Movement disorders in complex regional pain syndrome

Pain Medicine 2010; 11: 1274–1277Wiley Periodicals, Inc. Movement Disorders in Complex Regional
Pain Syndromepme_9161274.1277
Jacobus J. van Hilten, MD, PhD
Movement Disorders in CRPS: Neurological Entity
or Psychogenic?
Department of Neurology, Leiden University MedicalCenter, Leiden, the Netherlands In the field of movement disorders, several issues contrib-uted to a long-lasting ambiguity concerning the neurologi-cal or psychiatric origin of the MDs in CRPS. First, the Reprint requests to: Jacobus J. van Hilten, failure to demonstrate abnormalities in routine neurophysi- Department of Neurology, Leiden University Medical ological studies in CRPS type 1 patients with MDs [8].
Center, P.O. Box 9600, 2300 RC Leiden, the Second, the concept that ultimately became dogma and Netherlands. Tel: 31-71-5262895; Fax: 31-71-5248253; related MDs like dystonia to dysfunction of the basal ganglia-thalamocortical circuitry. Because in CRPS, MDsare frequently preceded by peripheral trauma, basalganglia involvement was neither demonstrated nor Abstract
obvious from a clinical point of view. Consequently, MDsthat occurred in the absence of basal ganglia involvement About 25% of the patients with complex regional
were for a long period considered non-organic. However, pain syndrome (CRPS) suffer movement disorders,
a unique psychological profile was never demonstrated in including loss of voluntary control, bradykinesia,
dystonia, myoclonus, and tremor. These movement
disorders are generally difficult to manage and add
The Clinical Profile of MDs in CRPS
considerably to the disease burden. Over the last
years, interesting findings have emerged that show
The execution of voluntary movement in patients with how tissue or nerve injury may induce spinal plas-
CRPS is commonly impaired, but these motor distur- ticity (central sensitization), which alters sensory
bances frequently remain unnoticed or are attributed to transmission and sensorimotor processing in the
the presence of pain. Loss of voluntary control is fre- spinal cord and is associated with disinhibition.
quently experienced by patients suffering weakness or These changes, in turn, set the stage for the devel-
dystonia. Typically, these patients report “My mind tells my opment of movement disorders seen in CRPS. There
hand/foot to move, but it won’t work” [2]. This so-called are no randomized control studies on the treatment
loss of voluntary control has been reported in other causes of movement disorders in CRPS but findings from
of dystonia [11] and has been ascribed to both dysfunc- fundamental and clinical research suggest that
tion of attention and abnormal sensorimotor integration strategies that enhance the central inhibitory state
may benefit these patients.
Bradykinesia or slowness of movement is very common in Key Words. Complex Regional Pain Syndrome
CRPS patients and is evaluated by means of repetitive (CRPS); Dystonia
finger or foot tapping. In CRPS patients, the performanceof these movements are typically slowed and frequently Introduction
associated with hesitancies. Interestingly, patients withunilateral upper extremity CRPS, may also show bradyki- Complex regional pain syndrome (CRPS) is characterized nesia on the non-affected extremity [14].
by poorly controllable pain, swelling, and changes in skinblood flow and sweating that usually develop in the distal Dystonia occurs in approximately 20% of patients with extremities [1]. The syndrome is commonly preceded by a CRPS and is characterized by fixed flexion postures of the minor to severe trauma or surgical intervention [1]. There fingers (Figure 1), wrist, and feet that may vary in severity is compelling evidence that patients with CRPS may [2,15]. In less affected patients without overt dystonia, this develop movement disorders (MDs) including loss of vol- may be provoked by repetitive tasks. Dystonia of the lower untary control, bradykinesia, dystonia, myoclonus, and extremity is usually characterized by inversion and/or tremor. These MDs may occur early in the disease course plantar flexion of the foot, with or without clawing or scis- and occasionally precede the onset of the more typical soring of the toes [2,15]. Dystonia may worsen by effort of features of CRPS [2–4]. Findings from different studies the involved extremity, under circumstances of cold tem- indicate that 9–49% of the CRPS patients may develop peratures and humidity, and in the more severely affected MDs [2–5]. The prevalence of MDs increases as the patients, by tactile and auditory stimuli. Contractures, which frequently are also characterized by flexion postures Movement Disorders in CRPS
central sensitization only involves pathways that deal withthe perception of pain and not those that mediate aresponse to pain. Indeed, two lines of research now showthat central sensitization may influence spinal motor cir-cuitry. First, findings from a recent study suggest that theinduction of central sensitization causes a spinal learningdeficit with respect to simple motor responses to shock[24]. Second, cutaneous afferents which mediate neuro-genic inflammation are also linked to spinal interneuronalcircuits that mediate nociceptive withdrawal reflexes(NWR) [25]. Animal models of neurogenic inflammationhave shown that SP released at the dorsal horn of the Figure 1 Shows examples of upper and lower
spinal cord, enhances NWRs [26,27]. In withdrawalreflexes, flexor muscles play a prominent role, and inter- extremity dystonia in CRPS patients.
estingly, in dystonia of CRPS there is a conspicuousinvolvement of flexor postures, which may hint towardsthe involvement of spinal motor programs that mediate are a potential pitfall in diagnosing dystonia in CRPS. In NWRs [15]. Neurophysiological studies have shown that dystonia, however, passive stretching of affected digits central disinhibition is a key characteristic of central provokes a contraction of the stretched muscle sug- nervous system involvement in CRPS patients with and gesting stretch reflex hyperexcitability [16]. The interval without dystonia [28–31]. Both SP-sensitized NWRs in between the onset of CRPS and dystonia in the first animal models and dystonia in CRPS patients respond to affected extremity may vary from less than one week in baclofen, a gamma-aminobutyric acid (GABA) B receptor 26% of the patients to more than one year in 25% of the agonist which enhances spinal GABA-ergic inhibition on patients [7]. Compared to CRPS patients without dysto- neurons of the spinal cord [32,33]. Collectively, findings nia, CRPS patients with dystonia have a younger age at from different sources of research suggest that peripheral onset and have an increased risk of spread of dystonia to tissue or nerve injury may induce central sensitization, other extremities [7]. Myoclonus (involuntary, brief, jerk-like which is associated with spinal changes that may contrib- contractions of a muscle or muscles) and tremor are fre- quently reported by CRPS patients with dystonia butrarely may occur as the sole or predominant MD [14].
In CRPS, there is a conspicuous tendency for dystonia tospread to other extremities. In two studies, 37 and 67% of MDs in CRPS: Mechanisms of Disease
the CRPS patients had two or more extremities affectedby dystonia [34,35]. Interestingly, the hazard of dystonia in Compelling evidence suggests that in CRPS, different subsequent extremities in patients with CRPS increases mechanisms may play a role. Similarities between the with the number of extremities already affected by dysto- classical symptoms of inflammation and the clinical fea- nia [7]. Apparently, once triggered, the underlying mecha- tures of CRPS have led several investigators to suggest nism of dystonia in CRPS has the capacity to facilitate the that inflammation must play an important role in the syn- occurrence of dystonia in other body parts. This accelle- drome [17–19]. Tissue injury stimulates C and Ad-fibers of rated disease course is a typical feature of maladaptive sensory nerves, which causes the release of the inflam- neuronal plasticity, as has been documented for pain [36].
matory neuropeptides substance P and Calcitonin-gene- CRPS occurs more frequently in women (~75%). The related-peptide from the afferent nerve endings [20].
gender imbalance is further increased in CRPS patients These neuropeptides may induce local vasodilatation and with dystonia (~85%) [2,7,35]. These findings may indicate increased capillary permeability causing edema and an that the female gender is a risk factor for clinical manifes- increase of skin blood flow, a process known as neuro- tations of maladaptive neuronal plasticity.
genic inflammation [20]. Indeed, several studies confirmedthat this mechanism is involved in the perturbed regulation Although most evidence seems to indicate that dystonia in of inflammation in CRPS [21,22]. Because neurogenic CRPS occurs in the context of central sensitization in the inflammation is initiated by sensory nerves, it remained spinal cord, the question remains if supraspinal involve- unclear how MDs may evolve in CRPS. However, nocice- ment may contribute to the development of MDs in CRPS.
ptive neurons in the dorsal horns of the spinal cord may Two functional magnetic resonance imaging (fMRI) studies become sensitized (central sensitization) by peripheral evaluated cerebral network function during the execution tissue or nerve injury [23]. In central sensitization, there is of voluntary movement in patients with CRPS with and an increased sensitivity of spinal neurons, despite a lack of without MDs [37,38]. One study that evaluated finger change of afferent input. As a result, pain becomes movements in CRPS patients without MDs revealed a chronic and non-noxious stimuli become painful [23]. On a significant reorganization of central motor circuits with molecular level, central sensitization is associated with increased activation of the primary motor cortex and changes in the release of neuropeptides, neurotransmit- supplementary motor cortices, and increased activation ters, prostaglandine E2, and the expression of N-methyl of the ipsilateral motor cortex [38]. Activity of the post- aspartate receptors in particular [23]. It seems unlikely that erior parietal cortices, supplementary motor cortices, and van Hilten
primary motor cortex correlated with the degree of motor 6 Veldman PH, Reynen HM, Arntz IE, Goris RJ. Signs dysfunction as assessed by the maximum finger tapping and symptoms of reflex sympathetic dystrophy: Pro- frequency. Another fMRI study on voluntary and imaginary spective study of 829 patients. Lancet 1993;342: hand movements in CRPS patients with dystonia showed altered ipsilateral and contralateral cerebral activationduring imaginary movement of the dystonic hand [37].
7 van Rijn MA, Marinus J, Putter H, van Hilten JJ. Onset Collectively, these studies provided important new insights and progression of dystonia in complex regional pain on the involvement of cortical circuitry in voluntary and imaginary motor tasks in patients with CRPS. However, itremains unclear if these findings play a role in the MDs of 8 Verdugo RJ, Ochoa JL. Abnormal movements in CRPS since Maihöfner et al. found that pain by itself is complex regional pain syndrome: Assessment of their sufficient to induce these cortical changes [38]. However, nature. Muscle Nerve 2000;23:198–205.
given the important role of supraspinal sensorimotor net-works in the execution of movement, it is not unlikely thatsupraspinal changes may contribute to some of the clini- 9 Van der Laan L, van Spaendonck K, Horstink M, Goris RJA. The symptom checklist-90 revised questionnaire:No psychological profiles in complex regional pain MDs in CRPS: Treatment Options
syndrome–dystonia. J Pain Symptom Manage 1999;17:357–62.
There are no randomized controlled studies of physicaltherapy, occupational therapy, or oral pharmacotherapy in 10 Reedijk WB, van Rijn MA, Roelofs K, et al. Psychologi- treatment of MDs in CRPS [39]. Splints or plaster casts are cal features of patients with complex regional pain often ineffective or may even worsen the dystonic postures syndrome type I related dystonia. Mov Disord 2008; of CRPS [39]. Benzodiazepines and high doses of baclofen may be beneficial in the treatment of dystonia andspasms in patients with CRPS but the extent of improve- 11 Berardelli A, Rothwell JC, Hallett M, et al. The patho- ment is rarely described. Also, no controlled studies exist physiology of primary dystonia. Brain 1998;121:1195– on the use of botulin toxin in dystonia in CRPS-I patients [39]. One study reported on the beneficial effects of intrath-ecal baclofen therapy in a small number of patients withCRPS-I and dystonia [33]. However, given the complexity 12 Apkarian AV, Thomas PS, Krauss BR, Szeverenyi NM.
of this treatment, it should only be considered for patients Prefrontal cortical hyperactivity in patients with sym- with CRPS-I if dystonia is a major problem and conven- pathetically mediated chronic pain. Neurosci Lett tional therapy has proven ineffective [39].
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