Doi:10.1016/s0885-3924(02)00675-9

Journal of Pain and Symptom Management Vol. 25 No. 4 April 2003 Treatment of Tremors in Complex Regional Pain Syndrome Annu Navani, MD, Lynn M. Rusy, MD, Richard D. Jacobson, MD, PhD,and Steven J. Weisman, MDDepartments of Anesthesiology (A.N., L.M.R.), Neurology (R.D.J.), Anesthesiology (S.J.W.),and Pediatrics (S.J.W.), Children's Hospital of Wisconsin and Medical College of Wisconsin, Milwaukee, Wisconsin, USA Abstract
A 14-year-old girl presented with Complex Regional Pain Syndrome, Type I (CRPS-1) of the
left ankle after a remote history of sprain. Allodynia, pain, temperature and color changes,
and swelling were successfully treated with physical therapy, transcutaneous electrical nerve
stimulation (TENS), gabapentin, amitriptyline, and tramadol. Five weeks later, she presented
with a continuous, involuntary, intermittent coarse tremor of the left foot causing increased
pain. The electromyogram showed rhythmic discharges of 3 Hz frequency lasting 20–80
milliseconds in the left tibialis, peroneus and gastrocnemius, suggestive of either basal ganglia
or spinal origin. Tremor and pain were controlled with epidural bupivacaine, but the tremor
reappeared after discontinuing epidural blockade. Carbidopa/levodopa 25/100 (Sinemet®)
was started and the tremor disappeared after two days. With continued physical therapy, pain
and swelling resolved within two months and carbidopa/ levodopa was discontinued after five
weeks with no recurrence of the tremor. Our success in the treatment of CRPS-associated tremor
in this young girl with carbidopa/levodopa suggests that this patient may have had
underlying movement disorder which was unmasked by the peripheral injury.
Symptom Manage 2003;25:386–390.
2003 U.S. Cancer Pain Relief Committee. Published by Elsevier. All rights reserved. Key Words
Reflex sympathetic dystrophy, parkinsonism, movement disorder, carbidopa-levodopa
sudomotor, dystrophic and trophic changes inthe affected body parts.1 The incidence of CRPS Complex Regional Pain Syndrome (CRPS) is a ranges from 1–2% after various fractures and clinical disorder, which is usually characterized 2–5% after peripheral nerve injuries.2 by severe burning pain, swelling, and vasomotor, CRPS may be accompanied by movement disorders, including dystonia or tremor.3–7Tremors at various frequencies have been doc-umented in many CRPS patients,3,5 and various Presented at the Midwest Anesthesia Residents' Con- medical and surgical treatment options have ference, March 24, 2001, Milwaukee, Wisconsin,USA.
been used, with limited success, to treat CRPS- Address reprint requests to: Annu Navani, MD, 591 Roll- associated tremors.
ing Oak Court, Vacaville, CA 95688, USA.
We present a case of severe tremors in a 14- Accepted for publication: June 23, 2002. year-old girl with post-traumatic CRPS Type 1, 2003 U.S. Cancer Pain Relief Committee 0885-3924/03/$–see front matter Published by Elsevier. All rights reserved.
Vol. 25 No. 4 April 2003 Complex Regional Pain Syndrome Tremor Treatment which were successfully controlled with medi- plantar responses in the lower extremities were cal management.
normal and symmetric. The magnetic resonanceimage of the spine was normal.
She was admitted to the hospital and treated with an initial dose of 20 ml of 0.25% bupiv- A 14-year-old athletic girl, 80 kg and 180 cm, acaine via a lumbar epidural catheter. This re- was evaluated for complaints of pain and dis- sulted in resolution of the tremor. She then re- coloration of her left ankle after multiple inju- ceived an infusion of 0.125% bupivacaine at 10 ries to that ankle. The initial trauma, which was ml/hr, but every time the epidural infusion a Grade I ankle sprain, occurred while playing was decreased or discontinued, the tremor re- basketball twelve months prior to the presenta- appeared. The epidural infusion was held for tion. After brief immobilization, she returned twelve hours for an electromyogram that to regular activities, but reinjured the ankle six showed rhythmic discharges of three Hz fre- times. She complained of intense pain in her quency lasting twenty to eighty milliseconds in left ankle, which prevented her from bearing the left tibialis (Fig. 1), peroneus and gastroc- weight. The pain was 9/10 on a numeric rating nemius muscles, suggestive of either basal gan- scale and was aggravated by light touch and im- glia or spinal origin. The nerve conduction proved by hanging the left ankle off the side of studies showed no evidence of mononeuropa- the bed. Acetaminophen with codeine pro- thy, polyneuropathy or radiculopathy.
vided no relief. Her foot turned purple occa- Carbidopa/levodopa 25/100 (Sinemet®) was started twice daily. Eighteen hours after carbi- On examination, the left ankle appeared dopa/levodopa was started, a decrease in tremor swollen and purplish when compared to the was noted. The tremor totally disappeared in other foot. The temperature of the affected three days. With continued physical therapy, the foot was 85.2 F compared to 93.7 in the right CRPS symptoms resolved within two months.
foot. Range of motion was decreased in her left The carbidopa/levodopa was discontinued five ankle (dorsiflexion 40, plantar flexion 60, weeks after discharge from the hospital, with eversion 30, and inversion 30). Muscle spasm no recurrence of the tremor.
and intense allodynia were present.
Radiographs showed osteochondritis of the talus. The magnetic resonance imaging of left ankle showed Grade-I osteochondral lesion of In 1888, Gowers suggested that movement posteromedial talar dome and a small amount disorders could be produced not only by cen- of fluid along posterior tibialis tendon. The ra- tral, but also by peripheral trauma.8 Recent ob- dionucleide three-phased bone scan showed servations have confirmed this.9,10 In 1988, Jan- diminished radionucleide delivery to left ankle.
kovic and colleagues described five patients with Treatment included transcutaneous electric the onset of tremors within one day to nine nerve stimulation, gabapentin (900 mg three months after peripheral injury.3 They noted that times a day), amitriptyline (25 mg at bedtime), 65% (15 out of 23 patients) had common ‘pre- and as needed tramadol (50 mg). Physical ther- disposing' factors like family history of essen- apy was started three times per week. In three tial tremor or dystonia, perinatal injury, or a weeks, there was improvement in symptoms.
prior exposure to dopamine receptor blocking After five weeks, she presented with a two-day drugs that could have increased the risk of history of continuous involuntary twitching of tremor.3 In 1995, Cardoso et al. studied pa- her left foot, with increased pain and discolora- tients in whom the onset of tremor, parkin- tion of the left ankle. There was a twenty-degree sonism or both was anatomically or temporally difference in temperature between the two feet, related to local injury.11 They noted the onset left being warmer than the right. Neurological of tremor within two months after the injury in examination was notable for an intermittent 21 out of 28 patients.11 coarse rest tremor of the left foot, primarily at In 1991, Deuschl and colleagues studied pos- the ankle, with a frequency of three to four Hz.
tural hand tremor in twenty-one patients suf- Muscle tone, bulk, and strength of all muscle fering from unilateral reflex sympathetic dys- groups, sensation, deep tendon reflexes and trophy (CRPS Type 1) in the upper extremity.
Navani et al. Vol. 25 No. 4 April 2003 Fig. 1. EMG showing rhythmic discharges of 3 Hz frequency lasting 20–80 milliseconds in the left tibialis.
They noted, on the affected side, an enhanced the activity of the sympathetic nervous system tremor amplitude, with a mean tremor fre- in CRPS. It has been suggested that the interac- quency of 7.2 Hz in 57% of patients.12 This tion between substance P and sympathetic ner- tremor decreased with loading and the investi- vous system directly initiates the intense and pro- gators concluded that the tremor in reflex sym- longed depolarization of anterior horn cells that pathetic dystrophy should be regarded as a may underlie dystonia of this condition.17,18 A form of enhanced physiological tremor.
similar hypothesis can be extended to explain It has been proposed that peripheral trauma other movement disorders, including tremors, alters the sensory input and induces cortical and associated with CRPS. Deuschl and colleagues subcortical reorganization generating a move- noted that their patients with enlarged tremor ment disorder in patients with CRPS.11 This hy- amplitudes displayed a greater degree of elec- pothesis might explain why the peripherally- tromyographic synchronization in the affected induced movement disorders have a tendency arm, and a higher coherence, compared with to spread beyond the original site of injury.
the healthy side or normal subjects.12 They sug- The neuronal networks in the thalamic ventra- gested that such synchronized discharges of the lis lateralis nucleus, which receive input from the motor neurons must be due to common cen- basal ganglia, may be involved in the genera- tral or peripheral inputs on the motor neuron tion of the tremor.11,13 Cohen et al. have shown that the transcranial magnetic stimulation in Enhanced proprioceptive reflexes have been the patients with unilateral limb amputations proposed as a major peripheral input causing evoked larger motor evoked potentials, recruited synchronization and thereby, tremor.19 Since larger percentage of motoneuron pool and gain of reflexes can be enhanced by sympa- elicited motor-evoked potentials at lower inten- thetic sensitization of muscle spindles, most sities of stimulation in muscles ipsilateral to the likely by their influence on beta 2-receptors,20 stump than in contralateral muscles.14 the enhanced tremor in reflex sympathetic dys- The mechanism by which the altered periph- trophy could be explained by this mechanism eral input can produce central effects is poorly and their reduction following sympathetic block- understood. Some of these changes seem to be ade.12 Mechanisms acting at the spinal level have mediated by retrograde axonal transport of also been proposed to account for the synchro- trophic factors such as ciliary neurotrophic fac- nization.14 For example, the gain of the flexion tor.15 Neural plasticity in response to peripheral reflex is enhanced by the stimulation of the trauma also may be mediated also by immedi- C-fiber afferents from the muscle, which is prob- ate early response genes (e.g., c-jun and c-fos), ably mediated by substance P released from the resulting in secondary chemical changes. The nociceptive primary afferents.21 expression of these genes seem to be markedly An alternative hypothesis is that trauma may increased in the spinal cord after peripheral cause a movement disorder by indirectly trig- nerve lesion (axotomy).8,16 gering or accelerating the progression of pre- The tremor, difficulty in the initiation of move- existing subclinical movement disorder.8,11 Mo- ment, and increase in reflexes and muscle tone tor symptoms may be transiently exacerbated may also be directly related to the change in in patients with Parkinson's disease after motor Vol. 25 No. 4 April 2003 Complex Regional Pain Syndrome Tremor Treatment vehicle accident or stress.22 This is also sup- Signs and symptoms of reflex sympathetic dystro- ported by animal models. For example, rats phy: prospective study of 829 patients. Lancet 1993; previously treated with neurotoxin 6-hydroxy dopamine to produce subclinical damage to 3. Jankovic J, Van der Linden C. Dystonia and tremor substantia nigra developed Parkinsonism signs induced by peripheral trauma: predisposing factors.
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