Acta Neurochirurgica, Suppl. 52, 137-139 (1991) © by Springer-Verlag 1991
Chronic Motor Cortex Stimulation for the Treatment of Central Pain T. Tsubokawa, Y. Katayama, T. Yamamoto, T. Hirayama, and S. Koyama Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan
Summary Twelve patients with deafferentation pain secondary to central nervous system lesions were subjected to chronic motor cortex stimulation. The motor cortex was mapped as carefully as possible and the electrode was placed in the region where muscle twitch of painful area can be observed with the lowest threshold. 5 of the 12 patients reported complete absence of previous pain with intermittent stimulation at 1 year following the initiation of this therapy. Improvements in hemiparesis was also observed in most of these patients. The pain of these patients was typically barbiturate-sensitive and morphine-resistant. Another 3 patients had some degree of residual pain but considerable reduction of pain was still obtained by stimulation. Thus, 8 of the 12 patients (67%) had continued effect of this therapy after 1 year. In 3 patients, revisions of the electrode placement were needed because stimulation became incapable of inducing muscle twitch even with higher stimulation intensity. The effect of stimulation on pain and capability of producing muscle twitch disappeared simultaneously in these cases and the effect reappeared after the revisions, indicating that appropriate stimulation of the motor cortex is definitely necessary for obtaining satisfactory pain control in these patients. None of the patients subjected to this therapy developed neither observable nor electroencephalographic seizure activity.
Keywords: Brain stimulation; motor cortex; central pain; thalamic pain; pain.
Introduction Any forms oftherapies, including chronic deep brain stimulation, provide satisfactory pain control in only one third of cases with deafferentation pain secondary to central nervous system (eNS) lesions. Analysis of our experience with deep brain stimulation has indicated that the best effect of thalamic stimulation was frequently obtained in deafferentation pain secondary to peripheral nervous system (PNS) lesions 2 ,3. In contrast, the effect of thalamic stimulation is often unsatisfactory for controlling deafferentation pain secondary to eNS lesions 2 ,3. In order of develop more effective treatment for
deafferentation pain secondary to eNS lesions, we have been exploring the effects of stimulation of various brain regions on such a pain for the last several years. We recently recognized that stimulation of the motor cortex can provide often excellent pain control in this group of patients. This clinical finding is in harmony with our experimental observation that thalamic hyperactivity following transection of the spinothalamic tract can be efficiently inhibited by stimulation of the motor cortexl. We summarize here the results obtained in a series of 12 patients treated by chronic epidural stimulation of the motor cortex. Patients and Methods Patient Population A total of 12 patients were treated by stimulation of the motor cortex (Table 1). Among these patients, 6 had either a small thalamic infarct or thalamic hemorrhage, 3 had a small lesion in the posterior limb of the capsula interna caused by a putaminal hemorrhage, and the remaining 3 had either a pontine hemorrhage, multiple sclerosis or postrhizotomy pain. Intervals following the onset of the original disease to the occurrence of pain were 1-4 years. The patients had been treated by various kinds of medication (anticonvulsants and/or antidepressants). All but 2 cases displayed hemiparesis of varying degrees. The patients and their families gave informed consent for the procedures described below to be carried out.
Pharmacological Characterization Pain in each patient, was characterized by responses to stepwise administration of thiopental and morphine (i.v., barbiturate and morphine tests). Changes in pain level was evaluated by each patient on standardized visual analog scale (V AS).
Surgical Procedures The location of the motor cortex was estimated by bony landmarks with conventional method. Under local anesthesia, paramedian skin incision was made 1-4 em lateral to the midline
138
T. Tsubokawa et al.
Table 1. Clinical data and the Effect of Motor Cortex Stimulation Parmacological characteristics of pain Case no.
Age/Sex
Original disease
Barbiturate test
Morphine test
1 2 3 4 5 6 7 8 9 10 11 12
12/M 54/M 62/M 53/F 52/M 66/F 59/F 58/F 53/M 55/F 42/F 48/F
putaminal hemorrhage thalamic infarct thalamic hemorrhage thalamic hemorrhage thalamic infarct putaminal hemorrhage thalamic infarct thalamic infarct pontine hemorrhage putaminal hemorrhage multiple sclerosis postrhizotomy pain
sensitive sensitive sensitive sensitive sensitive? sensitive sensitive? non-sensitive sensitive? sensitive? unclear sensitive?
non-sensitive non-sensitive non-sensitive non-sensitive non-sensitive non-sensitive non-sensitive non-sensitive non-sensitive sensitive? sensitive? non-sensitive
Result"
excellent excellent excellent excellent excellent excellent good good good fair poor poor
"Excellent, 100% reduction; good, 80-60% reduction, fair, 60-40% reduction, poor, less than 40% reduction of pain on visual analog scale.
and contralateral to the painful area. The trephination was then placed over the estimated area of the motor cortex. An electrode array having 4 plate electrode (diameter, 0.5 cm) each separated by 1 em (M 3587, Medtronic Co.) was inserted into the epidural space. The locations of the sensory and motor cortices were confirmed from phase reversal of the N 20wave of somatosensory evoked potential recorded from the electrode. When the electrode was moved from the sensory cortex to the motor cortex, the N 20 wave turned to positive. The location of the motor cortex was again confirmed by motor evoked potential recoded in response to stimulation with the electrode. The motor cortex was mapped as carefully as possible and the electrode was placed in the region where muscle twitch of painful area could be observed at the lowest threshold. The stimulation system was internalized after a period of 1 week of test stimulation. During this period, the effects of stimulation with different parameters were examined. Electroencephalograms were repeatedly recorded at predetermined interval.
Stimulation Procedures
Stimulations were usually applied for 5-10 min. for each time and no stimulations were given at night. The frequency and intensity were usually adjusted to 50-120Hz and the level slightly lower than the threshold for muscle twitch of painful area (less than 1 rnA with 0.1-0.5 ms pulse). The effects of chronic stimulation of the motor cortex was evaluated at predetermined interval after the initiation of this therapy. Each patient was asked to express pain levels by VAS. The effect of chronic stimulation of the motor cortex was classified into 4 categories; excellent, complete disappearance of pain; good, reduction of pain level for 80-100%; fair, reduction of pain level for 40-60%; and poor, reduction of pain level less than 40%.
Results
In 10 of the 12 patients, satisfactory pain control was obtained during the initial 1 month after the initiation
of this therapy. Pain subsided within a few minutes after the onset of stimulation and this effect continued for 3-6 hours following 5-10 min. stimulation. Usually, stimulation for 5-7 times a day was necessary during this earlier period. Five of the 12 patients reported complete absence of previous pain with intermittent stimulation at 1 year following the initiation of this therapy (Table 1). During this later period, these patients stimulated for 2-3 times a day. Interestingly, improvements in hemiparesis was also observed in most of these cases. The pain of these patients was typically barbituratesensitive and morphine-resistant. Another 3 patients had some degree of residual pain but considerable reduction of pain was still obtained by stimulation. Thus, 8 of the 12 patients (67%) had continued effect of this therapy after 1 year. Three patients did not respond favourably to this therapy. These patients tended to show different characteristic pharmacologically as well as neurologically in their pain. Their pain was questionable sensitive to barbiturate or morphine, or both. It appeared that abnormal severe pain evoked by movements of extremities is not responsive to this therapy. Conclusions, however, await further experience. In 3 patients, revisions of the electrode placement were needed because stimulation became incapable of inducing muscle twitch even with higher stimulation intensity. Either epidural granulation or dislocation of the electrode was the cause of this change in 2 cases, and disconnection in one case. The effect of stimulation
139
Chronic Motor Cortex Stimulation for the Treatment of Central Pain
_II
iii
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II."
If
U · '....
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50
Fig. I. A representative example of inhibitory effects of sensory and motor cortex stimulation on hyperactive thalamic neuron in the cat. Recording from thalamic relay neuron (low threshold mechanoreceptive neuron) at 3 weeks following spinothalamic tractotomy. S.C, sensory cortex stimulation; M.C, motor cortex stimulation. scales, ms
of pain and capability of producing muscle twitch disappeared simultaneously in these cases and the effect reappeared after the revisions, indicating that appropriate stimulation of the motor cortex is definitely necessary for obtaining satisfactory pain control in these patients. Stable stimulation with the technique employed in the present series of patients, which involves epidural placement of the electrode, was difficult to achieve in one patient who demonstrated moderately dilated subarachnoid space over the cerebral cortex. None of the patients subjected to this therapy developed neither observable not electroencephalographic seizure activity.
cats 1. Such hyperactivity can be inhibited more efficiently by stimulation of the motor cortex rather than sensory cortex (Fig. 1). It may be that motor cortex afferents and/or efferents activated orthodromically or antidromically can inhibit abnormal hyperactivity within the eNS underlying deafferentation pain. The result of the present study indicates that deafferentation pain secondary to eNS lesions is better controlled by stimulation of the motor cortex rather than thalamic stimulation. It is suggested that there may be a certain subgroup of patients which respond more favourably to this therapy. The effect of stimulation of the motor cortex on hemiparesis also appears to be worthy of further studies.
Discussion
Deafferentation pain secondary to eNS lesions is the most difficult pain to control even after the advent of chronic deep brain stimulation therapy2,3. Thalamic stimulation was not useful for controlling these pain. Even if the initial effect is satisfactory, tolerance to stimulation frequently develops within 7 months. In contrast, chronic stimulation of the motor cortex appears to provide better control of such pain. It also appears that the effect of stimulation of the motor cortex continues longer. Thalamic hyperactivity is observed following experimental transection of the spinothalamic tract in
References I. Hirayama T, Tsubokawa T, Katayama Y, Yamamoto Y, Koyama S (1990) Chronic changes in activity of thalamic relay neurons following spinothalamic tractotomy in cat. Effects of motor cortex stimulation. Pain 5 [Suppl]: 273 2. Tsubokawa T (1985) Chronic stimulation of deep brain structures for treatment of chronic pain. In: Tasker RR (ed) Neurosurgery state of arts review, Vol 2. Stereotaxic Surgery, Hanley and Belfus Inc., Philadelphia, pp 253 - 255 3. Tsubokawa T, Katayama y , Yamamoto T. Hirayama T (1985) Deafferentation pain and stimulation of thalamic sensory relay nucleus. Appi Neurophysiol48: 166-171 Correspondence: T . Tsubokawa, Department of Neurological Surgery, Nihon University School of Medicine, Tokyo 173.Japan.
Chronic Motor Cortex Stimulation for the Treatment of Central Pain T. Tsubokawa, Y. Katayama, T. Yamamoto, T. Hirayama, and S. Koyama Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan
Summary Twelve patients with deafferentation pain secondary to central nervous system lesions were subjected to chronic motor cortex stimulation. The motor cortex was mapped as carefully as possible and the electrode was placed in the region where muscle twitch of painful area can be observed with the lowest threshold. 5 of the 12 patients reported complete absence of previous pain with intermittent stimulation at 1 year following the initiation of this therapy. Improvements in hemiparesis was also observed in most of these patients. The pain of these patients was typically barbiturate-sensitive and morphine-resistant. Another 3 patients had some degree of residual pain but considerable reduction of pain was still obtained by stimulation. Thus, 8 of the 12 patients (67%) had continued effect of this therapy after 1 year. In 3 patients, revisions of the electrode placement were needed because stimulation became incapable of inducing muscle twitch even with higher stimulation intensity. The effect of stimulation on pain and capability of producing muscle twitch disappeared simultaneously in these cases and the effect reappeared after the revisions, indicating that appropriate stimulation of the motor cortex is definitely necessary for obtaining satisfactory pain control in these patients. None of the patients subjected to this therapy developed neither observable nor electroencephalographic seizure activity.
Keywords: Brain stimulation; motor cortex; central pain; thalamic pain; pain.
Introduction Any forms oftherapies, including chronic deep brain stimulation, provide satisfactory pain control in only one third of cases with deafferentation pain secondary to central nervous system (eNS) lesions. Analysis of our experience with deep brain stimulation has indicated that the best effect of thalamic stimulation was frequently obtained in deafferentation pain secondary to peripheral nervous system (PNS) lesions 2 ,3. In contrast, the effect of thalamic stimulation is often unsatisfactory for controlling deafferentation pain secondary to eNS lesions 2 ,3. In order of develop more effective treatment for
deafferentation pain secondary to eNS lesions, we have been exploring the effects of stimulation of various brain regions on such a pain for the last several years. We recently recognized that stimulation of the motor cortex can provide often excellent pain control in this group of patients. This clinical finding is in harmony with our experimental observation that thalamic hyperactivity following transection of the spinothalamic tract can be efficiently inhibited by stimulation of the motor cortexl. We summarize here the results obtained in a series of 12 patients treated by chronic epidural stimulation of the motor cortex. Patients and Methods Patient Population A total of 12 patients were treated by stimulation of the motor cortex (Table 1). Among these patients, 6 had either a small thalamic infarct or thalamic hemorrhage, 3 had a small lesion in the posterior limb of the capsula interna caused by a putaminal hemorrhage, and the remaining 3 had either a pontine hemorrhage, multiple sclerosis or postrhizotomy pain. Intervals following the onset of the original disease to the occurrence of pain were 1-4 years. The patients had been treated by various kinds of medication (anticonvulsants and/or antidepressants). All but 2 cases displayed hemiparesis of varying degrees. The patients and their families gave informed consent for the procedures described below to be carried out.
Pharmacological Characterization Pain in each patient, was characterized by responses to stepwise administration of thiopental and morphine (i.v., barbiturate and morphine tests). Changes in pain level was evaluated by each patient on standardized visual analog scale (V AS).
Surgical Procedures The location of the motor cortex was estimated by bony landmarks with conventional method. Under local anesthesia, paramedian skin incision was made 1-4 em lateral to the midline
138
T. Tsubokawa et al.
Table 1. Clinical data and the Effect of Motor Cortex Stimulation Parmacological characteristics of pain Case no.
Age/Sex
Original disease
Barbiturate test
Morphine test
1 2 3 4 5 6 7 8 9 10 11 12
12/M 54/M 62/M 53/F 52/M 66/F 59/F 58/F 53/M 55/F 42/F 48/F
putaminal hemorrhage thalamic infarct thalamic hemorrhage thalamic hemorrhage thalamic infarct putaminal hemorrhage thalamic infarct thalamic infarct pontine hemorrhage putaminal hemorrhage multiple sclerosis postrhizotomy pain
sensitive sensitive sensitive sensitive sensitive? sensitive sensitive? non-sensitive sensitive? sensitive? unclear sensitive?
non-sensitive non-sensitive non-sensitive non-sensitive non-sensitive non-sensitive non-sensitive non-sensitive non-sensitive sensitive? sensitive? non-sensitive
Result"
excellent excellent excellent excellent excellent excellent good good good fair poor poor
"Excellent, 100% reduction; good, 80-60% reduction, fair, 60-40% reduction, poor, less than 40% reduction of pain on visual analog scale.
and contralateral to the painful area. The trephination was then placed over the estimated area of the motor cortex. An electrode array having 4 plate electrode (diameter, 0.5 cm) each separated by 1 em (M 3587, Medtronic Co.) was inserted into the epidural space. The locations of the sensory and motor cortices were confirmed from phase reversal of the N 20wave of somatosensory evoked potential recorded from the electrode. When the electrode was moved from the sensory cortex to the motor cortex, the N 20 wave turned to positive. The location of the motor cortex was again confirmed by motor evoked potential recoded in response to stimulation with the electrode. The motor cortex was mapped as carefully as possible and the electrode was placed in the region where muscle twitch of painful area could be observed at the lowest threshold. The stimulation system was internalized after a period of 1 week of test stimulation. During this period, the effects of stimulation with different parameters were examined. Electroencephalograms were repeatedly recorded at predetermined interval.
Stimulation Procedures
Stimulations were usually applied for 5-10 min. for each time and no stimulations were given at night. The frequency and intensity were usually adjusted to 50-120Hz and the level slightly lower than the threshold for muscle twitch of painful area (less than 1 rnA with 0.1-0.5 ms pulse). The effects of chronic stimulation of the motor cortex was evaluated at predetermined interval after the initiation of this therapy. Each patient was asked to express pain levels by VAS. The effect of chronic stimulation of the motor cortex was classified into 4 categories; excellent, complete disappearance of pain; good, reduction of pain level for 80-100%; fair, reduction of pain level for 40-60%; and poor, reduction of pain level less than 40%.
Results
In 10 of the 12 patients, satisfactory pain control was obtained during the initial 1 month after the initiation
of this therapy. Pain subsided within a few minutes after the onset of stimulation and this effect continued for 3-6 hours following 5-10 min. stimulation. Usually, stimulation for 5-7 times a day was necessary during this earlier period. Five of the 12 patients reported complete absence of previous pain with intermittent stimulation at 1 year following the initiation of this therapy (Table 1). During this later period, these patients stimulated for 2-3 times a day. Interestingly, improvements in hemiparesis was also observed in most of these cases. The pain of these patients was typically barbituratesensitive and morphine-resistant. Another 3 patients had some degree of residual pain but considerable reduction of pain was still obtained by stimulation. Thus, 8 of the 12 patients (67%) had continued effect of this therapy after 1 year. Three patients did not respond favourably to this therapy. These patients tended to show different characteristic pharmacologically as well as neurologically in their pain. Their pain was questionable sensitive to barbiturate or morphine, or both. It appeared that abnormal severe pain evoked by movements of extremities is not responsive to this therapy. Conclusions, however, await further experience. In 3 patients, revisions of the electrode placement were needed because stimulation became incapable of inducing muscle twitch even with higher stimulation intensity. Either epidural granulation or dislocation of the electrode was the cause of this change in 2 cases, and disconnection in one case. The effect of stimulation
139
Chronic Motor Cortex Stimulation for the Treatment of Central Pain
_II
iii
II" I' 1f.'1 _.IIw.'WWM~ .t .t'
II."
If
U · '....
'" Jr'~"""'"-
50
Fig. I. A representative example of inhibitory effects of sensory and motor cortex stimulation on hyperactive thalamic neuron in the cat. Recording from thalamic relay neuron (low threshold mechanoreceptive neuron) at 3 weeks following spinothalamic tractotomy. S.C, sensory cortex stimulation; M.C, motor cortex stimulation. scales, ms
of pain and capability of producing muscle twitch disappeared simultaneously in these cases and the effect reappeared after the revisions, indicating that appropriate stimulation of the motor cortex is definitely necessary for obtaining satisfactory pain control in these patients. Stable stimulation with the technique employed in the present series of patients, which involves epidural placement of the electrode, was difficult to achieve in one patient who demonstrated moderately dilated subarachnoid space over the cerebral cortex. None of the patients subjected to this therapy developed neither observable not electroencephalographic seizure activity.
cats 1. Such hyperactivity can be inhibited more efficiently by stimulation of the motor cortex rather than sensory cortex (Fig. 1). It may be that motor cortex afferents and/or efferents activated orthodromically or antidromically can inhibit abnormal hyperactivity within the eNS underlying deafferentation pain. The result of the present study indicates that deafferentation pain secondary to eNS lesions is better controlled by stimulation of the motor cortex rather than thalamic stimulation. It is suggested that there may be a certain subgroup of patients which respond more favourably to this therapy. The effect of stimulation of the motor cortex on hemiparesis also appears to be worthy of further studies.
Discussion
Deafferentation pain secondary to eNS lesions is the most difficult pain to control even after the advent of chronic deep brain stimulation therapy2,3. Thalamic stimulation was not useful for controlling these pain. Even if the initial effect is satisfactory, tolerance to stimulation frequently develops within 7 months. In contrast, chronic stimulation of the motor cortex appears to provide better control of such pain. It also appears that the effect of stimulation of the motor cortex continues longer. Thalamic hyperactivity is observed following experimental transection of the spinothalamic tract in
References I. Hirayama T, Tsubokawa T, Katayama Y, Yamamoto Y, Koyama S (1990) Chronic changes in activity of thalamic relay neurons following spinothalamic tractotomy in cat. Effects of motor cortex stimulation. Pain 5 [Suppl]: 273 2. Tsubokawa T (1985) Chronic stimulation of deep brain structures for treatment of chronic pain. In: Tasker RR (ed) Neurosurgery state of arts review, Vol 2. Stereotaxic Surgery, Hanley and Belfus Inc., Philadelphia, pp 253 - 255 3. Tsubokawa T, Katayama y , Yamamoto T. Hirayama T (1985) Deafferentation pain and stimulation of thalamic sensory relay nucleus. Appi Neurophysiol48: 166-171 Correspondence: T . Tsubokawa, Department of Neurological Surgery, Nihon University School of Medicine, Tokyo 173.Japan.
