Spinal cord stimulation in the treatment of refractory painful polineuropathy induced by chemotherapy

Abstracts

JUSTIFICATIVAS E OBJETIVOS: Polineuropatia dolorosa pós-quimioterapia tem sido muitas vezes uma condição refratária ao tratamento clínico conservador. O objetivo deste relato de caso foi mostrar o uso da estimulação medular como técnica alternativa aos métodos convencionais para tratar paciente com quadro doloroso de difícil controle. RELATO DO CASO: Paciente de 72 anos, com polineuropatia dolorosa pós-quimioterapia há mais ou menos dez anos, apresentava dor de forte intensidade (escala analógica visual = 10) em membros inferiores, contínua e diária, apesar do uso de várias medicações específicas para dor neuropática. Foi submetido a implante de eletrodo peridural apresentando melhora significativa das dores (escala analógica visual = 3) e diminuição do uso de medicação. CONCLUSÃO: A estimulação da medula espinhal constitui uma opção terapêutica em pacientes com neuropatia periférica refratária ao tratamento médico convencional quando bem indicada e realizada dentro de critérios estabelecidos.

ANALGESIA; DOR, Crônica

CLINICAL REPORT

Spinal cord stimulation in the treatment of refractory painful polineuropathy induced by chemotherapy^*

Estimulación medular espinal para tratamiento de la polineuropatía dolorosa refractaria inducida por quimioterapia

José Luciano Braun Filho^I; Leandro Mamede Braun, TSA^II

^IDiretor Chefe da CLIMDOR; Titulado na Área de Atuação em Dor AMB/SBA; Membro do Conselho Superior da Sociedade Brasileira para o Estudo da Dor; Diretor da Federação Latino-Americana das Associações para o Estudo da Dor

^IIMembro da CLIMDOR; Anestesiologista Assistente do CET de Anestesia da Universidade Federal de Pernambuco

^{Correspondence to}

SUMMARY

BACKGROUND AND OBJECTIVES: Painful polyneuropathy after chemotherapy is often refractory to conservative clinical treatment. The objective of this report was to demonstrate that spinal cord stimulation is an alternative to conventional methods used in the treatment of patients with pain that is difficult to control.

CASE REPORT: A 72 year old patient with painful polyneuropathy after chemotherapy approximately 10 years ago, presented severe, continuous, daily pain (visual analog scale = 10) in the lower limbs despite the use of several drugs specific for neuropathic pain. An epidural electrode was implanted, with significant improvement in pain (visual analog scale = 3) and reduction in the consumption of medication.

CONCLUSION: Spinal cord stimulation constitutes a therapeutic option in patients with peripheral neuropathy refractory to conventional clinical management when properly indicated and within established criteria.

Key Words: ANALGESIA: spinal cord electric stimulation; PAIN, Chronic: neuropathic, post-chemotherapy.

RESUMEN

JUSTIFICATIVAS Y OBJETIVOS: La polineuropatía dolorosa pos-quimioterapia ha sido en muchas ocasiones una condición refractaria al tratamiento clínico conservador. El objetivo de este relato de caso fue mostrar el uso de la estimulación medular como técnica alternativa a los métodos convencionales para tratar paciente con cuadro doloroso de difícil control.

RELATO DEL CASO: Paciente de 72 años, con polineuropatía dolorosa pos-quimioterapia hace más o menos 10 años, presentaba dolor de fuerte intensidad (escala analógica visual = 10) en miembros inferiores, continua y diaria, a pesar del uso de varias medicaciones específicas para dolor neuropático. Se sometió a implante de electrodo peridural presentando una mejoría significativa de los dolores (escala analógica visual = 3) y una disminución del uso de medicación.

CONCLUSIÓN: La estimulación de la médula espinal constituye una opción terapéutica en pacientes con neuropatía periférica refractaria al tratamiento médico convencional cuando se indica y se realiza dentro de criterios establecidos.

INTRODUCTION

Electrical stimulation of the spinal cord has been used to treat patients with different painful conditions, with varying degrees of success ¹. The first experiences of Shealey, in 1967 and, later, Cook, in 1976, were done by implanting spinal cord stimulation electrodes in patients with incapacitating peripheral vasculopathies. There was an important degree of pain control, as well as improvement in ischemic ulcer cicatrisation ².

The method is based on the gate theory of pain³, in which activation of large diameter afferent fibers, A-b fibers, inhibits painful transmission in small diameter fibers, fibers A-delta, to spinal neurons that project to upper brain centers. Linderoth and Foreman proposed that the antidromic activation of the posterior horn by stimulation of the spinal cord could inhibit the hyperexcitability of neurons sensitized by a peripheral nerve lesion. Besides, spinal and supraspinal structures could also be involved in the analgesia obtained through stimulation of the spinal cord. Since the first cases reported 30 years ago ^6,7, the indications of spinal stimulation have varied, used in different conditions such as post-laminectomy syndrome, complex regional painful syndrome, postherpetic neuralgia, diabetic neuropathy, ischemic pain secondary to vascular disease and angina ^1,8,10. Implantation of electrodes for spinal cord stimulation should be carefully done in selected patients, whose conservative treatment has not been effective. There should be a positive response, with a minimum of 50% relief in the severity of pain during the trial period ¹.

Electrical stimulation of the spinal cord is an interventional technique to manage pain, which involves the implantation of one or more electrodes in the epidural space, their anchorage and positioning, initially for the test period and, posteriorly, with tunnel formation and connection of the electrodes to an implantable generator. Implantation of electrodes in the epidural space for spinal cord stimulation could be done through a laminectomy or percutaneous, through a specific epidural needle. The technique of laminectomy is beyond the scope of this paper. The percutaneous technique is the preferred method for several reasons, such as: 1) it is less aggressive and bloody; 2) does not require general anesthesia; and 3) assures the proper positioning of the electrode, obtaining adequate response of the stimulated area, since the patient remains awake. In this technique, the electrode is positioned, through a needle used to puncture the epidural space via the paramedian approach. The electrode is introduced in the posterior epidural space until the desired level guided by fluoroscopy. An electrical stimulus is, then, delivered in an attempt to cover the desired area with a paresthetic feeling induced by the electrical stimulus. If the patient presents a good response in the trial period, which might last from one to five days, the definitive generator is implanted in the superior gluteal region, where the patient can reach it with his/her dominant hand and, therefore, adjust the parameters by means of a remote control.

Painful peripheral neuropathy after chemotherapy is observed in many patients treated with chemotherapeutic agents for different types of malignant neoplasia, with varying frequency and severity (depending on the drug used, duration of the treatment, and the presence of comorbidities) ^11-14.

Pain is the main complaint in those patients and, many times, it has profound negative effects in the quality of life of patients who have been cured or with increased survival ⁹. The main drugs involved in the genesis of peripheral neuropathy include platinum compounds, alkaloids and taxol. Patients affected by this type of neuropathy have been treated with different types of medication including opioids, anticonvulsants and antidepressants, often without demonstrating satisfactory response. In the case presented here spinal cord stimulation was an effective alternative in pain control.

CASE REPORT

Male patient, 72 years old, retired, right-handed, had a past medical history of renal cancer approximately 10 years before this consultation. At that time, he was treated with nephrectomy associated with adjuvant chemotherapy with vincristine. Approximately 1 year before consultation, after the end of the last course of chemotherapy, he developed pain, mainly in the soles, bilaterally, gradually progressive, characterized by stabbing pain and a burning sensation irradiating to the hips. The patient sought several doctors in different subspecialties from September 2004 on, when his symptoms started, without improvement of the pain. In August 2005, he was referred to our service. At that time, he complained of severe pain (visual analog scale = 10), and had been medicated with 25 mg of amitriptine a day, associated with codeine (90 mg/day), and paracetamol (3 g/day).

A therapeutic regimen with gradually increasing doses of amitriptyline, gabapentin and tramadol up to 50 mg of amitriptyline/day, 2400 mg of gabapentin/day and 400 mg of tramadol/day was instituted. Eventually, increasing doses of methadone, up to 30 mg/d, replaced the tramadol. At that time the patient was also being followed by a psychologist and undergoing physical therapy.

With this treatment, the patient referred only a 30% improvement in pain (visual analog scale = 7). Due to the failure in controlling his symptom pharmacologically and the development of side effects, it was proposed to the patient a trial of spinal cord stimulation, which was instituted after he signed an informed consent.

A test of spinal cord stimulation was scheduled for 5 months after institution of the new therapeutic conservative regimen. Under sterile conditions, patient in ventral decubitus, monitoring and venoclysis, 2 mg of midazolam and 20 µg of fentanyl were administered. Oxygen (3 L.min^-1) was administered by a nasal catheter. After anesthetizing the area of the puncture with lidocaine without vasoconstrictor, a paramedian puncture was performed at the level of L₂, with a 16G Tuohy needle (Figure 1). Proper positioning of the needle in the epidural space was determined by the loss of resistance technique and confirmed by fluoroscopy. An octopolar electrode was introduced in the posterior epidural space and advanced up to the level of T₁₀. After connecting it to an external generator, an electrical stimulus was applied resulting in paresthesia in most of the area affected by pain followed by significant analgesia for 24 hours after beginning stimulation (visual analog scale = 3). After 72 hours, an implantable generator was connected to the octopolar electrode (Genesis, ANS, Inc., plano, TX). The parameters of the generator that had the best results were frequency of 80 hz, pulse amplitude of 300 µs, and voltage between 0 and 4V.

One month after implanting the electrode, the patient referred relief of the pain (visual analog scale = 3), with an important improvement in his quality of life, using the stimulator approximately 18 hours a day and taking amitriptyline, 25 mg, and gabapentin, 900 mg/day. This improvement was maintained three months after the procedure.

DISCUSSION

Post-chemotherapy neuropathy causing neuropathic pain is common in patients treated for a wide scope of malignant neoplasia. Usually, patients develop sensory symptoms, which can start months or years after chemotherapy ¹⁵. It is rarely associated with motor or autonomic dysfunction ^18-20. Sensory symptoms are usually symmetrical and described as dysesthetic paresthesias, electrical shocks, burning or stabbing pain and often present in a "glove" or "boot" distribution ¹⁹.

This case has two important aspects. First, the patient referred an improvement in pain greater than 50% after spinal cord stimulation, which was confirmed by other studies that reported better evolution when a trial test is done before implanting the definitive generator. Second and most important aspect the reduction in the medication needed to control pain and discontinuation of the opioid, with reduction in side effects. The mechanisms responsible for those results are not known, but several hypotheses have been postulated. The influence of the spinal cord stimulation in the modulation of excitatory amino acids in the spinal cord, dorsal root ganglion, activation of supraspinal structures and their control over inhibitory descending pathways are the mechanisms that might be affected by the stimulation of the posterior horns of the spinal cord ^3,21,22.

This report of a case of refractory, painful polyneuropathy, induced by chemotherapy and treated with spinal cord stimulation shows that it can be an important alternative for those patients. However, more studies are needed to validate this result.

REFERENCES

Submitted em 01 de agosto de 2006

Accepted para publicação em 11 de junho de 2007

* Received from Clínica Multidisciplinar de Dor do Recife (CLIMDOR)

• 01. Kumar K, Toth C, Nath RK et al. Epidural spinal cord stimulation for treatment of chronic pain-some predictors of success. A 15-year experience. Surg Neurol, 1998;50:110-121.
• 02. Barolat G Spinal cord stimulation for chronic pain management. Arch Med Res,2000;31:258-262.
• 03. Melzack R, Wall PD Pain mechanisms: a new theory. Science, 1965;150:971-979.
• 04. Holsheimer J Which neuronal elements are activated directly by spinal cord stimulation. Neuromodulation, 2002;5:25-31.
• 05. EJ-Khoury C, Hawwa N, Baliki M et al. Attenuation of neuropathic pain by segmental and supraspinal activation of the dorsal column system in awake rats. Neuroscience, 2002; 112:541-553.
• 06. Shealy CN, Mortimer JT, Reswick JB Electrical inhibition of pain by stimulation of the dorsal columns: preliminary clinical report. Anesth Analg, 1967;46:489-491.
• 07. Shealy CN, Taslitz N, Mortimer JT et al. Electrical inhibition of pain: experimental evaluation . Anesth Analg, 1967;46:299-305.
• 08. Kay AD, McIntyre MD, Macrae WA et al. Spinal cord stimulation: a long-term evaluation in patients with chronic pain. Brit J Neurosurg, 2001;15:335-341.
• 09. Harke H, Gretenkort P, Ladleif HU et al. Spinal cord stimulation in postherpetic neuralgia and in acute herpes zoster pain. Anesth Analg, 2002;94:694-700.
• 10. Alo KM, Holsheimer J New trends in neuromodulation for neuropathic pain. Neurosurgery, 2002;50:690-703.
• 11. Quasthoff S, Hartung HP Chemotherapy-induced peripheral neuropathy. J Neurol, 2002;249:9-17.
• 12. Forsyth PA, Balmaceda C, Peterson K et al. Prospective study of paclitaxel-induced peripheral neuropathy with quantitative sensory testing. J Neuro-Oncol, 1997;35:47-53.
• 13. Holland JF, Scharlau C, Gailani S et al. Vincristine treatment of advanced cancer: a cooperative study of 392 cases. Cancer Res, 1973;33:1258-1264.
• 14. Weiss HD, Walker MD, Wiernik PH Neurotoxicity of commonly used antineoplastic agents. N Engl J Med, 1974;291:127-133.
• 15. Dixon WJ Efficient analysis of experimental observations. Ann Rev Pharmacol Toxicol, 1980;20:441-462.
• 16. Chan AW, MacFarlane IA, Bowsher D et al. Weighted needle pinprick sensory thresholds: a simple test of sensory function in diabetic peripheral neuropathy. J Neurol Neurosurg Psychiatry, 1992;55:56-59.
• 17. Fuchs PN, Campbell JN, Meyer RA Secondary hyperalgesia persists in capsaicin desensitized skin. Pain, 2000;84:141-149.
• 18. Gibson SJ, Polak JM, Katagiri T et al. A comparison of the distributions of eight peptides in spinal cord from normal controls and cases of motor neurone disease with special reference to Onuf's nucleus. Brain Res, 1988;474:255-278.
• 19. Rowinsky EK, Chaudhry V, Cornblath DR et al. Neurotoxicity of Taxol. J Natl Cancer Inst Monogr, 1993;15:107-115.
• 20. Thompson SW, Davis LE, Kornfeld M et al. Cisplatin neuropathy. Clinical, electrophysiologic, morphologic, and toxicologic studies. Cancer, 1984;54:1269-1275.
• 21. Linderoth B, Foreman R Physiology of spinal cord stimulation: review and update. Neuromodulation, 1999;2:150-164.
• 22. Cui JG, O'Connor WT, Ungerstedt U et al. Spinal cord stimulation attenuates augmented dorsal horn release of excitatory amino acids in mononeuropathy via a GABAergic mechanism. Pain, 1997;73:87-95.
• 23. Meyerson BA, Ren B, Herregodts P et al. Spinal cord stimulation in animal models of mononeuropathy: effects of the withdrawal response and the flexor reflex. Pain, 1995;61:229-243.
• 24. Mizobuchi K, Kuwabara S, Tomas S et al. Properties of human skin mechanoreceptors in peripheral neuropathy. Clin Neurophysiol, 2002;113:310-315.
• 25. Nurse MA, Nigg BM Quantifying a relationship between tactile and vibration sensitivity of the human foot with plantar pressure distributions during gait. Clin Biomech, 1999;14:667-672.

Publication Dates

• Publication in this collection
  14 Sept 2007
• Date of issue
  Oct 2007

History

• Accepted
  11 June 2007
• Received
  01 Aug 2006