Oxytocin-Dependent Regulation of TRPs Expression in Trigeminal Ganglion Neurons Attenuates Orofacial Neuropathic Pain Following Infraorbital Nerve Injury in Rats.

We evaluated the mechanisms underlying the oxytocin (OXT)-induced analgesic effect on orofacial neuropathic pain following infraorbital nerve injury (IONI). IONI was established through tight ligation of one-third of the infraorbital nerve thickness. Subsequently, the head withdrawal threshold for mechanical stimulation (MHWT) of the whisker pad skin was measured using a von Frey filament. Trigeminal ganglion (TG) neurons innervating the whisker pad skin were identified using a retrograde labeling technique. OXT receptor-immunoreactive (IR), transient receptor potential vanilloid 1 (TRPV1)-IR, and TRPV4-IR TG neurons innervating the whisker pad skin were examined on post-IONI day 5. The MHWT remarkably decreased from post-IONI day 1 onward. OXT application to the nerve-injured site attenuated the decrease in MHWT from day 5 onward. TRPV1 or TRPV4 antagonism significantly suppressed the decrement of MHWT following IONI. OXT receptors were expressed in the uninjured and Fluoro-Gold (FG)-labeled TG neurons. Furthermore, there was an increase in the number of FG-labeled TRPV1-IR and TRPV4-IR TG neurons, which was inhibited by administering OXT. This inhibition was suppressed by co-administration with an OXT receptor antagonist. These findings suggest that OXT application inhibits the increase in TRPV1-IR and TRPV4-IR TG neurons innervating the whisker pad skin, which attenuates post-IONI orofacial mechanical allodynia.

[Frontal Lobe Signs Caused by Migration of a Burr Hole Cap into the Brain after Deep Brain Stimulation Surgery:A Case Report].

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.

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.

Brain magnetic resonance imaging examination in a patient with non-magnetic resonance conditional pacemaker.

Clinical dilemmas arise when patients with a non-magnetic resonance (MR) conditional pacemaker are required to undergo magnetic resonance imaging (MRI). We encountered a pacemaker patient with debilitating non-motor symptoms of Parkinson׳s disease, who required an MRI prior to deep brain stimulation (DBS) surgery. MRI was performed safely without adverse events despite the presence of a conventional pacemaker.

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.

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.

[Successful treatment with bilateral deep brain stimulation of the subthalamic nucleus for benign tremulous parkinsonism].

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]2ß-carbomethoxy-3ß-(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.

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.

Neuromodulation of vegetative state through spinal cord stimulation: where are we now and where are we going?

BACKGROUND: Vegetative state (VS) is a complex condition that represents a challenging frontier for medicine and neuroscience research. Nowadays there is no scientifically validated treatment for VS patients, and their chronic long-term assistance is very demanding for healthcare systems worldwide. OBJECTIVES: The present paper is a systematic review of the role of spinal cord stimulation (SCS) as a treatment of patients with VS. METHODS: Published literature on this topic was analyzed systematically. Clinical and epidemiological characteristics of VS, present therapeutic options and social costs of VS were also evaluated. RESULTS: Only 10 papers have been published since 1988, and overall 308 VS patients have been treated with SCS worldwide; 51.6% displayed a clinical improvement and an amelioration of the environmental interaction. These effects are probably mediated by the stimulation of the reticular formation-thalamus-cortex pathway and by cerebral blood flow augmentation induced by SCS. CONCLUSIONS: The experience on this topic is still very limited, and on this basis it is still hard to make any rigorous assessment. However, the most recent experiments represent significant progress in the research on this topic and display SCS as a possible therapeutic tool in the treatment of VS.

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.

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.

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.

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.