Toshiki Obuchi

Deep Brain Stimulation Influences Brain Structure in Alzheimer's Disease

BACKGROUND Deep Brain Stimulation (DBS) is thought to improve the symptoms of selected neurological disorders by modulating activity within dysfunctional brain circuits. To date, there is no evidence that DBS counteracts progressive neurodegeneration in any particular disorder. OBJECTIVE/HYPOTHESIS We hypothesized that DBS applied to the fornix in patients with Alzheimers Disease (AD) could have an effect on brain structure. METHODS In six AD patients receiving fornix DBS, we used structural MRI to assess one-year change in hippocampal, fornix, and mammillary body volume. We also used deformation-based morphometry to identify whole-brain structural changes. We correlated volumetric changes to hippocampal glucose metabolism. We also compared volumetric changes to those in an age-, sex-, and severity-matched group of AD patients (n = 25) not receiving DBS. RESULTS We observed bilateral hippocampal volume increases in the two patients with the best clinical response to fornix DBS. In one patient, hippocampal volume was preserved three years after diagnosis. Overall, mean hippocampal atrophy was significantly slower in the DBS group compared to the matched AD group, and no matched AD patients demonstrated bilateral hippocampal enlargement. Across DBS patients, hippocampal volume change correlated strongly with hippocampal metabolism and with volume change in the fornix and mammillary bodies, suggesting a circuit-wide effect of stimulation. Deformation-based morphometry in DBS patients revealed local volume expansions in several regions typically atrophied in AD. CONCLUSION We present the first in-human evidence that, in addition to modulating neural circuit activity, DBS may influence the natural course of brain atrophy in a neurodegenerative disease.

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.

On-Demand Control System for Deep Brain Stimulation for Treatment of Intention Tremor

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.

Thalamic Sensory Relay Nucleus Stimulation for the Treatment of Peripheral Deafferentation Pain

We applied chronic deep brain stimulation (DBS) of the thalamic nucleus ventralis caudalis (Vc) for the treatment of peripheral deafferentation pain. The subjects included 11 cases of phantom limb pain and 7 of root or nerve injury pain without phantom sensation. In the phantom limb pain patients, the spike density markedly increased in the same area of the Vc where microstimulation induced paresthesia in the part with phantom sensation. Reorganization of the receptive field representation within the Vc was also demonstrated by microrecording and microstimulation. In the root or nerve injury pain patients with severe allodynia and without phantom sensation, oscillating neural hyperactivity appeared when the allodynia was induced during single-cell recording in the Vc. In both groups stimulation of these areas with the DBS electrode was useful for achieving pain reduction. Inhibition of spinothalamic tract neurons, restoration of the original receptive field representation and modulation of thalamocortical rhythmic oscillations are proposed to play important roles in a possible mechanism of Vc-DBS for the treatment of deafferentation pain.

Direction and predictive factors for the shift of brain structure during deep brain stimulation electrode implantation for advanced Parkinson's disease.

Objectives.  The aims of this study were to clarify the direction and degree of brain shift, and to determine the predictive factors for a brain shift during deep brain stimulation (DBS) of the subthalamic nucleus (STN).

Nexframe Frameless Stereotaxy with Multitract Microrecording: Accuracy Evaluated by Frame-Based Stereotactic X-Ray

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

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.

F-Wave Suppression Induced by Suprathreshold High-Frequency Repetitive Trascranial Magnetic Stimulation in Poststroke Patients with Increased Spasticity

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.

Thalamic deep brain stimulation for the treatment of action myoclonus caused by perinatal anoxia.

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

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.