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We have applied bipolar dual-lead spinal cord stimulation (SCS) between two cylinder-type electrodes placed on the ventral and dorsal sides of the spinal cord (dual-VD-SCS). A 36-year-old man suffered from burning pain from his right elbow down to his hand after brachial plexus avulsion. The areas with paresthesia induced by conventional SCS did not include the painful hand area. However, dual-VD-SCS completely induced paresthesia in the painful hand area. We speculate that dual-VD-SCS can be applied to stimulate deeper sites of the dorsal column and dorsal horn than conventional SCS and is useful for pain reduction.

We report a rare complication in a patient with Parkinson's disease who underwent deep brain stimulation(DBS)surgery. The patient was a 60-year-old woman who presented with frontal lobe signs, including ataxic gait and memory disturbance, that were caused by the unexpected migration of a burr hole cap into the brain three to four months after surgery. The patient had no incidence of a head injury prior to development of symptoms. The patient underwent surgery to extract the migrated cap from the frontal lobe, and her symptoms improved several months after the operation. The cap serves to fix the DBS lead to the skull using an adjunctive burr hole ring. It was intraoperatively confirmed that only the cap detached from the ring, and no cap or ring defects were detected in a postoperative quality check by the manufacturer. We have previously utilized a burr hole ring and cap, which are packaged along with the DBS electrode, when employing the product made by Medtronic Inc. No previous report has described the cap packed in the official DBS kit to have migrated into the intracranial space. It seems unlikely that the cap migration into the intracranial space would occur without the cap and/or ring breaking through either traumatic injury or from manufacturing defects. It is important to consider the migration of a burr hole cap into the intracranial space in the absence of head injury as a possible device complication after DBS surgery.

Despite the recognition of the usefulness of subthalamic nucleus deep brain stimulation (STN-DBS) for the treatment of Parkinson’s disease (PD), preoperative predictive factors for the long-term outcome of STN-DBS are not sufficiently established. We performed this study to determine such predictive factors. The subjects were 66 patients who were classified into two groups on the basis of their activities of daily living (ADL) evaluated five years after the STN-DBS surgery: 33 patients were assigned to the independent ADL group (group I) and the remaining 33 patients to the dependent ADL group (group D). Group I patients showed a Schwab and England (S&E) scale score of more than 70 during the off-period, indicating that these patients can maintain their independent ADL all the time. Group D patients showed a score of 70 or lower during the off-period, indicating that these patients cannot maintain their independent ADL for an entire day. We studied the differences in the preoperative state between these two groups. Statistically significant differences were noted in PD onset age, age at surgery, preoperative unified Parkinson’s disease rating scale (UPDRS) part I score, part II score, total subscore for axial symptoms in part III, mini-mental state examination (MMSE) score and S&E score. Multiple logistic regression analysis showed that the significant independent variables related to long-term independent ADL were the age at surgery, MMSE score and preoperative S&E scale score during the off-period. The PD onset age, age at surgery, preoperative high-level ADL, cognitive function, and axial symptoms are important predictive factors for the long-term outcome of STN-DBS.

Object Holmes' tremor (HT) is generally considered to be a symptomatic tremor associated with lesions of the cerebellum, midbrain, or thalamus. Deep brain stimulation (DBS) therapy for essential tremor and parkinsonian tremor has proved quite successful. In contrast, surgical treatment outcomes for HT have often been disappointing. The use of 2 ipsilateral DBS electrodes implanted in parallel within the thalamus for severe essential tremor has been reported. Since dual-lead stimulation within a single target can cover a wider area than single-lead stimulation, it produces greater effects. On the other hand, DBS of the subthalamic area (SA) was recently reported to be effective for refractory tremor. Methods The authors implanted 2 DBS electrodes (one at the nucleus ventralis oralis/nucleus ventralis intermedius and the other at the SA) in 4 patients with HT. For more than 2 years after implantation, each patient's tremor was evaluated using a tremor rating scale under the following 4 conditions of stimulation: “on” for both thalamus and SA DBS; “off” for both thalamus and SA DBS; “on” for thalamus and “off” for SA DBS; and “on” for SA and “off” for thalamus DBS. Results The tremor in all patients was improved for more than 2 years (mean 25.8 ± 3.5 months). Stimulation with 2 electrodes exerted greater effect on the tremor than did 1-electrode stimulation. Interestingly, in all patients progressive effects were observed, and in one patient treated with DBS for 1 year, tremor did not appear even while stimulation was temporarily switched off, suggesting irreversible improvement effects. The presence of both resting and intentional/action tremor implies combined destruction of the pallidothalamic and cerebellothalamic pathways in HT. A larger stimulation area may thus be required for HT patients. Multitarget, dual-lead stimulation permits coverage of the wide area needed to suppress the tremor without adverse effects of stimulation. Some reorganization of the neural network may be involved in the development of HT because the tremor appears several months after the primary insult. The mechanism underlying the absence of tremor while stimulation was temporarily off remains unclear, but the DBS may have normalized the abnormal neural network. Conclusions The authors successfully treated patients with severe HT by using dual-electrode DBS over a long period. Such DBS may offer an effective and safe treatment modality for intractable HT.

A 62-year-old man complained of resting tremor and posture tremor. In spite of presence of the tremor, other parkinsonian component was very mild. [(11)C]2β-carbomethoxy-3β-(4-fluorophenyl)-tropane ([(11)C]CFT) PET showed asymmetrical reduction of the uptake and [(11)C]raclopride PET showed slightly increased uptake in the striatum. Although he was diagnosed as having benign tremulous parkinsonism (BTP), anti-parkinsonian medications, including anti-cholinergic agent, dopamine agonist and l-dopa, were not effective for his tremor. His tremor gradually deteriorated enough to disturb writing, working, and eating. Because his quality of life (QOL) was disturbed by the troublesome tremor, deep brain stimulation of the subthalamic nucleus (STN-DBS) was performed. After STN-DBS, his tremor was dramatically improved. According to clinical course of our patient as well as previous reports, STN-DBS should be considered as a therapeutic option for BTP patients with severe tremor.

Objectives Intention tremor becomes evident only when patients intend to move their body and is characterized by dysmetria. We have developed an on-demand control system that triggers the switching on/off of deep brain stimulation (DBS) instantly for the control of intention tremor. Material and Methods We used surface electrodes for the recording of electromyographic (EMG) activity, and the power of EMG activity was analyzed instantly employing the fast Fourier transform. The on-demand control system switched on DBS when only the power of tremor frequency exceeded the on-trigger threshold, and the system switched off DBS when the total power of EMG activity decreased below the off-trigger threshold. Results The on-demand control system triggered the switching on/off of DBS accurately, and controlled intention tremor completely. Our on-demand control system is small and portable, and suitable for clinical use. Conclusions The on-demand control system for DBS is useful for controlling intention tremor and may decrease the incidence of tolerance to DBS and may be a powerful tool for various applications of neuromodulation therapy.

Objective High-intensity and high-frequency repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex was carried out in poststroke patients with increased spasticity, and the changes in F-wave parameters in comparison with M-wave parameters induced by rTMS were examined. Methods Ten-hertz rTMS pulses were delivered to the primary motor cortex of the lesion side at 110% intensity of the resting motor threshold, and F-waves were obtained from the first dorsal interosseous muscle. F-waves were recorded before (pre-stim) and immediately after the end of rTMS (post-stim) in poststroke patients. Results F-wave persistence and F/M Amp.Ratio increased significantly in patients with lesions in upper motor tract as compared with healthy subjects (Wilcoxon rank sum test, p = 0.00023 and p = 0.0073, respectively). After the rTMS application, both F-wave persistence and F/M Amp.Ratio decreased significantly (paired t-test, p = 0.0095 and p = 0.037, respectively). However, the F-wave amplitude did not show a statistically significant variance in poststroke patients. Conclusions High-frequency suprathreshold rTMS may suppress the F-waves by enhancing the inhibitory effect on spinal excitability through the corticospinal tract, and F-wave persistence and F/M Amp.Ratio can be used to determine the effect of rTMS on patients with increased spasticity.

Twenty-one vegetative state (VS) patients and 10 minimally conscious state (MCS) patients were treated by spinal cord stimulation (SCS) following an electrophysiological evaluation 3 months or more after the onset of brain injury.A flexible four-contact cylindrical electrode was inserted into the epidural space of the cervical vertebrae, and placed at cervical levels C2-C4. Five-hertz stimulation was applied for 5 min every 30 min during the daytime at an intensity that produced muscle twitches of the upper extremities.Both the fifth wave in the auditory brainstem response (ABR) and N20 in the somatosensory evoked potential (SEP) were detected in 8 of the 21 VS patients and 9 of the 10 MCS patients. Of the 3 VS patients and 7 MCS patients who recovered following SCS therapy, all showed a preserved fifth wave in the ABR and N20 in the SEP, and all had received SCS therapy within 9 months after the onset of brain injury. Although the 3 patients who recovered from VS remained in a bedridden state, all 7 patients who recovered from MCS were able to emerge from the bedridden state within 12 months after the start of SCS.Five-hertz cervical SCS caused increased cerebral blood flow (CBF) and induced muscle twitches of the upper extremities, and MCS patients showed a remarkable recovery of consciousness and motor function in the upper extremities compared with the lower extremities. This SCS method could be a new neuromodulation and neurorehabilitation technique, and MCS patients may be good candidates for SCS therapy.

Twenty-one vegetative state (VS) patients and 10 minimally conscious state (MCS) patients were treated by spinal cord stimulation (SCS) following an electrophysiological evaluation 3 months or more after the onset of brain injury.

Minimally conscious state (MCS) is characterized by inconsistent but clearly discernible behavioral evidence of consciousness, and can be distinguished from coma and the vegetative state (VS). Ten MCS patients were evaluated neurologically and electrophysiologically over 3 months after the onset of brain injury, and were treated by spinal cord stimulation (SCS). A flexible four-contact, cylinder electrode was inserted into the epidural space of the cervical vertebrae, and placed at the C2-C4 levels. Stimulation was applied for 5 minutes every 30 minutes during the daytime at an intensity that produced motor twitches of the upper extremities. We used 5 Hz for SCS, considering that the induced muscle twitches can be a useful functional neurorehabilitation for MCS patients. Eight of the 10 MCS patients satisfied the electrophysiological inclusion criteria, which we proposed on the basis of the results of deep brain stimulation for the treatment of patients in the VS. Seven patients recovered from MCS following SCS therapy, and were able to carry out functional interactive communication and/or demonstrate the functional use of two different objects. Cervical SCS increased cerebral blood flow (CBF) diffusely in the brain, and CBF increased by 22.2% during the stimulation period compared with CBF before stimulation in MCS patients (p < 0.0001, paired t-test). Five-Hz cervical SCS could increase CBF and induce muscle twitches of the upper extremities. This SCS therapy method may be suitable for treating MCS.

Object The objective of this study was to evaluate the efficacy of chronic subthalamic nucleus (STN) stimulation for alleviating pain related to Parkinson disease (PD). Methods Among 163 consecutive patients undergoing STN stimulation, 69 were identified as experiencing pain preoperatively that was related to their PD. All 69 patients suffering from pain were followed up prospectively for 12 months after surgery. All patients described the severity of their pain according to a visual analog scale (VAS) preoperatively and at 2 weeks, 6 months, and 12 months postoperatively. Pain unrelated to PD was not studied. Results Several types of pain related to PD, the categories of which were based on a modification of 2 previous classifications (Ford and Honey), can occur in such patients: 1) musculoskeletal pain, 2) dystonic pain, 3) somatic pain exacerbated by PD, 4) radicular/peripheral neuropathic pain, and 5) central pain. The overall mean VAS score was significantly decreased postoperatively by 75% and 69% at 2 weeks and 6 months, respectively (p < 0.001). The mean VAS score at 12 months was also decreased by 80%, but 6 instances of pain (3 reports of somatic back pain and 3 reports of radicular/peripheral neuropathic pain) required additional spinal surgery to alleviate the pain severity. The results were analyzed using the Wilcoxon signed-rank test and demonstrated a significant reduction in VAS scores at all follow-up assessments (p < 0.001). Musculoskeletal pain and dystonic pain were well alleviated by STN stimulation. In contrast, somatic pain exacerbated by PD and peripheral neuropathic pain originating from lumbar spinal diseases, such as spondylosis deformans and/or canal stenosis, often deteriorated postoperatively despite attenuation of the patients' motor disability. Patients with central pain were poor responders. Conclusions This study found that STN stimulation produced significant improvement of overall pain related to PD in patients with advanced PD, and the efficacy continued for at least 1 year. The present results indicate that musculoskeletal pain and dystonic pain responded well to STN stimulation, but patients with back pain (somatic pain) and radicular/peripheral neuropathic pain originating from spinal disease have a potential risk for postoperative deterioration of their pain.

Recent studies have indicated the importance of subcortical mapping of the corticospinal tract (CT) during tumor resection close to the primary motor area. It is substantial evidence that the corticospinal descending direct wave (D-wave) can be used as a guide for mapping of the primary motor cortex (M1) and for monitoring of the CT functional integrity. In the present study, the authors investigated the feasibility of D-wave recordings after subcortical stimulation. The authors examined 14 patients with brain tumors close to the M1 and/or CT, who exhibited no obvious motor deficit before surgery. Subcortical white matter was electrically stimulated in monopolar or bipolar fashion by recording the descending wave (D-wave) from the spinal epidural space using a catheter-type electrode. Subcortical D-wave was more clearly recorded after monopolar stimulation than after bipolar stimulation. The features of the subcortical D-wave, including its waveform, conduction velocity, and latency, were nearly identical to those of the corticospinal D-wave recorded after M1 stimulation. Subcortical D-wave amplitude was prone to change depending on the distance from the stimulation points to the CT. Changes in parameters of subcortical D-wave may provide valuable information to prevent postoperative motor deficit. Further studies are required to clarify the relationship between the distance from the stimulating point to the CT and the amplitude of the subcortically elicited D-wave.

Deep brain stimulation (DBS) is an important component of the therapy for movement disorders and intractable pain. In Japan, the first case of DBS for controlling central pain syndrome was experienced in 1979 and DBS of the thalamic nucleus ventralis caudalis and periaqueductal gray matter have been used for pain control for many years. Neurosurgeons also initiated a clinical trial of DBS for controlling movement disorders, such as tremor, Parkinson′s disease (PD) and dystonia. Our government approved DBS to be covered by the public insurance system for pain control in 1992 and for movement disorders in 2000. In particular, DBS for subthalamic nucleus (STN) is currently the most common therapeutic surgical procedure for patients with PD. The long-lasting beneficial effects of STN-DBS on motor function have now largely been acknowledged. However, behavioral and/or psychiatric changes have been demonstrated in certain case reports and case series. DBS is also a successful therapeutic option for patients with primary dystonia and tremor syndrome who do not respond sufficiently to conservative therapies. The most common target of DBS in patients with dystonia is the internal region of the globus pallidus (GPi). GPi-DBS leads to long-lasting and remarkable improvement of dystonic movements in majority of patients. In Parkinson′s tremor or post-stroke movement disorder, the intermediate ventral nucleus of the thalamus (Vim) and the subthalamic region have proven to be promising targets for DBS electrodes. Especially in patients with essential tremor, Vim-DBS leads to an acute reduction of the tremor. In addition, DBS is beginning to be used as a new therapeutic procedure for psychiatric diseases, such as depression and obsessive-compulsive neurosis in many countries. We will summarize our experiences and previous reports, and discuss the mechanism and future perspectives for DBS in the management of central nervous system disorders.

One hundred and seven patients in vegetative state (VS) were evaluated neurologically and electrophysiologically over 3 months (90 days) after the onset of brain injury. Among these patients, 21 were treated with deep brain stimulation (DBS). The stimulation sites were the mesencephalic reticular formation (two patients) and centromedian-parafascicularis nucleus complex (19 cases). Eight of the patients recovered from VS and were able to obey verbal commands at 13 and 10 months in the case of head trauma and at 19, 14, 13, 12, 12 and 8 months in the case of vascular disease after comatose brain injury, and no patients without DBS recovered from VS spontaneously within 24 months after brain injury. The eight patients who recovered from VS showed desynchronization on continuous EEG frequency analysis. The Vth wave of the auditory brainstem response and N20 of the somatosensory evoked potential could be recorded, although with a prolonged latency, and the pain-related P250 was recorded with an amplitude of > 7 μV. Sixteen (14.9%) of the 107 VS patients satisfied these criteria in our electrophysiological evaluation, 10 of whom were treated with DBS and six of whom were not treated with DBS. In these 16 patients, the recovery rate from VS was different between the DBS therapy group and the no DBS therapy group (P < 0.01, Fisher's exact probability test) These findings indicate that DBS may be useful for the recovery of patients from VS if the candidates are selected on the basis of electrophysiological criteria.

A model that explains the pathophysiological condition of involuntary movements as the degree of output levels of the basal ganglia has been proposed. Because high frequency deep brain stimulation (DBS) has an effect similar to ablation, an initial hypothesis regarding the mechanism of DBS was the inhibition of excessive activity at the target site. A recent theory states that an abnormal neural activity pattern such as oscillation in the basal ganglia disrupts motor control. Local field potential recordings for Parkinson disease (PD) have shown increased beta-band oscillations associated with motor symptoms of PD. High-frequency stimulation of the subthalamic nucleus suppresses beta-band oscillations. Meanwhile, at the target site, high-frequency DBS has inhibitory effects on the soma and excitation effects on the axon, thereby influencing the target site and the neural activity of the projection site. DBS possibly acts by modifying or obstructing an abnormal nerve activity pattern in the neural network by combining different effects on the soma and axons, rather than by just suppressing the target site.

Objective: The development of image-guided systems rendered it possible to perform frameless stereotactic surgery for deep brain stimulation (DBS). As well as stereotactic targeting, neurophysiological identification of the target is important. Multitract microrecording is an effective technique to identify the best placement of an electrode. This is a report of our experience of using the Nexframe frameless stereotaxy with Ben’s Gun multitract microrecording drive and our study of the accuracy, usefulness and disadvantages of the system. Methods: Five patients scheduled to undergo bilateral subthalamic nucleus (STN) DBS were examined. The Nexframe device was adjusted to the planned target, and electrodes were introduced using a microdrive for multitract microrecording. In addition to the Nexframe frameless system, we adopted the Leksell G frame to the same patients simultaneously to use a stereotactic X-ray system. This system consisted of a movable X-ray camera with a crossbar and was adopted to be always parallel to the frame with the X-ray film cassette. The distance between the expected and actual DBS electrode placements was measured on such a stereotactic X-ray system. In addition, the distance measured with this system was compared with that measured by conventional frame-based stereotaxy in 20 patients (40 sides). Results: The mean deviations from 10 planned targets were 1.3 ± 0.3 mm in the mediolateral (x) direction, 1.0 ± 0.9 mm in the anteroposterior (y) direction and 0.5 ± 0.6 mm in the superoposterior (z) direction. The data from the frame-based stereotaxy in our institute were 1.5 ± 0.9 mm in the mediolateral (x) direction, 1.1 ± 0.7 mm in the anteroposterior (y) direction and 0.8 ± 0.6 mm in the superoposterior (z) direction. Then, differences were not statistically significant in any direction (p > 0.05). The multitract microrecording procedure associated with the Nexframe was performed without any problems in all of the patients. None of these electrodes migrated during and/or after the surgery. However, the disadvantage of the system is the narrow surgical field for multiple electrode insertion. Coagulating the cortex and inserting multiple electrodes under such a narrow visual field were complicated. Conclusion: The Nexframe with multitract microrecording for STN DBS still has some problems that need to be resolved. Thus far, we do not consider that this technology in its present state can replace conventional frame-based stereotactic surgery. The accuracy of the system is similar to that of frame-based stereotaxy. However, the narrow surgical field is a disadvantage for multiple electrode insertion. Improvement on this point will enhance the usefulness of the system.

For the treatment of intractable neuropathic pain, drug challenge test is necessary and useful to examine the pharmacological background of the pain in each case. Based on the results of drug challenge test, we can select the candidates for low-dose ketamine drip infusion (LDKDI) therapy and cerebrospinal stimulation therapy. In cerebrospinal stimulation therapy, dual-lead spinal cord stimulation should be selected at first, since we can insert electrodes percutaneously and this is suitable for both the test stimulation and chronic implantation. For the treatment of peripheral deafferentation pain, which includes phantom limb pain and peripheral nerve injury pain, deep brain stimulation therapy of the thalamic relay nucleus is suitable. Motor cortex stimulation therapy is suitable for the treatment of central deafferentation pain, which includes post-stroke pain. LDKDI therapy combined with cerebrospinal stimulation therapy achieves remarkable pain reduction in the treatment of neuropathic pain.

Introduction. Chronic thalamic stimulation has been confirmed as an effective treatment for tremor. The optimal target has been commonly accepted to be situated within the ventral thalamus, but a standard trajectory of the deep brain stimulation (DBS) electrode has not yet been established. Materials and Methods. A 53-year-old man with an 11-year history of essential tremor was treated by DBS of the thalamus. In this patient, we had a chance to compare the effects of different trajectory angles of the DBS electrode on tremor. Results. Intraoperative stimulation with the DBS electrode temporarily inserted at a high angle to the horizontal plane of the anterior commissure-posterior commissure (AC-PC) line to cover only the nucleus ventralis intermedius (Vim) was not effective. In contrast, stimulation with the DBS electrode permanently implanted at a low angle, covering a wide area extending from the nucleus ventralis oralis (Vo) to the Vim, reduced the tremor. Conclusion. We report on the case of a patient who showed different effects on tremor depending on the trajectory angle of the DBS electrode to the AC-PC line. The insertion trajectory of the DBS electrode may be an important factor for the treatment of tremor.

Striatal hand is a deformity encountered in Parkinson's disease and other parkinsonisms. It is characterized by extension that occurs at all the interphalangeal joints, flexion at the metacarpophalangeal joints, and ulnar deviation. It can be differentiated from levodopa-induced dystonia and primary dystonia, since the deformity exists continuously even during sleep. We experienced a case of Parkinson's disease with severe striatal hand deformity which was successfully treated by deep brain stimulation of the subthalamic nucleus (STN-DBS). Although the precise mechanism remains unclear, rigidity is assumed to contribute to the limb deformities. Based on our experience, it seems possible therefore that the effect of STN-DBS on the hand deformity was a secondary effect on muscular rigidity. STN-DBS is assumed to represent a useful treatment option for striatal hand deformity.

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.

✓Beginning-of-dose motor deterioration (BDMD) is a complication of levodopa medications in Parkinson disease (PD) that is presumably caused by inhibitory effects of levodopa. Only limited experience of BDMD has been described in the literature. The authors report the case of a patient with PD who demonstrated a marked BDMD while being treated with standard levodopa medications. This 55-year-old woman had a 12-year history of PD and a 10-year history of levodopa treatment. Marked exacerbation of symptoms occurred 15 to 20 minutes after every dose of levodopa at 100 mg and lasted approximately 15 minutes. The PD symptoms, particularly tremor and rigidity, were exacerbated more markedly during this period than during the wearing-off deterioration. The BDMD could be controlled very well by subthalamic nucleus (STN) stimulation without any change in the regimen of levodopa medications. These observations suggest that the BDMD was inhibited by STN stimulation through a direct effect.

In an attempt to control hypokinetic and hyperkinetic movement disorders, deep brain stimulation (DBS) has been developed during the last two decades by several investigators. In 1987, Benabid and his colleagues suggested the usefulness of high-frequency stimulation of the ventral intermediate nucleus of the thalamus for treating drug-resistant tremors and avoiding the adverse effects of thalamotomy. Since then, DBS has been used as an alternative to functional neurosurgery for movement disorders, and more recently, it has been applied to the treatment of epilepsy, obsessive-compulsive disorders and cluster headache, in addition to other applications in experimental models. In regard to the treatment of movement disorders, recent clinical studies have demonstrated that DBS affords great benefits in terms of improvement of the activities of daily living in patients with Parkinson's disease (PD), essential tremor, dystonia and poststroke hyperkinetic movement disorders. We have treated patients with movement disorders by DBS of the thalamic nuclei ventralis oralis (Voa/Vop) et intermedius (Vim), globus pallidus internus (GPi), and subthalamic nucleus (STN). The site of permanent electrode placement was identified using magnetic resonance imaging and multiunit extracellular recording. The implantable pulse generator was internalized after postoperative test stimulation for one week. The stimulation parameters were modified by physicians at each follow-up visit on the basis of the findings on neurological examination, as well as the patient's report concerning the activities of daily living. The advantages of DBS include reversibility and controllability of stimulation. In addition, DBS carries a smaller risk of side effects, particularly when employed bilaterally. Thalamic DBS is useful for controlling tremor that is unresponsive to medication. DBS of the STN and GPi improves the motor functions in PD patients, mainly during the off-period. Moreover, STN-DBS attenuates levodopa-induced dyskinesia through reducing the requirement of DOPA, whereas GPi-DBS directly attenuates DOPA-induced dyskinesia. In addition, GPi-DBS is very useful for controlling the symptoms of idiopatic generalized dystonia. According to reports, DBS is associated with few serious adverse effects associated with DBS. In general, the operative mortality is less than 1%. The incidences of hemorrhage are in the range of about 1-6%, and the incidences of device-related complications, such as infection or skin erosion, are in the range of 3-26%. DBS is clinically effective in well-selected patients and should be considered as a treatment option for patients with medically refractory movement disorders. Despite its clinical usefulness, the mechanism underlying the efficacy of DBS is still unclear. There is no proof currently that long-term DBS can reset neural networks or induce profound modifications of functional organization. Several researchers have proposed hypotheses concerning the mechanism underlying the efficacy of DBS, including 1) jamming of neural transmission, 2) direct inhibition of spike initiation at the level of the membrane that may be due to the activation of inhibitory terminals, 3) functional changes due to a decrease or increase in the amount of neurotransmitter released, and 4) retrograde activation of upstream neural structures. From the viewpoint of basic neuroscience, the development of DBS is intriguing. Investigation regarding the mechanism underlying the efficacy of DBS may provide clues for further clarification of various processes in the central nervous system.

The corticospinal motor evoked potential (MEP) evoked by motor cortex stimulation was investigated as an intraoperative index for the placement of stimulation electrodes in the epidural space over the motor cortex for the treatment of post-stroke pain. A grid of plate electrodes was placed in the epidural space to cover the motor cortex, sensory cortex, and premotor cortex employing a magnetic resonance imaging-guided neuronavigation system in two patients with severe post-stroke pain in the right extremities, a 66-year-old man with dysesthesia manifesting as burning and aching sensation, and a 67-year-old woman with dysesthesia manifesting as pricking sensation. The D-wave of the corticospinal MEP was recorded with a flexible wire electrode placed in the epidural space of the spinal cord during anodal monopolar stimulation of each plate electrode under general anesthesia. The grid electrode was fixed in position with dural sutures and the craniotomy closed. The effect of pain reduction induced by anodal monopolar stimulation of the same plate electrodes was examined using the visual analogue scale (VAS) on a separate day in the awake state without anesthesia. Comparison of the percentage VAS reduction and the recorded amplitude of the D-wave employing the same stimulation electrode revealed significant correlations in Case 1 (r = 0.828, p < 0.01) and Case 2 (r = 0.807, p < 0.01). The grid electrode was then replaced with two RESUME electrodes over the hand and foot areas, and the optimum positions were identified by D-wave recording before electrode fixation. Both patients reported satisfactory pain alleviation with lower stimulation voltages than usually required for patients with similar symptoms. These results indicate the potential of D-wave recording as an intraoperative indicator for the placement of stimulating electrodes over the motor cortex for pain relief.

Objectives Spinal cord stimulation (SCS) is not typically recommended for the treatment of central poststroke pain (CPSP). We examined whether the pharmacological evaluation of CPSP is useful for selecting the candidates for SCS. Materials and Methods Changes in visual analog scale (VAS) scores for pain following pharmacological evaluation using morphine, thiopental, and ketamine were compared with those following SCS in 22 CPSP patients. Results Twelve of the 22 (54.5%) patients in the ketamine test and thiopental test, and 5 (22.7%) of the 22 patients in the morphine test showed a more than 40% reduction in VAS score and were judged as “sensitive.” Pain relief by SCS was estimated as excellent (≧60% VAS score reduction) in three patients, good (30–59% reduction) in nine patients, and fair (10–29% reduction) in seven patients 24 months after the start of SCS. The remaining 3 patients evaluated as having poor pain relief (

To date, deep brain stimulation (DBS) has already been performed on more than 120,000 patients worldwide and in more than 7,000 patients in Japan. However, fundamental understanding of DBS effects on the pathological neural circuitry remains insufficient. Recent studies have specifically shown the importance of cortico-striato-thalamo-cortical (CSTC) loops, which were identified as functionally and anatomically discrete units. Three main circuits exist in the CSTC loops, namely, the motor, associative, and limbic circuits. From these theoretical backgrounds, it is determined that DBS sometimes influences not only motor functions but also the cognitive and affective functions of Parkinson's disease (PD) patients. The main targets of DBS for PD are subthalamic nucleus (STN) and globus pallidus interna (GPi). Ventralis intermedius (Vim)-DBS was found to be effective in improving tremor. However, Vim-DBS cannot sufficiently improve akinesia and rigidity. Therefore, Vim-DBS is seldom carried out for the treatment of PD. In this article, we review the present state of DBS, mainly STN-DBS and GPi-DBS, for PD. In the first part of the article, appropriate indications and practical effects established in previous studies are discussed. The findings of previous investigations on the complications caused by the surgical procedure and on the adverse events induced by DBS itself are reviewed. In the second part, we discuss target selection (GPi vs. STN) and the effect of DBS on nonmotor symptoms. In the final part, as issues that should be resolved, the suitable timing of surgery, symptoms unresponsive to DBS such as on-period axial symptoms, and the related postoperative programing of stimulation parameters, are discussed.

Background Cortical stimulation via a subdural grid electrode (SGE) is one of the most reliable methods for identifying eloquent areas before surgery. However, the physiological conditions of the cortex during stimulation cannot be monitored electrophysiologically because of electrical artifacts. In the present case, we tested whether or not multichannel near-infrared spectroscopy (NIRS) topography, a noninvasive optical imaging technique, is applicable for monitoring the physiological conditions of the stimulated cortex. Case description The patient (a 27-year-old right-handed man) suffered from glioma in the left frontal lobe. For preoperative cortical mapping, SGEs were implanted over the left motor cortex before tumor resection. Employing NIRS topography, we undertook 2 dimensional imaging of the changes in oxyhemoglobin (Oxy-Hb) and deoxyhemoglobin (Deoxy-Hb) concentration during electrical stimulation. Five-hertz stimulation with 5 mA at the left-hand area produced a localized increase in Oxy-Hb and a decrease in Deoxy-Hb, associated with slight twitching of the right hand. In contrast, 50-Hz stimulation produced significant increases in both Oxy-Hb and Deoxy-Hb at the stimulation site, and the area with such cerebral blood oxygenation (CBO) changes propagated beyond the hand area associated with prominent muscle contractions of the right upper extremity, suggesting that 50-Hz stimulation caused epileptic discharge. Conclusion Near-infrared spectroscopy topography may represent a useful tool for imaging the degree and extent of the physiological effects of electrical stimulation on the cortex, and permits safe and accurate cortical mapping.

Previous investigators have reported encouraging results for malignant gliomas treated using a combination of human interferon beta (IFN-beta) with nimustine hydrochloride (ACNU) and radiation therapy (termed IAR therapy). This study was undertaken to examine further the efficacy of the IAR regimen followed by maintenance therapy with IFN-beta and ACNU in patients with newly diagnosed malignant astrocytomas. Fifty-eight patients were enrolled onto the trial. IFN-beta (2 x 10(6) IU/m(2)/day x 5 days/week for 8 consecutive weeks) and ACNU (80 mg/m(2) on days 1 and 36) were administered intravenously concomitant with radiation therapy followed by IFN-beta (every 2 weeks) and ACNU (every 6 weeks). Of 33 patients assessable for a response, 11 responded (33%), with 4 complete responses. The estimated median overall survival (OS) was 16 months, with values of 58 and 13 months for anaplastic astrocytoma (AA) and glioblastoma (GB) patients, respectively. The overall progression free survival (PFS) was 11 months, with values of 31 and 7 months for AA and GB patients, respectively. The IAR therapy was safe and well tolerated. Based on a statistical analysis of the factors that affected the PFS and OS, histologic grade, postoperative Karnofsky performance scale (KPS), and extent of surgery were identified as independent predictors. The postoperative KPS stood out as the most powerful prognostic factor, which was also the best predictor for the response to IAR therapy. Our findings suggest a possible benefit for IAR therapy followed by maintenance therapy mainly in AA. In addition, they emphasize the importance of a preserved KPS after cytoreductive surgery, which could produce a potential benefit for adjuvant therapy and could ultimately lead to a prolonged survival.

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.

Development of instruments for spinal cord stimulation is remarkable. We can implant two cylinder-type stimulation electrodes in parallel into the spinal epidural space. We call this method for dual-lead SCS. Dual lead-SCS is useful to induce paresthesia over the painful area, and the success rate of pain reduction induced by dual-lead SCS is increasing. For dual-lead stimulation, the RestoreSensor, the EonMini, and the Precision Plus are suitable and useful for the treatment of intractable pain. Based on the results of a drug-challenge test with ketamine, we applied dual-SCS for the treatment of various kinds of neuropathic pain. Comparing with the results of single-lead SCS, dual-lead SCS has obvious advantages to evoke paresthesia over the painful area, and showed a remarkable effects for pain reduction. Dual-lead SCS combined with low-dose ketamine drip infusion method is useful for the treatment of various kinds of neuropathic pain. Even if the direct effect of ketamine is transient, effects that provide release from central sensitization and the wind-up phenomenon may be important to increase the effects of dual-lead SCS. Based on the development of dual-lead SCS, SCS therapy has become an important and powerful method for the treatment of intractable pain.

When chronic deep brain stimulation (DBS) was first developed, the Extrel type DBS system was typically used. The Extrel type DBS system contained (1) an external transmitter, ((2) an antenna, ((3) a receiver with an extension cable, and (4) a stimulation electrode. The energy evoked by the external pulse transmitter was transmitted through the antenna using a radio-frequency-coupled link, and the subcutaneous receiver decoded the radio frequency signal and delivered it to the stimulation electrode. Later, the Itrel type DBS system was developed. The Itrel system contains (1) an implantable pulse generator (IPG) which can be powered by its own battery, (2) an extension cable, and (3) a stimulation electrode. All of the Itrel type DBS systems have become completely internalized. One new IPG even contains a rechargeable battery for the prolongation of battery life; as a result, the time before IPG replacement required has increased up to 9 years.