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.

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.

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.

[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.

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.

On-demand control system for deep brain stimulation for treatment of intention 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.

F-wave suppression induced by suprathreshold high-frequency repetitive trascranial magnetic stimulation in poststroke patients with increased spasticity.

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.

Fatal hemorrhage from AVM after DBS surgery: case report.

OBJECTIVES: Intracranial hemorrhage is a crucial complication of deep brain stimulation (DBS) surgery. The bleeding caused by mechanical tissue injury due to microelectrode and/or DBS electrode lead insertion has been well studied. However, hemorrhage caused by a congenital underlying disease such as vascular malformation has not been examined carefully. MATERIALS AND METHODS: We encountered a case of intracerebral hemorrhage from arteriovenous malformation (AVM) after DBS surgery. Preoperative magnetic resonance (MR) imaging did not show any abnormality in the patient. Computed tomography (CT) images taken immediately after the surgery did not show any intracranial hematoma and other abnormal findings. However, the patient did not recover from the general anesthesia, and hemorrhage in the left occipital lobe was detected by CT performed a day after the surgery. The location of the hematoma was markedly distant from the trajectory of DBS leads. Evacuation of the hematoma under general anesthesia was immediately performed. RESULTS: As an intraoperative finding, we noted the presence of abnormal vessels inside the hematoma in the occipital lobe. Tissue specimens including the abnormal vessels were obtained for histopathological analysis, results of which led to the diagnosis was AVM. CONCLUSION: Despite its low incidence, we would like to advise that such a type of hemorrhage could occur and measures should be taken to prevent its occurrence as much as possible. Preoperative detection of abnormal vessels by MR angiography and/or CT angiography might be helpful. Moreover, paying close attention to the possible leakage of cerebrospinal fluid during surgery might be important.

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.

[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.

Somatostatin-immunoreactive senile plaque-like structures in the frontal cortex and nucleus accumbens of aged tree shrews and Japanese macaques.

BACKGROUND: Previously, we demonstrated decreased expression of somatostatin mRNA in aged macaque brain, particularly in the prefrontal cortex. To investigate whether or not this age-dependent decrease in mRNA is related to morphological changes, we analyzed somatostatin cells in the cerebra of aged Japanese macaques and compared them with those in rats and tree shrews, the latter of which are closely related to primates. METHODS: Brains of aged macaques, tree shrews, and rats were investigated by immunohistochemistry with special emphasis on somatostatin. RESULTS: We observed degenerating somatostatin-immunoreactive cells in the cortices of aged macaques and tree shrews. Somatostatin-immunoreactive senile plaque-like structures were found in areas 6 and 8 and in the nucleus accumbens of macaques, as well as in the nucleus accumbens and the cortex of aged tree shrews, where amyloid accumulations were observed. CONCLUSIONS: Somatostatin degenerations may be related to amyloid accumulations and may play roles in impairments of cognitive functions during aging.

Effect of subthalamic nucleus deep brain stimulation on the autonomic nervous system in Parkinson's disease patients assessed by spectral analyses of R-R interval variability and blood pressure variability.

OBJECTIVE: Autonomic nervous system impairment is an untoward symptom that is typically observed in advanced Parkinson's disease (PD) patients. However, details of the effects of subthalamic nucleus deep brain stimulation (STN-DBS) on the autonomic nervous system remain unclear. METHODS: Twenty-eight patients with advanced PD (12 males and 16 females) who underwent bilateral STN-DBS and 13 age-matched healthy controls were included in this study. We analyzed the dynamic cardiovascular autonomic function regulating the R-R interval and blood pressure by spectral and transfer function analyses of cardiovascular variability before and after STN-DBS. RESULTS: Vagally mediated arterial-cardiac baroreflex function improved after STN-DBS compared to that before STN-DBS (p < 0.05). However, there were no statistically significant differences in the results of the comparison of vagally mediated arterial-cardiac baroreflex function between on-stimulation and off-stimulation. CONCLUSIONS: The vagal component in cardiac autonomic dysfunction associated with PD is expected to improve after STN-DBS. We considered that the patients improved their lifestyle; in particular, increasing the amount of exercise by STN-DBS and the best pharmachological treatment may have positive effects on parasympathetic activities.

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.

Changes in motor function induced by chronic motor cortex stimulation in post-stroke pain patients.

BACKGROUND: In well-designed multicenter studies, the protocol of continuing motor cortex stimulation (MCS) temporarily for 3-6 weeks was employed with rehabilitation therapy, and these studies showed some recovery of motor weakness in post-stroke patients. OBJECTIVES: We aimed to clarify the effects of long-term MCS and the optimal stimulation conditions to improve motor weakness in post-stroke patients. METHODS: We applied chronic MCS in 6 post-stroke pain patients with motor weakness. We then examined the correlation between the duration of daily MCS applied over 6 months and motor function assessed on the basis of the Fugl-Meyer Assessment (FMA) score of the patients. RESULTS: In the 6 patients with motor weakness, the FMA score of the upper extremity increased in 4 patients who underwent daily MCS for less than 4 h. On the other hand, 2 patients who continued excessive MCS to control their complicating post-stroke pain showed decreased FMA scores and worsened motor function owing to their increased rigidity and/or spasticity. These 2 patients recovered their motor function after their daily MCS was restricted to less than 4 h. CONCLUSIONS: These findings indicate that MCS could be a new therapeutic approach to improving motor performance after stroke by attenuating rigidity and/or spasticity. However, it may be important to define the appropriate number of hours and conditions of daily MCS.

Deep brain stimulation for the treatment of vegetative state.

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.