Benefit of spinal cord stimulation for patients with central poststroke pain: a retrospective multicenter study.

OBJECTIVE: Spinal cord stimulation (SCS) has been considered an ineffective procedure for patients with central poststroke pain (CPSP). However, recent case series that included small numbers of patients reported the possible efficacy of SCS as a treatment of CPSP. This multicenter retrospective study aimed to examine the outcomes of using SCS to treat patients with CPSP and to explore factors related to outcomes. METHODS: The authors reviewed the medical records of patients with CPSP who underwent SCS to collect data regarding their background, surgical information, and outcomes of SCS at trial stimulation and last follow-up after long-term implantation in six study centers. Outcomes were evaluated with a pain score for intensity (range 0-10) and the Patient Global Impression of Changes (PGIC) scale. Factors associated with outcomes were explored with univariable and multivariable analyses. RESULTS: The authors collected data from a total of 166 patients (mean age 63.4 years; mean pain score at baseline 8.2). Of these patients, 163 underwent trial stimulation. The mean pain score decreased by 42.0%, 104 (64%) patients had ≥ 30% decrease in pain score, and 96 (59%) reported much or very much improved condition on the PGIC scale at trial stimulation. Moreover, 106 (64%) patients underwent long-term implantation of SCS devices. The mean decrease in pain score was 41.4%, 63 (59%) patients continued to show ≥ 30% decrease in pain score at last follow-up, and 60 (56%) reported much or very much improved condition on the PGIC scale at last follow-up (median [range] follow-up period 24 [24-63] months). Eleven device-related complications and 10 permanent explantations were observed. Univariable and multivariable analyses suggested that young age, less sensory disturbance, implantation of cervical leads, treatment of upper-limb pain, and extensive treated regions were associated with satisfactory outcomes at last follow-up after long-term implantation. CONCLUSIONS: These findings indicate that SCS may modestly benefit patients with CPSP. SCS has therapeutic potential for patients with intractable CPSP owing to the lower invasiveness of the SCS procedure and refractory nature of CPSP. Nevertheless, trial stimulation is necessary because of the high initial failure rate.

Activation peptide of coagulation factor IX improves the prognosis after traumatic brain injury.

Recently, coagulation factor IX and its activation peptide have been reported to suppress the permeability of vascular endothelial cells. In this study, the therapeutic effects of a synthesized activation peptide is investigated in traumatic brain injury model rats. In cerebral contusion, dysfunction of the blood brain barrier with increasing vascular permeability promotes the progression of neuropathy after injury. The model rats were generated by controlled cortical impact. Then, rats were intravenously injected with 350 µg/kg of the synthesized activation peptide or PBS as a control, every day for a month. Behavioral studies were conducted during a month of observation. For morphological analysis, macro- and microscopic observation were performed. Water content of brain tissue was used to assess edema. To assess the function of blood brain barrier, Evans Blue method was employed. In the neurological examinations and beam-walking, the treated rats performed significantly better than control rats. Measurements of cerebral defect volume showed that the treatment significantly reduced it by 82%. Nissl stain showed that neural cells adjacent to impacts were lost in control rats, but saved in treated rats. The treatment significantly reduced brain edema and extravascular leakage of Evans blue. Intravenous injection with a synthesized activation peptide significantly reduced damage to neural tissue and improved neural functioning in the model rats.

The Japan Neurosurgical Database: Overview and Results of the First-year Survey.

The Japan Neurosurgical Database (JND) is a prospective observational study registry established in 2017 by the Japan Neurosurgical Society (JNS) to visualize real-world clinical practice, promote science, and improve the quality of care and neurosurgery board certification in Japan. We summarize JND's aims and methods, and describes the 2018 survey results. The JND registered in-hospital patients' clinical data mainly from JNS training institutions in 2018. Caseload, patient demographics, and in-hospital outcomes of the overall cohort and a neurosurgical subgroup were examined according to major classifications of main diagnosis. Neurosurgical caseload per neurosurgeon in training in core hospitals in 2018 was calculated as an indicator of neurosurgical training. Of 523,283 cases (male 55.3%) registered from 1360 participating institutions, the neurosurgical subgroup comprised of 33.9%. Among the major classifications, cerebrovascular diseases comprised the largest proportion overall and in the neurosurgical subgroup (53.1%, 41.0%, respectively), followed by neurotrauma (19.1%, 25.5%), and brain tumor (10.4%, 12.8%). Functional neurosurgery (6.4%, 3.7%), spinal and peripheral nerve disorders (5.1%, 10.1%), hydrocephalus/developmental anomalies (2.9%, 5.3%), and encephalitis/infection/inflammatory and miscellaneous diseases (2.9%, 1.6%) comprised smaller proportions. Most patients were aged 70-79 years in the overall cohort and neurosurgical subgroup (27.8%, 29.4%). Neurotrauma and cerebrovascular diseases in the neurosurgical subgroup comprised a higher and lower proportion, respectively, than in the overall cohort in elderly patients (e.g. 80 years, 46.9% vs. 33.5%, 26.8% vs. 54.4%). The 2018 median neurosurgical caseload per neurosurgeon in training was 80.7 (25-75th percentile 51.5-117.5). These initial results from 2018 reveal unique aspects of neurosurgical practice in Japan.

Suppression of Superficial Microglial Activation by Spinal Cord Stimulation Attenuates Neuropathic Pain Following Sciatic Nerve Injury in Rats.

We evaluated the mechanisms underlying the spinal cord stimulation (SCS)-induced analgesic effect on neuropathic pain following spared nerve injury (SNI). On day 3 after SNI, SCS was performed for 6 h by using electrodes paraspinally placed on the L4-S1 spinal cord. The effects of SCS and intraperitoneal minocycline administration on plantar mechanical sensitivity, microglial activation, and neuronal excitability in the L4 dorsal horn were assessed on day 3 after SNI. The somatosensory cortical responses to electrical stimulation of the hind paw on day 3 following SNI were examined by using in vivo optical imaging with a voltage-sensitive dye. On day 3 after SNI, plantar mechanical hypersensitivity and enhanced microglial activation were suppressed by minocycline or SCS, and L4 dorsal horn nociceptive neuronal hyperexcitability was suppressed by SCS. In vivo optical imaging also revealed that electrical stimulation of the hind paw-activated areas in the somatosensory cortex was decreased by SCS. The present findings suggest that SCS could suppress plantar SNI-induced neuropathic pain via inhibition of microglial activation in the L4 dorsal horn, which is involved in spinal neuronal hyperexcitability. SCS is likely to be a potential alternative and complementary medicine therapy to alleviate neuropathic pain following nerve injury.

Bipolar dual-lead spinal cord stimulation between two electrodes on the ventral and dorsal sides of the spinal cord: consideration of putative mechanisms.

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.

Predictive Factors for Long-term Outcome of Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease.

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.

Spinal Cord Stimulation for Vegetative State and Minimally Conscious State: Changes in Consciousness Level and Motor Function.

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.

Glioblastoma Multiforme Developed during Chronic Deep Brain Stimulation for Parkinson Disease.

BACKGROUND: In this reported case, 7 years after the start of deep brain stimulation (DBS) of the bilateral subthalamic nucleus (STN), glioblastoma multiforme (GBM) developed around the implanted DBS lead. CASE REPORT: The brain tumor formed from the subcortical white matter to the corpus callosum bilaterally around the DBS lead but did not extend in the direction of the contact points of the lead. The GBM showed a typical invasion pattern of the butterfly type. We report the first case of GBM that developed 7 years after the start of STN-DBS. CONCLUSION: Considering the low rate of GBM occurrence in association with DBS, the location of the glioma, and the pattern of tumor invasion, we speculate that GBM developed spontaneously and extended to some degree around the DBS lead. Moreover, there is a very slight possibility that continuous electrical brain stimulation itself induced the development of the brain glioma.

Importance of Pharmacological Evaluation in the Treatment of Poststroke Pain by Spinal Cord Stimulation.

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 (<10% reduction) only underwent test SCS. VAS score reduction induced by SCS was more significant in ketamine-sensitive patients than in ketamine-resistant patients during the test SCS (p < 0.01, Mann-Whitney's U test) and 24 months after the start of chronic SCS (p < 0.05). However, there were no significant differences in results for thiopental-sensitive/thiopental-resistant or morphine-sensitive/morphine-resistant patients during the test SCS and 24 months after chronic SCS. Analysis of the rate of VAS score reduction by pharmacological evaluation and SCS showed significant correlations with the results of the ketamine test (r = 0.670, p = 0.001, Pearson's correlation coefficient test), but not with those of the thiopental (r = 0.291, p = 0.231) or morphine test (r = 0.327, p = 0.175). CONCLUSION: We speculate that the pharmacological evaluation of CPSP patients can be a useful tool for selecting candidates for SCS.

[Blood PCB Concentrations and their Tendencies Examined in Fukuoka 2011-2014 Annual Inspections for Yusho].

We measured PCBs of blood of 154 people in the Yusho medical check-up from January 2011 through December 2014 and analyzed their PCB blood patterns. Eleven examinees were newly certified as Yusho patients during these 4 years. Of these 11, we identified three Yusho patients with the A pattern, five with the B pattern, and three with the BC pattern. We found no Yusho patients with the C pattern. The B pattern was found in 27 of the 154 examinees, such that the probability that an examinee with the B pattern would be certified as a Yusho patient was about 20%. Since 2012, any family members living with a Yusho patient have also been certified as Yusho patients. The number of such family cohabitants was 16, among whom the PCB pattern was uniformly the C pattern. There were 20 examinees born after 1989, and all those examinees were Yusho-suspected persons. The total PCB concentrations of this younger-age group was less than 0.5 ng/g on average and was low compared with the normal controls.

Deep brain stimulation for Parkinson's disease: recent trends and future direction.

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.

[Systematic review of complications for proper informed consent(13)stereotactic and functional neurosurgery].

We conducted a systematic review to assess the incidence of various surgical complications both during and after stereotactic and functional neurosurgery. Initially, we considered that surgical complications and the adverse effects of stimulation should be differentiated. In some reports, intracranial hemorrhage, infection, device-related problems, and epileptic seizure have been regarded as major and serious surgical complications. The established rates of hemorrhagic complications are 3.7%[95% confidence interval(CI):2.8-4.6%]for coagulation surgery and 4.6%(95% CI:3.8-5.3%)for deep brain stimulation(DBS). However, the rates of significant permanent neurological deficits originating from hemorrhage were relatively low. The average rates were 1.2%(95% CI:0.7-1.6%)for coagulation surgery and 1.0%(95% CI:0.6-1.3%)for DBS. Almost all of the patients with infectious complications had undergone DBS, and these complications were very rarely encountered after coagulation surgery. The rate of the occurrence of infection in DBS patients was 4.0%(95% CI:3.5-4.5%). Device-related problems were complications of DBS, and the main problems were migration and fracture. Epileptic seizure was noted in 0.4%(95% CI:0.1-0.7%)of the patients who underwent coagulation surgery and in 3.2%(95% CI:2.3-4.0%)of those who underwent DBS. The actual rate of occurrence of epileptic seizure was speculated to be much lower than the above rate because we did not include analytical reports that did not mention epileptic seizure. The exact rate of the occurrence of adverse effects caused by DBS was difficult to determine. Skill in the programming of the stimulation parameters, disease progression, and the balance between drugs and stimulation may affect the postoperative adverse events. However, we can advise patients and their families of the potential for psychiatric symptoms, depression, and cognitive dysfunction, which could seriously infringe on the patient's quality of life, after DBS.

[Instruments for spinal cord stimulation].

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.

Multitarget, dual-electrode deep brain stimulation of the thalamus and subthalamic area for treatment of Holmes' tremor.

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.

Acute stress exposure preceding transient global brain ischemia exacerbates the decrease in cortical remodeling potential in the rat retrosplenial cortex.

Doublecortin (DCX)-immunoreactive (-ir) cells are candidates that play key roles in adult cortical remodeling. We have previously reported that DCX-ir cells decrease after stress exposure or global brain ischemia (GBI) in the cingulate cortex (Cg) of rats. Herein, we investigate whether the decrease in DCX-ir cells is exacerbated after GBI due to acute stress exposure preconditioning. Twenty rats were divided into 3 groups: acute stress exposure before GBI (Group P), non-stress exposure before GBI (Group G), and controls (Group C). Acute stress or GBI was induced by a forced swim paradigm or by transient bilateral common carotid artery occlusion, respectively. DCX-ir cells were investigated in the anterior cingulate cortex (ACC) and retrosplenial cortex (RS). The number of DCX-ir cells per unit area (mm(2)) decreased after GBI with or without stress preconditioning in the ACC and in the RS (ANOVA followed by a Tukey-type test, P<0.001). Moreover, compared to Group G, the number in Group P decreased significantly in RS (P<0.05), though not significantly in ACC. Many of the DCX-ir cells were co-localized with the GABAergic neuronal marker parvalbumin. The present study indicates that cortical remodeling potential of GABAergic neurons of Cg decreases after GBI, and moreover, the ratio of the decrease is exacerbated by acute stress preconditioning in the RS.

[Examination of alkali digestion temperature in isomer specific analysis of PCB in whole blood sample].

We compared concentrations of PCB congeners between conventional 80 degrees C alkali digestion method and 30 degrees C alkali digestion method using 22 individual blood samples collected during 2009 annual Yusho examinations. The mean concentration of tri-CB in 30 degrees C alkali digestion method was lower than that of conventional method. However, concentration of total PCBs, 2,3',4,4',5-pentaCB (PCB118), 2,2',4,4',5,5'-hexaCB (PCB153) and 2,3,3',4,4', 5-hexaCB (PCB156), which were used as index for Yusho diagnosis, were equivalent between the methods. It was considered that the 30 degrees C alkali digestion method was available for blood PCB congener specific analysis in Yusho diagnosis.

Daily repetitive transcranial magnetic stimulation of primary motor cortex for neuropathic pain: a randomized, multicenter, double-blind, crossover, sham-controlled trial.

There is little evidence for multisession repetitive transcranial magnetic stimulation (rTMS) on pain relief in patients with neuropathic pain (NP), although single-session rTMS was suggested to provide transient pain relief in NP patients. We aimed to assess the efficacy and safety of 10 daily rTMS in NP patients. We conducted a randomized, double-blind, sham-controlled, crossover study at 7 centers. Seventy NP patients were randomly assigned to 2 groups. A series of 10 daily 5-Hz rTMS (500 pulses/session) of primary motor cortex (M1) or sham stimulation was applied to each patient with a follow-up of 17days. The primary outcome was short-term pain relief assessed using a visual analogue scale (VAS). The secondary outcomes were short-term change in the short form of the McGill pain questionnaire (SF-MPQ), cumulative changes in the following scores (VAS, SF-MPQ, the Patient Global Impression of Change scale [PGIC], and the Beck Depression Inventory [BDI]), and the incidence of adverse events. Analysis was by intention to treat. This trial is registered with the University hospital Medical Information Network Clinical Trials Registry. Sixty-four NP patients were included in the intention-to-treat analysis. The real rTMS, compared with the sham, showed significant short-term improvements in VAS and SF-MPQ scores without a carry-over effect. PGIC scores were significantly better in real rTMS compared with sham during the period with daily rTMS. There were no significant cumulative improvements in VAS, SF-MPQ, and BDI. No serious adverse events were observed. Our findings demonstrate that daily high-frequency rTMS of M1 is tolerable and transiently provides modest pain relief in NP patients.

Comparison between pharmacologic evaluation and repetitive transcranial magnetic stimulation-induced analgesia in poststroke pain patients.

BACKGROUND: It has been reported that poststroke pain has a complex pharmacologic background and that only about one-half of poststroke pain patients are sensitive to motor cortex stimulation induced by repetitive transcranial magnetic stimulation (rTMS). OBJECTIVES: The relationship between pharmacologic background and effects of rTMS of the primary motor cortex was investigated to clarify the pharmacologic basis of rTMS-induced analgesia in poststroke pain patients. METHODS: Changes in visual analog scale (VAS) score for pain following drug challenge tests using ketamine, morphine, and thiopental were compared with the changes in VAS score following rTMS of the primary motor cortex (frequency 5 Hz, at 100% resting motor threshold, 500 pulses per session) in 20 poststroke pain patients. RESULTS: In our drug challenge test, 10 of 20 (50%) patients in ketamine test, 7 of 20 (35%) in thiopental test, and 3 of 20 (15%) in morphine test showed more than 40% reduction of VAS score. VAS score decreased immediately after rTMS of motor cortex and persisted for 300 min (p < 0.05, Bonferroni's multiple comparisons). Comparison of the magnitude of VAS score reduction between drug challenge test and rTMS showed significant correlations with ketamine test (r = 0.503, p = 0.012), morphine test (r = 0.526, p = 0.009), and thiopental test (r = 0.609, p = 0.002) by regression analysis. CONCLUSIONS: rTMS-induced VAS score reduction correlated well with morphine, ketamine, and thiopental tests. However, ketamine sensitivity was observed in more cases compared with morphine and thiopental in poststroke pain patients. We speculate that additional pharmacologic therapy using ketamine as determined on the basis of the ketamine test may be useful for enhancing the efficacy of rTMS in poststroke pain patients.

Simulation to locate burr hole sites in a patient for deep brain stimulation surgery and clipping of intracranial aneurysm.

BACKGROUND AND OBJECTIVE: Deep brain stimulation (DBS) candidates with neurologic diseases such as unruptured aneurysm present additional challenges to neurosurgeons when craniotomy must precede DBS surgery. Such craniotomy may potentially overlap with intended burr hole sites for the later insertion of DBS electrodes, and the skin incision for craniotomy may lie very close to or intersect with that for the burr holes. We report here a case of forehead craniotomy prior to DBS surgery in which we employed a neuronavigation system to simulate locations for the craniotomy and burr holes. METHOD: A 62-year-old male patient with Parkinson's disease was a candidate for DBS. He also had an aneurysm and was planned first to undergo frontal craniotomy for clipping before the DBS surgery. The locations of the craniotomy, burr holes, and skin incisions were therefore simulated using a neuronavigation system during craniotomy. RESULTS: Two weeks after the craniotomy, the patient underwent DBS surgery. Planning software confirmed the absence of cortical veins beneath the entry points of tentative burr holes and aided trajectory planning. The DBS surgery was performed without the interference of the burr holes and head pins and the craniotomy. CONCLUSION: Simulation of the locations of craniotomy and burr holes using a neuronavigation system proved valuable in the present case of frontal craniotomy before DBS surgery.

Deep brain stimulation and spinal cord stimulation for vegetative state and minimally conscious state.

OBJECTIVE: On the basis of the findings of the electrophysiological evaluation of vegetative state (VS) and minimally conscious state (MCS), the effect of deep brain stimulation (DBS) was examined according to long-term follow-up results. The results of spinal cord stimulation (SCS) on MCS was also examined and compared with that of DBS. METHODS: One hundred seven patients in VS and 21 patients in MCS were evaluated neurologically and electrophysiologically over 3 months after the onset of brain injury. Among the 107 VS patients, 21 were treated by DBS. Among the 21 MCS patients, 5 were treated by DBS and 10 by SCS. RESULTS: Eight of the 21 patients recovered from VS and were able to follow verbal instructions. These eight patients showed desynchronization on continuous electroencephalographic frequency analysis. The Vth wave of the auditory brainstem response and N20 of somatosensory evoked potential were recorded even with a prolonged latency, and pain-related P250 was recorded with an amplitude of more than 7 µV. In addition, DBS and SCS induced a marked functional recovery in MCS patients who satisfied the electrophysiological inclusion criteria. CONCLUSION: DBS for VS and MCS patients and SCS for MCS patients may be useful, when the candidates are selected on the basis of the electrophysiological inclusion criteria. Only 16 (14.9%) of the 107 VS patients and 15 (71.4%) of the 21 MCS patients satisfied the electrophysiological inclusion criteria.