Treatment of Thalamic Pain by Chronic Motor Cortex Stimulation TAKASHI TSUBOKAWA, YOICHI KATAYAMA, TAKAMITSU YAMAMOTO, TERUYASU HIRAYAMA, and SEIGOU KOYAMA Erom the Department of Neuorological Surgery, Nihon University School of Medicine, Tokyo, Japan
TSUBOKAWA, T., ET AL.: Treatment of Thalamic Pain by Chronic Motor Cortex Stimulation. All forms 0/ therapy, including chronic stimulation of Ihe thaiamic relay nucleus, can provide satisfactory pain control in only 20%-30% of cases of thalamic pain syndrome. In order to deveJop a more effective treatment for thaJamic pain syndrome, we investigated the effects of stimulation of various brain regions on the burst hyperactivity 0/thaJamic neurons recorded in cats after deafferentiation of the spinotholamic pathway. Complete, long- term inhibifion of the burst fiyperacfivity was induced by slimuJation of the motor cortex. Based on this experimental finding, we treated seven cases of thalamic pain syndrome by chronic motor cortex stimulation employing epidural plate electrodes. Excellent or good pain controJ was obtained in all cases ivithout any complications or side effects. During the stimulation, an increase in regional blood flow of the cerebral cortex and (halamus. a marked rise in temperature of the painful skin regions, and improved movements of the painful limbs were observed. These results suggest that thalamic pain syndrome can be most effectively treated by chronic motor cortex stimulation. (PACE, Vol. 14, January 1991} thalamic pain, cortex stimulation, chronic, blood flow, glucose metabolism
Introduction All forms of therapy, including chronic stimulation of the thalamic relay nucleus, can provide satisfactory pain control in only 20%-30% of cases of thalamic pain syndrome.^ In order to develop a more effective treatment for thalamic pain syndrome, we, therefore, investigated the effects of stimulation of various brain regions on the hurst hyperacfivity of thalamic neurons recorded in cats and in humans during stereotaxic surgery for the relief of thalamic pain. Complete and long-term inhibition of the hurst hyperactivity was induced hy stimulation of fho motor cortex (Fig. 1}.^ Based on these findings, we treated seven cases of thalamic pain syndrome by epidural motor cortex chronic stimulation. This presentation describes the chronic stim-
Address for reprints: Takashi Tsubokawa, M.D., D.M.Sc, Department of Neurological Surgery, Nihon University School of Medicine, Tokyo 173, Japan. Fax:
PACE. Vol. 14
ulation technique for motor cortex stimulation and the effect on thalamic pain.
Methods Clinical Evaluation and History of the Treated Cases Suffering from Thalamic Pain All seven cases selected as candidates for chronic motor corfex stimulation treatment, suffered from severe thalamic pain caused by stroke. Six cases had small lesions in the thalamic relay nucleus caused by thalamic lateroventral infarct (four cases) or small thalamic hemorrhage (two cases). The other case had a small lesion in the posterior limb of the internal capsule caused by hemorrhage of the putamen. The intervals after the onset of the primary stroke were 1-4 years. The patients had been treated with various kinds of medication (anticonvulsants and antidcpressants) and psychotherapy, but their pain could not be Gontrolled at
January 1991
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i
50msec
B Motor Cortex
C Sensory Cortex 46sec
0
Figure 1. Effects on burs! firing neurons in (he vicinity of the dcjmcij>ed thalamic area following either motor or sensory cortex stimtilalion. {A) High frequency burst firing recorded at the border zone of the damaged thaJamic relay nucleus. (B) Long-lusting inhibitory effects on the burst firing by motor corfex stimu/alion. (CJ Effect on the burst firing by st^nsory cortex stimulation.
alL Five cases displayed slight motor weakness, but they could walk without help. Before chronic implantation of the stimulating electrode, all cases were examined for lesions by both X-CT and MRI, and were also checked by the morphine and barbiturate tests.'^ The thalamic pain in four of the cases was barbiturate sensitive and insensitive to the morphine test. In two cases, the barbiturate test was partially sensitive and there was no sensitivity to the morphine test. The other case was insensitive to the morphine and barbiturate tests. Chronic Implantation of the Stimulating Electrode at the Kpidural Space on the Motor Cortex
Under local anesthesia, the location of the central sulcus was mapped on the scalp using
132
Kronlein's anatomical measurements (Fig, 2). Trephination was performed on the line, which indicates the central sulcus and 3- to 4-cm lateral to the midline for upper extremity pain or 1-cm lateral to the midline for lower extremity pain. A quadruple disc stimulating electrode (5 mm in diameter at the active point, 10 mm between the poles IMedtronic, Inc., model 3587, Minneapolis, MN, USA]) was inserted into the epidural space corresponding to the motor cortex. The location of the electrode was identified by recording somatosensory evoked potentials through the electrode in response to stimulation of the peripheral nerves which innervated the painful area. Whenever the electrode was placed in the right position on the motor cortex, the N^o of the sensory evoked potential could be recorded as P20 (phase reversal to N20) (Fig. 2). The electrode was
January 1991
PACE. Vol. 14
CORTEX STIMULATION FOR THALAMIC PAIN
so%
Nasion 100% Inion
Kronlein
Figure 2. Idf;nti/icafion o/ the location of ihe. slinuiJaling electrode. A( Ihe first .step, the central suJcus was drawn on the scalp using Kroniein's method Qi\d Ihe electrode inserted into the epidurnl space. A/ler insertion, somatosensory evoked polenliuls were recorded from (he inserfed electrode, whenever the eJectrode VJQ.?, placed on the motor cor(ex, and the N20 wave showed phase reversal.
moved to the correct position by using this response. After checking that the stimulating electrode had been placed on the motor cortex by recording the V-iu of the somatosensory evoked potentials, the electrode was connected to a transmitter which was implanted in the subcutaneous area of the anterior chest wall as an internal chronic stimulation system. The strength of the stimulation was below the threshold for muscle twitching (< 1.0 mA maximum with 0.1-0.5 msec width, 50—120 Hz square wave, ramp type current). The clinical effectiveness for thalamic pain and the side effects or complications in all seven cases were followed up for more than 1 year after using the chronic stimulation. At 4-10 days after implantation of the chronic stimulating system and the beginning of stimulation, the regional cerebral blood flow was esti-
PACE, Vol. 14
mated by the T^' amphetamine SPECT scanning method and the skin temperature was measured by thermography. in order to check the effects of the chronic motor cortex stimulation. Results In all cases, the intractable thalamic pain was subject to satisfactory control. The pain subsided within a few minutes after initiation of the stimulation, and the effect on the pain continued for 4-5 hours following 5 minutes stimulation. Usually, 5-10 minutes of stimulation was applied 5 to 6 times per day at the early stage, but this was changed to about 2 to 3 times in the daytime only at the chronic stage after implantation. The regional cerebral blood flow showed a marked increase to 150%-200% of the level in the prestimulation period in the stimulated cortex
January 1991
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and the ipsilateral thalamic and brain stem area. The skin temperature in the painful area increased to almost the same level as that in the contralateral nonpainful area. At 1 year after the implantation, five of tbe cases did not have any complaints about pain without any supplemental medication, and the other two cases also had satisfactory pain control witb some supplemental medication. Tbey did not suffer any side effects such as seizures or sensory disturbance or any complications. The niotor disability also underwent improvement in all cases with previous disturbance of motor function, mainly of coordination.
cerebral blood flow of the cortex and thalamus was increased and the skin temperature was also increased during the motor cortex stimulation in effective cases. Based on these results, chronic motor cortex stimulation is considered not only to exert an inhibitory effect on tbe burst firing occurring in the vicinity of thalamic lesions, but also to have certain neuroplastic effects on the damaged thalamus, as suggested by an increase of regional cerebral blood flow and metabolism in the brain and increased skin temperature in the painful area.
Conclusion Discussion Chronic motor cortex stimulation was able to induce remarkable pain relief in cases suffering from thalamic pain who failed to derive any beneficial effect from medical and psychological treatments. Furthermore, according to the 1-year follow-up results, 71% of the treated cases were able to maintain excellent effects. The regional
Severe thalamic pain can be controlled by chronic motor cortex stimulation. The pain relief mechanism is based not only on an inhibitory effect on the burst firing in the vicinity of the damaged thalamus. but also on the effect of increased regional cerebral blood flow and glucose metabolism in the cortex and thalamus contralateral to the painful area.
References 1. Tsubokawa T, Katayama Y, Yaniamoto T, et al. Deafferentation pain and stimulation of thalamic sensory relay nucleus. Appl Neurophysiol 1985; 48:166-171. 2. Hirayama T, Tsubokawa T, Katayama Y, et al. Chronic changes in activity of thalamic relay neurons following spino thalamic tractomy in cat. Ef-
134
January 1991
fects of motor cortex stimulation. Pain 1990; 5fSuppl.1:273. Tsubokawa T. Chronic stimulation of deep brain structures for for treatment of chronic pain. In Tasker RR (ed.): Neurosurgery State of Arts Review, Vol. 2, Stereotaxic Surgery. Hanley and Belfus, Inc., Philadelphia, 1985, pp. 235-255 .
PACE, Vol. 14
TSUBOKAWA, T., ET AL.: Treatment of Thalamic Pain by Chronic Motor Cortex Stimulation. All forms 0/ therapy, including chronic stimulation of Ihe thaiamic relay nucleus, can provide satisfactory pain control in only 20%-30% of cases of thalamic pain syndrome. In order to deveJop a more effective treatment for thaJamic pain syndrome, we investigated the effects of stimulation of various brain regions on the burst hyperactivity 0/thaJamic neurons recorded in cats after deafferentiation of the spinotholamic pathway. Complete, long- term inhibifion of the burst fiyperacfivity was induced by slimuJation of the motor cortex. Based on this experimental finding, we treated seven cases of thalamic pain syndrome by chronic motor cortex stimulation employing epidural plate electrodes. Excellent or good pain controJ was obtained in all cases ivithout any complications or side effects. During the stimulation, an increase in regional blood flow of the cerebral cortex and (halamus. a marked rise in temperature of the painful skin regions, and improved movements of the painful limbs were observed. These results suggest that thalamic pain syndrome can be most effectively treated by chronic motor cortex stimulation. (PACE, Vol. 14, January 1991} thalamic pain, cortex stimulation, chronic, blood flow, glucose metabolism
Introduction All forms of therapy, including chronic stimulation of the thalamic relay nucleus, can provide satisfactory pain control in only 20%-30% of cases of thalamic pain syndrome.^ In order to develop a more effective treatment for thalamic pain syndrome, we, therefore, investigated the effects of stimulation of various brain regions on the hurst hyperacfivity of thalamic neurons recorded in cats and in humans during stereotaxic surgery for the relief of thalamic pain. Complete and long-term inhibition of the hurst hyperactivity was induced hy stimulation of fho motor cortex (Fig. 1}.^ Based on these findings, we treated seven cases of thalamic pain syndrome by epidural motor cortex chronic stimulation. This presentation describes the chronic stim-
Address for reprints: Takashi Tsubokawa, M.D., D.M.Sc, Department of Neurological Surgery, Nihon University School of Medicine, Tokyo 173, Japan. Fax:
PACE. Vol. 14
ulation technique for motor cortex stimulation and the effect on thalamic pain.
Methods Clinical Evaluation and History of the Treated Cases Suffering from Thalamic Pain All seven cases selected as candidates for chronic motor corfex stimulation treatment, suffered from severe thalamic pain caused by stroke. Six cases had small lesions in the thalamic relay nucleus caused by thalamic lateroventral infarct (four cases) or small thalamic hemorrhage (two cases). The other case had a small lesion in the posterior limb of the internal capsule caused by hemorrhage of the putamen. The intervals after the onset of the primary stroke were 1-4 years. The patients had been treated with various kinds of medication (anticonvulsants and antidcpressants) and psychotherapy, but their pain could not be Gontrolled at
January 1991
131
TSUBOKAWA, ET AL.
i
50msec
B Motor Cortex
C Sensory Cortex 46sec
0
Figure 1. Effects on burs! firing neurons in (he vicinity of the dcjmcij>ed thalamic area following either motor or sensory cortex stimtilalion. {A) High frequency burst firing recorded at the border zone of the damaged thaJamic relay nucleus. (B) Long-lusting inhibitory effects on the burst firing by motor corfex stimu/alion. (CJ Effect on the burst firing by st^nsory cortex stimulation.
alL Five cases displayed slight motor weakness, but they could walk without help. Before chronic implantation of the stimulating electrode, all cases were examined for lesions by both X-CT and MRI, and were also checked by the morphine and barbiturate tests.'^ The thalamic pain in four of the cases was barbiturate sensitive and insensitive to the morphine test. In two cases, the barbiturate test was partially sensitive and there was no sensitivity to the morphine test. The other case was insensitive to the morphine and barbiturate tests. Chronic Implantation of the Stimulating Electrode at the Kpidural Space on the Motor Cortex
Under local anesthesia, the location of the central sulcus was mapped on the scalp using
132
Kronlein's anatomical measurements (Fig, 2). Trephination was performed on the line, which indicates the central sulcus and 3- to 4-cm lateral to the midline for upper extremity pain or 1-cm lateral to the midline for lower extremity pain. A quadruple disc stimulating electrode (5 mm in diameter at the active point, 10 mm between the poles IMedtronic, Inc., model 3587, Minneapolis, MN, USA]) was inserted into the epidural space corresponding to the motor cortex. The location of the electrode was identified by recording somatosensory evoked potentials through the electrode in response to stimulation of the peripheral nerves which innervated the painful area. Whenever the electrode was placed in the right position on the motor cortex, the N^o of the sensory evoked potential could be recorded as P20 (phase reversal to N20) (Fig. 2). The electrode was
January 1991
PACE. Vol. 14
CORTEX STIMULATION FOR THALAMIC PAIN
so%
Nasion 100% Inion
Kronlein
Figure 2. Idf;nti/icafion o/ the location of ihe. slinuiJaling electrode. A( Ihe first .step, the central suJcus was drawn on the scalp using Kroniein's method Qi\d Ihe electrode inserted into the epidurnl space. A/ler insertion, somatosensory evoked polenliuls were recorded from (he inserfed electrode, whenever the eJectrode VJQ.?, placed on the motor cor(ex, and the N20 wave showed phase reversal.
moved to the correct position by using this response. After checking that the stimulating electrode had been placed on the motor cortex by recording the V-iu of the somatosensory evoked potentials, the electrode was connected to a transmitter which was implanted in the subcutaneous area of the anterior chest wall as an internal chronic stimulation system. The strength of the stimulation was below the threshold for muscle twitching (< 1.0 mA maximum with 0.1-0.5 msec width, 50—120 Hz square wave, ramp type current). The clinical effectiveness for thalamic pain and the side effects or complications in all seven cases were followed up for more than 1 year after using the chronic stimulation. At 4-10 days after implantation of the chronic stimulating system and the beginning of stimulation, the regional cerebral blood flow was esti-
PACE, Vol. 14
mated by the T^' amphetamine SPECT scanning method and the skin temperature was measured by thermography. in order to check the effects of the chronic motor cortex stimulation. Results In all cases, the intractable thalamic pain was subject to satisfactory control. The pain subsided within a few minutes after initiation of the stimulation, and the effect on the pain continued for 4-5 hours following 5 minutes stimulation. Usually, 5-10 minutes of stimulation was applied 5 to 6 times per day at the early stage, but this was changed to about 2 to 3 times in the daytime only at the chronic stage after implantation. The regional cerebral blood flow showed a marked increase to 150%-200% of the level in the prestimulation period in the stimulated cortex
January 1991
133
TSUBOKAWA, ET AL.
and the ipsilateral thalamic and brain stem area. The skin temperature in the painful area increased to almost the same level as that in the contralateral nonpainful area. At 1 year after the implantation, five of tbe cases did not have any complaints about pain without any supplemental medication, and the other two cases also had satisfactory pain control witb some supplemental medication. Tbey did not suffer any side effects such as seizures or sensory disturbance or any complications. The niotor disability also underwent improvement in all cases with previous disturbance of motor function, mainly of coordination.
cerebral blood flow of the cortex and thalamus was increased and the skin temperature was also increased during the motor cortex stimulation in effective cases. Based on these results, chronic motor cortex stimulation is considered not only to exert an inhibitory effect on tbe burst firing occurring in the vicinity of thalamic lesions, but also to have certain neuroplastic effects on the damaged thalamus, as suggested by an increase of regional cerebral blood flow and metabolism in the brain and increased skin temperature in the painful area.
Conclusion Discussion Chronic motor cortex stimulation was able to induce remarkable pain relief in cases suffering from thalamic pain who failed to derive any beneficial effect from medical and psychological treatments. Furthermore, according to the 1-year follow-up results, 71% of the treated cases were able to maintain excellent effects. The regional
Severe thalamic pain can be controlled by chronic motor cortex stimulation. The pain relief mechanism is based not only on an inhibitory effect on the burst firing in the vicinity of the damaged thalamus. but also on the effect of increased regional cerebral blood flow and glucose metabolism in the cortex and thalamus contralateral to the painful area.
References 1. Tsubokawa T, Katayama Y, Yaniamoto T, et al. Deafferentation pain and stimulation of thalamic sensory relay nucleus. Appl Neurophysiol 1985; 48:166-171. 2. Hirayama T, Tsubokawa T, Katayama Y, et al. Chronic changes in activity of thalamic relay neurons following spino thalamic tractomy in cat. Ef-
134
January 1991
fects of motor cortex stimulation. Pain 1990; 5fSuppl.1:273. Tsubokawa T. Chronic stimulation of deep brain structures for for treatment of chronic pain. In Tasker RR (ed.): Neurosurgery State of Arts Review, Vol. 2, Stereotaxic Surgery. Hanley and Belfus, Inc., Philadelphia, 1985, pp. 235-255 .
PACE, Vol. 14
