Pain Physician 2007; 10:573-578 • ISSN 1533-3159
Case Report
Treatment of CRPS with ECT
Marie Wojcik Wolanin,MD, Vasko Gulevski, MD, and Robert J. Schwartzman, MD From: Drexel University College of Background: Electroconvulsive therapy (ECT) is a well-established treatment method
for medically refractory depression. ECT has also been used in the treatment of pain for Dr. Wolanin and Dr. Gulevski are over 50 years. The mechanism of action of ECT is still unknown, although several obser- with the Department of Neurology, vations have been made regarding the effect of ECT on pain processes. It has been re- Drexel Universiy College of Medicine, ported that several patients with medically refractory depression and Complex Regional Philadelphia, PA/ Pain Syndrome who were treated with ECT for their depression were also cured of their Dr. Schwartzman is professor and chairman of the Department of Neurology, Drexel University College of Medicine.
Objective: We report a case of CRPS in a patient who also suffered from medically re-
fractory depression. She was treated with ECT for her depression and subsequently was
Address correspondence: relieved of all her CRPS symptoms. Robert J. Schwartzman, MD Professor and Chairman Case Report: A 42 year-old female patient underwent a series of 12 standard bitempo-
Department of Neurology ral electroconvulsive therapy treatments for medically refractory depression. Physical ex- Drexel University College of Medicine Broad and Vine Street, MS423 amination and Quantitative Sensory Testing was done before and after the patient's treat- Philadelphia, PA 19102-1192 ment with ECT. This standard treatment procedure for refractory depression completely E-mail: [email protected] resolved the patient's depressive symptoms. In addition, the patient's CRPS symptoms were also reversed. Physical examination as well as Quantitative Sensory Testing done be- Disclaimer: No external funding was fore and after the ECT treatment correlated with her CRPS symptom improvement. provided for this study. Conflict of interest: None Conclusion: ECT was effective in the treatment of severe refractory CRPS in this pa-
Manuscript received: 04/16/2007 Revisions accepted: 06/04/2007 Accepted for Publication Key words: Iimpedance, posture change, spinal cord stimulation
Pain Physician 2007; 10:573-578
Free full manuscript: Pain perception is a matrix that combines both the ventrobasilar complex of the thalamus and SI and
affective and discriminative components SII of the cortex (5-8). This discriminative component (1). However, the division of a pain matrix inscribes the intensity, localization, and quality of into distinct sensory-discriminative and affective- pain. The affective component involves the emotional motivational components is evolving in complexity due reaction, stimulus-related selective attention, and the to recent brain imaging advances (2-3). Treede et al (4) motor drive to avoid further pain. The anatomy of this propose a division of central nociceptive pathways into medial system includes Laminas I, V, and the deeper 2 major systems. The lateral system, primarily involved layers of the dorsal horn, VMpo, MDvc, parafasicular, in the discriminative component of pain, is composed and intralaminar thalamic nuclei as well as the insula of lamina I and V of the dorsal horn that projects to and anterior cingulate cortex. The CL component of Pain Physician: July 2007:10:573-578 the intralaminar thalamus is also linked to SI and SII of difficulty initiating voluntary movement of the left the lateral system (5-8). The insular cortex also projects upper extremity. She suffered with severe generalized to the amygdale (9), another component of the limbic mechanical dynamic and static allodynia, hyperalge- system, which modulates emotion. In addition to the sia, and cold allodynia, which had spread from her left medial cortex, the prefrontal cortex is important for arm to all extremities. She also noted the spread of a affect, emotion, and memory (10). pinprick and cold stimulus to a portion of a derma- The pain matrix is modulated by the Diffuse Nox- tome on the entire ipsilateral side of the body after ious Inhibitory Controls (DNIC) system, which limits an extremity was stimulated. She noted hyperhidrosis, the intensity and spread of pain (11-12). Stimulation swelling, and increased hair growth of the affected of the rostroventromedial medulla (RVM) nuclei of left arm and hand. this system can inhibit and/or facilitate nociceptive The patient was involved in a second automo- and non-nociceptive input. This is a major relay for the bile accident in 2000 in which she fractured her right DNIC, which has input from the cortex and the periaq- wrist that required open reduction and internal fixa- ueductal gray (PAG) (13-18). In this nucleus, ON cells, tion. Prior to this accident, the patient led a very ac- which fire after a pain stimulus, and OFF cells, which tive lifestyle and was working as a judge. Her general- fire after pain is blocked, are thought to be important ized pain, autonomic dysfunction, and difficulty with in the maintenance of chronic pain (19-22).
movement progressed and she eventually became too Electroconvulsive therapy (ECT) has been used in the treatment of pain for over 50 years. In 1946, Pi- By 2001, four years after the initial injury, she had setsky (23) successfully treated a patient with phan- complex regional pain syndrome (all components of tom limb pain and depression with ECT and more 2005 IASP criteria) in all her extremities, back, and recently, Rasmussen and Rummans (24) presented 2 face. On physical examination in 2001, the patient pre- patients with phantom limb pain that improved with sented with mechanical dynamic and static allodynia ECT treatment. Complex Regional Pain Syndrome of 8/10 pain (Likert Numeric Rating Scale/NRS, 0 being (CRPS) and comorbid depression have also been treat- no pain and 10 being the worst pain imaginable) and ed successfully with ECT (25-26), which has analgesic 8/10 NRS pain to deep compression of the muscles in properties that are independent of the improvement her left upper extremity. Small joint pain was 8/10 on of depression (27).
a NRS in all extremities and was associated with cold In this report, we present a patient who meets all allodynia. She exhibited hyperalgesia to a pinprick of the IASP diagnostic and research criteria for CRPS in all extremities, the face, and back which was associ- all her extremities who had failed conventional treat- ated with spread of the stimulus of >6 cm and lasted ment modalities for 5 years (28). ECT administered for for >30 seconds. The patient was weak (4-/5) in both refractory depression induced immediate improve- proximal and distal muscles of all extremities and had ment in the affective component of her pain and a difficulty initiating movement. She had cold hyperhi- gradual complete reversal of CRPS signs and symp- drotic cyanotic extremities that demonstrated dilated toms. Quantitative sensory testing correlated with her veins and livedo reticularis. clinical recovery. The patient had the following studies: CT of the head, multiple CTs of the cervical and lumbar spine, ase RepoRt
CT of the abdomen and pelvis, abdominal ultrasound, A 42-year-old female patient was involved in a multiple MRIs of the cervical and lumbar spine, an motor vehicle accident in 1997 in which she suffered MRI of the brain with gadolinium, and multiple EMGs, a flexion-extension injury of her neck. She had imme- which were negative. An EEG done to evaluate an diate pain in the C2 and C3 distribution of her neck episode of shaking and dysarthric speech showed left as well as in the C4 distribution across the trapezius anterior midtemporal slowing and excessive beta ac- ridge. She continued working, but her pain gradually tivity. A DEXA scan demonstrated osteopenia of the spread to all distributions of both the cervical and bra- lumbar spine and both hips. ENG showed nonspecific chial plexus on the left side. She was treated with non- central vestibular pathology. General bloodwork, in- steroidal anti-inflammatory agents, anticonvulsants, cluding CBC, liver profile, sed rate, single and double opioids and intense physical therapy with minimal stranded DNA, SS-A and SS-B antibodies, rheumatoid benefit. Her pain was associated with weakness and panel and Lyme's antibody titers was negative. Cardiac Treatment of CRPS with ECT evaluation, including a dobutamine stress echo test, lodynia, no hyperalgesia to pinprick or a cold stimulus was negative. Endoscopy, colonoscopy, ERCP, 24-hour and exhibited none of the inflammatory aspects of pH study and gastric emptying study were undertaken CRPS. There was no autonomic dysregulation; she had to evaluate constipation and demonstrated persistent normal temperatures in her extremities, was not hy- gastroparesis. The patient had undergone a fundo- perhidrotic, and demonstrated no erythema. She had plication procedure in 2001. Her eating schedule was minimal difficulty initiating movements and minimal altered and she was treated with Zelnorm and Mira- 5-/5 weakness bilaterally in her dorsal and volar inter- lax for irritable bowel syndrome, which was partially osseii and abductor pollicis brevis. The patient was no longer depressed. QST done in 2006 was normal in the The patient was treated with the following medi- hands. AST showed a baseline capillary flow that was cations for her pain and depression: Topamax, Cele- slightly high but otherwise was normal in the hands.
brex, Neurontin, Oxycontin, Oxy IR, Flexeril, Lamictal, Table I demonstrates cold and warm detection Reglan, Vioxx, Klonopin, Ambien, Effexor, Xanax, thresholds and cold and heat pain thresholds dur- Paxil, Wellbutrin, Lithium, Prozac, and Seroquel. A se- ing Quantitative Sensory Testing on 3 separate occa- ries of spinal epidural steroids for back pain and cervi- sions during the patient's illness. The first set of data, cal botox injections for neck pain were administered. acquired in 2001 before her ECT treatment, show The patient underwent a 4-day course of inpatient IV that her cold detection thresholds were within the lidocaine, which was gradually titrated to the cardiac normal 1-2o C change in temperature. The patient's arrhythmic dose of 5 mg/L. All of the above treatments warm detection thresholds were minimally high with did not relieve her pain. It is worthy to note that the a +4o C change. In 2003, several months after her patient did not receive a stellate ganglion block. How- ECT treatment, her cold and warm detection thresh- ever, although widely used, this technique has little olds remained normal, although the warm detection proven value in diagnosing or treating CRPS. Quanti- thresholds slightly improved. By 2006, her detection tative Sensory Testing (QST) of her upper extremities thresholds were completely normal. done in 2002 showed severe cold allodynia and heat The patient's cold pain threshold was highly ab- hyperalgesia. Her Autonomic Sensory Testing (AST) normal in 2001. The <10o C change in temperature was showed normal capillary flow and normal sympatheti- well below the normal >22o C change that most peo- cally mediated vasoconstrictor reflexes in the hands. ple experience. The +5o C change in heat pain thresh- The patient was examined in 2003, one month old was also well below the normal >10o C range. after having received a series of 12 treatments with Her second set of data from 2003 taken after the ECT bitemporal electroconvulsive therapy under standard treatment showed minimal improvement in her cold anesthesia for her severe, medically refractory depres- and heat pain thresholds. However, by 2006, both pain sion. On physical examination, the patient related 1/10 thresholds were well within the normal range. NRS mechanical dynamic and static allodynia and 3/10 After 4 years of intractable pain and failed treat- NRS mechanical allodynia with deep compression of ment attempts, following ECT, the patient made a full the muscles. The patient stated that she had evoked physical and social recovery. She no longer requires pain with arm movement 3/10 on a NRS, but had no any pain or depression medication. She now leads a deep joint pain. She exhibited 5-/5 strength in her ex- normal life and has returned to working full-time as tremities, had no hyperalgesia or spread to pinprick or a cold stimulus, and had no dysautonomic features (normal temperature, no hyperhidrosis, and no live- do reticularis). Her major complaint on this visit was In 2005, the IASP proposed changes to its diag- short- term memory loss. The patient described having nostic criteria for Complex Regional Pain Syndrome. had no spontaneous or evoked pain immediately after Current clinical evidence for CRPS in a patient should the ECT. Repeat QST in 2003 after the ECT showed cold allodynia and heat hyperalgesia in the hands. AST was 1) continuing pain disproportionate to any inciting The patient was seen again in 2007. On physical 2) At least one symptom in 3 of 4 categories- sensory examination, she had no criterion factors for CRPS. (hyperesthesia and/or allodynia), vasomotor (tem- She had 0/10 NRS mechanical dynamic and static al- perature asymmetry and/or skin color changes Pain Physician: July 2007:10:573-578 Table I. Quantitative Sensory Testing. Threshold Changes in degrees C from Baseline of 32oC Test site
and/or skin color asymmetry), sudomotor/edema this proband prior to ECT. She had both a high number (edema and/or sweating changes and/or sweat- on her Likert scale for spontaneous pain, mechanical ing asymmetry) and motor/trophic (decreased dynamic and static allodynia and hyperalgesia as well range of motion and/or motor dysfunction such as an abnormal QST. After her treatment with ECT, our as weakness, tremor, dystonia and/or trophic patient's affective component was immediately im- changes in hair, nails, skin), proved; however, her QST showed no improvement of 3) must display at least one sign at time of evalua- her cold allodynia and heat hyperalgesia in her hands. tion in 2 or more of the following categories (as Over the next few years, her Likert numbers still re- described above): sensory, vasomotor, sudomo- mained low for discriminative CRPS factors, but her tor/edema, motor/trophic and QST pain thresholds improved to the normal range. It 4) There is no other diagnosis that better explains the is important to note that her temperature detection signs and symptoms (28). thresholds were within the normal range both before As noted earlier, our patient satisfied all the di- and after her ECT treatment, which rules out small fi- agnostic criteria for CRPS, but after her treatment ber neuropathy as a cause of her decreased pain sensa- with ECT, she currently remains asymptomatic. tion after ECT. As with any treatment, a placebo effect Just as revisions to the diagnostic criteria for CRPS must be taken into consideration. However, given the are occurring to improve therapeutic outcomes, con- often naturally progressive course of chronic CRPS, it is cepts of pain perception are evolving as well. How- highly unlikely that the placebo effect was causative in ever, at present, pain perception is often compart- the recovery of this patient (31). mentalized into an affective component measured The mechanism of action of ECT is still unknown, by a patient's response to validated neuropsychologi- although several observations have been made regard- cal tests, such as the McGill pain questionnaire, while ing the effect of ECT on pain processes. King and Nuss the discriminative component may be measured by a (25) and McDaniel (26) both postulated that massive Likert numeric rating scale of hyperalgesia, allodynia quantities of neurotransmitters are released during and spontaneous pain as well as QST and AST (29,30). ECT that induce changes in CNS post-synaptic receptors Most patients with CRPS will have both components throughout the nervous system. The neurotransmitters affected to some degree, which was the case with affected include serotonin, dopamine, norepinephrine Treatment of CRPS with ECT (27), substance P, neuropeptide Y, somatostatin, TSH, sual cortex was found in CRPS patients. However, CRPS and CRH (26). Other neuromodulators, including en- patients with allodynia have widespread cerebral fMRI kephalin, immune-reactive dynorphin, and beta-en- activation that includes the ipsilateral and contralater- dorphins, have also been implicated in the effects of al SI, the primary motor cortex, the contralateral pari- ECT on pain (26,32,33). King and Nuss (25) and Abdi etal association cortex, bilateral SII, insula, and frontal et al (32) have postulated that the electrical current cortex as well as the anterior and posterior cingulate transmission through the thalamus and hypothala- cortex. Deactivations were detected in the ipsilateral mus which occurs during bilateral ECT alters path- superior frontal cortices, contralateral inferior frontal ways for pain sensation and perception. Wasan et al cortices, visual cortices, and the contralateral temporal (27) suggested that disrupted affective processing of and posterior insular (vestibular) cortices. In addition, pain in CRPS leads to enhanced receptive fields, in- Maihofner et al (35) have also used magnetic source im- tensified pain perception and increased pain sensory aging to show that the brain reorganizes with pain in input. ECT may interrupt this inappropriate process- CRPS, particularly in the primary somatosensory cortex, ing of pain by disrupting the memory for pain. In ad- and recovers from cortical reorganization when CRPS dition, Wasan et al (27) have postulated that ECT may pain is reduced. Therefore, it is possible that ECT may stimulate the lateral thalamic structures involved in trigger the recovery process of the brain that has been descending pain inhibition. Fukui et al (33) have stud- reorganized by CRPS pain to its original form. Because ied the effect of ECT on regional cerebral blood flow. our patient's symptoms did not immediately completely They found that patients with chronic neuropathic improve, it can be postulated that ECT may begin the pain have decreased blood flow to the thalamus. Af- process that restores the brain to its normal functional ter treatment with ECT, one of their patients had in- somatotopic processing capacity, but it may require a creased regional cerebral blood flow to the thalamus prolonged period of time to completely recover. and a dramatic reduction in pain. Functional changes in the brains of CRPS patients have been described with functional MRI (fMRI). Mai- Further controlled randomized studies will be nec- hofner et al (34) have shown that activation of the essary to elucidate possible mechanisms involved in ECT contralateral SI, bilateral SII, and insular cortex all for the benefit of severe refractory CRPS. contribute to the encoding of non-painful stimuli. Deactivation of the ipsilateral SI and the primary vi- RefeRenCes
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