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Objective. For targeting the subthalamic nucleus (STN), we attempted to quantify the changes in multiple cell activities by computing the neural noise level and multiple-cell spike density (MSD). Methods. We analyzed the neural noise level and MSD by stepwise recording at every 0.25-mm increment during the final tracking in 90 sides of 45 patients with Parkinson's disease. The MSD was analyzed with cut-off levels ranging from 1.2- to 2.0-fold the neural noise level in the internal capsule or zona incerta in each trajectory. Results. The dorsal boundary of the STN was identified from an increase in the neural noise ratio in all sides. The ventral boundary was identifiable, however, from a decrease in the neural noise ratio in only 70 sides (78%). In contrast, both the dorsal and ventral boundaries were clearly identified from an increase and a decrease in the MSD, respectively, in all of the 90 sides. Conclusion. MSD analysis by semimicroelectrode recording represents a useful, practical, and apparently reliable means for identifying the boundaries of the STN.

The cationic di-μ-hydroxo dinuclear complexes of molybdenocene and tungstenocene [Cp2M(μ-OH)2MCp2]+ (Cp = η-C5H5; M = Mo or W) react with tropolone to afford corresponding tropolonato complexes [Cp2M(trop)]+ (trop = C7H5O2). The products were investigated by IR, 1H NMR, and 13C NMR spectroscopy as well as by X-ray crystallography (M = W). The structure shows that the central metal is surrounded by a distorted tetrahedral array of the two centers of cyclopentadienyl ligands and the two oxygen atoms of tropolonato ligand. The reaction has been extended to the synthesis of calix[4]arene receptor functionalized at the 1,3-positions of the upper rim with two tropolonato-molybdenocene centers.

Clinical course and characteristics of the motor deficits were investigated in patients who underwent surgical resection of the frontal lobe for tumorous lesions. The extent of resection was classified into four groups. In Group A, resection was limited within the area above the superior frontal sulcus and posterior to a line vertical to the AC-PC line at the AC (VCA line). Resection was extended anterior to the VCA line in Group B or below the superior frontal sulcus in Group C. In Group D, resection was extended to both of these two boundaries. In results, permanent and severe motor deficit is rarely induced when resection of the frontal lobe is limited to only the SMA proper (corresponding roughly to Group A), the SMA proper and pre-SMA (corresponding roughly to Group B), or the SMA proper and premotor cortex (corresponding roughly to Group C), insofar as the primary motor cortex is preserved. Disturbance in fine movements of the upper extremity is frequently induced for the long term when wide areas of the SMA proper, pre-SMA as well as premotor cortex are resected all together (corresponding roughly to Group D).

We analyzed the conscious sensory responses to cortical stimulation of 31 patients with post-stroke pain who underwent motor cortex stimulation (MCS) therapy. During surgery for electrode placement, a sensory response (tingle projected to a localized peripheral area) was elicited by high-frequency stimulation (50 Hz) in 23 (84%) from the somatosensory cortex, and in 16 (52%) from the motor cortex without muscle contraction. Unpleasant painful sensation was induced or their original pain was exacerbated in 12 patients (39%) when the somatosensory cortex was stimulated and in two (6%) when the motor cortex was stimulated. Somatosensory responses were induced in eight (25%) even by low-frequency stimulation (1-2 Hz) of the motor cortex at an intensity below the threshold for muscle contraction. In contrast, among 20 nonpain patients who underwent a similar procedure for cortical mapping in epilepsy or brain tumor surgery, a sensory response was produced by high-frequency stimulation in only eight (40%; p < 0.02) from the somatosensory cortex and four (20%; p < 0.03) from the motor cortex. Pain sensation was not induced by stimulation of the somatosensory cortex (p < 0.002) or motor cortex in any of these patients. In addition, none of these patients reported a sensory response to low-frequency stimulation. In both of the two post-stroke pain patients who reported abnormal pain sensation in response to stimulation of the motor cortex, MCS failed to control their post-stroke pain. These findings imply that the sensitivity of the perceptual system even to activity of the motor cortex is heightened in post-stroke pain patients, which can sometimes hinder pain control by MCS.

It has become increasingly popular to use functional magnetic resonance imaging (fMRI) as a tool for preoperative functional brain mapping. We, however, have sometimes experienced the eloquent area (localized by fMRI), which did not match-up with the results from the intraoperative electrical cortical mapping. In this study, to clarify a reliability of fMRI, such cases were reported in detail and mechanisms would cause that phenomenon were discussed. Seventeen patients with brain tumor located in the region of motor and/or language cortex were investigated, and high dissociation between fMRI and electrical cortical mapping was noted in four cases. Of the four cases, two cases were reported their clinical course and studied the deoxyhemoglobin (Deoxy-Hb) consumption using near infrared spectroscopy (NIRS) during task performance. As a result, decreasing of Deoxy-Hb during the task was not shown. Blood oxygen level-dependent (BOLD) signals, which were observed in normal brain, would not be expected in the case where a brain tumor is close to the eloquent area. It suggests that fMRI cannot always localize the eloquent area in pathological brain. Therefore, care must be taken to adopt the information from fMRI, when operative strategy is going to be made.

Dystonia is a movement disorder characterized by sustained muscle contractions leading to twisting movements and abnormal postures. There is no certain medical treatment such as ablative surgical treatment, which has often been disappointing. Recently, deep brain stimulation has become well established as a safe and effective therapy in the treatment of movement disorders. In this study, five cases of dystonia underwent the deep brain stimulation (DBS) targeted in globus pallidus internus (GPi); these cases shall be reported on. Among them, two cases were generalized dystonia and three cases of them were cervical dystonia. The electrode for chronic stimulation was inserted by a stereotactic surgical procedure. During the surgery, unitary potentials were recorded in order to decide the appropriate electrode location. The results were evaluated with Fahn–Marsden dystonia movement scales for generalized dystonia and a modified Toronto Western Spasmodic Torticollis Rating Scale for cervical dystonia. As a result, no complication caused by surgery and/or electrical stimulation was noted in these cases. The averages of the scale change, 6 months after the surgery, improved both types of dystonia. The chronic GPi stimulation therapy would be expected as an effective treatment for dystonia.

✓ Reversibility and adaptability are preferred features of long-term therapeutic deep brain stimulation (DBS). In such therapy, a permanent stimulating electrode with four contact points is placed at the stimulation site and, generally speaking, bipolar stimulation is induced by various pairs of adjacent contact points on one electrode. The stimulation sites are thus all located along the trajectory of the implanted electrode. In a patient with unilateral severe essential tremor, the authors implanted two electrodes side by side and parallel to each other in the unilateral thalamic ventralis intermedius nucleus. Using these electrodes, the authors were able to deliver current flow not only along the electrode trajectory, but also between the two electrodes in a direction parallel to the anterior commissure—posterior commissure line. Although individual stimulations, delivered by each of the two electrodes using all parameters and all stimulation points, were unable to stop the patient's tremor completely without adverse effects, the new stimulation method, in which electrical currents passed between the two electrodes, effected complete abolition of the tremor without adverse effects. With the aid of this method, one can use two electrodes, implanted in parallel and side by side, to achieve maximum efficacy and to reduce adverse effects in some instances of DBS therapy.

The effects of spinal cord stimulation (SCS), deep brain stimulation (DBS) of the thalamic nucleus ventralis caudalis (VC) and motor cortex stimulation (MCS) were analyzed in 19 patients with phantom limb pain. All of the patients underwent SCS and, if the SCS failed to reduce the pain, the patients were considered for DBS and/or MCS. Satisfactory pain control for the long-term was achieved in 6 of 19 (32%) by SCS, 6 of 10 (60%) by DBS and 1 (20%) of 5 by MCS. SCS and DBS of the VC sometimes produced a dramatic effect on the pain, leading to a long pain-free interval and infrequent use of stimulation. The effects of both DBS of the VC and MCS were tested in four. One patient of them reported better pain control by MCS than by DBS, whereas two reported the opposite results. There is no evidence at present for an advantage of MCS over SCS and DBS of the VC in controlling phantom limb pain.

The results of a double blinded evaluation of the effects of globus pallidus (GPi; n=7) and subthalamic nucleus (STN; n=11) stimulation in patients with advanced Parkinson's disease are summarized. The patients were evaluated at 6–8 months after surgery. In order to determine the benefits afforded by the stimulation to the actual daily activities, the patients were maintained on-medication with optimal doses and schedules. The stimulation was turned off overnight for at least 12 h. It was turned on in the morning (or maintained turned off), and the best and worst scores during daytime activity were recorded, as on-period and off-period scores, respectively. A reduction in total motor score on the Unified Parkinson's Disease Rating Scale was clearly elicited by GPi and STN stimulation at both the off-period (−57 and −29%, respectively) and the on-period (−36 and −25%, respectively). The difference in effects between GPi and STN stimulation appeared to be due largely to an unintended difference in the patients’ preoperative symptoms. The benefits provided by stimulation to the actual daily activities appears to be limited in patients who have become unresponsive to a large dose of levodopa. Two advantages of GPi and STN stimulation were identified. Firstly, the stimulation can supplement a reduced action of levodopa during the off-period. It thus improves the patient's daily activities through attenuation of the motor fluctuations. Secondly, the stimulation can replace part of the action of levodopa during the on-period. It thus attenuates dopa-induced dyskinesia through a reduced dose of medication. More importantly, the stimulation improves the daily activities in dopa-intolerant patients who are being administered a small dose of levodopa because of unbearable side effects. In addition, GPi stimulation has its own inhibitory effect on dopa-induced dyskinesia. Clinically important improvement was observed in severe gait freezing in 2 patients following unilateral anterodorsal GPi stimulation on the right side alone.

Deep brain stimulation (DBS) has been applied mainly for the treatment of intractable pain and involuntary movement disorders. Based on the rising numbers of patients undergoing DBS therapy, the possibility of emergent application of cardioversion for the treatment of occasional severe arrhythmia in DBS patients has also increased. However, there has been insufficient discussion about cardioversion in DBS patients. We employed a radiofrequency receiver that transmits to the brain impulses provided by an external generator through an antenna applied to the skin in front of the receiver. We experienced a patient who displayed almost complete cessation of his action tremor with thalamic stimulation. He also developed central dysesthetic pain and showed complete disappearance of his action tremor, even without stimulation, following successful application of cardioversion. It is considered that slight changes in the high-voltage electrical current or high-voltage electrical current spread induced central dysesthetic pain and almost identical effects to thalamotomy. We report for the first time a case of thalamotomy induced by cardioversion in a DBS patient. Clearly, we need to bear in mind that cardioversion has the capability to cause brain lesions in DBS patients with a radiofrequency receiver implanted subcutaneously at the anterior chest wall.

This is the first thesis describing a new technique for awake craniotomy using a laryngeal mask. Awake craniotomy with propofol infusion has become increasingly popular for the optimal excision of brain tumours located in eloquent areas. During awake craniotomy, tracheal intubation is not performed and propofol infusion is limited to within doses which render the patient just sedated. This asleep-awake procedure is occasionally associated with difficulty in controlling brain volume, especially in patients with a significant mass effect of their brain tumours, since sufficient sedation with propofol tends to cause hypercapnea. We report an intraoperative wake-up procedure employing a laryngeal mask, which enables general anaesthesia to be performed at a sufficient dose of propofol and with control of the brain volume under mechanically assisted ventilation. Before the beginning of cortical mapping, propofol infusion is completely terminated, so allowing the patient to wake up within 5-15 min. Following completion of the tumour excision, general anaesthesia is re-induced at a sufficient dose of propofol. The laryngeal mask can be temporarily removed and repositioned with ease, if necessary. In our experience, this technique is applicable for the optimal excision of brain tumours, especially in patients who are very obese or those who have very large lesions.

Background: Perinatal anoxia rarely causes myoclonus as the main neurologic abnormality. The exact neuronal mechanism underlying myoclonus induced by perinatal anoxia remains unknown. Some studies have indicated that the development of involuntary movements may be related to the maturation of the thalamus after birth. Objectives and Methods: Here, we describe the first case of a patient who developed action myoclonus after experiencing perinatal anoxia and was successfully treated by chronic deep brain stimulation (DBS) of the thalamus (thalamic DBS). Results andConclusion: The effectiveness of chronic thalamic DBS in this patient supports the concept of involvement of the thalamus in postperinatal anoxic myoclonus.

When microelectrode recording of single cell activity is employed for targeting the subthalamic nucleus (STN), multiple sampling of single cells is needed to determine whether the electrode has passed through the ventral boundaries of the STN. In contrast, stepwise recording of multiple cell activities by a semimicroelectrode reveals robust changes in such activities at the dorsal and ventral boundaries. We attempted to quantify changes in multiple cell activities by computing multiple-cell spike density (MSD). We analyzed MSD in 60 sides of 30 patients with Parkinson’s disease. Neural noise level was defined as the lowest cut-off level at which neural noise is separated from larger amplitude spikes. MSD was analyzed at cut-off levels ranging from 1.2 to 2.0-fold the neural noise level in the white matter in each trajectory. Both the dorsal and ventral boundaries were clearly identified by an increase and a decrease (p < 0.0001) in MSD, respectively, in all the 60 sides. The cut-off level of 1.2-fold showed the clearest change in MSD between the STN and the pars reticulata of substantia nigra. MSD analysis by semimicroelectrode recording represents the most practical means of identifying the boundaries of STN.

Twenty-one cases of a vegetative state (VS) and 5 cases of a minimally conscious state (MCS) caused by various kinds of brain damage were evaluated neurologically and electrophysiologically at 3 months after brain injury. These cases were treated by deep brain stimulation (DBS) therapy, and followed up for over 10 years. The mesencephalic reticular formation was selected as a target in 2 cases of VS, and the CM-pf complex was selected as a target in the other 19 cases of VS and 5 cases of MCS. Eight of the 21 patients emerged from the VS, and became able to obey verbal commands. However, they remained in a bedridden state except for 1 case. Four of the 5 MCS patients emerged from the bedridden state, and were able to enjoy their life in their own home. DBS therapy may be useful for allowing patients to emerge from the VS, if the candidates are selected according to appropriate neurophysiological criteria. Also, a special neurorehabilitation system may be necessary for emergence from the bedridden state in the treatment of VS patients. Further, DBS therapy is useful in MCS patients to achieve consistent discernible behavioral evidence of consciousness, and emergence from the bedridden state.

Object. Histopathological studies on spinal cord injury (SCI) have demonstrated time-dependent spread of tissue damage during the initial several hours postinjury. When the long tract within the spinal cord is stimulated, a large monophasic positivity occurs at the injury site. This type of potential, termed the killed-end evoked potential (KEEP), indicates that a nerve impulse approaches but does not pass beyond the injury site. The authors tested the hypothesis that the damage spread can be evaluated as a progressive shift of the KEEP on a real-time basis. The effect of high-dose methylprednisolone sodium succinate (MPSS) on the spread of tissue damage was also examined by this methodology. Methods. The KEEP was recorded using an electrode array placed on the spinal cord at the T-10 level in cats. This electrode array consisted of multiple 0.2-mm-diameter electrodes, each separated by 0.5 mm. Spinal cord injury was induced using a vascular clip (65 g pinching pressure for 30 seconds). The midline posterior surface of the spinal cord was stimulated bipolarly at the C-7 level by applying a single pulse at supramaximal intensity. During the initial period of 6 hours postinjury, the localization of the largest KEEP shifted progressively up to 2.5 mm rostral from the injury site. The amplitude of the KEEP recorded at the injury site decreased to 55 to 70% and became slightly shortened in latency as the localization of the largest KEEP shifted rostrally. These findings imply that the injury site KEEP represents the volume-conducted potential of the largest KEEP at the site of the conduction block. It moved away from the injury site in association with the damage spread, and this was confirmed histopathologically. A decrease in amplitude of KEEP at the injury site appeared to be the most sensitive measure of the damage spread, because the amplitude of the volume-conducted KEEP is inversely proportional to the square of the distance between the recording site and site of conduction block. Administered immediately after SCI, MPSS clearly inhibited these events, especially within 30 minutes postinjury. Conclusions. The KEEP enables sequential evaluation to be made of the time-dependent spread of tissue damage in SCI in the same animal. It is, therefore, useful for detecting the effect of therapeutic interventions and for determining the therapeutic time window. The efficiency of MPSS to inhibit the spread of damaged tissue appeared to be maximized when it was administered within the initial 30-minute period postinjury.

It has been reported that parkinsonian and essential tremor can be controlled by deep brain stimulation or radiofrequency lesion within the cluster of cells with a tremor-frequency activity in the ventral thalamic nuclei. However, there have been very few reports about the exact localization of cells with tremor-frequency activity in the ventral thalamic nuclei. In the present study, we investigated the localization of cells with tremor-frequency activity in the ventral thalamic nuclei employing autopower spectrum and coherence analysis. Activity of a total of 130 cells, 63 in patients with parkinsonian tremor and 67 in patients with essential tremor, were recorded from the area anterior to the nucleus ventralis caudalis. Among these cells, 31 cells showed a coherence of greater than 0.4 to the electromyographic activity of both agonist and antagonist muscles. The proportion of cells exhibiting tremor-frequency activity were 26.8% in the nucleus ventralis intermedius (Vim) and 25.0% in the nuclei ventralis oralis posterior et anterior (Vop + Voa). There were no significant differences in proportion by nuclear location or disease. The present study demonstrated that cells with tremor-frequency activity are widely distributed over the area extending from the Vim to the Vop + Voa. This indicates that the best location for placing electrodes for deep brain stimulation or a radiofrequency lesion cannot be defined by identification of cells with tremor-frequency activity alone.

Twenty-one cases of a persistent vegetative state (PVS) caused by various kinds of brain damage were evaluated neurologically and electrophysiologically at 3 months after the brain injury. The 21 cases were treated by deep brain stimulation (DBS) therapy, and followed up for over 10 years. The stimulation sites were the mesencephalic reticular formation (2 cases) and CM-pf complex (19 cases). Eight of the patients emerged from the PVS, and became able to obey verbal commands. However, they remained in a bedridden state. These 8 cases revealed a desynchronization on continuous EEG frequency analysis. The Vth wave of the ABR and N20 of the SEP could be recorded even with a prolonged latency, and the painrelated P250 was recorded with an amplitude of over 7 µV. The mean survival time of these 8 cases was 6.1 years, as compared to 3.1 years for the other 13 cases. Overall, 4 cases are alive after more than 10 years. DBS therapy may be useful for allowing patients to emerge from a PVS, if the candidates are selected according to neurophysiological criteria. The fact that 19% (4/21) of the PVS cases treated with DBS survived for over 10 years should be stressed in comparison with the usual survival period for the untreated PVS.

We investigated the clinical course and characteristics of the motor deficits in patients who underwent surgical resection of the frontal lobe for tumorous lesions. Only patients who met the following criteria were included in the present study: 1) postoperative MRI revealed that resection of the frontal lobe involved the area closely adjacent to the primary motor cortex, but 2) the D wave of the corticospinal MEP did not decrease in amplitude below 50% of the original level during surgery. The extent of resection was classified into 4 groups. In Group A (6 cases), resection was limited within the area above the superior frontal sulcus and posterior to a line vertical to the line connecting the anterior and posterior commissures at the anterior commissure (AC vertical line). Resection was extended anterior to the AC vertical line in Group B (4 cases) or below the superior frontal sulcus in Group C (5 cases). In Group D (3 cases), resection was extended to both of these two boundaries. Severe motor paresis and/or apraxia of the upper and lower extremities were noted in all patients of Group D immediately after surgery. A complete recovery in the lower extremity was observed in these patients, while disturbance in the fine movements of the upper extremity remained for more than 1 year after the surgery. Disturbance in the fine movements and/or apraxia of the upper extremity were observed immediately after surgery in 2 of the Group A patients (33%), 2 of the Group B patients (50%) and 3 of the Group C patients (60%). However, a rapid recovery occurred in these patients, and only a subtle or mild disturbance remained for more than 1 year after the surgery in one of the Group B and one of the Group C patients. Permanent and severe motor deficit is rarely induced when resection of the frontal lobe is limited to only the SMA proper (corresponding roughly to Group A), the SMA proper and pre-SMA (corresponding roughly to Group B), or the SMA proper and premotor cortex (corresponding roughly to Group C), insofar as the primary motor cortex is preserved. Disturbance in fine movements of the upper extremity is frequently induced for the long term when wide areas of the SMA proper, pre-SMA as well as premotor cortex are resected altogether (corresponding roughly to Group D).

We analyzed the effects of spinal cord stimulation (SCS), deep brain stimulation (DBS) of the thalamic nucleus ventralis caudalis (VC) and motor cortex stimulation (MCS) in 45 patients with post-stroke pain. Satisfactory pain control was obtained more frequently as the stimulation site was moved to higher levels (7% by SCS, 25% by DBS and 48% by MCS). A painful sensation was sometimes produced by stimulation of the VC as well as the post-central, pre-central and pre-frontal cortices. Such a sensation occurred less frequently as the stimulation site was moved to higher levels (50% at the VC, 39% at the post-central cortex, 6% at the pre-central cortex and 3% at the pre-frontal cortex). These findings imply that abnormal processing of nociceptive information develops at the level of deafferentation and spreads to higher levels to a varying extent. This may be one of the reasons why satisfactory pain control was obtained more frequently as the stimulation site was moved to higher levels.

The results of a double-blind evaluation of the effects of internal globus pallidus (GPi) stimulation in 7 patients with advanced Parkinson’s disease are summarized. The evaluation was performed 6–8 months after surgery while the patients were on medication with an optimal dose and schedule. The stimulation was turned off for at least 12 h. It was turned on in the morning (or maintained turned off), and the best and worst scores during their daytime activity were recorded as the on-period and off-period scores, respectively. A significant reduction in the total score on part III of the Unified Parkinson’s Disease Rating Scale was induced by GPi stimulation at the off-period (–57%) as well as the on-period (–36%). Clinically important improvement was also achieved in severe gait freezing (kinesia paradoxa) in 2 patients when stimulation was applied to the anterodorsal portion of the GPi. Such an effect was observed during unilateral stimulation of the right side alone.

During surgery on the skull base, preservation of the integrity of the ocular motor nerves is vitally important. Intraoperative electrophysiological monitoring methods for protecting such functions have been reported by several investigators. However, these methods so far have not been popularized sufficiently, due to the difficulty and complexity of the procedures involved. The authors have developed an extremely simple but far more reliable method using electro-oculography under total intravenous anesthesia with propofol to preserve the integrity of the ocular motor nerves. The ocular motor nerves were stimulated with a monopolar electrode intracranially, and the polarity of the waves was recorded using surface electrodes placed around the eyeball, yielding precise information concerning the locations of the oculomotor nerve and/or abducent nerve. In addition, by performing continuous monitoring, invasive procedures affecting the ocular motor nerves could be detected as spontaneous ocular movements. In practice at our department, this method has been applied in 12 cases with tumors close to the ocular motor nerves, and has produced excellent results.

✓ Intraoperative monitoring techniques for protecting the integrity of the oculomotor nerves during skull base surgery have been reported by several investigators, all of which involved the use of electromyographic responses to extraocular muscles. However, these techniques have not yet become popular because of the complexity of the procedures. The authors report an extremely simple and far more reliable technique in which electrooculographic (EOG) monitoring is used. The oculomotor nerves were stimulated with a monopolar electrode during skull base exposure. The polarity of the EOG responses recorded with surface electrodes placed on the skin around the eyeball yielded precise information concerning the location and function of the oculomotor and abducent nerves. In addition, with the aid of continuous EOG monitoring that detected transient changes in the background waves, surgical procedures that might impinge on oculomotor nerve function could be avoided. The present technique has been used in eight patients with skull base tumors and with it, the authors have achieved excellent results.