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Neuropathic pain controlled for more than a year by monthly sessions of repetitive transcranial magnetic stimulation of the motor cortex
Neurophysiologie clinique 34 (2004) 91–95
www.elsevier.com/locate/neucli
ORIGINAL ARTICLE
Neuropathic pain controlled for more than a year by monthly sessions of repetitive transcranial magnetic stimulation of the motor cortex Douleur neuropathique contrôlée pendant plus d’un an par des séances mensuelles de stimulation magnétique corticale transcrânienne répétitive Jean-Pascal Lefaucheur a,*, X. Drouot a, I. Ménard-Lefaucheur a, J.P. Nguyen b a
Service de Physiologie—Explorations Fonctionnelles, CHU Hôpital Henri Mondor, 51 avenue de Lattre de Tassigny, Créteil 94010, France b Service de Neurochirurgie, Hôpital Henri Mondor, Assistance Publique—Hôpitaux de Paris 51 avenue de Lattre de Tassigny, Créteil 94010, France et INSERM U421, Faculté de Médecine de Créteil, France Received 28 October 2003; accepted 9 February 2004 Available online 12 March 2004
KEYWORDS Brachial plexus; Chronic pain; Motor cortex stimulation; Repetitive transcranial magnetic stimulation; Thoracic outlet surgery
MOTS CLÉS Chirurgie du syndrome du défilé thoracique ; Douleur chronique ; Plexus brachial ; Stimulation du cortex moteur ; Stimulation magnétique transcrânienne répétitive
Abstract Neuropathic pain can be controlled by motor cortex stimulation using surgicallyimplanted electrodes in a majority of selected patients. Analgesic effects were also found to result from repetitive transcranial magnetic stimulation (rTMS) of the cortex. We report the case of a woman, in whom drug-resistant peripheral pain was controlled for 16 months by monthly sessions of motor cortex rTMS until a durable pain relief was obtained after surgical implantation of a cortical stimulator. This case illustrates the value of rTMS in helping patients to wait for surgery. © 2004 Elsevier SAS. All rights reserved. Résumé Les douleurs neuropathiques d’une majorité de patients sélectionnés peuvent être contrôlées par une stimulation du cortex moteur utilisant des électrodes implantées chirurgicalement. La stimulation magnétique transcrânienne répétitive (SMTr) du cortex permet également d’obtenir des effets antalgiques. Nous rapportons le cas d’une femme chez qui une douleur périphérique résistant aux médicaments fut contrôlée pendant 16 mois par des séances mensuelles de SMTr du cortex moteur jusqu’à ce qu’un soulagement durable de la douleur soit obtenu après l’implantation chirurgicale d’un stimulateur cortical. Ce cas illustre l’intérêt de la SMTr à aider les patients à attendre la chirurgie. © 2004 Elsevier SAS. All rights reserved.
* Corresponding author. Tel.: +33-1-49-81-26-94; fax: +33-1-49-81-46-60. E-mail address: [email protected] (J.-P. Lefaucheur). © 2004 Elsevier SAS. All rights reserved. doi: 10.1016/j.neucli.2004.02.001
92
Introduction Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive way to stimulate a targeted cortical region and to modulate its activity, that has been proposed for therapeutic application in various neuro-psychiatric disorders, such as severe depressive episodes [19]. Recently, we showed that a 20-min session of rTMS applied at 10 Hz over the motor cortex could produce analgesic effects in patients with neurogenic pain [6,7]. These effects were transient, but relevant for about a week [8]. Other authors confirmed that some patients with chronic pain could be improved for a few days after a single rTMS session, even if they did not find significant effects in a whole series of patients with pain of various origins [15]. These analgesic effects could be expected, since precentral motor cortex stimulation by means of surgically implanted electrodes is used to treat drug-resistant neurogenic pain, either of peripheral or central origin [2,10,11,12,17,18]. At present, about 270 patients with chronic pain treated by motor cortex stimulation have been reported in the literature. Even if they were not all systematically improved, a relevant pain relief was observed in 52–73% of the patients with facial or post-stroke pain, and in 44–88% of the patients for the other indications [13]. The mode of action of this treatment remains unclear, but experimental data argue for a contribution of some descending modulation triggered by the motor cortico-thalamic output that could take place in the spinal cord and/or the brainstem [4,14]. Surgical implantations are limited by the cost of the materials and the availability of trained neurosurgical teams. Therefore, patients can wait for the surgery for a long time notwithstanding an unbearable, drug-resistant pain.
Case report We report the case of a 37-year-old woman, in whom drug-resistant neuropathic pain was controlled for more than a year by a monthly session of motor cortex rTMS until the surgical implantation of a cortical stimulator produced a durable pain relief. Her pain was related to a thoracic outlet syndrome with a lesion of the left brachial plexus. Eight years after the first sensory symptoms occurred at the left hand, she underwent surgical decompression through a supraclavicular approach encompassing first rib resection. The surgical treatment worsened the pain. Subsequently, she was treated by various analgesic drugs (antiepileptics:
J.-P. Lefaucheur et al. carbamazepine, clonazepam, gabapentin; antidepressants: clomipramine, amitriptyline; opioids: morphine), which have been stopped because of side effects or ineffectiveness. At the time of the study, her treatment was limited to dextropropoxyphen and nonsteroidal anti-inflammatory drugs. The patient was referred to our hospital to evaluate the indication of motor cortex stimulation to treat a drug-resistant chronic neuropathic pain. She suffered from a permanent aching pain, involving the left upper limb and predominating distally, without any paresthesia or burning sensation. Some paroxysms occurred in case of left arm elevation or abduction. A mild sensory deficit was found at quantitative sensory testing, the first perception thresholds for both thermal and mechanical sensation being moderately elevated at the left hand compared to the right hand. A dynamic mechanical allodynia was present, but we did not find allodynia to thermal stimuli or any type of hyperalgesia. Motor strength was normal and symmetrical for both upper limbs. Neurophysiological examination was consistent with a lesion of the sensory part of the lower trunk of the left brachial plexus. Nerve conduction study disclosed a reduced amplitude of the sensory action potentials of the ulnar and the medial antebrachial cutaneous nerves at the left upper limb compared to the right side. Somatosensory evoked potentials to both median and ulnar nerves did not reveal any central conduction time asymmetry. Electromyography did not show evidence of denervation in the intrinsic hand muscles. Test sessions of motor cortex rTMS were performed as preoperative assessment to determine the value of cortical stimulation to relieve the pain of this patient. Since she was significantly improved following these test sessions and since she did not want to undergo surgical implantation in a first time, a series of rTMS sessions was proposed and accepted by the patient. A 20-min session of rTMS was performed every month following a previously described protocol [6–8]. This procedure ensured to stimulate over the precentral gyrus [20]. Briefly, rTMS was applied using a Super-Rapid Magstim magnetic stimulator (The Magstim Company, Whitland, UK) and a eightshaped coil (70 mm double coil-9925-00, The Magstim Company, Whitland, UK) centered over the motor cortical area corresponding to the painful hand. Each session consisted of a series of 20 trains of magnetic pulses (5-s duration, 55-s intertrain interval) at a stimulation rate of 10 Hz and at 80% of rest motor threshold intensity using a “real” eightshaped coil. The patient was instructed to rate her daily pain on a 0–10 visual analog scale (VAS) collected in a
Neuropathic pain control by rTMS diary for five consecutive days after each rTMS session. The period of assessment was limited to 5 days, since it was previously shown that pain relief lasted only a few days after a single rTMS session [8]. The patient’s global impression of change was also rated on a seven-point verbal scale, from “very much worse” to “very much improved” [3]. For three sessions, the “real” coil was replaced by a “sham” eight-shaped coil (Placebo Coil System 1730-23-00, The Magstim Company, Whitland, UK), the patient being unaware of this replacement. Sixteen months after the first rTMS session, a quadripolar Resume electrode (Medtronic, Minneapolis, USA) was implanted into the epidural space over the central sulcus region corresponding to the painful hand. The site of implantation was determined under neuronavigation guidance and electrophysiological mapping, using somatosensory evoked potentials and motor evoked potentials as previously described [12,13]. The chronic cortical stimulation was performed with an Itrel 2 implantable pulse generator (Medtronic, Minneapolis, USA) delivering monophasic square pulses in a cycling mode. Stimulation parameters were adapted for the best pain control. Pain level was rated for five days on VAS at three and six months after the implantation. The VAS scores before the series of rTMS sessions, after the first three or the last three “real” rTMS sessions, after the three “sham” rTMS sessions, after the three “real” rTMS sessions preceding or following the “sham” rTMS sessions, and after surgical implantation have been compared with a Kruskal–Wallis nonparametric ANOVA test and
93 Dunn’s post tests. A value of P < 0.05 was considered as significant.
Results No adverse effect was observed for more than a year of monthly session of rTMS. The mean VAS scores are illustrated in Fig. 1. The initial mean VAS scores were higher than 7/10. Following rTMS session, the mean VAS scores were always lower than 5.5/10, except following four sessions (months 6, 9, 10, 13), three of which corresponding to the “sham” sessions. Statistical analysis by the Kruskal–Wallis test showed that the variation of the VAS scores among the conditions was significantly greater than expected by chance (P < 0.0001). Compared to the initial VAS scores, Dunn’s post tests revealed that the VAS scores were reduced after both the first three and the last three “real” rTMS sessions (P < 0.001 and 0.01, respectively), but not after the three “sham” rTMS sessions (P > 0.05). Pain intensity was also reduced following surgical implantation (P < 0.001). The “sham” rTMS sessions were significantly less effective than the “real” rTMS sessions to relieve pain (P < 0.001, 0.05, 0.05 and 0.01, respectively by comparing the effects on VAS scores of the three “sham” sessions to the first three or the last three “real” rTMS sessions, and to the three “real” rTMS sessions preceding or following the “sham” rTMS sessions). Following each rTMS session, the pain was relieved satisfactorily for a week and returned progressively to its initial level within a month. For
Figure 1 Effects of monthly sessions of repetitive transcranial magnetic stimulation (rTMS) of the motor cortex on pain level scored on a 0–10 visual analog scale (mean of daily scores for 5 days +/– standard deviation). Months 1 and 2 consisted of the basal pain level on the days before the first rTMS session. Months 3–18 corresponded to the days following each rTMS session. At months 6, 9 and 13 (*), the “real” coil was replaced by a “sham” coil. Months 22 and 25 took place 3 and 6 months following the surgical implantation of the cortical stimulator.
94 this patient, one monthly rTMS session was sufficient to make a clinical impact in her quality of life. The rTMS-induced analgesic effects did not fade away with time, as shown by the absence of significant difference between the VAS scores obtained after the first three and the last three “real” rTMS sessions (P > 0.05). Finally, the rTMS-induced analgesic effects have been found somewhat less important than those obtained after chronic implantation of a cortical stimulator (P < 0.05). All the various components of pain were relieved by rTMS: mostly the spontaneous pain, but also paroxysms and allodynia were concomitantly alleviated. Compared to the initial VAS scores, pain intensity was reduced on average by 1.2 points (15%) after “sham” rTMS, by three points (40%) after “real” rTMS and by four points (52%) after surgical implantation, defining this patient as a “satisfactory responder” to motor cortex stimulation [12,13]. The patient expressed her global impression of change as “no change” after all the “sham” rTMS sessions and some “real” rTMS sessions, as “much improved” by most of the “real” rTMS session and later as “very much improved” by the implanted stimulation. This lead the patient to stop dextropropoxyphen intake about 6 months after the surgical implantation.
J.-P. Lefaucheur et al. recent report of a depressive patient [1]. In patients with severe depression, repeated daily rTMS sessions for one or two weeks need to be performed to prolong clinical efficacy [5]. However, in contrast to depression, which is a recurrent disease, chronic pain is permanent. Therefore, the use of rTMS alone is devoid of interest to manage patients with chronic pain in long term, but it could allow these patients to wait for surgical implantation with a good level of pain control, which could not be offered by analgesic drugs. Moreover, rTMS response could be a useful indicator of the success of the subsequent surgical procedure. At present, in our department, pain control by repeated rTMS sessions has been obtained in three additional patients (one with traumatic brachial plexus lesion and two with thalamic stroke) for a preoperative period of few months. In conclusion, motor cortex rTMS may be clinically useful in the management of chronic, drug-resistant pain to maintain a satisfactory level of pain relief in selected patients until the implantation of a cortical stimulator.
References [1]
Discussion This case shows for the first time that a patient with drug-resistant neurogenic pain could respond for a prolonged period to repeated sessions of subthreshold 10 Hz-rTMS over the motor cortex. Farrar et al. [3] recently have demonstrated that a clinically meaningful reduction of chronic pain in placebo-controlled trials would be a two point decrease or 30% reduction on a 0–10 numerical rating scale. In an accompanying editorial Rowbotham [16] proposed a most cautious approach for individual patients that would be to define meaningful improvement as a 30% reduction of pain intensity and a category rating of ‘much improved’ or ‘very much improved’. From the above assumptions, we can conclude that the patient of the present study experienced a clinically meaningful pain reduction induced by 10 Hz-rTMS over the motor cortex. She presented a significant reduction of pain intensity level on a 11-point numerical scale concomitant with a global impression of improvement, an association which is not systematically observed in pain studies [9]. However, clinical effects of a single rTMS session are only transitory. A maintenance treatment should require further sessions, as suggested by a
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
Abraham G, O’Brien S. Repetitive transcranial magnetic stimulation is useful for maintenance treatment. Can J Psychiatry 2002;47:386. Carroll D, Joint C, Maartens N, Shlugman D, Stein J, Aziz TZ. Motor cortex stimulation for chronic neuropathic pain: a preliminary study of 10 cases. Pain 2000;84:431–7. Farrar JT, Young Jr JP, LaMoreaux L, Werth JL, Poole RM. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 2001;94:149–58. Garcia-Larrea L, Peyron R, Mertens P, Gregoire MC, Lavenne F, Le Bars D, et al. Electrical stimulation of motor cortex for pain control: a combined PET-scan and electrophysiological study. Pain 1999;83:259–73. George MS, Wassermann EM, Kimbrell TA, Little JT, Williams WE, Danielson AL, et al. Mood improvement following daily left prefrontal repetitive transcranial magnetic stimulation in patients with depression: a placebocontrolled crossover trial. Am J Psychiatry 1997;154: 1752–6. Lefaucheur JP, Drouot X, Keravel Y, Nguyen JP. Pain relief induced by repetitive transcranial magnetic stimulation of precentral cortex. NeuroReport 2001;12:2963–5. Lefaucheur JP, Drouot X, Ménard-Lefaucheur I, Zerah F, Bendib B, Cesaro P, et al. Neurogenic pain relief by repetitive transcranial magnetic cortical stimulation depends on the origin and the site of pain. J Neurol Neurosurg Psychiatry 2004;75:612–6. Lefaucheur JP, Drouot X, Nguyen JP. Interventional neurophysiology for pain control: duration of pain relief following repetitive transcranial magnetic stimulation of the motor cortex. Neurophysiol Clin 2001;31:247–52. Mamie C, Morabia A, Bernstein M, Klopfenstein CE, Forster A. Treatment efficacy is not an index of pain intensity. Can J Anaesth 2000;47:1166–70.
Neuropathic pain control by rTMS [10] Mertens P, Nuti C, Sindou M, Guenot M, Peyron R, GarciaLarrea L, et al. Precentral cortex stimulation for the treatment of central neuropathic pain: results of a prospective study in a 20-patient series. Stereotact Funct Neurosurg 1999;73:122–5. [11] Meyerson BA, Lindblom U, Linderoth B, Lind G, Herregodts P. Motor cortex stimulation as treatment of trigeminal neuropathic pain. Acta Neurochir Suppl (Wien) 1993; 58:150–3. [12] Nguyen JP, Lefaucheur JP, Decq P, Uchiyama T, Carpentier A, Fontaine D, et al. Chronic motor cortex stimulation in the treatment of central and neuropathic pain. Correlations between clinical, electrophysiological and anatomical data. Pain 1999;82:245–51. [13] Nguyen JP, Lefaucheur JP, Keravel Y. Motor cortex stimulation. In: Simpson BA, editor. Pain research and clinical management, 15. Amsterdam: Elsevier Science B.V; 2003. p. 197–209 electrical stimulation and the relief of pain. [14] Peyron R, Garcia-Larrea L, Deiber MP, Cinotti L, Convers P, Sindou M, et al. Electrical stimulation of precentral cortical area in the treatment of central pain. Electrophysiological and PET study. Pain 1995;62:275–86.
95 [15] Rollnik JD, Wüstefeld S, Däuper J, Karst M, Fink M, Kossev A, et al. Repetitive transcranial magnetic stimulation for the treatment of chronic pain—a pilot study. Eur Neurol 2002;48:6–10. [16] Rowbotham MC. Editorial: what is a ‘clinical meaningful’ reduction in pain? Pain 2001;94:131–2. [17] Tsubokawa T, Katayama Y, Yamamoto T, Hirayama T, Koyama S. Chronic motor cortex stimulation for the treatment of central pain. Acta Neurochir (Wien) (Suppl) 1991; 52:137–9. [18] Tsubokawa T, Katayama Y, Yamamoto T, Hirayama T, Koyama S. Chronic motor cortex stimulation in patients with thalamic pain. J Neurosurg 1993;78:393–401. [19] Wassermann EM, Lisanby SH. Therapeutic application of repetitive transcranial magnetic stimulation: a review. Clin Neurophysiol 2001;112:1367–77. [20] Wassermann EM, Wang B, Zeffiro TA, Sadato N, PascualLeone A, Toro C, et al. Locating the motor cortex on the MRI with transcranial magnetic stimulation and PET. Neuroimage 1996;3:1–9.
www.elsevier.com/locate/neucli
ORIGINAL ARTICLE
Neuropathic pain controlled for more than a year by monthly sessions of repetitive transcranial magnetic stimulation of the motor cortex Douleur neuropathique contrôlée pendant plus d’un an par des séances mensuelles de stimulation magnétique corticale transcrânienne répétitive Jean-Pascal Lefaucheur a,*, X. Drouot a, I. Ménard-Lefaucheur a, J.P. Nguyen b a
Service de Physiologie—Explorations Fonctionnelles, CHU Hôpital Henri Mondor, 51 avenue de Lattre de Tassigny, Créteil 94010, France b Service de Neurochirurgie, Hôpital Henri Mondor, Assistance Publique—Hôpitaux de Paris 51 avenue de Lattre de Tassigny, Créteil 94010, France et INSERM U421, Faculté de Médecine de Créteil, France Received 28 October 2003; accepted 9 February 2004 Available online 12 March 2004
KEYWORDS Brachial plexus; Chronic pain; Motor cortex stimulation; Repetitive transcranial magnetic stimulation; Thoracic outlet surgery
MOTS CLÉS Chirurgie du syndrome du défilé thoracique ; Douleur chronique ; Plexus brachial ; Stimulation du cortex moteur ; Stimulation magnétique transcrânienne répétitive
Abstract Neuropathic pain can be controlled by motor cortex stimulation using surgicallyimplanted electrodes in a majority of selected patients. Analgesic effects were also found to result from repetitive transcranial magnetic stimulation (rTMS) of the cortex. We report the case of a woman, in whom drug-resistant peripheral pain was controlled for 16 months by monthly sessions of motor cortex rTMS until a durable pain relief was obtained after surgical implantation of a cortical stimulator. This case illustrates the value of rTMS in helping patients to wait for surgery. © 2004 Elsevier SAS. All rights reserved. Résumé Les douleurs neuropathiques d’une majorité de patients sélectionnés peuvent être contrôlées par une stimulation du cortex moteur utilisant des électrodes implantées chirurgicalement. La stimulation magnétique transcrânienne répétitive (SMTr) du cortex permet également d’obtenir des effets antalgiques. Nous rapportons le cas d’une femme chez qui une douleur périphérique résistant aux médicaments fut contrôlée pendant 16 mois par des séances mensuelles de SMTr du cortex moteur jusqu’à ce qu’un soulagement durable de la douleur soit obtenu après l’implantation chirurgicale d’un stimulateur cortical. Ce cas illustre l’intérêt de la SMTr à aider les patients à attendre la chirurgie. © 2004 Elsevier SAS. All rights reserved.
* Corresponding author. Tel.: +33-1-49-81-26-94; fax: +33-1-49-81-46-60. E-mail address: [email protected] (J.-P. Lefaucheur). © 2004 Elsevier SAS. All rights reserved. doi: 10.1016/j.neucli.2004.02.001
92
Introduction Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive way to stimulate a targeted cortical region and to modulate its activity, that has been proposed for therapeutic application in various neuro-psychiatric disorders, such as severe depressive episodes [19]. Recently, we showed that a 20-min session of rTMS applied at 10 Hz over the motor cortex could produce analgesic effects in patients with neurogenic pain [6,7]. These effects were transient, but relevant for about a week [8]. Other authors confirmed that some patients with chronic pain could be improved for a few days after a single rTMS session, even if they did not find significant effects in a whole series of patients with pain of various origins [15]. These analgesic effects could be expected, since precentral motor cortex stimulation by means of surgically implanted electrodes is used to treat drug-resistant neurogenic pain, either of peripheral or central origin [2,10,11,12,17,18]. At present, about 270 patients with chronic pain treated by motor cortex stimulation have been reported in the literature. Even if they were not all systematically improved, a relevant pain relief was observed in 52–73% of the patients with facial or post-stroke pain, and in 44–88% of the patients for the other indications [13]. The mode of action of this treatment remains unclear, but experimental data argue for a contribution of some descending modulation triggered by the motor cortico-thalamic output that could take place in the spinal cord and/or the brainstem [4,14]. Surgical implantations are limited by the cost of the materials and the availability of trained neurosurgical teams. Therefore, patients can wait for the surgery for a long time notwithstanding an unbearable, drug-resistant pain.
Case report We report the case of a 37-year-old woman, in whom drug-resistant neuropathic pain was controlled for more than a year by a monthly session of motor cortex rTMS until the surgical implantation of a cortical stimulator produced a durable pain relief. Her pain was related to a thoracic outlet syndrome with a lesion of the left brachial plexus. Eight years after the first sensory symptoms occurred at the left hand, she underwent surgical decompression through a supraclavicular approach encompassing first rib resection. The surgical treatment worsened the pain. Subsequently, she was treated by various analgesic drugs (antiepileptics:
J.-P. Lefaucheur et al. carbamazepine, clonazepam, gabapentin; antidepressants: clomipramine, amitriptyline; opioids: morphine), which have been stopped because of side effects or ineffectiveness. At the time of the study, her treatment was limited to dextropropoxyphen and nonsteroidal anti-inflammatory drugs. The patient was referred to our hospital to evaluate the indication of motor cortex stimulation to treat a drug-resistant chronic neuropathic pain. She suffered from a permanent aching pain, involving the left upper limb and predominating distally, without any paresthesia or burning sensation. Some paroxysms occurred in case of left arm elevation or abduction. A mild sensory deficit was found at quantitative sensory testing, the first perception thresholds for both thermal and mechanical sensation being moderately elevated at the left hand compared to the right hand. A dynamic mechanical allodynia was present, but we did not find allodynia to thermal stimuli or any type of hyperalgesia. Motor strength was normal and symmetrical for both upper limbs. Neurophysiological examination was consistent with a lesion of the sensory part of the lower trunk of the left brachial plexus. Nerve conduction study disclosed a reduced amplitude of the sensory action potentials of the ulnar and the medial antebrachial cutaneous nerves at the left upper limb compared to the right side. Somatosensory evoked potentials to both median and ulnar nerves did not reveal any central conduction time asymmetry. Electromyography did not show evidence of denervation in the intrinsic hand muscles. Test sessions of motor cortex rTMS were performed as preoperative assessment to determine the value of cortical stimulation to relieve the pain of this patient. Since she was significantly improved following these test sessions and since she did not want to undergo surgical implantation in a first time, a series of rTMS sessions was proposed and accepted by the patient. A 20-min session of rTMS was performed every month following a previously described protocol [6–8]. This procedure ensured to stimulate over the precentral gyrus [20]. Briefly, rTMS was applied using a Super-Rapid Magstim magnetic stimulator (The Magstim Company, Whitland, UK) and a eightshaped coil (70 mm double coil-9925-00, The Magstim Company, Whitland, UK) centered over the motor cortical area corresponding to the painful hand. Each session consisted of a series of 20 trains of magnetic pulses (5-s duration, 55-s intertrain interval) at a stimulation rate of 10 Hz and at 80% of rest motor threshold intensity using a “real” eightshaped coil. The patient was instructed to rate her daily pain on a 0–10 visual analog scale (VAS) collected in a
Neuropathic pain control by rTMS diary for five consecutive days after each rTMS session. The period of assessment was limited to 5 days, since it was previously shown that pain relief lasted only a few days after a single rTMS session [8]. The patient’s global impression of change was also rated on a seven-point verbal scale, from “very much worse” to “very much improved” [3]. For three sessions, the “real” coil was replaced by a “sham” eight-shaped coil (Placebo Coil System 1730-23-00, The Magstim Company, Whitland, UK), the patient being unaware of this replacement. Sixteen months after the first rTMS session, a quadripolar Resume electrode (Medtronic, Minneapolis, USA) was implanted into the epidural space over the central sulcus region corresponding to the painful hand. The site of implantation was determined under neuronavigation guidance and electrophysiological mapping, using somatosensory evoked potentials and motor evoked potentials as previously described [12,13]. The chronic cortical stimulation was performed with an Itrel 2 implantable pulse generator (Medtronic, Minneapolis, USA) delivering monophasic square pulses in a cycling mode. Stimulation parameters were adapted for the best pain control. Pain level was rated for five days on VAS at three and six months after the implantation. The VAS scores before the series of rTMS sessions, after the first three or the last three “real” rTMS sessions, after the three “sham” rTMS sessions, after the three “real” rTMS sessions preceding or following the “sham” rTMS sessions, and after surgical implantation have been compared with a Kruskal–Wallis nonparametric ANOVA test and
93 Dunn’s post tests. A value of P < 0.05 was considered as significant.
Results No adverse effect was observed for more than a year of monthly session of rTMS. The mean VAS scores are illustrated in Fig. 1. The initial mean VAS scores were higher than 7/10. Following rTMS session, the mean VAS scores were always lower than 5.5/10, except following four sessions (months 6, 9, 10, 13), three of which corresponding to the “sham” sessions. Statistical analysis by the Kruskal–Wallis test showed that the variation of the VAS scores among the conditions was significantly greater than expected by chance (P < 0.0001). Compared to the initial VAS scores, Dunn’s post tests revealed that the VAS scores were reduced after both the first three and the last three “real” rTMS sessions (P < 0.001 and 0.01, respectively), but not after the three “sham” rTMS sessions (P > 0.05). Pain intensity was also reduced following surgical implantation (P < 0.001). The “sham” rTMS sessions were significantly less effective than the “real” rTMS sessions to relieve pain (P < 0.001, 0.05, 0.05 and 0.01, respectively by comparing the effects on VAS scores of the three “sham” sessions to the first three or the last three “real” rTMS sessions, and to the three “real” rTMS sessions preceding or following the “sham” rTMS sessions). Following each rTMS session, the pain was relieved satisfactorily for a week and returned progressively to its initial level within a month. For
Figure 1 Effects of monthly sessions of repetitive transcranial magnetic stimulation (rTMS) of the motor cortex on pain level scored on a 0–10 visual analog scale (mean of daily scores for 5 days +/– standard deviation). Months 1 and 2 consisted of the basal pain level on the days before the first rTMS session. Months 3–18 corresponded to the days following each rTMS session. At months 6, 9 and 13 (*), the “real” coil was replaced by a “sham” coil. Months 22 and 25 took place 3 and 6 months following the surgical implantation of the cortical stimulator.
94 this patient, one monthly rTMS session was sufficient to make a clinical impact in her quality of life. The rTMS-induced analgesic effects did not fade away with time, as shown by the absence of significant difference between the VAS scores obtained after the first three and the last three “real” rTMS sessions (P > 0.05). Finally, the rTMS-induced analgesic effects have been found somewhat less important than those obtained after chronic implantation of a cortical stimulator (P < 0.05). All the various components of pain were relieved by rTMS: mostly the spontaneous pain, but also paroxysms and allodynia were concomitantly alleviated. Compared to the initial VAS scores, pain intensity was reduced on average by 1.2 points (15%) after “sham” rTMS, by three points (40%) after “real” rTMS and by four points (52%) after surgical implantation, defining this patient as a “satisfactory responder” to motor cortex stimulation [12,13]. The patient expressed her global impression of change as “no change” after all the “sham” rTMS sessions and some “real” rTMS sessions, as “much improved” by most of the “real” rTMS session and later as “very much improved” by the implanted stimulation. This lead the patient to stop dextropropoxyphen intake about 6 months after the surgical implantation.
J.-P. Lefaucheur et al. recent report of a depressive patient [1]. In patients with severe depression, repeated daily rTMS sessions for one or two weeks need to be performed to prolong clinical efficacy [5]. However, in contrast to depression, which is a recurrent disease, chronic pain is permanent. Therefore, the use of rTMS alone is devoid of interest to manage patients with chronic pain in long term, but it could allow these patients to wait for surgical implantation with a good level of pain control, which could not be offered by analgesic drugs. Moreover, rTMS response could be a useful indicator of the success of the subsequent surgical procedure. At present, in our department, pain control by repeated rTMS sessions has been obtained in three additional patients (one with traumatic brachial plexus lesion and two with thalamic stroke) for a preoperative period of few months. In conclusion, motor cortex rTMS may be clinically useful in the management of chronic, drug-resistant pain to maintain a satisfactory level of pain relief in selected patients until the implantation of a cortical stimulator.
References [1]
Discussion This case shows for the first time that a patient with drug-resistant neurogenic pain could respond for a prolonged period to repeated sessions of subthreshold 10 Hz-rTMS over the motor cortex. Farrar et al. [3] recently have demonstrated that a clinically meaningful reduction of chronic pain in placebo-controlled trials would be a two point decrease or 30% reduction on a 0–10 numerical rating scale. In an accompanying editorial Rowbotham [16] proposed a most cautious approach for individual patients that would be to define meaningful improvement as a 30% reduction of pain intensity and a category rating of ‘much improved’ or ‘very much improved’. From the above assumptions, we can conclude that the patient of the present study experienced a clinically meaningful pain reduction induced by 10 Hz-rTMS over the motor cortex. She presented a significant reduction of pain intensity level on a 11-point numerical scale concomitant with a global impression of improvement, an association which is not systematically observed in pain studies [9]. However, clinical effects of a single rTMS session are only transitory. A maintenance treatment should require further sessions, as suggested by a
[2]
[3]
[4]
[5]
[6]
[7]
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