount psychological issues that may contribute to or exacerbate this condition; however, the effects of general anesthesia and sodium amytal on idiopathic dystonia are not well known and may produce transient amelioration of symptoms through muscle relaxation. One of our patients retained his laterocollis even under general anesthesia, which strongly speaks against a psychological cause. Schott12 proposed a potential relationship between peripheral trauma-induced movement disorders and causal-
3/9 Unk 0/9 0/5 1/6 4/29 9/9 16/16 7/9 4/5 6/6 26/29 1/9 15/16 0/9 1/5 0/6 2/29 8/9 16/16 9/9 4/5 6/6 43/45 2/9 Unk Unk 1/5 0/6 3/20 1/9 Unk Unk Unk 2/6 3/15 1/9 Unk Unk 0/5 1/6 2/20 9/9 15/16 6/9 2/5 3/6 35/45 Current Sa et al.15 Tarsy14 Goldman and Ahllskog7 Truong et al.6 Total
CRPS, complex regional pain syndrome; Unk, unknown.
1/9 Unk 1/9 0/5 0/6 2/29
Laterocollis Series
9/9 15/16 7/9 5/5 5/6 41/45
Tonic contractions Improves with rest/ support Worsens with action Honeymoon effect Family history Immediate onset after injury
TABLE 3. Overview of characteristics of posttraumatic cervical dystonia in the literature
Geste antagoniste
Turns en bloc
CRPS
POSTTRAUMATIC CERVICAL DYSTONIA
1497
gia or reflex sympathetic dystrophy currently referred to as CRPS. The incidence of each is similar; both are rare occurrences after nonspecific and often minor trauma. There is a variable interval between the inciting traumatic event and the onset of the movement disorder or causalgia. Pain is a main component of both disorders and each disorder may spread proximally.12 Common neurotransmitters involved in the movement disorder and in nociception were proposed as potential explanations.12 Of 9 patients in the current series, 3 developed CRPS-I in the upper extremity on the affected side. The timing of development of the CRPS-I is of interest. As seen in Case 1, CRPS-I progressed over the course of 5 years and was not obvious at onset. Schwartzman and Kerrigan25 noted that 5 of their patients had dystonic features before the onset of CRPS-I. Weakness of the affected arm was also seen in our posttraumatic cervical dystonia patients who developed CRPS-I. CRPS-I could represent the extreme of severity within the spectrum of posttraumatic torticollis syndrome and may develop over time after initiation of posttraumatic cervical dystonia. Others have also noted CRPS in posttraumatic dystonia patients. Marsden and associates9 reported 4 cases of muscle spasm associated with reflex sympathetic dystrophy (RSD) after trauma who developed dystonia within a period of 4 months to 1 year after the injury. Bhatia and colleagues10 described the causalgia dystonia syndrome, in which patients had features of both CRPS-I and dystonia of the affected limb; 10 of 18 patients had onset of dystonia immediately after the trauma. Schwartzman and Kerrigan25 reported 33 patients with dystonia in their series of 200 CRPS-I patients. Interestingly, 7 of 16 patients with upper body dystonia also had contraction of the trapezius and sternocleidomastoid muscles that is often found in torticollis. The development of CRPS in posttraumatic torticollis as well as the finding of dystonia in CRPS suggests a possible common mechanism or cause. This is in agreement to Schott’s proposal.12 The pathophysiology of dystonia is unknown; peripheral trauma as well as CRPS-I may provide altered sensory input via an enhanced inflammatory response or ischemic factors,8 initiating a cascade of events that develops into dystonia or CRPS-I. A single event occurring in the appropriate setting may be all that is necessary to develop posttraumatic cervical dystonia. Much research remains to define the details of a possible mechanism for the development of this syndrome. Acknowledgments: We thank Dr. D. Tarsy for his comments and Dr. J. Jankovic for constructive suggestions and extensive editorial help.
Movement Disorders, Vol. 19, No. 12, 2004
1498
A.L. WHONE ET AL. REFERENCES
1. Krauss JK, Jankovic J. Head injury and post-traumatic movement disorders. Neurosurgery 2002;50:927–940. 2. Jankovic J. Can peripheral trauma induce dystonia and other movement disorders? Yes! Mov Disord 2001;16:7–12. 3. Samii A, Pal PK, Schulzer M, Mak E, Tsui JK. Post-traumatic cervical dystonia: a distinct entity? Can J Neurol Sci 2000;27:55– 59. 4. Weiner WJ. Can peripheral trauma induce dystonia? No! Mov Disord 2001;6:13–22. 5. Pahor AL, Cole J. The Birmingham mummy: the first torticollis in history. J Laryngol Otol 1995;109:273–276. 6. Truong DD, Dubinski R, Hermanowicz N, Olson WL, Silverman B, Koller C. Posttraumatic torticollis. Arch Neurol 1991;48:221– 223. 7. Goldman S, Ahlskog JE. Posttraumatic cervical dystonia. Mayo Clin Proc 1993;68:443– 448. 8. Van der Laan L, ter Laak, HJ, Gabreels-Festen A, Gabreels F, Goris RJ. Complex regional pain syndrome type I (RSD). Pathology of skeletal muscle and peripheral nerve. Neurology 1998;51: 20 –25. 9. Marsden CD, Obeso JA, Traub MM, Rothwell, JC, Kranz H, La Cruza F. Muscle spasms associated with Sudeck’s atrophy after injury. BMJ 1984;288:173–176. 10. Bhatia K, Bhatt MH, Marsden CD. The causalgia dystonia syndrome. Brain 1993;116:843– 851. 11. Rowbotham MC. Complex regional pain syndrome type I (reflex sympathetic dystrophy): more than a myth. Neurology 1998;51:4 –5. 12. Schott GD. Induction of involuntary movements by peripheral trauma: an analogy with causalgia. Lancet 1986;2:712–716. 13. Krauss JK, Mohadjer M, Braus DF, Wakhloo AK, Nobbe F, Mundinger F. Dystonia following head trauma: a report of nine patients and review of the literature. Mov Disord 1992;7:263–272. 14. Tarsy D. Comparison of acute- and delayed-onset posttraumatic cervical dystonia. Mov Disord 1998;13:481– 485. 15. Sa DS, Mailis-Gagnon A, Nicholson K, Lang AE. Posttraumatic painful torticollis. Mov Disord 2003;18:1482–1491. 16. Cook SD. Trauma does not precipitate multiple sclerosis. Arch Neurol 2000;57:1077–1078. 17. Jankovic J, Van der Linden C. Dystonia and tremor induced by peripheral trauma: predisposing factors. J Neurol Neurosurg Psychiatry 1988;51:1512–1519. 18. Dewey R, Maraganore DM, Matsumoto JY. Posttraumatic cervical dystonia manifesting as isolated spasm of the middle scalene muscle. Mayo Clinic Proc 1994;69:187–188. 19. Hollinger P, Burgunder J. Posttraumatic focal dystonia of the shoulder. Eur Neurol 2000;44:153–155. 20. Sankhla C, Lai EC, Jankovic J. Peripherally induced oromandibular dystonia. J Neurol Neurosurg Psychiatry 1988;65:722– 728. 21. Schrag A, Bhatia KP, Quinn NP, Marsden CD. Atypical and typical cranial dystonia following dental procedures. Mov Disord 1999;14:492– 496. 22. Jankovic J. Post-traumatic movement disorders: central and peripheral mechanisms. Neurology 1994;44:2008 –2014. 23. Fletcher NA, Harding AE, Marsden CD. The relationship between trauma and idiopathic torsion dystonia. J Neurol Neurosurg Psychiatry 1991;54:713–717. 24. Bressman S, de Leon D, Raymond D, et al. The role of the DYT 1 gene in secondary dystonia. In: Fahn S, Marsden CD, DeLong M, editors. Dystonia 2: advances in Neurology. Vol. 78. Philadelphia: Lippincott-Raven Publishers; 1998. p 107–115. 25. Schwartzman RJ, Kerrigan J. The movement disorder of reflex sympathetic dystrophy. Neurology 1990;40:57– 61.
Movement Disorders, Vol. 19, No. 12, 2004
Opioid Binding in DYT1 Primary Torsion Dystonia: 11 An C-Diprenorphine PET Study Alan L. Whone, MRCP,1* Sarah Von Spiczak,1 Mark Edwards, MRCP,2 Enza-Maria Valente, MD, PhD,2 Alexander Hammers, PhD,1 Kailash P. Bhatia, MD,2 and David J. Brooks, MD, DSc1 1 Division of Neuroscience and MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom; 2Institute of Neurology, Queen Square, London, United Kingdom
Abstract: The opioid transmitters enkephalin and dynorphin are known to regulate pallidal output and consequently cortical excitability. Indeed, abnormal basal ganglia opioid transmission has been reported in several involuntary movement disorders, including levodopa-induced dyskinesias in Parkinson’s disease (PD), tardive dyskinesias/dystonia, Huntington’s disease, and Tourette’s syndrome. Moreover, a previous 11C-diprenorphine PET study investigating levodopa-induced dyskinesias found reduced opioid receptor availability in PD with but not without dyskinesias. We wished to investigate if a similar alteration in basal ganglia opioid binding was present in DYT1 primary torsion dystonia (PTD). Regional cerebral 11Cdiprenorphine binding was investigated in 7 manifesting carriers of the DYT1 gene and 15 age-matched normal controls using a region-of-interest (ROI) approach and statistical parametric mapping (SPM). No difference in regional mean 11C-diprenorphine binding was found between DYT1-PTD and controls, and no correlation between the severity of dystonia and opioid binding was seen. We conclude that aberrant opioid transmission is unlikely to be present in DYT1-PTD and altered opioid transmission is not a common mechanism underlying all disorders of involuntary movement. © 2004 Movement Disorder Society Key words: DYT1; dystonia; opioid;
11
C-diprenorphine
The most common cause of young-onset inherited primary torsion dystonia (PTD) is a three base pair (bp) (GAG) deletion in the DYT1 gene. Although expression and function of the encoded protein, Torsin A, have been elucidated in part, the mechanisms producing the generalised dystonia remain uncertain.1,2 At a systems level,
*Correspondence to: Dr. Alan L. Whone, MRC Cyclotron Building, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom. E-mail:
[email protected] Received 14 September 2003; Revised 12 March 2004; Accepted 23 April 2004 Published online 15 July 2004 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.20238
