Teruyasu Hirayama

Chronic motor cortex stimulation for the treatment of central pain.

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.

Treatment of Thalamic Pain by Chronic Motor Cortex Stimulation

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 fhalamic pain syndrome, we investigated the effects of stimulation of various brain regions on the burst hyperactivity of thalamic neurons recorded in cats after deafferentiation of the spinothalamic pathway. Complete, long‐ term inhibition of the burst hyperactivity was induced by stimulation 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 control was obtained in all cases without any complications or side effects. During the stimulation, an increase in regional blood flow of the cerebral cortex and thalamus, 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.

Pharmacological classification of central post-stroke pain : comparison with the results of chronic motor cortex stimulation therapy

Abstract In an attempt to clarify the neurochemical background of central post‐stroke pain and to undertake a pharmacological analysis, the basic pharmacological characteristics of this intractable pain syndrome were investigated by the morphine, thiamylal and ketamine tests. In addition, the correlation between the pharmacological characteristics and the effects of chronic motor cortex stimulation therapy was examined. The study employed 39 central post‐stroke pain patients who had intractable hemibody pain associated with dysesthesias, and radiologically demonstrated lesions in the thalamic area (thalamic pain, n=25) or suprathalamic area (suprathalamic pain, n=14). The pharmacological evaluations showed that definite pain reduction occurred in eight of the 39 cases (20.5%) by the morphine test, in 22 of the 39 cases (56.4%) by the thiamylal test, and in 11 of 23 cases (47.8%) by the ketamine test. Based on these pharmacological assessments, there was no obvious difference between thalamic and suprathalamic pain. A comparison of the long‐term follow‐up results of chronic motor cortex stimulation therapy revealed that thiamylal and ketamine‐sensitive and morphine‐resistant cases displayed long‐lasting pain reduction with chronic motor cortex stimulation therapy, whereas the remaining cases did not show good results. We conclude that pharmacological classification of central post‐stroke pain by the morphine, thiamylal and ketamine tests could be useful for predicting the effects of chronic motor cortex stimulation therapy. It has recently been suggested that excitatory amino acids may be involved in the development of central post‐stroke pain. However, the fact that only 23 of the present 39 cases (59.0%) of thalamic and suprathalamic pain were sensitive to the thiamylal or ketamine test reflects the complex pharmacological background and the difficulties associated with treating central post‐stroke pain.

Deep-brain stimulation in a persistent vegetative state: Follow-up results and criteria for selection of candidates

Eight cases of a persistent vegetative state caused by brain damage were treated by chronic deep-brain stimulation (stimulation target: the mesencephalic reticular formation and/or non-specific thalamic nucleus) over a period of more than 6 months. Three of the patients are currently able to communicate and to express their demands by voice and one other patient has recovered very close to this state. These four cases showed changeable spectrograms with desynchronization on continuous EEG recording and all components of the BSR and SER could be recorded except for prolonged latency of both N20 (SER) and the V wave (BSR) 2 months after the initial coma. Following chronic deep-brain stimulation, EEG and behavioural arousal responses were observed with increased r-CBF, r-CMRO2 and r-CMRGL in the whole brain tissue. After 3-6 months of chronic deep brain stimulation, the prolonged coma scale rose in four of the eight cases and three cases emerged from the persistent vegetative state. Transmitter substances and their metabolites were also found to be increased in the CSF after chronic deep-brain stimulation. Based on these findings, chronic deep-brain stimulation represents a useful kind of treatment that can lead to emergence from a persistent vegetative state, if the candidate is selected by electrophysiological studies 2 months after the initial insult and if the stimulation is applied for more than 6-8 months using a high-safety chronic deep-brain stimulating instrument.

Thalamic relay nucleus stimulation for relief of intractable pain. Clinical results and β-endorphin immunoreactivity in the cerebrospinal fluid

Abstract Deep brain stimulation (thalamic relay nucleus, periaqueductal gray and internal capsule) was applied to various cases of intractable pain, and the resulting degree of pain reduction and alteration in &bgr;‐endorphin immunoreactivity in the cerebrospinal fluid (CSF) were compared. The following results were obtained.(1) The studies on intractable pain revealed that the levels of &bgr;‐endorphin immunoreactivity in the CSF were lower than those in the control group.(2) Thalamic relay nucleus stimulation proved effective not only for deafferentation pain, but also for somatogenic pain. No relationship was, however, noted between pain reduction and the rate of increase of &bgr;‐endorphin immunoreactivity in the CSF.(3) The incidence of stimulation tolerance following prolonged stimulation of the thalamic relay nucleus can be reduced to a minimum by administration of l‐DOPA. It is concluded that the increase in &bgr;‐endorphin in the CSF is not the direct and major cause of pain reduction during treatment by thalamic relay nucleus stimulation. It may be assumed that neuronal facilitation on the monoaminergic descending pain inhibitory system plays a role in reducing pain.

Deafferentation Pain and Stimulation of the Thalamic Sensory Relay Nucleus: Clinical and Experimental Study

This report summarizes our clinical experience in which the effects of both thalamic sensory relay nucleus (TSRN) and periaqueductal gray (PAG) stimulation were tested in the same series of patients with various forms of pain. The clinical data indicated that neurogenic pain due to deafferentation at the level of the peripheral nerves or the spinal cord was often controlled by TSRN stimulation but not by PAG stimulation. We also review the results of our experimental investigations in cats which were undertaken in an attempt to clarify the neurophysiologic basis of such differential clinical effects of TSRN and PAG stimulation. It appeared that abnormal hyperactivity within the trigeminal medullary dorsal horn following retrogasserian rhizotomy was far more frequently inhibited by TSRN stimulation than by PAG stimulation.

Growth of totally thrombosed giant aneurysm within the posterior cranial fossa

SummaryWe report a case in which growth of a totally thrombosed giant aneurysm of the posterior cranial fossa was demonstrated by computed tomography (CT) scans repeated after 4 years. A magnetic resonance (MR) image demonstrated an onion-skin-like, laminated structure within a calcified wall. The laminated structure had developed around an old thrombosis, without any communication to the flowing blood. It showed intensities indicating recent clots, revealing that the giant aneurysm had grown by recurrent intramural hemorrhage rather than by intraluminal accumulation of thrombotic materials. This case illustrates that totally thrombosed giant aneurysms still have the potential of growth.

Thalamic neuronal hyperactivity following transection of the spinothalamic tract in the cat: involvement ofN-methyl-d-aspartate receptor

Single neuron activities responding to peripheral stimuli with short latencies were recorded within the thalamic nucleus ventralis posterolateralis (VPL) after transection of the spinothalamic tract (STT) in the cat under alpha-chloralose anesthesia. The VPL neurons showed spontaneous and evoked hyperactivity after STT transection, which was revealed at 1-2 weeks. The spontaneous hyperactivity further progressed until 3-4 weeks. These hyperactivities were observed in core-area neurons as well as neurons found in the shell area, suggesting that some, if not many, of the N-methyl-D-aspartate (NMDA) receptor antagonist (MK-801, 4-16 mg; i.v.) attenuated both the spontaneous and evoked hyperactivity observed after STT transection. No such effects were demonstrated in sham-operated animals. These findings suggest that VPL neurons become hyperactive after STT transection through recruitment of NMDA receptors. The hyperactivity of VPL neurons may represent an important background process in the production of deafferentation pain induced by lesions involving the STT.

Characterization and Modification of Brain Activity with Deep Brain Stimulation in Patients in a Persistent Vegetative State: Pain‐Related Late Positive Component of Cerebral Evoked Potential

A series of eight patients in a persistent vegetative state (PVS) were subjected to chronic deep brain stimulation (DBS) for the purpose of promoting recovery from the PVS. The characteristics of the brain activity in these patients were evaluated from the late positive component of the cerebral evoked potential in response to painful stimuli (pain‐related P250). While any neurological scoring system for the comatose state includes evaluations of motor reactions to painful stimuli, the pain‐related P250 is unique in terms of its ability to assess the cortical responsiveness to painful stimuli directly and quantitatively without involving functions of the motor system. It was found that the pain‐related P250 was more or less depressed in patients in a PVS. It was repeatedly demonstrated in four patients, however, that the pain‐related P250 could be transiently increased by preceding stimulation of the mesencephalic reticular formation. Furthermore, a persistent increase in the pain‐related P250 was produced in these four patients following chronic DBS of the mesencephalic reticular formation or nonspecific thalamic nuclei for more than 6 months, and this was correlated with the clinical improvements. These results imply that responsiveness at the cortical level to pain is depressed in the PVS. It also appears that some fraction of the depression may, however, be functionally produced and potentially reversible.

Response of Regional Cerebral Blood Flow and Oxygen Metabolism to Thalamic Stimulation in Humans as Revealed by Positron Emission Tomography

To clarify functional neural pathways originating from the thalamic nucleus ventralis posterolateralis (VPL) in humans, the responses of regional CBF (rCBF) and regional CMRO2 (rCMRO2) to VPL stimulation were investigated by positron emission tomography in five patients who had undergone chronic implantation of electrodes into the VPL for therapeutic purposes. Measurement of rCBF and rCMRO2 under continuous inhalation of C15O2 and 15O2 by steady-state methods revealed significant increases of rCBF and rCMRO2 in the frontal, postcentral, and thalamic regions. The increases in rCBF and rCMRO2 of the postcentral regions were clearly predominant in the stimulated hemisphere insofar as the stimulation produced moderate paresthesia in restricted areas of the body. These results indicate that the VPL relays peripheral somatosensory information, which has previously been demonstrated to be transmitted to the frontal as well as postcentral regions.