Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Neurology
Published in: BMC Neurology 1/2011

Open Access 01-12-2011 | Research article

Fixed Dystonia in Complex Regional Pain Syndrome: a Descriptive and Computational Modeling Approach

Authors: Alexander G Munts, Winfred Mugge, Thomas S Meurs, Alfred C Schouten, Johan Marinus, G Lorimer Moseley, Frans CT van der Helm, Jacobus J van Hilten

Published in: BMC Neurology | Issue 1/2011

Login to get access

Abstract

Background

Complex regional pain syndrome (CRPS) may occur after trauma, usually to one limb, and is characterized by pain and disturbed blood flow, temperature regulation and motor control. Approximately 25% of cases develop fixed dystonia. Involvement of dysfunctional GABAergic interneurons has been suggested, however the mechanisms that underpin fixed dystonia are still unknown. We hypothesized that dystonia could be the result of aberrant proprioceptive reflex strengths of position, velocity or force feedback.

Methods

We systematically characterized the pattern of dystonia in 85 CRPS-patients with dystonia according to the posture held at each joint of the affected limb. We compared the patterns with a neuromuscular computer model simulating aberrations of proprioceptive reflexes. The computer model consists of an antagonistic muscle pair with explicit contributions of the musculotendinous system and reflex pathways originating from muscle spindles and Golgi tendon organs, with time delays reflective of neural latencies. Three scenarios were simulated with the model: (i) increased reflex sensitivity (increased sensitivity of the agonistic and antagonistic reflex loops); (ii) imbalanced reflex sensitivity (increased sensitivity of the agonistic reflex loop); (iii) imbalanced reflex offset (an offset to the reflex output of the agonistic proprioceptors).

Results

For the arm, fixed postures were present in 123 arms of 77 patients. The dominant pattern involved flexion of the fingers (116/123), the wrists (41/123) and elbows (38/123). For the leg, fixed postures were present in 114 legs of 77 patients. The dominant pattern was plantar flexion of the toes (55/114 legs), plantar flexion and inversion of the ankle (73/114) and flexion of the knee (55/114).
Only the computer simulations of imbalanced reflex sensitivity to muscle force from Golgi tendon organs caused patterns that closely resembled the observed patient characteristics. In parallel experiments using robot manipulators we have shown that patients with dystonia were less able to adapt their force feedback strength.

Conclusions

Findings derived from a neuromuscular model suggest that aberrant force feedback regulation from Golgi tendon organs involving an inhibitory interneuron may underpin the typical fixed flexion postures in CRPS patients with dystonia.
Appendix
Available only for authorised users
Literature
1.
2.
Albanese A, Asmus F, Bhatia KP, Elia AE, Elibol B, et al: EFNS guidelines on diagnosis and treatment of primary dystonias. European Journal of Neurology. 2011, 18: 5-18. 10.1111/j.1468-1331.2010.03042.x.CrossRefPubMed
3.
Tinazzi M, Fiorio M, Fiaschi A, Rothwell JC, Bhatia KP: Sensory functions in dystonia: insights from behavioral studies. Mov Disord. 2009, 24: 1427-1436. 10.1002/mds.22490.CrossRefPubMed
4.
Berardelli A, Rothwell JC, Hallett M, Thompson PD, Manfredi M, et al: The pathophysiology of primary dystonia. Brain. 1998, 121: 1195-1212. 10.1093/brain/121.7.1195.CrossRefPubMed
5.
6.
7.
Jankovic J: Peripherally induced movement disorders. Neurologic Clinics. 2009, 27: 821-32. 10.1016/j.ncl.2009.04.005.CrossRefPubMed
8.
van Hilten JJ, Geraedts EJ, Marinus J: Peripheral trauma and movement disorders. Parkinsonism Relat Disord. 2007, 13 (Suppl 3): S395-S399.CrossRefPubMed
9.
Allen G, Galer BS, Schwartz L: Epidemiology of complex regional pain syndrome: a retrospective chart review of 134 patients. Pain. 1999, 80: 539-544. 10.1016/S0304-3959(98)00246-2.CrossRefPubMed
10.
Janig W, Baron R: Complex regional pain syndrome: mystery explained?. Lancet Neurol. 2003, 2: 687-697. 10.1016/S1474-4422(03)00557-X.CrossRefPubMed
11.
Veldman PH, Reynen HM, Arntz IE, Goris RJ: Signs and symptoms of reflex sympathetic dystrophy: prospective study of 829 patients. Lancet. 1993, 342: 1012-1016. 10.1016/0140-6736(93)92877-V.CrossRefPubMed
12.
Birklein F, Schmelz M, Schifter S, Weber M: The important role of neuropeptides in complex regional pain syndrome. Neurology. 2001, 57: 2179-2184.CrossRefPubMed
13.
Huygen FJ, de Bruijn AG, De Bruin MT, Groeneweg JG, Klein J, et al: Evidence for local inflammation in complex regional pain syndrome type 1. Mediators Inflamm. 2002, 11: 47-51. 10.1080/09629350210307.CrossRefPubMedPubMedCentral
14.
Leis S, Weber M, Isselmann A, Schmelz M, Birklein F: Substance-P-induced protein extravasation is bilaterally increased in complex regional pain syndrome. Exp Neurol. 2003, 183: 197-204. 10.1016/S0014-4886(03)00163-8.CrossRefPubMed
15.
Niehof SP, Huygen FJ, van der Weerd RW, Westra M, Zijlstra FJ: Thermography imaging during static and controlled thermoregulation in complex regional pain syndrome type 1: diagnostic value and involvement of the central sympathetic system. Biomed Eng Online. 2006, 5: 30-10.1186/1475-925X-5-30.CrossRefPubMedPubMedCentral
16.
Wasner G, Schattschneider J, Heckmann K, Maier C, Baron R: Vascular abnormalities in reflex sympathetic dystrophy (CRPS I): mechanisms and diagnostic value. Brain. 2001, 124: 587-599. 10.1093/brain/124.3.587.CrossRefPubMed
17.
Schott GD: Peripherally-triggered CRPS and dystonia. Pain. 2007, 130: 203-207. 10.1016/j.pain.2007.04.013.CrossRefPubMed
18.
van Hilten JJ, Blumberg H, Schwartzman RJ: Factor IV: Movement Disorders and Dystrophy--Pathophysiology and Measurement. CRPS: Current Diagnosis and Therapy, Progress in Pain Research and Management. Edited by: Wilson P, Stanton-Hicks M, Harden RN. 2005, Seattle: IASP Press, 119-137.
19.
Ibrahim NM, Martino D, van de Warrenburg BP, Quinn NP, Bhatia KP, et al: The prognosis of fixed dystonia: a follow-up study. Parkinsonism Relat Disord. 2009, 15: 592-597. 10.1016/j.parkreldis.2009.02.010.CrossRefPubMed
20.
Schrag A, Trimble M, Quinn N, Bhatia K: The syndrome of fixed dystonia: an evaluation of 103 patients. Brain. 2004, 127: 2360-2372. 10.1093/brain/awh262.CrossRefPubMed
21.
McCrea DA: Can sense be made of spinal interneuron circuits?. Movement control. Edited by: Cordo P, Harnad S. 1994, Cambridge: Cambridge University Press, 31-41.CrossRef
22.
van de Beek WJ, Vein A, Hilgevoord AA, van Dijk JG, van Hilten BJ: Neurophysiologic aspects of patients with generalized or multifocal tonic dystonia of reflex sympathetic dystrophy. J Clin Neurophysiol. 2002, 19: 77-83. 10.1097/00004691-200201000-00011.CrossRefPubMed
23.
Schouten AC, van de Beek WJ, van Hilten JJ, Van der Helm FC: Proprioceptive reflexes in patients with reflex sympathetic dystrophy. Exp Brain Res. 2003, 151: 1-8. 10.1007/s00221-003-1420-x.CrossRefPubMed
24.
Marsden CD, Obeso JA, Traub MM, Rothwell JC, Kranz H, et al: Muscle spasms associated with Sudeck's atrophy after injury. Br Med J (Clin Res Ed). 1984, 288: 173-176. 10.1136/bmj.288.6412.173.CrossRef
25.
Schwartzman RJ, Kerrigan J: The movement disorder of reflex sympathetic dystrophy. Neurology. 1990, 40: 57-61.CrossRefPubMed
26.
van Rijn MA, Marinus J, Putter H, van Hilten JJ: Onset and progression of dystonia in complex regional pain syndrome. Pain. 2007, 130: 287-293. 10.1016/j.pain.2007.03.027.CrossRefPubMed
27.
Merskey H, Bogduk N: Relatively generalized syndromes. Classification of chronic pain. Description of chronic pain syndromes and definitions of pain terms. Edited by: Merskey H, Bogduk N. 1994, Seattle: IASP Press, 40-43.
28.
Burke RE, Fahn S, Marsden CD, Bressman SB, Moskowitz C, et al: Validity and reliability of a rating scale for the primary torsion dystonias. Neurology. 1985, 35: 73-77.CrossRefPubMed
29.
Stroeve S: Impedance characteristics of a neuromusculoskeletal model of the human arm I. Posture control. Biol Cybern. 1999, 81: 475-494. 10.1007/s004220050577.CrossRefPubMed
30.
Winters JM, Stark L: Analysis of fundamental human movement patterns through the use of in-depth antagonistic muscle models. IEEE Trans Biomed Eng. 1985, 32: 826-839.CrossRefPubMed
31.
Johnson MT, Kipnis AN, Lee MC, Ebner TJ: Independent control of reflex and volitional EMG modulation during sinusoidal pursuit tracking in humans. Exp Brain Res. 1993, 96: 347-362.CrossRefPubMed
32.
Maihofner C, Baron R, DeCol R, Binder A, Birklein F, et al: The motor system shows adaptive changes in complex regional pain syndrome. Brain. 2007, 130: 2671-2687. 10.1093/brain/awm131.CrossRefPubMed
33.
Schwenkreis P, Janssen F, Rommel O, Pleger B, Volker B, et al: Bilateral motor cortex disinhibition in complex regional pain syndrome (CRPS) type I of the hand. Neurology. 2003, 61: 515-519.CrossRefPubMed
34.
van Hilten JJ, van de Beek WJ, Vein AA, van Dijk JG, Middelkoop HA: Clinical aspects of multifocal or generalized tonic dystonia in reflex sympathetic dystrophy. Neurology. 2001, 56: 1762-1765.CrossRefPubMed
35.
Pierrot-Deseilligny E, Burke D: The circuitry of the human spinal cord: its role in motor control and movement disorders. 2005, New York: Cambridge University PressCrossRef
36.
Santini M, Ibata Y: The fine structure of thin unmyelinated axons within muscle spindles. Brain Res. 1971, 33: 289-302. 10.1016/0006-8993(71)90104-1.CrossRefPubMed
37.
Barker D, Saito M: Autonomic innervation of receptors and muscle fibres in cat skeletal muscle. Proc R Soc Lond B Biol Sci. 1981, 212: 317-32. 10.1098/rspb.1981.0042.CrossRefPubMed
38.
Grünewald RA, Yoneda Y, Shipman JM, Sagar HJ: Idiopathic focal dystonia: a disorder of muscle spindle afferent processing?. Brain. 1997, 120: 2179-85. 10.1093/brain/120.12.2179.CrossRefPubMed
39.
Bowman WC, Goldberg AA, Raper C: A comparison between the effects of a tetanus and the effects of sympathomimetic amines on fast- and slow-contracting mammalian muscles. Br J Pharmacol Chemother. 1962, 19: 464-84.CrossRefPubMedPubMedCentral
40.
41.
Francini F, Peruzzi P, Staderini G: Effects of sympathetic lumbar trunk stimulation on the myotatic reflex activity of the quadriceps muscle in decerebrate cat. Boll Soc Ital Biol Sper. 1978, 54: 1353-6.PubMed
42.
Snider RM, Gerald MC: Studies on the mechanism of (+)-amphetamine enhancement of neuromuscular transmission: muscle contraction, electrophysiological and biochemical results. J Pharmacol Exp Ther. 1982, 221: 14-21.PubMed
43.
Grassi C, Filippi GM, Passatore M: Tension development in lumbrical muscles and concomitant increase of activity in A-alpha and A-beta afferents during sympathetic stimulation in the cat. Brain Res. 1987, 435: 15-23. 10.1016/0006-8993(87)91581-2.CrossRefPubMed
44.
Kiefer RT, Rohr P, Ploppa A, Dieterich HJ, Grothusen J, Koffler S, Altemeyer KH, Unertl K, Schwartzman RJ: Efficacy of ketamine in anesthetic dosage for the treatment of refractory complex regional pain syndrome: an open-label phase II study. Pain Med. 2008, 9: 1173-201. 10.1111/j.1526-4637.2007.00402.x.CrossRefPubMed
45.
Schwartzman RJ, Alexander GM, Grothusen JR, Paylor T, Reichenberger E, Perreault M: Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo controlled study. Pain. 2009, 147 (1-3): 107-15. 10.1016/j.pain.2009.08.015.CrossRefPubMed
46.
Rudomin P: Presynaptic selection of afferent inflow in the spinal cord. J Physiol Paris. 1999, 93: 329-347. 10.1016/S0928-4257(00)80061-3.CrossRefPubMed
47.
Buesa I, Ortiz V, Aguilera L, Torre F, Zimmermann M, et al: Disinhibition of spinal responses to primary afferent input by antagonism at GABA receptors in urethane-anaesthetised rats is dependent on NMDA and metabotropic glutamate receptors. Neuropharmacology. 2006, 50: 585-594. 10.1016/j.neuropharm.2005.11.005.CrossRefPubMed
48.
Saito K, Konishi S, Otsuka M: Antagonism between Lioresal and substance P in rat spinal cord. Brain Research. 1975, 97: 177-180. 10.1016/0006-8993(75)90928-2.CrossRefPubMed
49.
van Hilten BJ, van de Beek WJ, Hoff JI, Voormolen JH, Delhaas EM: Intrathecal baclofen for the treatment of dystonia in patients with reflex sympathetic dystrophy. New England Journal of Medicine. 2000, 343: 625-630. 10.1056/NEJM200008313430905.CrossRefPubMed
50.
Munts AG, van der Plas AA, Voormolen JH, Marinus J, Teepe-Twiss IM, et al: Intrathecal glycine for pain and dystonia in complex regional pain syndrome. Pain. 2009, 146: 199-204. 10.1016/j.pain.2009.07.030.CrossRefPubMed
51.
Rudomin P: Presynaptic inhibition of muscle spindle and tendon organ afferents in the mammalian spinal cord. Trends Neurosciences. 1990, 13: 499-505. 10.1016/0166-2236(90)90084-N.CrossRef
52.
Crago PE, Houk JC, Rymer WZ: Sampling of total muscle force by tendon organs. J Neurophysiol. 1982, 47: 1069-1083.PubMed
53.
Houk J, Henneman E: Responses of Golgi tendon organs to active contractions of the soleus muscle of the cat. J Neurophysiol. 1967, 30: 466-481.PubMed
54.
Jami L: Golgi tendon organs in mammalian skeletal muscle: functional properties and central actions. Physiol Rev. 1992, 72: 623-666.PubMed
55.
Jankowska E, McCrea D, Rudomin P, Sykova E: Observations on neuronal pathways subserving primary afferent depolarization. J Neurophysiol. 1981, 46: 506-516.PubMed
Metadata
Title
Fixed Dystonia in Complex Regional Pain Syndrome: a Descriptive and Computational Modeling Approach
Authors
Alexander G Munts
Winfred Mugge
Thomas S Meurs
Alfred C Schouten
Johan Marinus
G Lorimer Moseley
Frans CT van der Helm
Jacobus J van Hilten
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2011
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/1471-2377-11-53

Other articles of this Issue 1/2011

BMC Neurology 1/2011 Go to the issue

Case report

Stuttered swallowing: Electric stimulation of the right insula interferes with water swallowing. A case report

Study protocol

Rationale and design of a prospective study: Cervical Dystonia Patient Registry for Observation of OnaBotulinumtoxinA Efficacy (CD PROBE)

Study protocol

Upper limb children action-observation training (UP-CAT): a randomised controlled trial in Hemiplegic Cerebral Palsy

Research article

Acute/subacute cerebral infarction (ASCI) in HIV-negative adults with cryptococcal meningoencephalitis (CM): a MRI-based follow-up study and a clinical comparison to HIV-negative CM adults without ASCI

Study protocol

The effect of static scanning and mobility training on mobility in people with hemianopia after stroke: A randomized controlled trial comparing standardized versus non-standardized treatment protocols

Research article

Effectiveness and costs of phototest in dementia and cognitive impairment screening