Magnetic resonance imaging-guided focused ultrasound thalamotomy for essential tremor: 5-year follow-up results.

OBJECTIVE: The objective of this study was to evaluate, at 4 and 5 years posttreatment, the long-term safety and efficacy of unilateral MRI-guided focused ultrasound (MRgFUS) thalamotomy for medication-refractory essential tremor in a cohort of patients from a prospective, controlled, multicenter clinical trial. METHODS: Outcomes per the Clinical Rating Scale for Tremor (CRST), including postural tremor scores (CRST Part A), combined hand tremor/motor scores (CRST Parts A and B), and functional disability scores (CRST Part C), were measured by a qualified neurologist. The Quality of Life in Essential Tremor Questionnaire (QUEST) was used to assess quality of life. CRST and QUEST scores at 48 and 60 months post-MRgFUS were compared to those at baseline to assess treatment efficacy and durability. All adverse events (AEs) were reported. RESULTS: Forty-five and 40 patients completed the 4- and 5-year follow-ups, respectively. CRST scores for postural tremor (Part A) for the treated hand remained significantly improved by 73.3% and 73.1% from baseline at both 48 and 60 months posttreatment, respectively (both p < 0.0001). Combined hand tremor/motor scores (Parts A and B) also improved by 49.5% and 40.4% (p < 0.0001) at each respective time point. Functional disability scores (Part C) increased slightly over time but remained significantly improved through the 5 years (p < 0.0001). Similarly, QUEST scores remained significantly improved from baseline at year 4 (p < 0.0001) and year 5 (p < 0.0003). All previously reported AEs remained mild or moderate, and no new AEs were reported. CONCLUSIONS: Unilateral MRgFUS thalamotomy demonstrates sustained and significant tremor improvement at 5 years with an overall improvement in quality-of-life measures and without any progressive or delayed complications. Clinical trial registration no.: NCT01827904 (ClinicalTrials.gov).

Differences in intrinsic functional networks in patients with essential tremor who had good and poor long-term responses after thalamotomy performed using MR-guided ultrasound.

OBJECTIVE: Thalamotomy at the nucleus ventralis intermedius using MR-guided focused ultrasound has been an effective treatment method for essential tremor (ET). However, this is not true for all cases, even for successful ablation. How the brain differs in patients with ET between those with long-term good and poor outcomes is not clear. To analyze the functional connectivity difference between patients in whom thalamotomy was effective and those in whom thalamotomy was ineffective and its prognostic role in ET treatment, the authors evaluated preoperative resting-state functional MRI in thalamotomy-treated patients. METHODS: Preoperative resting-state functional MRI data in 85 patients with ET, who were experiencing tremor relief at the time of treatment and were followed up for a minimum of 6 months after the procedure, were collected for the study. The authors conducted a graph independent component analysis of the functional connectivity matrices of tremor-related networks. The patients were divided into thalamotomy-effective and thalamotomy-ineffective groups (thalamotomy-effective group, ≥ 50% motor symptom reduction; thalamotomy-ineffective group, < 50% motor symptom reduction at 6 months after treatment) and the authors compared network components between groups. RESULTS: Seventy-two (84.7%) of the 85 patients showed ≥ 50% tremor reduction from baseline at 6 months after thalamotomy. The network analysis shows significant suppression of functional network components with connections between the areas of the cerebellum and the basal ganglia and thalamus, but enhancement of those between the premotor cortex and supplementary motor area in the noneffective group compared to the effective group. CONCLUSIONS: The present study demonstrates that patients in the noneffective group have suppressed functional subnetworks in the cerebellum and subcortex regions and have enhanced functional subnetworks among motor-sensory cortical networks compared to the thalamotomy-effective group. Therefore, the authors suggest that the functional connectivity pattern might be a possible predictive factor for outcomes of MR-guided focused ultrasound thalamotomy.

A Fully Implantable Miniaturized Liquid Crystal Polymer (LCP)-Based Spinal Cord Stimulator for Pain Control.

Spinal cord stimulation is a therapy to treat the severe neuropathic pain by suppressing the pain signal via electrical stimulation of the spinal cord. The conventional metal packaged and battery-operated implantable pulse generator (IPG) produces electrical pulses to stimulate the spinal cord. Despite its stable operation after implantation, the implantation site is limited due to its bulky size and heavy weight. Wireless communications including wireless power charging is also restricted, which is mainly attributed to the electromagnetic shielding of the metal package. To overcome these limitations, here, we developed a fully implantable miniaturized spinal cord stimulator based on a biocompatible liquid crystal polymer (LCP). The fabrication of electrode arrays in the LCP substrate and monolithically encapsulating the circuitries using LCP packaging reduces the weight (0.4 g) and the size (the width, length, and thickness are 25.3, 9.3, and 1.9 mm, respectively). An inductive link was utilized to wirelessly transfer the power and the data to implanted circuitries to generate the stimulus pulse. Prior to implantation of the device, operation of the pulse generator was evaluated, and characteristics of stimulation electrode such as an electrochemical impedance spectroscopy (EIS) were measured. The LCP-based spinal cord stimulator was implanted into the spared nerve injury rat model. The degree of pain suppression upon spinal cord stimulation was assessed via the Von Frey test where the mechanical stimulation threshold was evaluated by monitoring the paw withdrawal responses. With no spinal cord stimulation, the mechanical stimulation threshold was observed as 1.47 ± 0.623 g, whereas the stimulation threshold was increased to 12.7 ± 4.00 g after spinal cord stimulation, confirming the efficacy of pain suppression via electrical stimulation of the spinal cord. This LCP-based spinal cord stimulator opens new avenues for the development of a miniaturized but still effective spinal cord stimulator.

Predictors of Outcomes After Focused Ultrasound Thalamotomy.

BACKGROUND: Magnetic resonance-guided focused ultrasound thalamotomy (FUS-T) is an emerging treatment for essential tremor (ET). OBJECTIVE: To determine the predictors of outcomes after FUS-T. METHODS: Two treatment groups were analyzed: 75 ET patients enrolled in the pivotal trial, between 2013 and 2015; and 114 patients enrolled in the postpivotal trials, between 2015 and 2016. All patients had medication-refractory, disabling ET, and underwent unilateral FUS-T. The primary outcome (hand tremor score, 32-point scale with higher scores indicating worse tremor) and the secondary outcome variables (Clinical Rating Scale for Tremor Part C score: 32-point scale with higher scores indicating more disability) were assessed at baseline and 1, 3, 6, and 12 mo. The operative outcome variables (ie, peak temperature, number of sonications) were analyzed. The results between the 2 treatment groups, pivotal and postpivotal, were compared with repeated measures analysis of variance and adjusted for confounding variables. RESULTS: A total of 179 patients completed the 12-mo evaluation. The significant predictors of tremor outcomes were patient age, disease duration, peak temperature, and number of sonications. A greater improvement in hand tremor scores was observed in the postpivotal group at all time points, including 12 mo (61.9% ± 24.9% vs 52.1% ± 24.9%, P = .009). In the postpivotal group, higher energy was used, resulting in higher peak temperatures (56.7 ± 2.5 vs 55.6 ± 2.8°C, P = .004). After adjusting for age, years of disease, number of sonications, and maximum temperature, the treatment group was a significant predictor of outcomes (F = 7.9 [1,165], P = .005). CONCLUSION: We observed an improvement in outcomes in the postpivotal group compared to the pivotal group potentially reflecting a learning curve with FUS-T. The other associations of tremor outcomes included patient age, disease duration, peak temperature, and number of sonications.

Gamma Knife Radiosurgery for Choroidal Hemangioma: A Single-Institute Series.

OBJECTIVE: Choroidal hemangioma (CH) is a benign vascular tumor that induces subretinal fluid collection or exudative retinal detachment and consequent visual symptoms. Current standard treatments for CH include cryotherapy, diathermy, photocoagulation, photodynamic therapy, transpupillary thermotherapy, and radiation therapy. Stereotactic radiosurgery has recently been applied to the treatment of CH because of its characteristic stiff dose-fall-off and accuracy. We have adopted gamma knife radiosurgery (GKRS) to treat CH and have retrospectively assessed tumor volume reductions and improvements to visual acuity achieved thereby. METHODS: Fourteen patients with CHs were treated with GKRS from November 2006 to December 2017. Eight patients had circumscribed CH, and 6 exhibited diffuse CHs and were diagnosed with Sturge-Weber syndrome. The mean age of patients was 27.1 years (range: 8-68 years) and the mean duration of clinical or radiological follow-up was 40.2 months (range: 5-105 months). The mean volume of the tumors at the time of GKRS was 533.5 mm3 (range: 124-1150 mm3), and the mean prescribed marginal dose was 11.6 Gy (range: 10-16 Gy) with 50% isodose lines. RESULTS: The tumor volume decreased by the last follow-up in all patients. The visual acuity improved in 9 patients (64%) and decreased in 1 (7%). Six patients (43%) required trans-pars plana vitrectomy before or after GKRS. There were no symptomatic complications from radiation injury during the follow-up periods. CONCLUSIONS: GKRS could be an acceptable alternative treatment for symptomatic CH when standard therapy is not feasible.

Three-year follow-up of prospective trial of focused ultrasound thalamotomy for essential tremor.

OBJECTIVE: To test the hypothesis that transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) thalamotomy is effective, durable, and safe for patients with medication-refractory essential tremor (ET), we assessed clinical outcomes at 3-year follow-up of a controlled multicenter prospective trial. METHODS: Outcomes were based on the Clinical Rating Scale for Tremor, including hand combined tremor-motor (scale of 0-32), functional disability (scale of 0-32), and postural tremor (scale of 0-4) scores, and total scores from the Quality of Life in Essential Tremor Questionnaire (scale of 0-100). Scores at 36 months were compared with baseline and at 6 months after treatment to assess for efficacy and durability. Adverse events were also reported. RESULTS: Measured scores remained improved from baseline to 36 months (all p < 0.0001). Range of improvement from baseline was 38%-50% in hand tremor, 43%-56% in disability, 50%-75% in postural tremor, and 27%-42% in quality of life. When compared to scores at 6 months, median scores increased for hand tremor (95% confidence interval [CI] 0-2, p = 0.0098) and disability (95% CI 1-4, p = 0.0001). During the third follow-up year, all previously noted adverse events remained mild or moderate, none worsened, 2 resolved, and no new adverse events occurred. CONCLUSIONS: Results at 3 years after unilateral tcMRgFUS thalamotomy for ET show continued benefit, and no progressive or delayed complications. Patients may experience mild degradation in some treatment metrics by 3 years, though improvement from baseline remains significant. CLINICALTRIALSGOV IDENTIFIER: NCT01827904. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with severe ET, unilateral tcMRgFUS thalamotomy provides durable benefit after 3 years.

Four-year follow-up results of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor.

BACKGROUND: Following the emergence of magnetic resonance-guided focused ultrasound as a promising tool for movement disorder surgery, thalamotomy for essential tremor using this technique has become a useful tool based on its efficacy and lack of adverse effects. Here, we summarize the 4-year results of previous reports focusing on the durability of effectiveness of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor. METHODS: From October 2013 to August 2014, 15 patients with intractable essential tremor were enrolled. Twelve of them completed clinical assessment through 4 years of postoperative follow-up. Tremor severity, task performance, and disability were measured using the Clinical Rating Scale of Tremor. RESULTS: The mean age of the 12 patients was 61.7 ± 8.1 years. Maximally delivered energy was 15,552.4 ± 6574.1 joules. The mean number of sonications was 17.3 ± 1.6. The mean postoperative lesion volume was 82.6 ± 29.023 mm3 and in 1 year was a mean of 9.667 ± 8.573 mm3 . Four years postoperatively, improvement of the hand tremor score was 56%, that of the disability score was 63%, that of the postural score was 70%, and that of the action score was 63% compared with baseline; all improvements were significant and sustained over the 4-year period after thalamotomy. There was no permanent adverse effect throughout the 4-year follow-up period. CONCLUSIONS: Magnetic resonance-guided focused ultrasound thalamotomy exhibits sustained clinical efficacy 4 years after the treatment of intractable essential tremor. Adverse events are generally transient. A large cohort of patients who have undergone magnetic resonance-guided focused ultrasound thalamotomy with longer follow-up is needed to confirm our findings. © 2019 International Parkinson and Movement Disorder Society.

Effects on cognition and quality of life with unilateral magnetic resonance-guided focused ultrasound thalamotomy for essential tremor.

OBJECTIVE Although neurosurgical procedures are effective treatments for controlling involuntary tremor in patients with essential tremor (ET), they can cause cognitive decline, which can affect quality of life (QOL). The purpose of this study is to assess the changes in the neuropsychological profile and QOL of patients following MR-guided focused ultrasound (MRgFUS) thalamotomy for ET. METHODS The authors prospectively analyzed 20 patients with ET who underwent unilateral MRgFUS thalamotomy at their institute in the period from March 2012 to September 2014. Patients were regularly evaluated with the Clinical Rating Scale for Tremor (CRST), neuroimaging, and cognition and QOL measures. The Seoul Neuropsychological Screening Battery was used to assess cognitive function, and the Quality of Life in Essential Tremor Questionnaire (QUEST) was used to evaluate the postoperative change in QOL. RESULTS The total CRST score improved by 67.3% (from 44.75 ± 9.57 to 14.65 ± 9.19, p < 0.001) at 1 year following MRgFUS thalamotomy. Mean tremor scores improved by 68% in the hand contralateral to the thalamotomy, but there was no significant improvement in the ipsilateral hand. Although minimal cognitive decline was observed without statistical significance, memory function was much improved (p = 0.031). The total QUEST score also showed the same trend of improving (64.16 ± 17.75 vs 27.38 ± 13.96, p < 0.001). CONCLUSIONS The authors report that MRgFUS thalamotomy had beneficial effects in terms of not only tremor control but also safety for cognitive function and QOL. Acceptable postoperative changes in cognition and much-improved QOL positively support the clinical significance of MRgFUS thalamotomy as a new, favorable surgical treatment in patients with ET.

A prospective trial of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor: Results at the 2-year follow-up.

OBJECTIVE: Magnetic resonance guided focused ultrasound (MRgFUS) has recently been investigated as a new treatment modality for essential tremor (ET), but the durability of the procedure has not yet been evaluated. This study reports results at a 2- year follow-up after MRgFUS thalamotomy for ET. METHODS: A total of 76 patients with moderate-to-severe ET, who had not responded to at least two trials of medical therapy, were enrolled in the original randomized study of unilateral thalamotomy and evaluated using the clinical rating scale for tremor. Sixty-seven of the patients continued in the open-label extension phase of the study with monitoring for 2 years. Nine patients were excluded by 2 years, for example, because of alternative therapy such as deep brain stimulation (n = 3) or inadequate thermal lesioning (n = 1). However, all patients in each follow-up period were analyzed. RESULTS: Mean hand tremor score at baseline (19.8 ± 4.9; 76 patients) improved by 55% at 6 months (8.6 ± 4.5; 75 patients). The improvement in tremor score from baseline was durable at 1 year (53%; 8.9 ± 4.8; 70 patients) and at 2 years (56%; 8.8 ± 5.0; 67 patients). Similarly, the disability score at baseline (16.4 ± 4.5; 76 patients) improved by 64% at 6 months (5.4 ± 4.7; 75 patients). This improvement was also sustained at 1 year (5.4 ± 5.3; 70 patients) and at 2 years (6.5 ± 5.0; 67 patients). Paresthesias and gait disturbances were the most common adverse effects at 1 year-each observed in 10 patients with an additional 5 patients experiencing neurological adverse effects. None of the adverse events worsened over the period of follow-up, and 2 of these resolved. There were no new delayed complications at 2 years. INTERPRETATION: Tremor suppression after MRgFUS thalamotomy for ET is stably maintained at 2 years. Latent or delayed complications do not develop after treatment. Ann Neurol 2018;83:107-114.

Comparative Evaluation of Magnetic Resonance-Guided Focused Ultrasound Surgery for Essential Tremor.

BACKGROUND: Treatment options for patients with drug-resistant essential tremor (ET) are limited. Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is an emerging technique to treat refractory ET. OBJECTIVES: To present MRgFUS as an alternative to radiofrequency (RF) thalamotomy or deep brain stimulation (DBS) for ET treatment. METHODS: We retrospectively analyzed 59 patients who underwent unilateral surgery for drug-resistant ET. Treatments included RF thalamotomy (n = 17), DBS (n = 19), and MRgFUS (n = 23). The outcomes measured were tremor severity and treatment-related complications. RESULTS: At 1 month postoperatively, 100% of RF thalamotomy patients, 89.5% of DBS patients, and 91.3% of MRgFUS patients exhibited absent/mild tremor (successful treatment); other patients exhibited partial relief. At 12 months postoperatively, treatment success for each procedure was observed in 70.6, 84.2, and 78.3% of patients, respectively. At 1 month postoperatively, treatment-related complications had occurred in 58.8, 5.3, and 13.0% of patients, respectively. At 12 months postoperatively, side effects persisted in 11.8, 21.1, and 4.4% of patients, respectively. No statistical differences in treatment success were observed between treatments or over time. Complication rates differed between treatment modalities (p < 0.01) and were lowest in the MRgFUS group. CONCLUSIONS: Patients with drug-resistant ET received equivalent results from RF thalamotomy, DBS, and MRgFUS. DBS and MRgFUS resulted in fewer treatment-related complications.

Rostral Agranular Insular Cortex Lesion with Motor Cortex Stimulation Enhances Pain Modulation Effect on Neuropathic Pain Model.

It is well known that the insular cortex is involved in the processing of painful input. The aim of this study was to evaluate the pain modulation role of the insular cortex during motor cortex stimulation (MCS). After inducing neuropathic pain (NP) rat models by the spared nerve injury method, we made a lesion on the rostral agranular insular cortex (RAIC) unilaterally and compared behaviorally determined pain threshold and latency in 2 groups: Group A (NP + MCS; n = 7) and Group B (NP + RAIC lesion + MCS; n = 7). Also, we simultaneously recorded neuronal activity (NP; n = 9) in the thalamus of the ventral posterolateral nucleus and RAIC to evaluate electrophysiological changes from MCS. The pain threshold and tolerance latency increased in Group A with "MCS on" and in Group B with or without "MCS on." Moreover, its increase in Group B with "MCS on" was more than that of Group B without MCS or of Group A, suggesting that MCS and RAIC lesioning are involved in pain modulation. Compared with the "MCS off" condition, the "MCS on" induced significant threshold changes in an electrophysiological study. Our data suggest that the RAIC has its own pain modulation effect, which is influenced by MCS.

Combined bilateral anterior cingulotomy and ventral capsule/ventral striatum deep brain stimulation for refractory obsessive-compulsive disorder with major depression: do combined procedures have a long-term benefit?

BACKGROUND: The ventral capsule (VC), ventral striatum (VS), and the anterior cingulate gyrus are parts of the obsessive-compulsive disorder (OCD) and depression circuits. We assessed whether a combination of bilateral anterior cingulotomy and VC/VS deep brain stimulation (DBS) had an additive effect in patients with OCD and major depression. METHODS: Three patients with refractory OCD underwent combined bilateral anterior cingulotomy and VC/VS DBS procedures. All patients met the inclusion criteria for the Korean guidelines of DBS for OCD. Baseline Yale-Brown Obsessive-Compulsive Disorder Scale (Y-BOCS) scores, Hamilton Depression Rating Scale scores, and global assessments of functioning were evaluated. These scores were also serially estimated for more than 24 months after surgery at 3-month intervals. RESULTS: The mean value of the baseline Y-BOCS scores was 34.7 (range 30-38); the mean Y-BOCS value decreased significantly to 23.0 (range 20-25) 3 months after the surgery. This score was maintained 2 years after surgery with a mean value of 19.0 (range 18-20). CONCLUSIONS: The combination of the two therapies did not yield superior outcomes, as the clinical outcomes were comparable to those of previous reports for VC/VS DBS alone. Wide-area VC/VS DBS may be sufficient to control refractory OCD.

'Is tinnitus accompanied by hemifacial spasm in normal-hearing patients also a type of hyperactive neurovascular compression syndrome? : A magnetoencephalography study.

BACKGROUND: Traditionally, tinnitus accompanied by hemifacial spasm has been considered a type of hyperactive neurovascular compression syndrome that is similar to hemifacial spasm alone because of the anatomically close relationship between the facial nerve and cochlear nerve as well as the hyperactive clinical nature. METHODS: Participants were 29 subjects who presented with hemifacial spasm and neuroradiological evidence of vascular compression of the cranial (facial/cochlear) nerve. We used magnetoencephalography (MEG) to estimate the activity of the cochlear nerve in patients with and without tinnitus on the ipsilateral side. We compared the difference in the latency and the ratio of the equivalent current dipole (ECD) strength between the ipsilateral and contralateral sides of the spasm and tinnitus. RESULTS: Cochlear nerve activity in patients with tinnitus was increased with a shorter latency (p = 0.016) and stronger ECD strength (p = 0.028) compared with patients without tinnitus. CONCLUSION: The MEG results from normal-hearing patients who had tinnitus accompanied by hemifacial spasm suggest that the hyperactivity of the auditory central nervous system may be a crucial pathophysiological factor in the generation of tinnitus in these patients. The neurovascular compression that causes sensory input from the pathologic facial nerve activity may contribute to this hyperactivity of the central auditory nervous system.

Simultaneous thalamic and posterior subthalamic electrode insertion with single deep brain stimulation electrode for essential tremor.

OBJECTIVES: The optimal target location of deep brain stimulation (DBS) is the subject of some controversy. We implanted electrodes that could stimulate both posterior subthalamic area (PSA) and ventralis intermedius nucleus of thalamus (Vim), and examined the benefits of bilateral DBS of Vim, PSA, and Vim + PSA in patients with essential tremor (ET). MATERIALS AND METHODS: Electrodes were inserted into the Vim and PSA in ten hemispheres of five consecutive patients. All patients were assessed for action tremor, including postural and kinetic tremors, both preoperatively and at six months and one year postoperatively. RESULTS: The preoperative mean postural tremor score was 1.9 (range 1.0-2.5) and kinetic tremor score was 2.6 (range 2.0-3.0). One year after surgery, these scores had decreased significantly to 0.1 (range 0.0-1.0) and 0.6 (range 0.0-1.5), respectively. The postural and kinetic tremor scores at six-months and one-year post-surgery were similar for Vim, PSA, and Vim + PSA stimulation. CONCLUSIONS: We were able to identify the optimal electrode placement site for each patient based on his or her individualized response to the stimulation. Overall, there was no statistically significant difference among the DBS sites in terms of the benefits afforded by the stimulation. We propose that our technique may be a useful surgical method to treat ET.

The effect of bilateral globus pallidus internus deep brain stimulation plus ventralis oralis thalamotomy on patients with cerebral palsy.

OBJECTIVE: We compared bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) with bilateral GPi DBS plus ventralis oralis (Vo) thalamotomy to analyze the effect of the combined Vo thalamotomy. METHODS: Between March 2003 and December 2008, 10 patients underwent DBS and/or Vo thalamotomy for treatment of cerebral palsy in our institute of neurosurgery and rehabilitation medicine. Four patients received bilateral posteroventral GPi DBS as group I and 6 patients received GPi DBS plus unilateral thalamotomy as group II. RESULTS: The movement and disability scores of group I improved by 32 and 14.3%, respectively, at the last follow-up compared with baseline. The movement and disability scores of group II improved by 31.5 and 0.18%. The BFMDRS-movement subscores of group II demonstrated statistically significant improvement in the contralateral arm compared to group I (p = 0.042). Body pain, vitality and mental health seemed to improve in group II, in terms of health-related quality of life. CONCLUSIONS: Contrary to our expectations, we were unable to demonstrate clear improvements in overall BFMDRS scores between group I and group II. However, movements of the contralateral upper extremities improved and health-related quality of life in group II showed satisfactory results.

Decrease of GABAergic markers and arc protein expression in the frontal cortex by intraventricular 192 IgG-saporin.

BACKGROUND/AIMS: Previous studies used 192 IgG-saporin to study cholinergic function because of its facility for selective lesioning; however, results varied due to differences in the methods of administration and behavioral tests used. We examined an animal model of dementia using 192 IgG-saporin to confirm its features before applying this model to research of therapeutic drugs or electrical stimulation techniques. METHODS: Features were verified by the Morris water maze test, immunochemistry, and Western blotting. Animals were examined after intraventricular injection of 192 IgG-saporin (0.63 µg/µl; 6, 8, and 10 µl) or phosphate-buffered saline. RESULTS: In the acquisition phase of the Morris water maze test, the latencies of the injection groups were significantly delayed, but recovered within 1 week. In the probe test, 2 of 4 indices (time in the platform zone and the number of crossings) were significantly different in the 8-µl injection group. Immunohistochemistry revealed the extent of cholinergic destruction. Activity-regulated cytoskeleton-associated protein and glutamate decarboxylase expression significantly decreased in the frontal cortex (8- and 10-µl groups), but not in the hippocampus. CONCLUSION: Spatial memory impairment was associated with cholinergic basal forebrain injury as well as frontocortical GABAergic hypofunction and synaptic plasticity deceleration.

Bilateral globus pallidus internus deep brain stimulation for DYT1+ generalized dystonia with previously received bilateral thalamotomy and unilateral pallidotomy.

Ablation of the globus pallidus internus (GPi) and thalamotomy have been extensively used in the past. Posteroventral GPi deep brain stimulation has been considered as a treatment for dystonia. However, to date, there is no report in the literature of any dystonia patient who underwent GPi deep brain stimulation who had previously undergone staged bilateral thalamotomy and unilateral pallidotomy. The authors of the present study have acquired relatively good clinical results, even in patients who previously received bilateral thalamotomy and unilateral pallidotomy for DYT1+ primary generalized dystonia.

Anatomy and physiology of the basal ganglia: implications for deep brain stimulation for Parkinson's disease.

Central to surgical management of movement disorders is an understanding of the anatomy and physiology of the basal ganglia. The basal ganglia have been a target for neuromodulation surgery since Russell Meyers' pioneering works in the late 1930s. With the development of deep brain stimulation as the gold standard of surgical intervention for movement disorders, there has been a concomitant evolution in the understanding of the role the basal ganglia plays in the genesis of normal and abnormal motor behaviors. The fundamental concept of the cortico-striato-pallido-thalamocortical loop will be explored in the context of deep brain stimulation. The current targets for deep brain stimulation for Parkinson's disease, the subthalamic nucleus, the globus pallidus internus, and the ventral intermediate nucleus, will be discussed in the framework of the current physiological and anatomical models of Parkinson's disease (PD). Finally, the current understandings of the mechanisms underpinning the beneficial effects of deep brain stimulation for PD will be discussed.

Endoscopic disconnection for hypothalamic hamartoma with intractable seizure. Report of four cases.

Although intractable epilepsy associated with hypothalamic hamartoma (HH) can be controlled by microsurgical resection of the lesion, excision of deep-seated lesions is often associated with morbidity and mortality. Endoscopic disconnection is less invasive and seems to be well suited for this indication. The authors discuss the role of endoscopic-assisted surgery in the management of HH-induced seizures. Four patients with HH-related intractable gelastic seizure underwent endoscopic disconnection surgery. Postoperatively, all patients exhibited improvement. Two patients became seizure free immediately after endoscopic disconnection surgery, one patient with a widespread seizure focus involving the motor strip continued to experience rare complex partial seizures but gelastic seizures ceased, and one experienced a reduced frequency of seizures but persistence of some generalized seizures. Three patients suffered postoperative disconnection-like syndrome, which continued 3 to 7 days and spontaneously disappeared. The authors advocate the endoscopic disconnection surgery as a safe and effective treatment for HH-related epilepsy by blocking the spread of epileptic discharges from the lesion.