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Spinal cord stimulation in the treatment of complex regional pain syndrome type 1: Is trial truly required?
Accepted Manuscript Title: Spinal Cord Stimulation In The Treatment Of Complex Regional Pain Syndrome Type 1: Is Trial Truly Required? Authors: Erica Garbin Risson, Ana Paula Serpa, J´essica Jacques Berger, Renata Fabiola Heil Koerbel, Andrei Koerbel PII: DOI: Reference:
S0303-8467(18)30228-2 https://doi.org/10.1016/j.clineuro.2018.06.014 CLINEU 5057
To appear in:
Clinical Neurology and Neurosurgery
Received date: Revised date: Accepted date:
10-4-2018 1-6-2018 9-6-2018
Please cite this article as: Risson EG, Serpa AP, Berger JJ, Koerbel RFH, Koerbel A, Spinal Cord Stimulation In The Treatment Of Complex Regional Pain Syndrome Type 1: Is Trial Truly Required?, Clinical Neurology and Neurosurgery (2018), https://doi.org/10.1016/j.clineuro.2018.06.014 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Spinal Cord Stimulation In The Treatment Of Complex Regional Pain Syndrome Type 1: Is Trial Truly Required?
Authors names and affiliations: Erica Garbin Risson (Risson EG) 1, Ana Paula Serpa (Serpa AP) 1, Jéssica Jacques Berger
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(Berger JJ) 1,
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Renata Fabiola Heil Koerbel (Koerbel RFH) 2, Andrei Koerbel (Koerbel A) 3*
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Department of Medicine, University of Joinville Region, Joinville, Brazil.
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Department of Intraoperative Monitoring – Neurological and Neurosurgical Clinic of
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Department of Neurosurgery – Neurological and Neurosurgical Clinic of Joinville.
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3
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Joinville.
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Research conducted at the Neurological and Neurosurgical Clinic of Joinville and
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attributed to the Medical Department of the University of Joinville Region
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(UNIVILLE), Joinville, Santa Catarina, Brazil.
*Corresponding
author: Andrei Koerbel, M.D., PhD
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Plácido Olímpio de Oliveira, 1244 - Anita Garibaldi, Joinville, Santa Catarina, Brazil 89202165.
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E-mail: [email protected]
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Highlights
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There is no real need for the percutaneous electrode implant test preceding the permanent implantation of the neurostimulator in patients with Complex Regional Pain Syndrome (CRPS) type 1. The surgeries are performed under intraoperative tests for precise location of the spinal cord electrode implantation. The treatment was effective in pain control and disability reduction in the cases included in this study.
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ABSTRACT
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Objective: Spinal cord stimulation has been proven highly effective in the treatment of
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Complex Regional Pain Syndrome (CRPS). The definitive implantation of a
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neurostimulator is usually preceded by a therapeutic test (trial), which has the purpose of
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identifying whether the patient would respond positively to neuromodulation or not. The present study aims to analyze the surgical results of spinal cord stimulation in type 1
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CRPS patients who have not undergone trial. Patients and Methods: From January 2011 to August 2017, 160 patients underwent
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implantation of spinal cord neurostimulator. Out of that total number of surgeries, 33
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patients were unequivocally diagnosed with type 1 Complex Regional Pain Syndrome and selected for this study. The efficacy of the surgical procedure concerning pain improvement was analyzed through the application of the Pain Disability Index and the
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Visual Analog Pain Scale. Results: The mean sample age was 48,08 years. The majority of the study subjects were female (66,66%). In respect to the Pain Disability Index, a 65% improvement in disability was observed subsequently to the neurostimulator implantation; in addition, the means of the scores for preoperative and postoperative periods were, respectively, 55 ± 8.69 (p
<0.0001) and 18.90 ± 11.58 (p <0.0001). Regarding the Visual Analogue Scale, the mean pain in the preoperative period was 9.43 ± 0.77 (p <0.0001), while the mean in postoperative period was 2.86 ± 2.08 (p <0.0001). Thus, an average reduction of 70% of painful symptoms was observed after the surgical procedure. Conclusion: Implantation of a spinal cord neurostimulator presented significant
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improvement in pain and disability of patients with type 1 CRPS in all cases. These results
were obtained following the criteria: 1) patients presenting unequivocal diagnosis of type
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1 CRPS; 2) submitted to constant current spinal cord neurostimulator implant; 3)
underwent intraoperative tests for precise location of the spinal cord electrode implantation. Therefore, it is possible to suggest that a trial may be unnecessary in that
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subgroup of patients. Further studies would be required to confirm these findings.
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Keywords: Chronic Pain, Complex Regional Pain Syndromes, Pain Management, Reflex
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INTRODUCTION
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Sympathetic Dystrophy, Spinal Cord Stimulation, Treatment Outcome.
Chronic pain syndromes have numerous etiologies and diverse forms of symptom
presentations; consequently, they were assorted and classified according to these
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characteristics. One of these syndromes is the Complex Regional Pain Syndrome (CRPS), a chronic pain condition that more commonly affects the extremities, although it can affect other regions of the body [1,2,3]. The condition usually occurs after soft tissue or nerve trauma or lesion; pain is described as persistent and disproportional to the triggering factor. The painful stimuli are also associated with localized autonomic dysfunction,
which leads to temperature variation of the affected area, abnormal sudomotor activity, hyperesthesia, edema, altered nail growth, and changes in skin color [4,5,6,7]. CRPS is divided into Type 1 and Type 2, which diverge as to the pain trigger mechanism. Type 1 corresponds to Reflex Sympathetic Dystrophy: a complex pain syndrome in which nerve lesions cannot be identified. Type 2 - previously known as
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causalgia -, on the other hand, may reveal a nerve lesion as a trigger for the pain stimuli [3,5,6,7,8]. Despite the separation, both share the same set of symptoms and treatments.
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Moreover, both conditions are highly debilitating and may cause progressive incapacity and a negative impact on the life quality of these patients [6].
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Conducting a therapeutic test prior to permanent implantation of the
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neurostimulator is a common practice [6]. Two surgeries are necessary for experimental
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stimulation and require the patient to remain connected to an extracorporeal
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neurostimulation system for a variable period. The purpose of this practice is to predict whether the response to the treatment will be favorable in the postoperative period
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[9,10,11].
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Type 1 CRPS has been associated with a better prognosis after treatment with spinal cord stimulation than the Type 2 and further conditions treated by the same method
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[12,13].
The authors' experience over the years has shown that the results obtained with
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spinal cord stimulation for patients suffering from type 1 CRPS are remarkably positive, producing superior results in comparison to other disorders. Thus, the authors developed a study on this specific subgroup of patients, aiming to determine the results of implanting the spinal neuromodulation system without previous trial, by performing exclusively
intraoperative tests while the patient is conscious in order to ensure correct electrode positioning.
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PATIENTS AND METHODS
From January 2011 to August 2017, among the total amount of patients referred
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to the senior author (Andrei Koerbel) at the Neurological and Neurosurgical Clinic of
Joinville for chronic pain treatment, 160 underwent implantation of spinal cord
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neurostimulator. Out of that total number of surgeries, 33 patients were unequivocally
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diagnosed with type 1 Complex Regional Pain Syndrome and selected for this study. All
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patients with chronic pain of other etiologies and those who refused to participate or to
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sign the informed consent forms were excluded from the study. Type 1 CPRS diagnosis was established whenever there was localized autonomic
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dysfunction associated with the distinct presence of two or more pain criteria symptoms,
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as follows: temperature changes on the affected area; abnormal sudomotor activity; hyperesthesia; edema; skin color changes; or change in tropism and nail growth.
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The existence of nerve damage as an etiological factor established the condition
as type 2, regardless of the presence of any of the CRPS pain criteria symptoms.
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Therefore, those patients were excluded from the study. All selected patients were refractory to clinical treatment, physical therapy, and
other available therapies, and had at least 6 months of progression. All patients were submitted to preoperative psychological assessment.
The surgeries were performed with the painful area facing superiorly as the patient was set in lateral decubitus. The patients were submitted to assisted local anesthesia associated with intermittent sedation during the procedures. All subjects underwent intraoperative tests and insertion of an implantable electrode by laminectomy. Every patient underwent a constant current spinal cord neurostimulator implantation, produced
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by St. Jude.
In cases of cervical electrode implantation, the Suguita cranial fixation system was
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used. The patients underwent sedation during the mini laminectomy and while the incision was prepared for the generator implantation. The selected area for the implant
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was prepared on the same side of the pain (located superiorly according to the lateral
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decubitus). The infraclavicular region was assigned to cervical electrodes and the
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abdominal area to thoracic electrodes. The electrodes were inserted into the subcutaneous
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tissue, connecting the two incisions (one over the spine and one over the generator implant area).
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During surgery, after placing the electrode on the desired spinal cord epidural area,
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the patient was awakened. Intraoperative tests were performed to select the spinal cord area that allowed adequate coverage of stimuli in regions enduring type 1 CRPS
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symptoms. After locating the area, the electrodes were fixated and the tests were repeated. Following confirmation of the correct positioning of the electrodes, the patient was again sedated until the end of the procedure – which encompassed the generator implantation
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and the closure by planes of both incisions. Some patients have implanted devices with Burst stimulation. However, they were not activated in the present research to avoid study bias, since some patients do not have devices containing this option. Therefore, only tonic stimulation was
used in the treatment of these patients during the study. New high frequency stimulation was not tested in this research. The impact of spinal cord stimulation on pain reduction was analyzed through the application of the Pain Disability Index (PDI) and the Visual Analogue Scale (VAS). Both questionnaires were applied in two identical copies. The first copy referred to the
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patient's condition in the preoperative phase. The second copy was answered according to the condition of the patient under neuromodulation treatment, ranging from 6 to 65
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months postoperatively.
The Pain Disability Index (PDI) is a validated tool that allows measuring the
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impact of chronic pain and the limitations it brings to daily activities. Seven categories of
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daily tasks were evaluated: family and home responsibilities, recreation, social activity,
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occupation, sexual behavior, self-care, and life-support activities (eating, sleeping). To
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each of these domains is assigned a score varying from 0-10; 0 corresponds to no disability, while 10 means that pain completely prevented the performance of such
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activity. The sum of the scores produces an index ranging from 0-70 - the higher the
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index, the greater the disability caused by the painful symptoms. The Visual Analogue Scale (VAS) was applied in order to estimate the pain
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intensity of the study subjects. It is a scale ranging from 0 to 10: 0 means total absence of pain and 10 represents the maximum pain level that the patient is able to bear.
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In respect to the questionnaire, the answers regarding the period preceding the
neurostimulator implantation were compared to those concerning the postoperative period (the moment when this study took place). Thus, we attempted to identify whether neurostimulation improved the appraised parameters.
The quantitative variables were analyzed by the calculation of means and standard deviations. The level of statistical significance adopted was 5% (p <0.05) and it was measured using Student's T-Test.
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RESULTS Thirty-three CRPS patients who were refractory to clinical treatments met the
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inclusion criteria. The mean age of participants was 48,08 years, varying from 23 to 68
years of age. The majority of them were female (66,66%). Table 1 displays the individual
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baseline characteristics of the subjects of this study.
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characteristics of the patients and their results following treatment. Table 2 exhibits the
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Regarding the Pain Disability Index, the means of the scores for preoperative and
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postoperative periods were, respectively, 55 ± 8.69 (p <0.0001) and 18.90 ± 11.58 (p <0.0001). Therefore, a 65% disability improvement was observed after the
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neurostimulator implantation.
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Table 3 demonstrates the variations found for each parameter studied. It indicates a significant attenuation of the disability related to the pain symptomatology in all the
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categories evaluated, suggesting an overall improvement in the quality of life of these patients. The factor that showed the greatest disability reduction was life-support activity, in which it was possible to confirm a 72% improvement in disability (p <0.0001). On the
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other hand, the lowest disability reduction parameter was occupation, with a 54% symptom decrease (p <0.0001). Concerning the Visual Analogue Scale, the mean pain score in the preoperative and postoperative periods were, respectively, 9.43 ± 0.77 (p <0.0001) and 2.86 ± 2.08 (p
<0.0001). Consequently, mean reduction of 70% in the score attributed to the painful symptoms was observed after the surgical procedure. All patients remain under therapy, despite follow-up over several years in most cases. In all circumstances, the temporary suspension of neurostimulation through remote control shutdown produced a recurrence of the symptoms and the need for treatment
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reactivation. Non-rechargeable generators were replaced by rechargeable generators in
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cases of battery termination.
In respect to postoperative complications, infection rate and new-onset neurological deficits were 0%.
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New electrode replacement procedures were required in 3 patients with electrode
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DISCUSSION
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occurred in any of these new surgeries.
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dysfunction throughout their respective treatments. No postoperative complications
The pathophysiological mechanisms involved in CRPS are still uncertain. It is
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believed that the interaction of several aspects may be necessary for this syndrome to develop [7,14]. These include factors of genetic and psychological origin, changes in the
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level of inflammatory mediators and circulating catecholamines, phenomena of central and peripheral sensitization, changes in cutaneous innervation and neuronal plasticity [14,15]. In the general population, it is estimated that less than 200,000 people in the US and 154,000 in Europe are affected by CRPS. Apparently, this incidence is higher after
fractures, ranging from 3.8-7% [6]. The prevalence is higher in females and the incidence is higher from 50 to 70 years of age [7,15]. In the present study, we also observed a greater frequency of CRPS in females. The mean age was 48,08 years, and although the incidence is more common in the aforementioned age range, this study presented 15 patients (45,45% of the sample) under 50 years of age.
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The Budapest criteria [16] for CRPS encompass the diagnosis of a pain continuous and disproportionate to the triggering event, including at least one
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symptom reported in three of the four categories: - Sensory – hyperalgesia and/or allodynia.
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- Vasomotor – temperature irregularity and/or skin color alterations/asymmetry.
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- Sudomotor/oedema – local oedema and/or sweating variations/asymmetry.
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- Motor/trophic – reduced range of motion and/or motor dysfunction (tremor,
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dystonia, weakness) and/or trophic modifications (nail, skin, hair). No patient was included in our present study without presenting visible
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alteration at the moment of the evaluation. Those alterations refer to the categories aforementioned. In addition, we considered two or more symptoms sufficient to
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raise the hypothesis of CRPS. Furthermore, any other possible causes of chronic
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pain were excluded in these patients.
There is a large arsenal of medications that may provide pain relief. These include
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corticosteroids - most commonly used in the acute phase -, analgesics, antidepressants, and anticonvulsants such as pregabalin, among other drugs available on the market [6,7,15,17]. However, because of its complexity, CRPS is one of the most difficult chronic pain conditions for the achievement of a satisfactory treatment [14].
In cases of pain refractory to the previously mentioned treatments or of greater complexity, further invasive measures are taken after a careful selection. Sympathectomies have been performed with frustrating long-term results [6,18]. Despite several therapies developed and tested during their treatment, cases presenting more than 6 to 12 months of CRPS evolution tend to fail most of the treatments
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described. The development of spinal cord stimulation brought significant control of the
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symptoms in cases that had failed the aforementioned CRPS treatments [9,17,19,20].
The spinal cord stimulation system consists of an implantable electrical current generator, associated with electrodes that are inserted into the epidural space [8,10,11]. It
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acts through low-voltage electrical impulses on the conducting pathways of painful
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stimuli in order to block them [21,22,23,24].
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The function of these stimuli is to alter the action potential of neuronal cells and
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to influence the local neurochemistry, inducing or inhibiting the secretion of some
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neurotransmitters. Furthermore, if the appropriate voltage and frequency are applied, it is possible to block the conduction of painful stimuli through the stimulation of inhibitory
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central circuits and the generation of the paresthetic sensation [21, 22,23,24].
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The treatment of pain syndromes through the implantation of the neurostimulator presents numerous indications and its effectiveness has been already proven [6,25,26,27,28,29]. Moreover, there is evidence that the long-term cost-effectiveness of
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spinal cord stimulation is superior to that of conventional drug therapies, decreasing health systems expenditure [30]. Complex Regional Pain Syndrome (CRPS) is a rare phenomenon, being more common in women, as also observed in the present study [6,7,15].
Complex Regional Pain Syndrome type 1 is a condition that manifests great refractoriness to conventional treatments. The delicate handling of this disorder is evidenced in many studies. This difficulty is due to the pathophysiological complexity of this dysfunction and the various mechanisms involved. The lack of knowledge about this condition also leads to late diagnosis, frustrating approaches,
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and inadequate treatment. Considering this scenario, spinal neurostimulation has been gaining space in the control of this pathology [6,11,19,21, 31,32,33,34].
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In a 2003 systematic review of spinal cord neurostimulation of complex
regional pain syndromes, Grabow TS [31] et al had already presented evidence suggesting that this was an effective pain management treatment in patients who did
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not respond to conservative measures. Kemler et al [12] further displayed data of
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improvement in pain and quality of life of CRPS patients treated with
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patients to neurostimulation once more.
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neurostimulation. Gopal et al [37], in 2016, attested the positive response of these
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A prospective cohort was carried out by Geurts et al. [17] and published in 2012: an 11-year research including an "n" higher than the one presented in our
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study. Even with long-term follow-up, and acknowledging interventions due to longterm complications, 63% of the patients still maintained painful symptoms after this Additionally, they reported at least 30% improvement in symptoms.
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period.
Considering the difficulty in obtaining an effective treatment of CRPS, these results
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are important. However, other studies should be carried out. Even though the number of articles regarding this subject is limited, there is
solid evidence of the benefit of spinal neurostimulation in the CRPS treatment. In addition, daily clinical practice demonstrates improvement in disability and quality of life of patients submitted to neurostimulation.
Regarding the operative technique used in this study, the patients were instructed preoperatively on how they should behave while awakening and answering to the intraoperative tests. They were sedated with propofol until the surgical approach was performed. In our experience, the patients have been able to cooperate properly during the surgeries. As the procedures are carried out under
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intraoperative tests, the main goal is to find the best location for the implant on the
spinal cord according to the painful area. This technique increases the surgical time
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and the required efforts from the patients and surgical team. Thus, any potential
lead migration would be a very undesirable complication after this meticulous, timeconsuming endeavor. Epidural paddle leads can provide wider covers on the spinal
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cord in very stable positions. Furthermore, the chances of migration are minimal
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when paddle leads are used and fixed by small laminectomies. Therefore, we prefer
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this approach instead of percutaneous techniques.
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The performance of a therapeutic test (trial) prior to the permanent implantation
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of the neurostimulator aims to increase the chances of a satisfactory treatment result [6]. The test consists of temporary implantation of electrodes associated to an extracorporeal
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stimulus generator. Throughout the test period, it is possible to assume whether the response to the treatment will be favorable. During periods of percutaneous stimulation
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tests, a few days are reserved for stimuli regulation in order to optimize pain management [9,10,11].
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However, there is no evidence that this practice – trial – can truly benefit the
patients in all cases. Furthermore, the definitive implant increases treatment costs – as it requires a longer hospitalization period, a two-step procedure, and the disposal of used materials [35,36,37,38,39]. In addition, the use of an external device, even if temporary, can create an entry for infection. Infections can greatly increase therapeutic costs, as they
require antibiotic therapy, explant of high-cost implanted systems and increase patient risks. Traditional two-stage surgery was associated with an infection rate of up to 8% [40]. The intraoperative therapeutic test technique showed much lower rates, reaching total absence of infection [37]. The patients submitted to the present study - implanted without previous trial - did not present any case of infection.
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Migration of the catheter is also a frequently cited complication. In conventional surgery, the reported incidence is 10%, whereas in procedures without therapeutic test,
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the incidence was 2.53% [37].
The major reason for indicating the percutaneous preoperative test, in the
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literature, is to identify which patient would benefit from the spinal cord stimulation
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therapy. Nevertheless, it is known that a considerable percentage of the cases treated with
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spinal cord stimulation may improve in the first months or years postoperatively and –
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using neuromodulation from medium to long-term - progress to pain control resistance.
doubt its real benefit.
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These patients would not be identified in the trial – hence another argument to put in
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The objective of the present study was to analyze the real need for the percutaneous electrode implant test preceding the permanent implantation of the
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neurostimulator. This objective was explored through the observation of the impact of spinal cord stimulation in improvement of pain and decrease of disability in patients with
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type 1 CRPS. In the literature review, which included databases such as BIREME and PubMed, we did not find articles that approached the subject with the same focus, or that used the same tools as we did in our study. This was a limiting factor, given the impossibility of comparison.
In respect to the reduction of painful symptoms, however, studies that analyzed spinal cord stimulation as a treatment for chronic pain, similarly expressed around 50% of symptom improvement [12,17,26,28,40,41]. The present study determined a 70% reduction in symptoms intensity. In all cases - except for one - the pain improvement was remarkable. The only
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exception was patient number 25, table 1. Although they stated a reduction of only 20% in the VAS, the patient considers the pain much less intense in comparison to the period
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preceding the neurostimulator implantation. Moreover, this patient describes that they “could not live without spinal cord stimulation anymore”. Thus, if a trial had been
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performed in this case, the patient would have gotten the stimulator implanted
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nonetheless.
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Regarding the parameters analyzed through the Pain Disability Index, there was a
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reduction of more than 60% in disability in almost all of the studied domains. The parameter with the lowest disability reduction was occupation, which displayed a 54%
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reduction. We believe that the reduced impact in the occupation category occurred due to
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some of the patients’ removal from their labor activities, given the painful symptoms prior to the surgical procedure.
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Findings in some domains, especially those concerning self-care, life-support
activities and social activities, expressed a greater than 65% reduction in disability. The
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total questionnaire score displayed a 65% reduction of disability when comparing the preoperative and postoperative period. Such findings clearly demonstrate the effectiveness of neurostimulation and reinforce that trial is not necessary in these specific cases.
In our study, we did not separately report mild adverse effects such as painful incision site, battery discomfort, and others. Even though these adverse effects were not individually analyzed in the presented data, their impact on the satisfaction rate of SCS implant could be indirectly measured by the Pain Disability Index (PDI) and the Visual Analogue Scale (VAS). Had these adverse effects influenced negatively
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the SCS treatment results, they would be indirectly captured in the scale and index cited. Although we agree that these mild adverse effects are important issues, we
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believe that analyzing them independently would not change the main goal of this work. Since these symptoms cannot be predicted by performing a trial, their
existence could not have changed the decision of implanting or not a definitive
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device.
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Part of the favorable results may be related to the thorough CRPS diagnosis. The
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criteria were applied and combined with the presence of autonomic signs in the anamnesis
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and physical examination of patients so that the CRPS diagnosis could be established.
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Furthermore, careful application of the intraoperative therapeutic test and the type of neurostimulator system implanted may also influence the results. It should be intently
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observed that all patients treated in this study had an unequivocal diagnosis of type 1 CRPS. The authors did not analyze neurostimulator implants in patients with a
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presumptive diagnosis of type 1 CRPS. All subjects selected for this study had typical CPRS symptoms, an absence of nerve damage triggering the condition, and two or more
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distinct dysautonomic symptoms. Moreover, all patients underwent constant current spinal cord stimulator implantation. Kemler et al. describes that in his carefully enrolled cases of chronic reflex sympathetic dystrophy, that after test-stimulation 12 from 36 patients did not have permanent implantation [12]. Although the authors cited in the introduction of their
study that chronic reflex sympathetic dystrophy is related to type 1 CRPS, their diagnose criteria for inclusion in their study was that of CRPS, not specifically type 1. Their exclusion criteria included current or previous neurologic abnormalities unrelated to reflex sympathetic dystrophy [12]. They did not mention a nerve lesion as a trigger for the pain stimuli as an excluding factor. That could be the main reason
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for the high incidence of non-responders in their trial. We selected only the
unequivocal type 1 CRPS cases. Despite the division, both conditions share the same
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set of symptoms and treatments. However, the type 2 CRPS patients are known to have considerably poorer responses to spinal cord stimulation. Another difference
between Kemler’s methods and those of the present article was the type of implanted
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device. The present work used constant current systems, whereas Kemler and
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colleagues used constant voltage ones. It is not possible to assume that it could have
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had an impact on the results, but it is worthy of mention. Future studies could focus
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on this specific issue. Finally, we cannot assure that some of the patients who did not
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receive a permanent implant in that study [12] wouldn’t have had some disability reduction and pain relief, had they been operated. Many dysautonomic symptoms
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in CRPS improve only after many days or weeks of continuous treatment. Although spinal neuromodulation in several cases does not fully control pain and
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dysautonomic symptoms, in this study symptoms were significantly reduced and the quality of life was considerably improved. Temporary withdrawal of therapy through the
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cessation of neurostimulation implicated recurrence of symptoms. Thus, every subject in the present article remained under therapy until the end of this study - which corroborates its undoubted benefit to all these patients. Table 4 demonstrates the costs of trials and definitive implants in Brazil. Thus, one can compare the values that could be saved in not performing unnecessary
trials and the expenses of eventual ineffective definitive implants. In Brazil, approximately 2,5 trials could pay one definitive implant. Therefore, further studies including control groups are highly desirable, also regarding an economic point of view.
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CONCLUSION
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Our findings suggest that the treatment was effective in pain control and disability reduction in all cases included in this study, which followed the criteria: 1) patients presenting unequivocal diagnosis of type 1 CRPS; 2) submitted to constant current spinal
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cord neurostimulator implant; 3) underwent intraoperative tests for precise location of the
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spinal cord electrode implantation. Therefore, it is possible to suggest that percutaneous
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electrode trial is dispensable in this subgroup of patients.
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the findings of the present study.
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Further studies including a larger number of patients would be required to confirm
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Declarations of interest: none.
REFERENCES
1. Fillingim, R. B., Bruehl, S., Dworkin, R. H., Dworkin, S. F., Loeser, J. D., Turk, D. C., … Wesselmann, U. (2014). The ACTTION-American Pain Society Pain
classifying
chronic
pain
conditions.
Journal
of
Pain,
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Taxonomy (AAPT): An evidence-based and multidimensional approach to 15(3),
SC R
https://doi.org/10.1016/j.jpain.2014.01.004.
241–249.
2. Lee, C., Crawford, C., Teo, L., Spevak, C., Buckenmaier, C. C., Crawford, P., … York, A. (2014). An Analysis of the Various Chronic Pain Conditions Captured in a
U
Systematic Review of Active Self-Care Complementary and Integrative Medicine
N
Therapies for the Management of Chronic Pain Symptoms. Pain Medicine (United
A
States), 15(S1). https://doi.org/10.1111/pme.12357.
M
3. Merskey, H., & Bogduk, N. (2002). Classification of Chronic Pain: Descriptions of
IASP Press.
ED
Chronic Pain Syndromes and Definitions of Pain Terms, (2nd ed., pp. 40-43). Seattle:
Pain
PT
4. Nation Institute of Neurological Disorders and Stroke. NINDS Complex Regional Syndrome
Information
Page.
Retrieved
January
2017
from
CC E
http://www.ninds.nih.gov/disorders/reflex_sympathetic_dystrophy/reflex_sympathet ic_dystrophy.htm.
A
5. Stanton-Hicks, M., Jänig, W., Hassenbusch, S., Haddox, J. D., Boas, R., & Wilson, P. (1995). Reflex sympathetic dystrophy: changing concepts and taxonomy. Pain, 63(1), 127–133. https://doi.org/10.1016/0304-3959(95)00110-E.
6. Bruehl, S. (2015). Complex regional pain syndrome. BMJ (Clinical Research Ed.), 351(2), h2730. https://doi.org/10.1136/bmj.h2730.
7. Cordon, F. C. O., & Lemonica, L. (2002). Síndrome Dolorosa Complexa Regional: Epidemiologia, Fisiopatologia, Manifestações Clínicas, Testes Diagnósticos e Propostas Terapêuticas. Revista Brasileira de Anestesiologia, 52(5), 618–627. https://doi.org/10.1590/S0034-70942002000500013. 8. Poree, L., Krames, E., Pope, J., Deer, T. R., Levy, R., & Schultz, L. (2013). Spinal
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cord stimulation as treatment for complex regional pain syndrome should be
considered earlier than last resort therapy. Neuromodulation, 16(2), 125–141.
SC R
https://doi.org/10.1111/ner.12035.
9. Song, J. J., Popescu, A., & Bell, R. L. (2014). Present and potential use of spinal cord
http://www.ncbi.nlm.nih.gov/pubmed/24850105.
U
stimulation to control chronic pain. Pain Physician, 17(3), 235–46. Retrieved from
N
10. National Institute for Health and Care Excellence (NICE). Spinal cord stimulation for
M
https://nice.org.uk/guidance/ta159.
A
chronic pain of neuropathic or ischaemic origin. Retrieved January 2016 from
ED
11. Colllet, B., Collins, A., Dickson, D., Elidge, P., Morley, S., Sanderson, K. … Murphy, P. (2009). Spinal cord stimulation for the management of pain: Recommendations for
PT
best clinical practice. In A consensus document prepared on behalf of the British Pain Society in consultation with the Society of British Neurological Surgeons. London:
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The British Pain Society.
12. Kemler, M. A., Barendse, G. A. M., van Kleef, M., de Vet, H. C. W., Rijks, C. P. M.,
A
Furnée, C. A., & van den Wildenberg, F. A. J. M. (2000). Spinal Cord Stimulation in Patients with Chronic Reflex Sympathetic Dystrophy. New England Journal of Medicine, 343(9), 618–624. https://doi.org/10.1056/NEJM200008313430904.
13. Dworkin, R. H., O’Connor, A. B., Kent, J., Mackey, S. C., Raja, S. N., Stacey, B. R., … Wells, C. D. (2013). Interventional management of neuropathic pain: NeuPSIG recommendations. Pain. Elsevier B.V. https://doi.org/10.1016/j.pain.2013.06.004. 14. Bruehl, S. (2010). An update on the pathophysiology of complex regional pain syndrome.
Anesthesiology.
Lippincott
Williams
Wilkins.
IP T
https://doi.org/10.1097/ALN.0b013e3181e3db38.
and
15. Goebel, A. (2011). Current Concepts in Adult CRPS. Reviews in Pain, 5(2), 3–11.
SC R
http://doi.org/10.1177/204946371100500202.
16. Goebel, A., Bisla, J., Carganillo, R., Cole, C., Frank, B., Gupta, R., et. al. (2017). A randomised placebo-controlled Phase III multicentre trial: Low-dose
U
intravenous immunoglobulin treatment for long-standing complex regional pain
N
syndrome (LIPS trial). Efficacy and Mechanism Evaluation, 4(5), 1-82.
A
Appendix 3, Research diagnostic criteria (the ‘Budapest Criteria’) for complex
M
regional pain syndrome. Doi:10.3310/eme04050.
ED
17. Geurts, J. W., Smits, H., Kemler, M. A., Brunner, F., Kessels, A. G. H., & Van Kleef, M. (2013). Spinal cord stimulation for complex regional pain syndrome type I: A
PT
prospective cohort study with long-term follow-up. Neuromodulation, 16(6), 523– 529. https://doi.org/10.1111/ner.12024.
CC E
18. Straube, S., Derry, S., Moore, R. A., & Cole, P. (2013, September 2). Cervico-thoracic or lumbar sympathectomy for neuropathic pain and complex regional pain syndrome.
A
Cochrane Database of Systematic Reviews. John Wiley and Sons Ltd. https://doi.org/10.1002/14651858.CD002918.pub3.
19. Harden, R. N., Oaklander, A. L., Burton, A. W., Perez, R. S. G. M., Richardson, K., Swan, M., … Bruehl, S. (2013). Complex Regional Pain Syndrome: Practical
Diagnostic and Treatment Guidelines, 4th Edition. Pain Medicine, 14(2), 180–229. https://doi.org/10.1111/pme.12033. 20. Slavin, K. V. (2014). Spinal Stimulation for Pain: Future Applications. Neurotherapeutics. Springer New York LLC. https://doi.org/10.1007/s13311-0140273-2.
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21. J.P., P., & Prager, J. P. (2010). What does the mechanism of spinal cord stimulation
tell us about complex regional pain syndrome? Pain Medicine (Malden, Mass.), 11(8),
SC R
1278–1283. https://doi.org/10.1111/j.1526-4637.2010.00915.x. 22. Cukiert, A. (2010). Neuromodulation (pp. 45-140). São Paulo: Alaúde.
23. Taylor, R. S. (2006). Spinal Cord Stimulation in Complex Regional Pain Syndrome
U
and Refractory Neuropathic Back and Leg Pain/Failed Back Surgery Syndrome:
N
Results of a Systematic Review and Meta-Analysis. Journal of Pain and Symptom
A
Management, 31(4 SUPPL.). https://doi.org/10.1016/j.jpainsymman.2005.12.010.
M
24. Moore, D. M. & McCrory, C. (2016). Spinal Cord Stimulation. BJA Education,
ED
16,(8), 258-263. https://doi.org/10.1093/bjaed/mkv072. 25. Turner, J. A., Loeser, J. D., Deyo, R. A., & Sanders, S. B. (2004). Spinal cord
PT
stimulation for patients with failed back surgery syndrome or complex regional pain syndrome: A systematic review of effectiveness and complications. Pain. Elsevier.
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https://doi.org/10.1016/j.pain.2003.12.016.
26. Tesfaye, S., Watt, J., Benbow, S. J., Pang, K. A., Miles, J., & MacFarlane, I. A.
A
(1996). Electrical spinal-cord stimulation for painful diabetic peripheral neuropathy. Lancet, 348(9043), 1698–1701. https://doi.org/10.1016/S0140-6736(96)02467-1.
27. Erdek, M. A., & Staats, P. S. (2003). Spinal-cord stimulation for angina pectoris and peripheral vascular disease. Anesthesiology Clinics of North America. W.B. Saunders. https://doi.org/10.1016/S0889-8537(03)00090-7.
28. Kapural, L., Narouze, S. N., Janicki, T. I., & Mekhail, N. (2006). Spinal cord stimulation is an effective treatment for the chronic intractable visceral pelvic pain. Pain Medicine, 7(5), 440–443. https://doi.org/10.1111/j.1526-4637.2006.00165.x. 29. Burchiel, K. J., Anderson, V. C., Brown, F. D., Fessler, R. G., Friedman, W. A., Pelofsky, S., … Shatin, D. (1996). Prospective, multicenter study of spinal cord
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stimulation for relief of chronic back and extremity pain. Spine, 21(23), 2786–2794. https://doi.org/10.1097/00007632-199612010-00015.
SC R
30. Kumar, K., & Rizvi, S. (2013). Cost-Effectiveness of Spinal Cord Stimulation
Therapy in Management of Chronic Pain. Pain Medicine, 14(11), 1631–1649. https://doi.org/10.1111/pme.12146.
U
31. Grabow, T. S., Tella, P. K., & Raja, S. N. (2003). Spinal cord stimulation for complex
N
regional pain syndrome: an evidence-based medicine review of the literature. The
A
Clinical Journal of Pain, 19(6), 371–83. https://doi.org/10.1097/00002508-
M
200311000-00005.
ED
32. Kapural, L. (2014). Spinal cord stimulation for intractable chronic pain. Current Pain and Headache Reports, 18(4). https://doi.org/10.1007/s11916-014-0406-7.
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33. Levy, R. M. (2012). Evidence-Based Review of Neuromodulation for Complex Regional Pain Syndrome: A Conflict Between Faith and Science? Neuromodulation:
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Technology at the Neural Interface, 15(6), 501–506. https://doi.org/10.1111/j.15251403.2012.00531.x.
A
34. Kumar, K., Rizvi, S., & Bnurs, S. B. (2011). Spinal cord stimulation is effective in management of complex regional pain syndrome I: Fact or fiction. Neurosurgery, 69(3), 566–578. https://doi.org/10.1227/NEU.0b013e3182181e60.
35. North, R. B., & Wetzel, F. T. (2002). Spinal cord stimulation for chronic pain of spinal origin: a valuable long-term solution. Spine, 27(22), 2584–2591; discussion 2592. https://doi.org/10.1097/01.BRS.0000032132.99599.78. 36. Weinand, M. E., Madhusudan, H., Davis, B. & Melgar, M. (2003). Acute vs.
Journal of the International Neuromodulation Society. 6(1), 15-9.
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Prolonged Screening for Spinal Cord Stimulation in Chronic Pain. Neuromodulation:
37. Gopal, H., Geraldo, J. F. & McCrory, C. (2016). Spinal cord stimulation for FBSS
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and CRPS: A review of 80 cases with on-table trial of stimulation. Journal of Back and Musculoskeletal Rehabilitation, 29(1), 7–13. DOI:10.3233/BMR-150608.
38. Kumar, K., Buchser, E., Linderoth, B., Meglio, M. and Van Buyten, J. (2007),
U
Avoiding Complications From Spinal Cord Stimulation: Practical Recommendations
N
From an International Panel of Experts. Neuromodulation: Technology at the Neural
A
Interface, 10: 24-33. https://doi:10.1111/j.1525-1403.2007.00084.x.
M
39. Follett, K. A., Boortz-Marx, R. L., Drake, J. M., DuPen, S., Schneider, S. J., Turner,
delivery and
ED
M. S., & Coffey, R. J. (2004, June). Prevention and management of intrathecal drug spinal
cord
stimulation
system
infections.
Anesthesiology.
PT
https://doi.org/10.1097/00000542-200406000-00034. 40. Kumar, K., Taylor, R. S., Jacques, L., Eldabe, S., Meglio, M., Molet, J., … North, R.
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B. (2007). Spinal cord stimulation versus conventional medical management for neuropathic pain: A multicentre randomised controlled trial in patients with failed
A
back
surgery
syndrome.
Pain,
132(1–2),
179–188.
https://doi.org/10.1016/j.pain.2007.07.028.
41. Calvillo, O., Racz, G., Didie, J., & Smith, K. (1998). Neuroaugmentation in the treatment of complex regional pain syndrome of the upper extremity. Acta Orthopaedica Belgica, 64(1), 57–63.
TABLES
UL
12
2
54
F
LUL
36
3
52
M
RLL
60
4
23
F
RUL
5
56
M
RLL
6
45
F
LUL
9
7
44
M
LLL
48
36
M
RLL + LLL
36
50
F
RUL
60
36
PT
72
A
9
CC E
8
SC R
U
N
F
81%
A
53
43
13
70%
9
3
67%
56
22
61%
9
2
78%
68
22
68%
10
5
50%
45
3
93%
9,5
1
89%
43
26
40%
8
4
50%
58
29
50%
10
2
80%
53
19
64%
8
2
75%
67
27
60%
10
5
50%
64
13
80%
10
3
70%
49
20
59%
10
2
80%
65
32
51%
10
5
50%
55
3
95%
10
0
100%
Cervi cal Cervi cal Thora cic Cervi cal Thora cic Cervi cal Thora cic Thora cic Cervi cal Cervi cal Thora cic Thora cic Thora cic
ED
1
Elect Disabili Pain rode ty Preope Postope Preope Postope improv impl improv rative rative rative rative ement antat ement PDI PDI VAS VAS percent ion percent age level age
M
Length of the painful Pain period Pati Ag Gen distribut before ent e der ion surgery (complet e months)
IP T
Table 1. Individual Characteristics and Results
10
61
F
LUL
24
11
41
F
LLL
36
12
38
F
RLL
96
13
53
F
RLL
96
52
10
10
0
100%
14 15
51 51
M
UL
120
Cervi cal
44
4
91%
9
0
100%
F
Left hemithor ax
60
Thora cic
70
7
90%
10
1
90%
Thora 54 10 81% 8 0 100% cic Thora LL 120 45 19 58% 10 0 100% 17 51 F cic Cervi RUL 12 60 35 42% 10 5 50% 18 49 F cal RLL Thora 48 49 32 35% 10 5 50% 19 54 F +LLL cic Thora LLL 24 61 9 85% 10 3 70% 20 36 F cic RLL + Thora 48 65 42 35% 9 5 44% 21 34 M LLL cic Thora LLL 48 63 10 84% 9 0 100% 22 60 F cic Cervi UL 60 53 6 89% 8 1 88% 23 55 M cal Cervi RUL 8 54 34 37% 10 0 100% 24 68 F cal Thora LLL 12 63 43 32% 10 8 20% 25 50 F cic Cervi RUL 36 33 24 27% 10 5 50% 26 62 F cal Cervi RUL 72 62 37 40% 10 5 50% 27 49 F cal Thora RLL 15 60 10 83% 10 4 60% 28 45 F cic Thora RLL 48 56 19 66% 10 3 70% 29 38 M cic LUL + Cervi 36 59 35 41% 10 5 50% 30 36 F RUL cal Thora LL 30 56 4 93% 10 5 50% 31 34 F cic Thora LLL 72 44 13 70% 8 2,4 70% 32 63 M cic Thora 50 M LL 180 46 8 83% 8 4 50% cic 33 RUL: Right Upper Limb; LUL: Left Upper Limb; UL: Upper Limbs; RLL: Right Lower Limb; LLL: Left Lower Limb; LL: Lower Limbs. 45
M
LL
36
A
CC E
PT
ED
M
A
N
U
SC R
IP T
16
Table 2. Baseline characteristics Complete years of age Mean Minimum Maximum
Pain location (%) Superior extremities Inferior extremities Thoracic region
13 (39,39) 19 (57,57) 1 (3,03)
Duration of pain before SCS* Whole months (SD)
52 (± 37)
N
M
Table 3. Pain Disability Index (PDI)
13 (39,39) 20 (60,60)
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Electrode implantation level (%) Cervical spine Thoracic spine SCS* = Spinal Cord Stimulation
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11 (33,33) 22 (66,66)
U
Gender (%) Male Female
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48,08 23 68
Postoperative Symptom Period Mean Reduction (SD) Percentage
P value (<0.05)
8,545 (1,257)
3,333 (1,964)
61%
<0.0001
8,485 (1,598)
3,212 (2,520)
62%
<0.0001
Social activity
8,061 (1,613)
2,485 (2,134)
69%
<0.0001
Occupation
8,970 (1,466)
4,091 (2,656)
54%
<0.0001
Sexual behavior
6,455 (2,618)
2,152 (2,105)
67%
<0.0001
Self-care Life-support activity
7,121 (2,266)
2,091 (1,764)
71%
<0.0001
7,364 (2,580)
2,030 (1,817)
72%
<0.0001
Total PDI Score
55 (8,696)
18,909 (11,589)
65%
<0.0001
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Family/home responsibilities
ED
Preoperative Period Mean (SD)
A
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Recreation
Table 4. Medical system expenses.
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U
Special Materials
Implantation - Laminectomy BRL (R$) USD ($)* R$ 3.353,36 $ 1.016,16 R$ 1.676,68 $ 508,08 R$ 1.777,59 $ 538,67 03 days R$ 2.208,00 $ 669,09 R$ 2.500,00 $ 757,57 R$ 2.500,00 $ 757,57 R$ 1.000,00 $ 303,03 Complete neurostimulator Electrode + Disposable extension device + Surgical field + Surgical field R$ 18.861,00 $ 5.715,45 R$ 72.768,00 $ 22.050,90 R$ 36.469,39 $ 11.051,31 R$ 87.783,63 $ 26.601,07 Considering USD $1 equivalent to BRL R$3,30.
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Medical fees Neurosurgeon Surgeon assistants Anesthesiologist Hospital fees Room (charge per day) Taxes and services Material and Medication Exams
Trial - Percutaneous BRL (R$) USD ($)* R$ 2.280,59 $ 691,08 R$ 1.140,29 $ 345,54 R$ 1.035,51 $ 313,79 07 days R$ 5.152,00 $ 1.561,21 R$ 5.000,00 $ 1.515,15 R$ 2.000,00 $ 606,06 R$ 1.000,00 $ 303,03
A
CC E
PT
ED
M
A
N
Total:
S0303-8467(18)30228-2 https://doi.org/10.1016/j.clineuro.2018.06.014 CLINEU 5057
To appear in:
Clinical Neurology and Neurosurgery
Received date: Revised date: Accepted date:
10-4-2018 1-6-2018 9-6-2018
Please cite this article as: Risson EG, Serpa AP, Berger JJ, Koerbel RFH, Koerbel A, Spinal Cord Stimulation In The Treatment Of Complex Regional Pain Syndrome Type 1: Is Trial Truly Required?, Clinical Neurology and Neurosurgery (2018), https://doi.org/10.1016/j.clineuro.2018.06.014 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Spinal Cord Stimulation In The Treatment Of Complex Regional Pain Syndrome Type 1: Is Trial Truly Required?
Authors names and affiliations: Erica Garbin Risson (Risson EG) 1, Ana Paula Serpa (Serpa AP) 1, Jéssica Jacques Berger
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(Berger JJ) 1,
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Renata Fabiola Heil Koerbel (Koerbel RFH) 2, Andrei Koerbel (Koerbel A) 3*
1
Department of Medicine, University of Joinville Region, Joinville, Brazil.
2
Department of Intraoperative Monitoring – Neurological and Neurosurgical Clinic of
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Department of Neurosurgery – Neurological and Neurosurgical Clinic of Joinville.
A
3
U
Joinville.
M
Research conducted at the Neurological and Neurosurgical Clinic of Joinville and
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attributed to the Medical Department of the University of Joinville Region
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(UNIVILLE), Joinville, Santa Catarina, Brazil.
*Corresponding
author: Andrei Koerbel, M.D., PhD
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Plácido Olímpio de Oliveira, 1244 - Anita Garibaldi, Joinville, Santa Catarina, Brazil 89202165.
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E-mail: [email protected]
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Highlights
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There is no real need for the percutaneous electrode implant test preceding the permanent implantation of the neurostimulator in patients with Complex Regional Pain Syndrome (CRPS) type 1. The surgeries are performed under intraoperative tests for precise location of the spinal cord electrode implantation. The treatment was effective in pain control and disability reduction in the cases included in this study.
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ABSTRACT
U
Objective: Spinal cord stimulation has been proven highly effective in the treatment of
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Complex Regional Pain Syndrome (CRPS). The definitive implantation of a
A
neurostimulator is usually preceded by a therapeutic test (trial), which has the purpose of
M
identifying whether the patient would respond positively to neuromodulation or not. The present study aims to analyze the surgical results of spinal cord stimulation in type 1
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CRPS patients who have not undergone trial. Patients and Methods: From January 2011 to August 2017, 160 patients underwent
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implantation of spinal cord neurostimulator. Out of that total number of surgeries, 33
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patients were unequivocally diagnosed with type 1 Complex Regional Pain Syndrome and selected for this study. The efficacy of the surgical procedure concerning pain improvement was analyzed through the application of the Pain Disability Index and the
A
Visual Analog Pain Scale. Results: The mean sample age was 48,08 years. The majority of the study subjects were female (66,66%). In respect to the Pain Disability Index, a 65% improvement in disability was observed subsequently to the neurostimulator implantation; in addition, the means of the scores for preoperative and postoperative periods were, respectively, 55 ± 8.69 (p
<0.0001) and 18.90 ± 11.58 (p <0.0001). Regarding the Visual Analogue Scale, the mean pain in the preoperative period was 9.43 ± 0.77 (p <0.0001), while the mean in postoperative period was 2.86 ± 2.08 (p <0.0001). Thus, an average reduction of 70% of painful symptoms was observed after the surgical procedure. Conclusion: Implantation of a spinal cord neurostimulator presented significant
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improvement in pain and disability of patients with type 1 CRPS in all cases. These results
were obtained following the criteria: 1) patients presenting unequivocal diagnosis of type
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1 CRPS; 2) submitted to constant current spinal cord neurostimulator implant; 3)
underwent intraoperative tests for precise location of the spinal cord electrode implantation. Therefore, it is possible to suggest that a trial may be unnecessary in that
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subgroup of patients. Further studies would be required to confirm these findings.
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Keywords: Chronic Pain, Complex Regional Pain Syndromes, Pain Management, Reflex
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INTRODUCTION
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Sympathetic Dystrophy, Spinal Cord Stimulation, Treatment Outcome.
Chronic pain syndromes have numerous etiologies and diverse forms of symptom
presentations; consequently, they were assorted and classified according to these
A
characteristics. One of these syndromes is the Complex Regional Pain Syndrome (CRPS), a chronic pain condition that more commonly affects the extremities, although it can affect other regions of the body [1,2,3]. The condition usually occurs after soft tissue or nerve trauma or lesion; pain is described as persistent and disproportional to the triggering factor. The painful stimuli are also associated with localized autonomic dysfunction,
which leads to temperature variation of the affected area, abnormal sudomotor activity, hyperesthesia, edema, altered nail growth, and changes in skin color [4,5,6,7]. CRPS is divided into Type 1 and Type 2, which diverge as to the pain trigger mechanism. Type 1 corresponds to Reflex Sympathetic Dystrophy: a complex pain syndrome in which nerve lesions cannot be identified. Type 2 - previously known as
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causalgia -, on the other hand, may reveal a nerve lesion as a trigger for the pain stimuli [3,5,6,7,8]. Despite the separation, both share the same set of symptoms and treatments.
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Moreover, both conditions are highly debilitating and may cause progressive incapacity and a negative impact on the life quality of these patients [6].
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Conducting a therapeutic test prior to permanent implantation of the
N
neurostimulator is a common practice [6]. Two surgeries are necessary for experimental
A
stimulation and require the patient to remain connected to an extracorporeal
M
neurostimulation system for a variable period. The purpose of this practice is to predict whether the response to the treatment will be favorable in the postoperative period
ED
[9,10,11].
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Type 1 CRPS has been associated with a better prognosis after treatment with spinal cord stimulation than the Type 2 and further conditions treated by the same method
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[12,13].
The authors' experience over the years has shown that the results obtained with
A
spinal cord stimulation for patients suffering from type 1 CRPS are remarkably positive, producing superior results in comparison to other disorders. Thus, the authors developed a study on this specific subgroup of patients, aiming to determine the results of implanting the spinal neuromodulation system without previous trial, by performing exclusively
intraoperative tests while the patient is conscious in order to ensure correct electrode positioning.
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PATIENTS AND METHODS
From January 2011 to August 2017, among the total amount of patients referred
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to the senior author (Andrei Koerbel) at the Neurological and Neurosurgical Clinic of
Joinville for chronic pain treatment, 160 underwent implantation of spinal cord
U
neurostimulator. Out of that total number of surgeries, 33 patients were unequivocally
N
diagnosed with type 1 Complex Regional Pain Syndrome and selected for this study. All
A
patients with chronic pain of other etiologies and those who refused to participate or to
M
sign the informed consent forms were excluded from the study. Type 1 CPRS diagnosis was established whenever there was localized autonomic
ED
dysfunction associated with the distinct presence of two or more pain criteria symptoms,
PT
as follows: temperature changes on the affected area; abnormal sudomotor activity; hyperesthesia; edema; skin color changes; or change in tropism and nail growth.
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The existence of nerve damage as an etiological factor established the condition
as type 2, regardless of the presence of any of the CRPS pain criteria symptoms.
A
Therefore, those patients were excluded from the study. All selected patients were refractory to clinical treatment, physical therapy, and
other available therapies, and had at least 6 months of progression. All patients were submitted to preoperative psychological assessment.
The surgeries were performed with the painful area facing superiorly as the patient was set in lateral decubitus. The patients were submitted to assisted local anesthesia associated with intermittent sedation during the procedures. All subjects underwent intraoperative tests and insertion of an implantable electrode by laminectomy. Every patient underwent a constant current spinal cord neurostimulator implantation, produced
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by St. Jude.
In cases of cervical electrode implantation, the Suguita cranial fixation system was
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used. The patients underwent sedation during the mini laminectomy and while the incision was prepared for the generator implantation. The selected area for the implant
U
was prepared on the same side of the pain (located superiorly according to the lateral
N
decubitus). The infraclavicular region was assigned to cervical electrodes and the
A
abdominal area to thoracic electrodes. The electrodes were inserted into the subcutaneous
M
tissue, connecting the two incisions (one over the spine and one over the generator implant area).
ED
During surgery, after placing the electrode on the desired spinal cord epidural area,
PT
the patient was awakened. Intraoperative tests were performed to select the spinal cord area that allowed adequate coverage of stimuli in regions enduring type 1 CRPS
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symptoms. After locating the area, the electrodes were fixated and the tests were repeated. Following confirmation of the correct positioning of the electrodes, the patient was again sedated until the end of the procedure – which encompassed the generator implantation
A
and the closure by planes of both incisions. Some patients have implanted devices with Burst stimulation. However, they were not activated in the present research to avoid study bias, since some patients do not have devices containing this option. Therefore, only tonic stimulation was
used in the treatment of these patients during the study. New high frequency stimulation was not tested in this research. The impact of spinal cord stimulation on pain reduction was analyzed through the application of the Pain Disability Index (PDI) and the Visual Analogue Scale (VAS). Both questionnaires were applied in two identical copies. The first copy referred to the
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patient's condition in the preoperative phase. The second copy was answered according to the condition of the patient under neuromodulation treatment, ranging from 6 to 65
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months postoperatively.
The Pain Disability Index (PDI) is a validated tool that allows measuring the
U
impact of chronic pain and the limitations it brings to daily activities. Seven categories of
N
daily tasks were evaluated: family and home responsibilities, recreation, social activity,
A
occupation, sexual behavior, self-care, and life-support activities (eating, sleeping). To
M
each of these domains is assigned a score varying from 0-10; 0 corresponds to no disability, while 10 means that pain completely prevented the performance of such
ED
activity. The sum of the scores produces an index ranging from 0-70 - the higher the
PT
index, the greater the disability caused by the painful symptoms. The Visual Analogue Scale (VAS) was applied in order to estimate the pain
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intensity of the study subjects. It is a scale ranging from 0 to 10: 0 means total absence of pain and 10 represents the maximum pain level that the patient is able to bear.
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In respect to the questionnaire, the answers regarding the period preceding the
neurostimulator implantation were compared to those concerning the postoperative period (the moment when this study took place). Thus, we attempted to identify whether neurostimulation improved the appraised parameters.
The quantitative variables were analyzed by the calculation of means and standard deviations. The level of statistical significance adopted was 5% (p <0.05) and it was measured using Student's T-Test.
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RESULTS Thirty-three CRPS patients who were refractory to clinical treatments met the
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inclusion criteria. The mean age of participants was 48,08 years, varying from 23 to 68
years of age. The majority of them were female (66,66%). Table 1 displays the individual
N
baseline characteristics of the subjects of this study.
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characteristics of the patients and their results following treatment. Table 2 exhibits the
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Regarding the Pain Disability Index, the means of the scores for preoperative and
M
postoperative periods were, respectively, 55 ± 8.69 (p <0.0001) and 18.90 ± 11.58 (p <0.0001). Therefore, a 65% disability improvement was observed after the
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neurostimulator implantation.
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Table 3 demonstrates the variations found for each parameter studied. It indicates a significant attenuation of the disability related to the pain symptomatology in all the
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categories evaluated, suggesting an overall improvement in the quality of life of these patients. The factor that showed the greatest disability reduction was life-support activity, in which it was possible to confirm a 72% improvement in disability (p <0.0001). On the
A
other hand, the lowest disability reduction parameter was occupation, with a 54% symptom decrease (p <0.0001). Concerning the Visual Analogue Scale, the mean pain score in the preoperative and postoperative periods were, respectively, 9.43 ± 0.77 (p <0.0001) and 2.86 ± 2.08 (p
<0.0001). Consequently, mean reduction of 70% in the score attributed to the painful symptoms was observed after the surgical procedure. All patients remain under therapy, despite follow-up over several years in most cases. In all circumstances, the temporary suspension of neurostimulation through remote control shutdown produced a recurrence of the symptoms and the need for treatment
IP T
reactivation. Non-rechargeable generators were replaced by rechargeable generators in
SC R
cases of battery termination.
In respect to postoperative complications, infection rate and new-onset neurological deficits were 0%.
U
New electrode replacement procedures were required in 3 patients with electrode
A
PT
DISCUSSION
ED
M
occurred in any of these new surgeries.
N
dysfunction throughout their respective treatments. No postoperative complications
The pathophysiological mechanisms involved in CRPS are still uncertain. It is
CC E
believed that the interaction of several aspects may be necessary for this syndrome to develop [7,14]. These include factors of genetic and psychological origin, changes in the
A
level of inflammatory mediators and circulating catecholamines, phenomena of central and peripheral sensitization, changes in cutaneous innervation and neuronal plasticity [14,15]. In the general population, it is estimated that less than 200,000 people in the US and 154,000 in Europe are affected by CRPS. Apparently, this incidence is higher after
fractures, ranging from 3.8-7% [6]. The prevalence is higher in females and the incidence is higher from 50 to 70 years of age [7,15]. In the present study, we also observed a greater frequency of CRPS in females. The mean age was 48,08 years, and although the incidence is more common in the aforementioned age range, this study presented 15 patients (45,45% of the sample) under 50 years of age.
IP T
The Budapest criteria [16] for CRPS encompass the diagnosis of a pain continuous and disproportionate to the triggering event, including at least one
SC R
symptom reported in three of the four categories: - Sensory – hyperalgesia and/or allodynia.
U
- Vasomotor – temperature irregularity and/or skin color alterations/asymmetry.
N
- Sudomotor/oedema – local oedema and/or sweating variations/asymmetry.
A
- Motor/trophic – reduced range of motion and/or motor dysfunction (tremor,
M
dystonia, weakness) and/or trophic modifications (nail, skin, hair). No patient was included in our present study without presenting visible
ED
alteration at the moment of the evaluation. Those alterations refer to the categories aforementioned. In addition, we considered two or more symptoms sufficient to
PT
raise the hypothesis of CRPS. Furthermore, any other possible causes of chronic
CC E
pain were excluded in these patients.
There is a large arsenal of medications that may provide pain relief. These include
A
corticosteroids - most commonly used in the acute phase -, analgesics, antidepressants, and anticonvulsants such as pregabalin, among other drugs available on the market [6,7,15,17]. However, because of its complexity, CRPS is one of the most difficult chronic pain conditions for the achievement of a satisfactory treatment [14].
In cases of pain refractory to the previously mentioned treatments or of greater complexity, further invasive measures are taken after a careful selection. Sympathectomies have been performed with frustrating long-term results [6,18]. Despite several therapies developed and tested during their treatment, cases presenting more than 6 to 12 months of CRPS evolution tend to fail most of the treatments
IP T
described. The development of spinal cord stimulation brought significant control of the
SC R
symptoms in cases that had failed the aforementioned CRPS treatments [9,17,19,20].
The spinal cord stimulation system consists of an implantable electrical current generator, associated with electrodes that are inserted into the epidural space [8,10,11]. It
U
acts through low-voltage electrical impulses on the conducting pathways of painful
N
stimuli in order to block them [21,22,23,24].
A
The function of these stimuli is to alter the action potential of neuronal cells and
M
to influence the local neurochemistry, inducing or inhibiting the secretion of some
ED
neurotransmitters. Furthermore, if the appropriate voltage and frequency are applied, it is possible to block the conduction of painful stimuli through the stimulation of inhibitory
PT
central circuits and the generation of the paresthetic sensation [21, 22,23,24].
CC E
The treatment of pain syndromes through the implantation of the neurostimulator presents numerous indications and its effectiveness has been already proven [6,25,26,27,28,29]. Moreover, there is evidence that the long-term cost-effectiveness of
A
spinal cord stimulation is superior to that of conventional drug therapies, decreasing health systems expenditure [30]. Complex Regional Pain Syndrome (CRPS) is a rare phenomenon, being more common in women, as also observed in the present study [6,7,15].
Complex Regional Pain Syndrome type 1 is a condition that manifests great refractoriness to conventional treatments. The delicate handling of this disorder is evidenced in many studies. This difficulty is due to the pathophysiological complexity of this dysfunction and the various mechanisms involved. The lack of knowledge about this condition also leads to late diagnosis, frustrating approaches,
IP T
and inadequate treatment. Considering this scenario, spinal neurostimulation has been gaining space in the control of this pathology [6,11,19,21, 31,32,33,34].
SC R
In a 2003 systematic review of spinal cord neurostimulation of complex
regional pain syndromes, Grabow TS [31] et al had already presented evidence suggesting that this was an effective pain management treatment in patients who did
U
not respond to conservative measures. Kemler et al [12] further displayed data of
N
improvement in pain and quality of life of CRPS patients treated with
M
patients to neurostimulation once more.
A
neurostimulation. Gopal et al [37], in 2016, attested the positive response of these
ED
A prospective cohort was carried out by Geurts et al. [17] and published in 2012: an 11-year research including an "n" higher than the one presented in our
PT
study. Even with long-term follow-up, and acknowledging interventions due to longterm complications, 63% of the patients still maintained painful symptoms after this Additionally, they reported at least 30% improvement in symptoms.
CC E
period.
Considering the difficulty in obtaining an effective treatment of CRPS, these results
A
are important. However, other studies should be carried out. Even though the number of articles regarding this subject is limited, there is
solid evidence of the benefit of spinal neurostimulation in the CRPS treatment. In addition, daily clinical practice demonstrates improvement in disability and quality of life of patients submitted to neurostimulation.
Regarding the operative technique used in this study, the patients were instructed preoperatively on how they should behave while awakening and answering to the intraoperative tests. They were sedated with propofol until the surgical approach was performed. In our experience, the patients have been able to cooperate properly during the surgeries. As the procedures are carried out under
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intraoperative tests, the main goal is to find the best location for the implant on the
spinal cord according to the painful area. This technique increases the surgical time
SC R
and the required efforts from the patients and surgical team. Thus, any potential
lead migration would be a very undesirable complication after this meticulous, timeconsuming endeavor. Epidural paddle leads can provide wider covers on the spinal
U
cord in very stable positions. Furthermore, the chances of migration are minimal
N
when paddle leads are used and fixed by small laminectomies. Therefore, we prefer
A
this approach instead of percutaneous techniques.
M
The performance of a therapeutic test (trial) prior to the permanent implantation
ED
of the neurostimulator aims to increase the chances of a satisfactory treatment result [6]. The test consists of temporary implantation of electrodes associated to an extracorporeal
PT
stimulus generator. Throughout the test period, it is possible to assume whether the response to the treatment will be favorable. During periods of percutaneous stimulation
CC E
tests, a few days are reserved for stimuli regulation in order to optimize pain management [9,10,11].
A
However, there is no evidence that this practice – trial – can truly benefit the
patients in all cases. Furthermore, the definitive implant increases treatment costs – as it requires a longer hospitalization period, a two-step procedure, and the disposal of used materials [35,36,37,38,39]. In addition, the use of an external device, even if temporary, can create an entry for infection. Infections can greatly increase therapeutic costs, as they
require antibiotic therapy, explant of high-cost implanted systems and increase patient risks. Traditional two-stage surgery was associated with an infection rate of up to 8% [40]. The intraoperative therapeutic test technique showed much lower rates, reaching total absence of infection [37]. The patients submitted to the present study - implanted without previous trial - did not present any case of infection.
IP T
Migration of the catheter is also a frequently cited complication. In conventional surgery, the reported incidence is 10%, whereas in procedures without therapeutic test,
SC R
the incidence was 2.53% [37].
The major reason for indicating the percutaneous preoperative test, in the
U
literature, is to identify which patient would benefit from the spinal cord stimulation
N
therapy. Nevertheless, it is known that a considerable percentage of the cases treated with
A
spinal cord stimulation may improve in the first months or years postoperatively and –
M
using neuromodulation from medium to long-term - progress to pain control resistance.
doubt its real benefit.
ED
These patients would not be identified in the trial – hence another argument to put in
PT
The objective of the present study was to analyze the real need for the percutaneous electrode implant test preceding the permanent implantation of the
CC E
neurostimulator. This objective was explored through the observation of the impact of spinal cord stimulation in improvement of pain and decrease of disability in patients with
A
type 1 CRPS. In the literature review, which included databases such as BIREME and PubMed, we did not find articles that approached the subject with the same focus, or that used the same tools as we did in our study. This was a limiting factor, given the impossibility of comparison.
In respect to the reduction of painful symptoms, however, studies that analyzed spinal cord stimulation as a treatment for chronic pain, similarly expressed around 50% of symptom improvement [12,17,26,28,40,41]. The present study determined a 70% reduction in symptoms intensity. In all cases - except for one - the pain improvement was remarkable. The only
IP T
exception was patient number 25, table 1. Although they stated a reduction of only 20% in the VAS, the patient considers the pain much less intense in comparison to the period
SC R
preceding the neurostimulator implantation. Moreover, this patient describes that they “could not live without spinal cord stimulation anymore”. Thus, if a trial had been
U
performed in this case, the patient would have gotten the stimulator implanted
N
nonetheless.
A
Regarding the parameters analyzed through the Pain Disability Index, there was a
M
reduction of more than 60% in disability in almost all of the studied domains. The parameter with the lowest disability reduction was occupation, which displayed a 54%
ED
reduction. We believe that the reduced impact in the occupation category occurred due to
PT
some of the patients’ removal from their labor activities, given the painful symptoms prior to the surgical procedure.
CC E
Findings in some domains, especially those concerning self-care, life-support
activities and social activities, expressed a greater than 65% reduction in disability. The
A
total questionnaire score displayed a 65% reduction of disability when comparing the preoperative and postoperative period. Such findings clearly demonstrate the effectiveness of neurostimulation and reinforce that trial is not necessary in these specific cases.
In our study, we did not separately report mild adverse effects such as painful incision site, battery discomfort, and others. Even though these adverse effects were not individually analyzed in the presented data, their impact on the satisfaction rate of SCS implant could be indirectly measured by the Pain Disability Index (PDI) and the Visual Analogue Scale (VAS). Had these adverse effects influenced negatively
IP T
the SCS treatment results, they would be indirectly captured in the scale and index cited. Although we agree that these mild adverse effects are important issues, we
SC R
believe that analyzing them independently would not change the main goal of this work. Since these symptoms cannot be predicted by performing a trial, their
existence could not have changed the decision of implanting or not a definitive
U
device.
N
Part of the favorable results may be related to the thorough CRPS diagnosis. The
A
criteria were applied and combined with the presence of autonomic signs in the anamnesis
M
and physical examination of patients so that the CRPS diagnosis could be established.
ED
Furthermore, careful application of the intraoperative therapeutic test and the type of neurostimulator system implanted may also influence the results. It should be intently
PT
observed that all patients treated in this study had an unequivocal diagnosis of type 1 CRPS. The authors did not analyze neurostimulator implants in patients with a
CC E
presumptive diagnosis of type 1 CRPS. All subjects selected for this study had typical CPRS symptoms, an absence of nerve damage triggering the condition, and two or more
A
distinct dysautonomic symptoms. Moreover, all patients underwent constant current spinal cord stimulator implantation. Kemler et al. describes that in his carefully enrolled cases of chronic reflex sympathetic dystrophy, that after test-stimulation 12 from 36 patients did not have permanent implantation [12]. Although the authors cited in the introduction of their
study that chronic reflex sympathetic dystrophy is related to type 1 CRPS, their diagnose criteria for inclusion in their study was that of CRPS, not specifically type 1. Their exclusion criteria included current or previous neurologic abnormalities unrelated to reflex sympathetic dystrophy [12]. They did not mention a nerve lesion as a trigger for the pain stimuli as an excluding factor. That could be the main reason
IP T
for the high incidence of non-responders in their trial. We selected only the
unequivocal type 1 CRPS cases. Despite the division, both conditions share the same
SC R
set of symptoms and treatments. However, the type 2 CRPS patients are known to have considerably poorer responses to spinal cord stimulation. Another difference
between Kemler’s methods and those of the present article was the type of implanted
U
device. The present work used constant current systems, whereas Kemler and
N
colleagues used constant voltage ones. It is not possible to assume that it could have
A
had an impact on the results, but it is worthy of mention. Future studies could focus
M
on this specific issue. Finally, we cannot assure that some of the patients who did not
ED
receive a permanent implant in that study [12] wouldn’t have had some disability reduction and pain relief, had they been operated. Many dysautonomic symptoms
PT
in CRPS improve only after many days or weeks of continuous treatment. Although spinal neuromodulation in several cases does not fully control pain and
CC E
dysautonomic symptoms, in this study symptoms were significantly reduced and the quality of life was considerably improved. Temporary withdrawal of therapy through the
A
cessation of neurostimulation implicated recurrence of symptoms. Thus, every subject in the present article remained under therapy until the end of this study - which corroborates its undoubted benefit to all these patients. Table 4 demonstrates the costs of trials and definitive implants in Brazil. Thus, one can compare the values that could be saved in not performing unnecessary
trials and the expenses of eventual ineffective definitive implants. In Brazil, approximately 2,5 trials could pay one definitive implant. Therefore, further studies including control groups are highly desirable, also regarding an economic point of view.
IP T
CONCLUSION
SC R
Our findings suggest that the treatment was effective in pain control and disability reduction in all cases included in this study, which followed the criteria: 1) patients presenting unequivocal diagnosis of type 1 CRPS; 2) submitted to constant current spinal
U
cord neurostimulator implant; 3) underwent intraoperative tests for precise location of the
N
spinal cord electrode implantation. Therefore, it is possible to suggest that percutaneous
A
electrode trial is dispensable in this subgroup of patients.
PT
ED
the findings of the present study.
M
Further studies including a larger number of patients would be required to confirm
A
CC E
Declarations of interest: none.
REFERENCES
1. Fillingim, R. B., Bruehl, S., Dworkin, R. H., Dworkin, S. F., Loeser, J. D., Turk, D. C., … Wesselmann, U. (2014). The ACTTION-American Pain Society Pain
classifying
chronic
pain
conditions.
Journal
of
Pain,
IP T
Taxonomy (AAPT): An evidence-based and multidimensional approach to 15(3),
SC R
https://doi.org/10.1016/j.jpain.2014.01.004.
241–249.
2. Lee, C., Crawford, C., Teo, L., Spevak, C., Buckenmaier, C. C., Crawford, P., … York, A. (2014). An Analysis of the Various Chronic Pain Conditions Captured in a
U
Systematic Review of Active Self-Care Complementary and Integrative Medicine
N
Therapies for the Management of Chronic Pain Symptoms. Pain Medicine (United
A
States), 15(S1). https://doi.org/10.1111/pme.12357.
M
3. Merskey, H., & Bogduk, N. (2002). Classification of Chronic Pain: Descriptions of
IASP Press.
ED
Chronic Pain Syndromes and Definitions of Pain Terms, (2nd ed., pp. 40-43). Seattle:
Pain
PT
4. Nation Institute of Neurological Disorders and Stroke. NINDS Complex Regional Syndrome
Information
Page.
Retrieved
January
2017
from
CC E
http://www.ninds.nih.gov/disorders/reflex_sympathetic_dystrophy/reflex_sympathet ic_dystrophy.htm.
A
5. Stanton-Hicks, M., Jänig, W., Hassenbusch, S., Haddox, J. D., Boas, R., & Wilson, P. (1995). Reflex sympathetic dystrophy: changing concepts and taxonomy. Pain, 63(1), 127–133. https://doi.org/10.1016/0304-3959(95)00110-E.
6. Bruehl, S. (2015). Complex regional pain syndrome. BMJ (Clinical Research Ed.), 351(2), h2730. https://doi.org/10.1136/bmj.h2730.
7. Cordon, F. C. O., & Lemonica, L. (2002). Síndrome Dolorosa Complexa Regional: Epidemiologia, Fisiopatologia, Manifestações Clínicas, Testes Diagnósticos e Propostas Terapêuticas. Revista Brasileira de Anestesiologia, 52(5), 618–627. https://doi.org/10.1590/S0034-70942002000500013. 8. Poree, L., Krames, E., Pope, J., Deer, T. R., Levy, R., & Schultz, L. (2013). Spinal
IP T
cord stimulation as treatment for complex regional pain syndrome should be
considered earlier than last resort therapy. Neuromodulation, 16(2), 125–141.
SC R
https://doi.org/10.1111/ner.12035.
9. Song, J. J., Popescu, A., & Bell, R. L. (2014). Present and potential use of spinal cord
http://www.ncbi.nlm.nih.gov/pubmed/24850105.
U
stimulation to control chronic pain. Pain Physician, 17(3), 235–46. Retrieved from
N
10. National Institute for Health and Care Excellence (NICE). Spinal cord stimulation for
M
https://nice.org.uk/guidance/ta159.
A
chronic pain of neuropathic or ischaemic origin. Retrieved January 2016 from
ED
11. Colllet, B., Collins, A., Dickson, D., Elidge, P., Morley, S., Sanderson, K. … Murphy, P. (2009). Spinal cord stimulation for the management of pain: Recommendations for
PT
best clinical practice. In A consensus document prepared on behalf of the British Pain Society in consultation with the Society of British Neurological Surgeons. London:
CC E
The British Pain Society.
12. Kemler, M. A., Barendse, G. A. M., van Kleef, M., de Vet, H. C. W., Rijks, C. P. M.,
A
Furnée, C. A., & van den Wildenberg, F. A. J. M. (2000). Spinal Cord Stimulation in Patients with Chronic Reflex Sympathetic Dystrophy. New England Journal of Medicine, 343(9), 618–624. https://doi.org/10.1056/NEJM200008313430904.
13. Dworkin, R. H., O’Connor, A. B., Kent, J., Mackey, S. C., Raja, S. N., Stacey, B. R., … Wells, C. D. (2013). Interventional management of neuropathic pain: NeuPSIG recommendations. Pain. Elsevier B.V. https://doi.org/10.1016/j.pain.2013.06.004. 14. Bruehl, S. (2010). An update on the pathophysiology of complex regional pain syndrome.
Anesthesiology.
Lippincott
Williams
Wilkins.
IP T
https://doi.org/10.1097/ALN.0b013e3181e3db38.
and
15. Goebel, A. (2011). Current Concepts in Adult CRPS. Reviews in Pain, 5(2), 3–11.
SC R
http://doi.org/10.1177/204946371100500202.
16. Goebel, A., Bisla, J., Carganillo, R., Cole, C., Frank, B., Gupta, R., et. al. (2017). A randomised placebo-controlled Phase III multicentre trial: Low-dose
U
intravenous immunoglobulin treatment for long-standing complex regional pain
N
syndrome (LIPS trial). Efficacy and Mechanism Evaluation, 4(5), 1-82.
A
Appendix 3, Research diagnostic criteria (the ‘Budapest Criteria’) for complex
M
regional pain syndrome. Doi:10.3310/eme04050.
ED
17. Geurts, J. W., Smits, H., Kemler, M. A., Brunner, F., Kessels, A. G. H., & Van Kleef, M. (2013). Spinal cord stimulation for complex regional pain syndrome type I: A
PT
prospective cohort study with long-term follow-up. Neuromodulation, 16(6), 523– 529. https://doi.org/10.1111/ner.12024.
CC E
18. Straube, S., Derry, S., Moore, R. A., & Cole, P. (2013, September 2). Cervico-thoracic or lumbar sympathectomy for neuropathic pain and complex regional pain syndrome.
A
Cochrane Database of Systematic Reviews. John Wiley and Sons Ltd. https://doi.org/10.1002/14651858.CD002918.pub3.
19. Harden, R. N., Oaklander, A. L., Burton, A. W., Perez, R. S. G. M., Richardson, K., Swan, M., … Bruehl, S. (2013). Complex Regional Pain Syndrome: Practical
Diagnostic and Treatment Guidelines, 4th Edition. Pain Medicine, 14(2), 180–229. https://doi.org/10.1111/pme.12033. 20. Slavin, K. V. (2014). Spinal Stimulation for Pain: Future Applications. Neurotherapeutics. Springer New York LLC. https://doi.org/10.1007/s13311-0140273-2.
IP T
21. J.P., P., & Prager, J. P. (2010). What does the mechanism of spinal cord stimulation
tell us about complex regional pain syndrome? Pain Medicine (Malden, Mass.), 11(8),
SC R
1278–1283. https://doi.org/10.1111/j.1526-4637.2010.00915.x. 22. Cukiert, A. (2010). Neuromodulation (pp. 45-140). São Paulo: Alaúde.
23. Taylor, R. S. (2006). Spinal Cord Stimulation in Complex Regional Pain Syndrome
U
and Refractory Neuropathic Back and Leg Pain/Failed Back Surgery Syndrome:
N
Results of a Systematic Review and Meta-Analysis. Journal of Pain and Symptom
A
Management, 31(4 SUPPL.). https://doi.org/10.1016/j.jpainsymman.2005.12.010.
M
24. Moore, D. M. & McCrory, C. (2016). Spinal Cord Stimulation. BJA Education,
ED
16,(8), 258-263. https://doi.org/10.1093/bjaed/mkv072. 25. Turner, J. A., Loeser, J. D., Deyo, R. A., & Sanders, S. B. (2004). Spinal cord
PT
stimulation for patients with failed back surgery syndrome or complex regional pain syndrome: A systematic review of effectiveness and complications. Pain. Elsevier.
CC E
https://doi.org/10.1016/j.pain.2003.12.016.
26. Tesfaye, S., Watt, J., Benbow, S. J., Pang, K. A., Miles, J., & MacFarlane, I. A.
A
(1996). Electrical spinal-cord stimulation for painful diabetic peripheral neuropathy. Lancet, 348(9043), 1698–1701. https://doi.org/10.1016/S0140-6736(96)02467-1.
27. Erdek, M. A., & Staats, P. S. (2003). Spinal-cord stimulation for angina pectoris and peripheral vascular disease. Anesthesiology Clinics of North America. W.B. Saunders. https://doi.org/10.1016/S0889-8537(03)00090-7.
28. Kapural, L., Narouze, S. N., Janicki, T. I., & Mekhail, N. (2006). Spinal cord stimulation is an effective treatment for the chronic intractable visceral pelvic pain. Pain Medicine, 7(5), 440–443. https://doi.org/10.1111/j.1526-4637.2006.00165.x. 29. Burchiel, K. J., Anderson, V. C., Brown, F. D., Fessler, R. G., Friedman, W. A., Pelofsky, S., … Shatin, D. (1996). Prospective, multicenter study of spinal cord
IP T
stimulation for relief of chronic back and extremity pain. Spine, 21(23), 2786–2794. https://doi.org/10.1097/00007632-199612010-00015.
SC R
30. Kumar, K., & Rizvi, S. (2013). Cost-Effectiveness of Spinal Cord Stimulation
Therapy in Management of Chronic Pain. Pain Medicine, 14(11), 1631–1649. https://doi.org/10.1111/pme.12146.
U
31. Grabow, T. S., Tella, P. K., & Raja, S. N. (2003). Spinal cord stimulation for complex
N
regional pain syndrome: an evidence-based medicine review of the literature. The
A
Clinical Journal of Pain, 19(6), 371–83. https://doi.org/10.1097/00002508-
M
200311000-00005.
ED
32. Kapural, L. (2014). Spinal cord stimulation for intractable chronic pain. Current Pain and Headache Reports, 18(4). https://doi.org/10.1007/s11916-014-0406-7.
PT
33. Levy, R. M. (2012). Evidence-Based Review of Neuromodulation for Complex Regional Pain Syndrome: A Conflict Between Faith and Science? Neuromodulation:
CC E
Technology at the Neural Interface, 15(6), 501–506. https://doi.org/10.1111/j.15251403.2012.00531.x.
A
34. Kumar, K., Rizvi, S., & Bnurs, S. B. (2011). Spinal cord stimulation is effective in management of complex regional pain syndrome I: Fact or fiction. Neurosurgery, 69(3), 566–578. https://doi.org/10.1227/NEU.0b013e3182181e60.
35. North, R. B., & Wetzel, F. T. (2002). Spinal cord stimulation for chronic pain of spinal origin: a valuable long-term solution. Spine, 27(22), 2584–2591; discussion 2592. https://doi.org/10.1097/01.BRS.0000032132.99599.78. 36. Weinand, M. E., Madhusudan, H., Davis, B. & Melgar, M. (2003). Acute vs.
Journal of the International Neuromodulation Society. 6(1), 15-9.
IP T
Prolonged Screening for Spinal Cord Stimulation in Chronic Pain. Neuromodulation:
37. Gopal, H., Geraldo, J. F. & McCrory, C. (2016). Spinal cord stimulation for FBSS
SC R
and CRPS: A review of 80 cases with on-table trial of stimulation. Journal of Back and Musculoskeletal Rehabilitation, 29(1), 7–13. DOI:10.3233/BMR-150608.
38. Kumar, K., Buchser, E., Linderoth, B., Meglio, M. and Van Buyten, J. (2007),
U
Avoiding Complications From Spinal Cord Stimulation: Practical Recommendations
N
From an International Panel of Experts. Neuromodulation: Technology at the Neural
A
Interface, 10: 24-33. https://doi:10.1111/j.1525-1403.2007.00084.x.
M
39. Follett, K. A., Boortz-Marx, R. L., Drake, J. M., DuPen, S., Schneider, S. J., Turner,
delivery and
ED
M. S., & Coffey, R. J. (2004, June). Prevention and management of intrathecal drug spinal
cord
stimulation
system
infections.
Anesthesiology.
PT
https://doi.org/10.1097/00000542-200406000-00034. 40. Kumar, K., Taylor, R. S., Jacques, L., Eldabe, S., Meglio, M., Molet, J., … North, R.
CC E
B. (2007). Spinal cord stimulation versus conventional medical management for neuropathic pain: A multicentre randomised controlled trial in patients with failed
A
back
surgery
syndrome.
Pain,
132(1–2),
179–188.
https://doi.org/10.1016/j.pain.2007.07.028.
41. Calvillo, O., Racz, G., Didie, J., & Smith, K. (1998). Neuroaugmentation in the treatment of complex regional pain syndrome of the upper extremity. Acta Orthopaedica Belgica, 64(1), 57–63.
TABLES
UL
12
2
54
F
LUL
36
3
52
M
RLL
60
4
23
F
RUL
5
56
M
RLL
6
45
F
LUL
9
7
44
M
LLL
48
36
M
RLL + LLL
36
50
F
RUL
60
36
PT
72
A
9
CC E
8
SC R
U
N
F
81%
A
53
43
13
70%
9
3
67%
56
22
61%
9
2
78%
68
22
68%
10
5
50%
45
3
93%
9,5
1
89%
43
26
40%
8
4
50%
58
29
50%
10
2
80%
53
19
64%
8
2
75%
67
27
60%
10
5
50%
64
13
80%
10
3
70%
49
20
59%
10
2
80%
65
32
51%
10
5
50%
55
3
95%
10
0
100%
Cervi cal Cervi cal Thora cic Cervi cal Thora cic Cervi cal Thora cic Thora cic Cervi cal Cervi cal Thora cic Thora cic Thora cic
ED
1
Elect Disabili Pain rode ty Preope Postope Preope Postope improv impl improv rative rative rative rative ement antat ement PDI PDI VAS VAS percent ion percent age level age
M
Length of the painful Pain period Pati Ag Gen distribut before ent e der ion surgery (complet e months)
IP T
Table 1. Individual Characteristics and Results
10
61
F
LUL
24
11
41
F
LLL
36
12
38
F
RLL
96
13
53
F
RLL
96
52
10
10
0
100%
14 15
51 51
M
UL
120
Cervi cal
44
4
91%
9
0
100%
F
Left hemithor ax
60
Thora cic
70
7
90%
10
1
90%
Thora 54 10 81% 8 0 100% cic Thora LL 120 45 19 58% 10 0 100% 17 51 F cic Cervi RUL 12 60 35 42% 10 5 50% 18 49 F cal RLL Thora 48 49 32 35% 10 5 50% 19 54 F +LLL cic Thora LLL 24 61 9 85% 10 3 70% 20 36 F cic RLL + Thora 48 65 42 35% 9 5 44% 21 34 M LLL cic Thora LLL 48 63 10 84% 9 0 100% 22 60 F cic Cervi UL 60 53 6 89% 8 1 88% 23 55 M cal Cervi RUL 8 54 34 37% 10 0 100% 24 68 F cal Thora LLL 12 63 43 32% 10 8 20% 25 50 F cic Cervi RUL 36 33 24 27% 10 5 50% 26 62 F cal Cervi RUL 72 62 37 40% 10 5 50% 27 49 F cal Thora RLL 15 60 10 83% 10 4 60% 28 45 F cic Thora RLL 48 56 19 66% 10 3 70% 29 38 M cic LUL + Cervi 36 59 35 41% 10 5 50% 30 36 F RUL cal Thora LL 30 56 4 93% 10 5 50% 31 34 F cic Thora LLL 72 44 13 70% 8 2,4 70% 32 63 M cic Thora 50 M LL 180 46 8 83% 8 4 50% cic 33 RUL: Right Upper Limb; LUL: Left Upper Limb; UL: Upper Limbs; RLL: Right Lower Limb; LLL: Left Lower Limb; LL: Lower Limbs. 45
M
LL
36
A
CC E
PT
ED
M
A
N
U
SC R
IP T
16
Table 2. Baseline characteristics Complete years of age Mean Minimum Maximum
Pain location (%) Superior extremities Inferior extremities Thoracic region
13 (39,39) 19 (57,57) 1 (3,03)
Duration of pain before SCS* Whole months (SD)
52 (± 37)
N
M
Table 3. Pain Disability Index (PDI)
13 (39,39) 20 (60,60)
A
Electrode implantation level (%) Cervical spine Thoracic spine SCS* = Spinal Cord Stimulation
SC R
11 (33,33) 22 (66,66)
U
Gender (%) Male Female
IP T
48,08 23 68
Postoperative Symptom Period Mean Reduction (SD) Percentage
P value (<0.05)
8,545 (1,257)
3,333 (1,964)
61%
<0.0001
8,485 (1,598)
3,212 (2,520)
62%
<0.0001
Social activity
8,061 (1,613)
2,485 (2,134)
69%
<0.0001
Occupation
8,970 (1,466)
4,091 (2,656)
54%
<0.0001
Sexual behavior
6,455 (2,618)
2,152 (2,105)
67%
<0.0001
Self-care Life-support activity
7,121 (2,266)
2,091 (1,764)
71%
<0.0001
7,364 (2,580)
2,030 (1,817)
72%
<0.0001
Total PDI Score
55 (8,696)
18,909 (11,589)
65%
<0.0001
PT
Family/home responsibilities
ED
Preoperative Period Mean (SD)
A
CC E
Recreation
Table 4. Medical system expenses.
IP T
U
Special Materials
Implantation - Laminectomy BRL (R$) USD ($)* R$ 3.353,36 $ 1.016,16 R$ 1.676,68 $ 508,08 R$ 1.777,59 $ 538,67 03 days R$ 2.208,00 $ 669,09 R$ 2.500,00 $ 757,57 R$ 2.500,00 $ 757,57 R$ 1.000,00 $ 303,03 Complete neurostimulator Electrode + Disposable extension device + Surgical field + Surgical field R$ 18.861,00 $ 5.715,45 R$ 72.768,00 $ 22.050,90 R$ 36.469,39 $ 11.051,31 R$ 87.783,63 $ 26.601,07 Considering USD $1 equivalent to BRL R$3,30.
SC R
Medical fees Neurosurgeon Surgeon assistants Anesthesiologist Hospital fees Room (charge per day) Taxes and services Material and Medication Exams
Trial - Percutaneous BRL (R$) USD ($)* R$ 2.280,59 $ 691,08 R$ 1.140,29 $ 345,54 R$ 1.035,51 $ 313,79 07 days R$ 5.152,00 $ 1.561,21 R$ 5.000,00 $ 1.515,15 R$ 2.000,00 $ 606,06 R$ 1.000,00 $ 303,03
A
CC E
PT
ED
M
A
N
Total: