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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 Alzheimer's 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.

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.

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.

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

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

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

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

Deep brain stimulation (DBS) is a surgical procedure used to treat various neurological disorders such as intractable pain, Parkinson’s disease, essential tremor, dystonia, and other movement disorders. It involves implanting electrodes in the brain, which send electrical impulses to modulate brain activity. This procedure is not considered radical and can significantly improve disabling neurological symptoms. Such symptoms used to commonly require invasive surgeries such as thalamotomy and pallidotomy, which destroy those parts of the brain where abnormal activity has occurred. In recent years, such surgeries have been performed less frequently because of the risk of severe complications and the availability of DBS, which is safer and has fewer complications. Deep brain stimulation allows abnormal brain activity to be regulated without destruction of brain tissue. This means that DBS offers numerous advantages over conventional surgeries as it is reversible and enables the surgeon to modulate and improve specific functions or symptoms. Despite DBS having become widely accepted as an effective therapy for various neurological disorders, its fundamental principles and mechanisms are still not precisely defined.

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.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.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.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.

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.

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.

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). Materials and Methods. To evaluate the brain shift during bilateral STN-DBS, the position of the anterior commissure (AC), posterior commissure (PC), midcommissure point (MC), and tip of the frontal lobe and anterior horn of the lateral ventricle were calculated pre- and poststereotactic operations in the three-dimensional direction employing special software (Leksell SurgiPlan). To determine the predictive factors for a brain shift, patient's age, operation hours, width of the third ventricle, bicaudate index (BCI), and cella media index (CMI) were compared with the shift of MC. Results. In 50 patients, the MC shifted mainly in the posterior direction (y-axis: 1.27 ± 0.7 mm), and the shifts in the inferior direction (z-axis: 0.11 ± 0.43 mm) and lateral direction (x-axis: 0.02 ± 0.39 mm) were small. The shift of the MC in the posterior direction correlated well with the shift of the tip of the anterior lobe and anterior horn. Among the predictive factors examined, namely, the patient's age, operation hours, width of the third ventricle, BCI, and CMI, only the CMI showed a correlation with the shift of the MC (r = 0.42, p

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.

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.

The corticospinal motor evoked potential (MEP) evoked by motor cortex stimulation was investigated as an intraoperative index for the placement of stimulation electrodes in the epidural space over the motor cortex for the treatment of post-stroke pain. A grid of plate electrodes was placed in the epidural space to cover the motor cortex, sensory cortex, and premotor cortex employing a magnetic resonance imaging-guided neuronavigation system in two patients with severe post-stroke pain in the right extremities, a 66-year-old man with dysesthesia manifesting as burning and aching sensation, and a 67-year-old woman with dysesthesia manifesting as pricking sensation. The D-wave of the corticospinal MEP was recorded with a flexible wire electrode placed in the epidural space of the spinal cord during anodal monopolar stimulation of each plate electrode under general anesthesia. The grid electrode was fixed in position with dural sutures and the craniotomy closed. The effect of pain reduction induced by anodal monopolar stimulation of the same plate electrodes was examined using the visual analogue scale (VAS) on a separate day in the awake state without anesthesia. Comparison of the percentage VAS reduction and the recorded amplitude of the D-wave employing the same stimulation electrode revealed significant correlations in Case 1 (r = 0.828, p0.01) and Case 2 (r = 0.807, p0.01). The grid electrode was then replaced with two RESUME electrodes over the hand and foot areas, and the optimum positions were identified by D-wave recording before electrode fixation. Both patients reported satisfactory pain alleviation with lower stimulation voltages than usually required for patients with similar symptoms. These results indicate the potential of D-wave recording as an intraoperative indicator for the placement of stimulating electrodes over the motor cortex for pain relief.

Introduction. The term “camptocormia” describes a forward-flexed posture. It is a condition characterized by severe frontal flexion of the trunk. Recently, camptocormia has been regarded as a form of abdominal segmental dystonia. Deep brain stimulation (DBS) is a promising therapeutic approach to various types of movement disorders. The authors report the neurological effects of DBS to the bilateral globus pallidum (GPi) in three cases of disabling camptocormia.

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.