Gamma Knife Thalamotomy for a Medically Refractory Tremors: Longitudinal Evaluation of Clinical Effects and MRI Response Patterns.

OBJECTIVE: The present longitudinal study evaluated the results of Gamma Knife surgery (GKS) for medically refractory tremors. METHODS: The outcome after Gamma Knife thalamotomy targeting the ventral intermediate nucleus (VIM) was analyzed in 17 patients (9 men and 8 women; mean age 72 years) with either Parkinson's disease or an essential tremor, who were followed up for at least 2 years after treatment. Clinical and magnetic resonance imaging (MRI) examinations were done before and every 3 months after GKS. RESULTS: The mean rates of symptom improvement (a decrease in the tremor frequency) were 6%, 39%, 63%, and 64% at 3, 6, 12, and 24 months after treatment, respectively. The defined MRI response patterns included a minimum reaction (in 3 patients), a normal reaction (in 11 patients), and a hyperreaction (in 3 patients). They were not associated with any evaluated pretreatment, radiosurgical, or outcome parameter, although 2 patients with a hyperreaction exhibited mild-to-moderate motor weakness in the contralateral limbs. Linear contrasting of the border between the thalamus and the internal capsule adjacent to the lesion site was noted on follow-up MRI in 13 cases and was associated with a higher symptom improvement rate. CONCLUSION: GKS allows effective and safe management of medically refractory tremors. The treatment is characterized by variable MRI response patterns. Some imaging findings during follow-up may be associated with clinical effects.

Efficacy and safety of perampanel monotherapy in patients with focal-onset seizures with newly diagnosed epilepsy or recurrence of epilepsy after a period of remission: The open-label Study 342 (FREEDOM Study).

OBJECTIVE: Our study assessed perampanel monotherapy in patients (aged ≥12 years) with focal-onset seizures (FOS) with or without focal to bilateral tonic-clonic seizures (FBTCS) in Japan and South Korea. METHODS: Study 342 (NCT03201900; FREEDOM) is a single-arm, open-label, Phase III study. Patients initially received perampanel in a 32-week 4-mg/d Treatment Phase (6-week Titration; 26-week Maintenance Periods). If they experienced a seizure during the 4-mg/d Maintenance Period, they could be up-titrated to 8 mg/d across an additional 30-week Treatment Phase (4-week Titration; 26-week Maintenance Periods). Primary endpoint was the seizure-freedom rate during the Maintenance Period (4 mg/d and last evaluated dose [4 or 8 mg/d]). Secondary endpoints included time to first seizure onset and to withdrawal during Maintenance. Treatment-emergent adverse events (TEAEs) were monitored. RESULTS: At data cutoff (February 28, 2019), 89 patients with FOS (84 [94.4%] with newly diagnosed epilepsy and 5 [5.6%] with recurrence of epilepsy after a period of remission) had received ≥1 perampanel dose; 16 patients discontinued during the 4-mg/d Titration Period, meaning 73 patients entered the 4-mg/d Maintenance Period and were included in the primary analysis set for efficacy. Seizure-freedom rate in the 26-week Maintenance Period was 46/73 (63.0%; 95% confidence interval [CI]: 50.9-74.0) at 4 mg/d and 54/73 (74.0%; 95% CI: 62.4-83.5) at 4 or 8 mg/d. Cumulative probability of seizure-onset and withdrawal rates during Maintenance was 30.8% (95% CI: 21.5-43.0) and 23.7% (95% CI: 15.4-35.3) at 4 mg/d, and 18.2% (95% CI: 11.0-29.3) and 23.3% (95% CI: 15.2-34.8) at 4 or 8 mg/d. Perampanel was generally well tolerated, and the most common TEAE was dizziness. SIGNIFICANCE: Perampanel monotherapy (4 to 8 mg/d) was efficacious and consistent with the known safety profile up to 26 weeks in patients (≥12 years) with primarily newly diagnosed FOS with or without FBTCS.

Safety and long-term efficacy of ventro-oral thalamotomy for focal hand dystonia: A retrospective study of 171 patients.

OBJECTIVE: To report the safety and long-term efficacy of ventro-oral thalamotomy for 171 consecutive patients with task-specific focal hand dystonia. METHODS: Between October 2003 and February 2017, 171 consecutive patients with task-specific focal hand dystonia underwent unilateral ventro-oral thalamotomy. Etiologies included writer's cramps (n = 92), musician's dystonias (n = 58), and other occupational task-related dystonias (n = 21). The task-specific focal hand dystonia scale was used to evaluate patients' neurologic conditions (range 1-5, high score indicated a better condition). The scores before surgery; at 1 week, 3 months, and 12 months postoperatively; and the last available follow-up period were determined. Postoperative complications and postoperative recurrence were also evaluated. RESULTS: The scores before surgery; at 1 week (1.72 ± 0.57, 4.33 ± 0.85 [p < 0.001]), 3 months (4.30 ± 1.06 [p < 0.001]), and 12 months (4.30 ± 1.13 [p < 0.001]); and the last available follow-up (4.39 ± 1.07 [p < 0.001]) postoperatively improved. The mean clinical follow-up period was 25.4 ± 32.1 months (range: 3-165). Permanent adverse events developed in 6 patients (3.5%). Eighteen patients developed recurrent dystonic symptoms postoperatively. Of these 18 patients, 9 underwent ventro-oral thalamotomy again, of which 7 achieved improvement. CONCLUSION: Ventro-oral thalamotomy is a feasible and reasonable treatment for patients with refractory task-specific focal hand dystonias. Prospective, randomized, and blinded studies are warranted to clarify more accurate assessment of the safety and efficacy of ventro-oral thalamotomy for task-specific focal hand dystonia. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with task-specific focal hand dystonia, ventro-oral thalamotomy improves dystonia.

Long-term outcome of pallidal stimulation for Meige syndrome.

OBJECTIVE Meige syndrome is characterized by blepharospasm and varied subphenotypes of craniocervical dystonia. Current literature on pallidal surgery for Meige syndrome is limited to case reports and a few small-scale studies. The authors investigated the clinical outcomes of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in patients with Meige syndrome. METHODS Sixteen patients who underwent GPi DBS at the Tokyo Women's Medical University Hospital between 2002 and 2015 were included in this study. Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) movement subscale (BFMDRS-M) scores (range 0-120) obtained at the following 3 time points were included in this analysis: before surgery, 3 months after surgery, and at the most recent follow-up evaluation. RESULTS The patients' mean age (± SD) at symptom onset was 46.7 ± 10.1 years, and the mean disease duration at the time of the authors' initial evaluation was 5.9 ± 4.1 years. In 12 patients, the initial symptom was blepharospasm, and the other 4 patients presented with cervical dystonia. The mean postoperative follow-up period was 66.6 ± 40.7 months (range 13-150 months). The mean total BFMDRS-M scores at the 3 time points were 16.3 ± 5.5, 5.5 ± 5.6 (66.3% improvement, p < 0.001), and 6.7 ± 7.3 (58.9% improvement, p < 0.001). CONCLUSIONS The results indicate long-term efficacy for GPi DBS for the majority of patients with Meige syndrome.

Usefulness of StereoEEG-based tailored surgery for medial temporal lobe epilepsy. Preliminary results in 11 patients.

OBJECTIVE: Surgical options for medial temporal lobe epilepsy (MTLE) include anterior temporal lobectomy (ATL) and selective amygdalohippocampectomy (SAH). Optimal criteria for choosing the appropriate surgical approach remain uncertain. This article reports 11 consecutive cases in which electrophysiological findings of stereoelectroencephalography (SEEG) were used to determine the optimal surgical approach. PATIENTS AND METHODS: Eleven consecutive patients with MTLE underwent SEEG evaluation and were placed in either the medial or the medial+lateral group based on the findings. Patients in the medial group underwent SAH using the subtemporal approach, and patients in the medial+lateral group underwent SEEG-guided anterior temporal lobectomy. SEEG findings were also compared with other examinations including flumazenil (FMZ)-positron emission tomography (PET), fluorine-18 labeled fluorodeoxyglucose (FDG)-PET, and magnetoencephalography (MEG). Results were evaluated to determine which examinations most consistently identified the epileptogenic zone. RESULTS: Of the 11 cases, 4 patients were placed in the medial group, and 7 patients in the medial+lateral group. Of patients, 90.9% were classified in class I of the Engel Epilepsy Surgery Outcome Scale, while 72.7% were classified in class I by the International League Against Epilepsy (ILAE) system. Analyzed by group, 100% of the medial group experienced an Engel class I outcome in the medial group, compared to 85.7% in the medial+lateral group. SEEG findings were comparable with FDG-PET results (10 of 11, 91%). CONCLUSION: Tailored surgery guided by SEEG is an electrophysiologically feasible treatment for MTLE that can result in favorable outcomes. Although seizures are thought to originate in the medial temporal lobe in MTLE, it is important for involvement of the lateral temporal cortex to be also considered in some cases.

Stereotactic Thalamotomy for Hairdresser's Dystonia: A Case Series.

BACKGROUND: Hairdresser's dystonia is a rarely reported form of focal hand dystonia, and the clinical course and treatment remains poorly understood. OBJECTIVES: The aim of this report was to clarify the impact of thalamotomy on hairdresser's dystonia. METHODS: Four consecutive patients with hairdresser's task-specific dystonia evaluated at Tokyo Women's Medical University Hospital between 2008 and 2013 were treated with stereotactic thalamotomy, and were recruited for this case series. RESULTS: The mean age at the onset of symptoms was 37.25 ± 10.64 years, the median duration of symptoms was 4.25 ± 1.3 years, and the mean follow-up period was 17 ± 12.37 months. Two of the 4 patients returned to work with significant improvement following the stereotactic thalamotomy and the beneficial effects persisted for the duration of their clinical follow-up. The other 2 patients experienced transient improvements for up to 3 months. Surgical complications included only dysarthria in 2 patients, and did not interfere with their daily activities. No patients experienced a deterioration of dystonic symptoms after thalamotomy. CONCLUSION: Although the benefits of thalamotomy remain vulnerable to incorrect or insufficient coagulation, stereotactic thalamotomy may be a feasible and effective procedure for patients with hairdresser's dystonia.

Long-term improvement of musician's dystonia after stereotactic ventro-oral thalamotomy.

OBJECTIVE: Musician's dystonia is a task-specific movement disorder that causes twisting or repetitive abnormal finger postures and movements, which tend to occur only while playing musical instruments. Such a movement disorder will probably lead to termination of the careers of affected professional musicians. Most of the currently available treatments have yet to provide consistent and satisfactory results. We present the long-term follow-up results of ventro-oral thalamotomy for 15 patients with musician's dystonia. METHODS: Between October 2003 and September 2010, 15 patients with medically intractable task-specific focal hand dystonia that occurred only while playing musical instruments underwent ventro-oral thalamotomy. We used Tubiana's musician's dystonia scale to evaluate the patients' pre- and postoperative neurological conditions. RESULTS: All patients except 1 (93%) experienced dramatic improvement of dystonic symptoms immediately after ventro-oral thalamotomy. The mean follow-up period was 30.8 months (range=4-108 months). None of the patients experienced recurrence or deterioration of symptoms during the follow-up periods. INTERPRETATION: Ventro-oral thalamotomy remarkably improved musician's dystonia, and the effect persisted for a long duration.

Gamma knife thalamotomy for Parkinson disease and essential tremor: a prospective multicenter study.

BACKGROUND: No prospective study of gamma knife thalamotomy for intractable tremor has previously been reported. OBJECTIVE: To clarify the safety and optimally effective conditions for performing unilateral gamma knife (GK) thalamotomy for tremors of Parkinson disease (PD) and essential tremor (ET), a systematic postirradiation 24-month follow-up study was conducted at 6 institutions. We present the results of this multicenter collaborative trial. METHODS: In total, 72 patients (PD characterized by tremor, n = 59; ET, n = 13) were registered at 6 Japanese institutions. Following our selective thalamotomy procedure, the lateral part of the ventralis intermedius nucleus, 45% of the thalamic length from the anterior tip, was selected as the GK isocenter. A single 130-Gy shot was applied using a 4-mm collimator. Evaluation included neurological examination, magnetic resonance imaging and/or computerized tomography, the unified Parkinson's disease rating scale (UPDRS), electromyography, medication change, and video observations. RESULTS: Final clinical effects were favorable. Of 53 patients who completed 24 months of follow-up, 43 were evaluated as having excellent or good results (81.1%). UPDRS scores showed tremor improvement (parts II and III). Thalamic lesion size fluctuated but converged to either an almost spherical shape (65.6%), a sphere with streaking (23.4%), or an extended high-signal zone (10.9%). No permanent clinical complications were observed. CONCLUSION: GK thalamotomy is an alternative treatment for intractable tremors of PD as well as for ET. Less invasive intervention may be beneficial to patients.

Adult-onset angiocentric glioma of epithelioid cell-predominant type of the mesial temporal lobe suggestive of a rare but distinct clinicopathological subset within a spectrum of angiocentric cortical ependymal tumors.

Angiocentric glioma (AG) is defined as an epilepsy-associated stable or slowly growing cerebral tumor primarily affecting children and young adults, histologically consisting mainly of monomorphic, bipolar spindle-shaped cells and occasional round to monopolar columnar epithelioid cells, showing angiocentric growth pattern and features of ependymal differentiation. We describe two clinicopathologically unusual cases of AG. Case 1 is a 54-year-old woman with a 10-year history of complex partial seizures. MRI revealed non-enhancing T1-low, T2/fluid-attenuated inversion recovery (FLAIR)-high intensity signal change in the left hippocampus and amygdala. After selective amygdalohippocampectomy, she had rare non-disabling seizures on medication for over 50 months (Engel's class I). Case 2 is a 37-year-old man with a 3-year history of complex partial seizures. MRI revealed non-enhancing T1-low, T2/FLAIR-high intensity signal change in the left uncus and amygdala. After combined amygdalohippocampectomy and anterior temporal lobectomy, he has been seizure-free for over 11 months. Histologically the tumors in both cases consisted mainly of infiltrating epithelioid cells (GFAP- ∼±, S-100-) with perinuclear epithelial membrane antigen (EMA)-positive dots and rings, showing conspicuous single- and multi-layered angiocentric arrangements. Occasional tumor cells showed spindle-shaped morphology (GFAP+, S-100+) with rare EMA-positive dots aligned radially and longitudinally along parenchymal blood vessels. Focal solid areas showed a Schwannoma-like fascicular arrangement with rare EMA-positive dots and/or sheets of epithelioid cells with abundant EMA dots. Electron microscopic investigation demonstrated features of ependymal differentiation. These cases, together with a few similar cases previously reported, appear to represent a rare but distinct clinicopathological subset of AG characterized by adult-onset, mesial temporal lobe localization and epithelioid cell-predominant histology.

[Three children with Rasmussen encephalitis showing marked improvement in daily life activity following the functional hemispherectomy].

We investigated seizure, intelligence quotient (IQ), and neurological outcomes including the process of motor function recovery after functional right hemispherectomy in 3 children with Rasmussen's encephalitis (RE). Before the procedure, they were unable to walk, nor sit without support due to progressive worsening of left hemiplegia and relentless epilepsia partialis continua (EPC) of the left extremities, which were refractory to antiepileptic drug and immunological treatment. After functional right hemispherectomy, EPC completely disappeared, although complete left hemiplegia was sustained. However, they recovered up to being able to walk independently with assistance devices, and to have an ordinary life with family support within 1.5 to 5 months through rehabilitation. At the same time, the interictal EEG improved on the unaffected side of hemisphere, exhibiting a posterior alpha rhythm. Their IQ also improved, and they were able to attend school. Early functional hemispherectomy should be considered before patients with RE are left in a serious condition due to progressive worsening of hemiplegia and seizures refractory to the available treatment.

Gamma Knife surgery for abducent nerve schwannoma. Report of 4 cases.

Abducent nerve schwannomas are extremely rare. The authors recently performed Gamma Knife surgery (GKS) in 4 patients with such tumors and describe their experiences with these cases. The patients consisted of 3 women and 1 man whose ages varied from 31 to 60 years (mean 46 years). Two patients had no symptoms, 1 complained of slight visual disturbances, and the other 1 had abducent nerve palsy. Neurofibromatosis was not diagnosed in any case. All 4 tumors were located in the cavernous sinus: 2 of these tumors within the borders of the sinus, 1 tumor extending into the orbit, and 1 tumor extending into the prepontine cistern. The volume of the neoplasms varied from 1.7 to 4.9 cm(3) (mean 3.0 cm(3)). No patient underwent tumor resection. Treatment was delivered with the aid of a Leksell Gamma Knife model C unit and the automatic positioning system. The dose directed to the tumor margin was 12 Gy in all cases. The dose directed to the anterior visual pathways was kept below 10 Gy and that to the brainstem below 14 Gy. The length of follow-up varied between 7 and 43 months (mean 27 months). There were no acute complications or side effects. Imaging studies showed temporary enlargement of all tumors during the 1st posttreatment year, but thereafter, there was a trend toward reduction in volume. None of the neoplasms displayed regrowth. In the 3 patients who did not have abducent nerve palsy before GKS, it appeared, at least temporarily, after the procedure. Purely intracavernous neoplasms in general followed uneventful posttreatment courses, but dumbbell-shaped tumors were associated with significant morbidity. The cisternocavernous schwannoma underwent cystic degeneration 2 years after GKS, and the patient developed diplopia. After GKS, the patient treated for an orbitocavernous schwannoma experienced a significant deterioration in vision, temporary blindness in 1 eye, and late development of permanent abducent nerve palsy, which were seemingly caused by compression of neurovascular structures within the anulus of Zinn during a temporary increase in the lesion's volume after irradiation. Gamma Knife surgery controls the growth of abducent nerve schwannomas and may be effectively used to manage intracavernous neoplasms. Caution, however, should be used in cases of dumbbell-shaped tumors, particularly those extending through the superior orbital fissure.

Gamma Knife robotic microradiosurgery of pituitary adenomas invading the cavernous sinus: treatment concept and results in 89 cases.

The objective of the present retrospective study was evaluation of results of "robotic microradiosurgery" of pituitary adenomas invading the cavernous sinus. Eighty-nine patients with such tumors underwent management using Leksell Gamma Knife model C with automatic positioning system. There were 77 residual and 12 recurrent neoplasms. The applied radiosurgical treatment plan was based on the use of multiple isocenters, mainly of smaller size, which were positioned compactly within the border of the lesion with resultant improved dose homogeneity, increased average dose within the target, and sharp dose fall outside the treated volume. The marginal dose varied from 12 to 25 Gy (mean, 18.2 Gy) in non-functional pituitary adenomas (43 cases), and from 12 to 35 Gy (mean, 25.2 Gy) in hormone-secreting ones (46 cases). The length of follow-up after treatment ranged from 24 to 76 months (mean, 36 months). Control of the tumor growth was attained in 86 cases (97%), whereas actual shrinkage of the lesion was marked in 57 cases (64%). In 18 out of 46 secreting neoplasms (39%), normalization of the excess of the pituitary hormone production was noted after radiosurgery. Treatment-associated morbidity was limited to transitory cranial nerve palsy in two patients (2%). No patient with either non-functional or hormone secreting tumor exhibited new pituitary hormone deficit after treatment. In conclusion, highly precise microanatomy-based Gamma Knife robotic microradiosurgery provides an opportunity for effective management of pituitary adenomas invading the cavernous sinus with preservation of the adjacent functionally important neuronal structures.

Role of proton magnetic resonance spectroscopy in preoperative evaluation of patients with mesial temporal lobe epilepsy.

A retrospective study was conducted for evaluation of the role of single-voxel proton magnetic resonance spectroscopy (1H-MRS) in preoperative investigation of patients with mesial temporal lobe epilepsy (MTLE). Eighteen cases, including both non-lesional and lesional MTLE, were analyzed. Selective amygdalohippocampectomy was performed in 8 cases, selective amygdalohippocampectomy combined with lesionectomy in 6 cases, lesionectomy in 3 cases, and anterior temporal lobe resection in one case. The length of follow-up varied from 24 to 71 months (median, 35 months). Before surgery, (1)H-MRS disclosed decrease of N-acetylaspartate (NAA) content (P=0.01) and more frequent (P=0.07) presence of lactate (Lac) on the side of the epileptogenic zone. Decrease of NAA content below 0.75 and/or unilateral presence of Lac provided 86% (95% CI: 68%-100%) lateralization accuracy. Metabolic parameters did not differ in subgroups with hippocampal sclerosis and brain tumors. On the long-term follow-up 12 patients (67%) were free of disabling seizures. There was a trend (P=0.05) for worse seizure outcome in cases with significant bilateral metabolic alterations characterized by predominance of choline-containing compounds' peak on 1H-MR spectra on both sides. In conclusion, 1H-MRS-detected reduction of NAA content and unilateral presence of Lac in the mesial temporal lobe structures may serve as additional diagnostic clues for lateralization of the epileptogenic zone in MTLE. Metabolic imaging has limited usefulness for differentiation of the hippocampal sclerosis and low-grade intraaxial brain tumor. Presence of significant bilateral metabolic alterations in the mesial temporal lobe structures is associated with worse postoperative seizure control.

Spectroscopy-supported frame-based image-guided stereotactic biopsy of parenchymal brain lesions: comparative evaluation of diagnostic yield and diagnostic accuracy.

OBJECTIVE: Comparative evaluation of diagnostic efficacy of stereotactic brain biopsy performed with and without additional use of spectroscopic imaging ((1)H-MRS) for target selection was done. METHODS: From 2002 to 2006, 30 patients with parenchymal brain lesions underwent (1)H-MRS-supported frame-based stereotactic biopsy, whereas in 39 others MRI-guided technique was used. Comparison of diagnostic yield of the procedure in these two groups was performed. Additionally, the diagnostic accuracy was evaluated in 37 lesions, which were surgically resected within 1 month thereafter. RESULTS: Stereotactic biopsy permitted establishment of a definitive histopathological diagnosis in 57 cases and diagnosis of low-grade glioma without specific tumor typing in 8 cases. In 4 cases tissue sampling was non-diagnostic. In 5 out of 8 cases with incomplete diagnosis and in all non-diagnostic cases target selection was performed without the use of (1)H-MRS (P=0.2073). The diagnostic yields of (1)H-MRS-supported and MRI-guided procedures were 100% and 90%, respectively (P=0.1268). Comparison of the histopathological diagnoses after stereotactic biopsy and surgical resection revealed complete diagnostic agreement in 13 cases, minor disagreement in 14 cases, and major disagreement in 10 cases. Among these last 10 cases, initial undergrading of non-enhancing WHO grade III gliomas was the most common (7 cases). The diagnostic accuracy of (1)H-MRS-supported and MRI-guided procedures was 67% and 79%, respectively (P=0.4756). CONCLUSION: While in the present study the diagnostic yield of (1)H-MRS-supported frame-based stereotactic brain biopsy was 100%, its statistically significant diagnostic advantages over MRI-guided technique were not proved. Optimal selection of the spectroscopic target for tissue sampling remains unclear.

Serial (1)H-MRS of thalamus during deep brain stimulation of bilateral globus pallidus internus for primary generalized dystonia.

INTRODUCTION: The physiological mechanisms of deep brain stimulation (DBS) are not completely clear. Our understanding of them may be facilitated with the use of proton magnetic resonance spectroscopy ((1)H-MRS). METHODS: Serial (1)H-MRS of both thalami was performed during the course of DBS of bilateral globus pallidus internus in a patient with primary generalized dystonia. RESULTS: Two days after microelectrode implantation, a pulse frequency of 185 Hz was applied for stimulation. It resulted in relief of symptoms and a decrease of Burke-Fahn-Marsden dystonia rating scale (BFMDRS) scores, and was accompanied by a prominent increase of N-acetylaspartate (NAA)/choline-containing compounds (Cho) ratio, a mild increase of NAA/creatine (Cr) ratio, and a moderate decrease of Cho/Cr ratio. Two weeks later, for a search of the optimal stimulation mode, the pulse frequency was switched to 60 Hz, which resulted in clinical deterioration and significant increase of BFMDRS scores. At that time, all investigated (1)H-MRS-detected metabolic parameters had nearly returned to the pretreatment levels. CONCLUSION: Use of serial (1)H-MRS investigations of various brain structures during DBS in cases of movement disorders permits detailed evaluation of the treatment response, has a potential for its possible prediction, and may facilitate understanding of the physiological mechanisms of stimulation.

Active hippocampal networks undergo spontaneous synaptic modification.

The brain is self-writable; as the brain voluntarily adapts itself to a changing environment, the neural circuitry rearranges its functional connectivity by referring to its own activity. How the internal activity modifies synaptic weights is largely unknown, however. Here we report that spontaneous activity causes complex reorganization of synaptic connectivity without any external (or artificial) stimuli. Under physiologically relevant ionic conditions, CA3 pyramidal cells in hippocampal slices displayed spontaneous spikes with bistable slow oscillations of membrane potential, alternating between the so-called UP and DOWN states. The generation of slow oscillations did not require fast synaptic transmission, but their patterns were coordinated by local circuit activity. In the course of generating spontaneous activity, individual neurons acquired bidirectional long-lasting synaptic modification. The spontaneous synaptic plasticity depended on a rise in intracellular calcium concentrations of postsynaptic cells, but not on NMDA receptor activity. The direction and amount of the plasticity varied depending on slow oscillation patterns and synapse locations, and thus, they were diverse in a network. Once this global synaptic refinement occurred, the same neurons now displayed different patterns of spontaneous activity, which in turn exhibited different levels of synaptic plasticity. Thus, active networks continuously update their internal states through ongoing synaptic plasticity. With computational simulations, we suggest that with this slow oscillation-induced plasticity, a recurrent network converges on a more specific state, compared to that with spike timing-dependent plasticity alone.

Outcome after pituitary radiosurgery for thalamic pain syndrome.

PURPOSE: To evaluate outcomes after pituitary radiosurgery in patients with post-stroke thalamic pain syndrome. METHODS AND MATERIALS: From 2002 to 2006, 24 patients with thalamic pain syndrome underwent pituitary radiosurgery at Tokyo Women's Medical University and were followed at least 12 months thereafter. The radiosurgical target was defined as the pituitary gland and its connection with the pituitary stalk. The maximum dose varied from 140 to 180 Gy. Mean follow-up after treatment was 35 months (range, 12-48 months). RESULTS: Initial pain reduction, usually within 48 h after radiosurgery, was marked in 17 patients (71%). However, in the majority of cases the pain recurred within 6 months after treatment, and at the time of the last follow-up examination durable pain control was marked in only 5 patients (21%). Ten patients (42%) had treatment-associated side effects. Anterior pituitary abnormalities were marked in 8 cases and required hormonal replacement therapy in 3; transient diabetes insipidus was observed in 2 cases, transient hyponatremia in 1, and clinical deterioration due to increase of the numbness severity despite significant reduction of pain was seen once. CONCLUSIONS: Pituitary radiosurgery for thalamic pain results in a high rate of initial efficacy and is accompanied by acceptable morbidity. It can be used as a primary minimally invasive management option for patients with post-stroke thalamic pain resistant to medical therapy. However, in the majority of cases pain recurrence occurs within 1 year after treatment.

Selective subtemporal amygdalohippocampectomy for refractory temporal lobe epilepsy: operative and neuropsychological outcomes.

OBJECT: The authors evaluated operative, neuropathological, and neuropsychological results after selective subtemporal amygdalohippocampectomy for refractory temporal lobe epilepsy in patients who were observed for at least 2 years after surgery. METHODS: Twenty-six consecutive patients underwent selective subtemporal amygdalohippocampectomy for nonlesional, medically refractory temporal lobe epilepsy. Neuropsychological evaluation using the Wechsler Adult Intelligence Scale was done before surgery in all patients, 2 months after surgery in 24 patients, and at 2-year follow up in 19 patients. A verbal paired associates learning test was administered before surgery and 2 months after surgery in 19 patients. The data were compared between the 13 patients in whom the language-dominant hemisphere was surgically treated and the six patients in whom the language-nondominant hemisphere was treated. After surgery, 84% of the patients attained either Engel Class I or II seizure outcome. There were no permanent subjective complications except postoperative memory impairment in one patient. Neuropathological examination confirmed hippocampal sclerosis in 19 patients. No significant differences in IQ and verbal memory test scores were observed between the patients in whom the language-dominant hemisphere was treated and those in whom the language-nondominant hemisphere was treated. Significant postoperative increases in verbal IQ, performance IQ, and full-scale IQ were observed over time. No significant differences were found between pre- and postoperative verbal memory test scores, and no subjective visual field loss was marked in any patient. CONCLUSIONS: Subtemporal selective amygdalohippocampectomy provides favorable surgical and neuropsychological outcomes and does not cause significant postoperative decline of verbal memory if performed on the language-dominant side.

Current treatment strategy for vestibular schwannoma: image-guided robotic microradiosurgery.

OBJECT: Gamma Knife surgery (GKS) is becoming a standard treatment for vestibular schwannoma (VS); it is ranked with microsurgery from the perspective of tumor control and audiofacial nerve function preservation. A new treatment technique that will improve the tumor shrinkage ratio, shorten the patient's recovery time, and even recover some cranial nerve function is described. METHODS: Along with advances in the GKS system, the authors have developed magnetic resonance imaging sequences specific to particular treatments. These newly developed sequences provide much clearer visualization of the distribution of the cranial nerves, especially in the area from the cisterns to the internal acoustic meatus. Magnetic resonance images have been fused with computed tomography scans to facilitate better delineation of the anatomical relationships. These dose-planning images allow for a higher isodose line (80%) inside the tumor. The aim is to shrink the tumor and not just to control it. To date 130 patients have been treated with GKS in conjunction with this new technique. Of the 130, 91 patients were observed for more than 12 months. The tumor shrinkage rate was 65.9% (76% for patients with > 24 months of follow up), the facial nerve preservation rate was 98.9%, the hearing preservation rate was 92.3%, and four (4%) of 91 patients recovered hearing function. Transient tumor enlargement was observed in most cases, but no severe complications were found. CONCLUSIONS: Although these results are preliminary, they would appear to represent a potential breakthrough in the treatment of VS. Longer follow-up periods and additional cases will firmly establish this method as an absolute treatment option for patients with a VS.