Surgical treatment and survival outcome of patients with adult thalamic glioma: a single institution experience of 8 years.

PURPOSE: Given the rarity in the population with adult thalamic gliomas (ATGs), comprehensive characteristics, treatments and survival outcome are not well characterized. This study was conducted to investigate the comprehensive characteristic and treatment of ATGs and identify the prognostic factors associated with overall survival (OS). METHODS: A retrospective analysis of newly diagnosed ATGs who underwent surgical resection consecutively was conducted. Survival analysis of OS was performed by Kaplan-Meier analysis. Cox proportional hazard model was used to investigate the possible prognostic factors associated with OS. RESULTS: A total of 102 patients with ATG were enrolled in this study. The median age was 41 years (range 18-68 years). There were 56 (54.9%) males. Sixty-two patients (60.8%) had glioblastoma (GBM). Among these patients, 46 patients (45.1%) had GTR/NTR, 50 patients (49.0%) had STR and 6 patients (5.9%) had PR. Postoperatively, 71.6% of these patients received adjuvant therapy. The median OS was 13.6 months (range 1 week-75 months). COX regression analysis revealed that ATG patients with longer duration of symptoms (p = 0.024), better pre-KPS (p = 0.045), maximal resection (p = 0.013), or lower tumor grade (p = 0.002) had longer OS, and these predictors are considered as independent prognostic factors. Survival analysis showed that ATGs with GTR/NTR plus chemoradiotherapy had significant OS advantage compared with other treatment regimens. CONCLUSIONS: This study comprehensively summarized the characteristics, treatments and survival outcomes of ATGs in the largest sample size. Maximal surgical resection can bring survival benefit. Combined-modality therapy regimen of GTR/NTR plus chemoradiotherapy may be better beneficial for OS than other regimens.

High-grade thalamic gliomas: Microsurgical treatment and prognosis analysis.

This retrospective study is aimed to investigate the efficacy of microsurgical treatment for high-grade thalamic gliomas, and to analyze the relevant prognosis. From May 2011 to Aug 2015, 49 patients with thalamic gliomas underwent microsurgical resection, and received chemotherapy and radiotherapy postoperatively. The postoperative symptoms and complications were documented, and the overall survival (OS) and the progression-free survival (PFS) data were collected. The prognostic factors were evaluated by univariate and multivariate analyses. Finally, there was no perioperative death. Twenty cases, 24 cases and 5 cases were achieved subtotal resection (>90%), partial resection (70-90%) and less than partial resection (<70%) respectively. All patients' pathological diagnosis was confirmed. The symptoms were improved in 32 cases, unchanged in 11 cases, and worsen in 6 cases. Postoperative complications were absent in 9 cases. The 6-month, 12-month, and 24-month OS were 71.4%, 38.9%, and 12.1% respectively; corresponding PFS were 66.6%, 27.1%, and 10.2% respectively. The median OS time and PFS time were 9.0 months (95% CI 6.9-11.1) and 9.0 months (95% CI 6.6-11.4) respectively. Multivariate analysis revealed extent of resection were independent prognostic factors for OS (p < .05), patients with postoperative adjuvant chemotherapy and radiotherapy had a significant prolonged OS (p < .001) and PFS (p < .001). The study shows that the short-term efficacy of microsurgery for high-grade thalamic gliomas is satisfactory. Microsurgery can effectively alleviate patients' symptoms and improve life quality. Postoperative adjuvant chemotherapy and radiotherapy are helpful for prolonging the survival time.

Distance between Active Electrode Contacts and Dentatorubrothalamic Tract in Patients with Habituation of Stimulation Effect of Deep Brain Stimulation in Essential Tremor.

Background Some patients under thalamic deep brain stimulation (DBS) for essential tremor (ET) experience habituation of tremor reduction. The nucleus ventralis intermedius (Vim) is the current main target side for ET in DBS. However, the dentatorubrothalamic tract (DRTT) is considered the relevant structure to stimulate. We investigated the distance between the active contact of the DBS electrode and the DRTT and compared this distance in patients with habituation of tremor reduction and good responders. Material and Methods In this retrospective study, we performed deterministic fiber tracking of the DRTT in 6 patients (12 hemispheres) with ET who underwent DBS in the Vim. We subsequently measured the distance between the active contact of the electrode and the ipsilateral DRTT in both hemispheres. The clinical tremor response of those 6 patients was analyzed accordingly. Results The distance between the active contact and the DRTT in patients with better and constant clinical tremor reduction was shorter (mean distance: 2.9 ± 2.2 mm standard deviation [SD]) than in patients who showed habituation of their response (mean distance: 6.1 ± 3.9 mm SD). After re-placement of a thalamic electrode inside the DRTT in one patient who experienced unsatisfying tremor reduction due to habituation of stimulation, the tremor alleviation was significant and persistent at a 13-month follow-up. Conclusion This retrospective analysis suggests that recurrence of ET tremor under chronic DBS might be associated with a larger distance between the DRTT and the active lead contact, in comparison with the smaller distances in patients with persistently good tremor control.

Diffusion Tensor Imaging-Based Thalamic Segmentation in Deep Brain Stimulation for Chronic Pain Conditions.

BACKGROUND/AIMS: Thalamic deep brain stimulation (DBS) for the treatment of medically refractory pain has largely been abandoned on account of its inconsistent and oftentimes poor efficacy. Our aim here was to use diffusion tensor imaging (DTI)-based segmentation to assess the internal thalamic nuclei of patients who have undergone thalamic DBS for intractable pain and retrospectively correlate lead position with clinical outcome. METHODS: DTI-based segmentation was performed on 5 patients who underwent sensory thalamus DBS for chronic pain. Postoperative computed tomography images obtained for electrode placement were fused with preoperative magnetic resonance images that had undergone DTI-based thalamic segmentation. Sensory thalamus maps of 4 patients were analyzed for lead positioning and interpatient variability. RESULTS: Four patients who experienced significant pain relief following DBS demonstrated contact positions within the DTI-determined sensory thalamus or in its vicinity, whereas 1 patient who did not respond to stimulation did not. Only 4 voxels (2%) within the sensory thalamus were mutually shared among patients; 108 voxels (58%) were uniquely represented. CONCLUSIONS: DTI-based segmentation of the thalamus can be used to confirm thalamic lead placement relative to the sensory thalamus and may serve as a useful tool to guide thalamic DBS electrode implantation in the future.

Factors associated with successful magnetic resonance-guided focused ultrasound treatment: efficiency of acoustic energy delivery through the skull.

OBJECTIVE: Magnetic resonance-guided focused ultrasound surgery (MRgFUS) was recently introduced as treatment for movement disorders such as essential tremor and advanced Parkinson's disease (PD). Although deep brain target lesions are successfully generated in most patients, the target area temperature fails to increase in some cases. The skull is one of the greatest barriers to ultrasonic energy transmission. The authors analyzed the skull-related factors that may have prevented an increase in target area temperatures in patients who underwent MRgFUS. METHODS: The authors retrospectively reviewed data from clinical trials that involved MRgFUS for essential tremor, idiopathic PD, and obsessive-compulsive disorder. Data from 25 patients were included. The relationships between the maximal temperature during treatment and other factors, including sex, age, skull area of the sonication field, number of elements used, skull volume of the sonication field, and skull density ratio (SDR), were determined. RESULTS: Among the various factors, skull volume and SDR exhibited relationships with the maximum temperature. Skull volume was negatively correlated with maximal temperature (p = 0.023, r(2) = 0.206, y = 64.156 - 0.028x, whereas SDR was positively correlated with maximal temperature (p = 0.009, r(2) = 0.263, y = 49.643 + 11.832x). The other factors correlate with the maximal temperature, although some factors showed a tendency to correlate. CONCLUSIONS: Some skull-related factors correlated with the maximal target area temperature. Although the number of patients in the present study was relatively small, the results offer information that could guide the selection of MRgFUS candidates.

Different magnetic resonance imaging patterns after transcranial magnetic resonance-guided focused ultrasound of the ventral intermediate nucleus of the thalamus and anterior limb of the internal capsule in patients with essential tremor or obsessive-compulsive disorder.

OBJECT: The authors report different MRI patterns in patients with essential tremor (ET) or obsessive-compulsive disorder (OCD) after transcranial MR-guided focused ultrasound (MRgFUS) and discuss possible causes of occasional MRgFUS failure. METHODS: Between March 2012 and August 2013, MRgFUS was used to perform unilateral thalamotomy in 11 ET patients and bilateral anterior limb capsulotomy in 6 OCD patients; in all patients symptoms were refractory to drug therapy. Sequential MR images were obtained in patients across a 6-month follow-up period. RESULTS: For OCD patients, lesion size slowly increased and peaked 1 week after treatment, after which lesion size gradually decreased. For ET patients, lesions were visible immediately after treatment and markedly reduced in size as time passed. In 3 ET patients and 1 OCD patient, there was no or little temperature rise (i.e., < 52°C) during MRgFUS. Successful and failed patient groups showed differences in their ratio of cortical-to-bone marrow thickness (i.e., skull density). CONCLUSIONS: The authors found different MRI pattern evolution after MRgFUS for white matter and gray matter. Their results suggest that skull characteristics, such as low skull density, should be evaluated prior to MRgFUS to successfully achieve thermal rise.

A role of diffusion tensor imaging fiber tracking in deep brain stimulation surgery: DBS of the dentato-rubro-thalamic tract (drt) for the treatment of therapy-refractory tremor.

INTRODUCTION: Deep brain stimulation (DBS) can alleviate tremor of various origins. A number of regions are targeted. In recent work our group was able to show the involvement of the dentato-rubro-thalamic tract (drt) in tremor control with fiber tracking techniques. Here we report for the first time the successful use of magnetic resonance tractography in combination with traditional landmark-based targeting techniques to perform the implantation of a bilateral DBS system in a patient with dystonic head tremor. METHODS: We report on a 37-year-old female with long-standing pure head tremor from myoclonus dystonia. She was identified as a candidate for thalamic DBS. The use of head fixation in a stereotactic frame would blur target symptoms (head tremor) during surgery and was therefore avoided. Her dentate-rubro-thalamic tracts were visualized with preoperative diffusion tensor imaging (DTI) and tractography, and then directly targeted stereotactically with DBS electrodes. RESULTS: Three months after implantation, tremor control was excellent (>90%). A close evaluation of the active electrode contact positions revealed clear involvement of the drt. CONCLUSION: This is the first time that direct visualization of fiber tracts has been employed for direct targeting and successful movement disorder tremor surgery. In the reported case, additional knowledge about the position of the drt, which previously has been shown to be a structure for modulation to achieve tremor control, led to a successful implantation of a DBS system, although there was a lack of intra-operatively testable tremor symptoms. In concordance with studies in optogenetic neuromodulation, fiber tracts are the emerging target structures for DBS. The routine integration of DTI tractography into surgical planning might be a leading path into the future of DBS surgery and will add to our understanding of the pathophysiology of movement disorders. Larger study populations will have to prove these concepts in future research.

Microglial responses around intrinsic CNS neurons are correlated with axonal regeneration.

BACKGROUND: Microglia/macrophages and lymphocytes (T-cells) accumulate around motor and primary sensory neurons that are regenerating axons but there is little or no microglial activation or T-cell accumulation around axotomised intrinsic CNS neurons, which do not normally regenerate axons. We aimed to establish whether there was an inflammatory response around the perikarya of CNS neurons that were induced to regenerate axons through a peripheral nerve graft. RESULTS: When neurons of the thalamic reticular nucleus (TRN) and red nucleus were induced to regenerate axons along peripheral nerve grafts, a marked microglial response was found around their cell bodies, including the partial enwrapping of some regenerating neurons. T-cells were found amongst regenerating TRN neurons but not rubrospinal neurons. Axotomy alone or insertion of freeze-killed nerve grafts did not induce a similar perineuronal inflammation. Nerve grafts in the corticospinal tracts did not induce axonal regeneration or a microglial or T-cell response in the motor cortex. CONCLUSIONS: These results strengthen the evidence that perineuronal microglial accumulation (but not T-cell accumulation) is involved in axonal regeneration by intrinsic CNS and other neurons.

Robotic neurological surgery applications: accuracy and consistency or pure fantasy?

INTRODUCTION: Minimally invasive surgery was born out of recent advances in neuroimaging and stereotaxy, and the scale of future neurosurgical procedures will soon be so small that it will not be possible for the unassisted surgeons. Hence, neurosurgical robotics is a natural evolution in this field. The aim of this study was to evaluate the performance of a new robotic system in a wide range of neurosurgical applications. METHODS: Patients undergoing image-guided surgical procedures were recruited to participate in this prospective ethically approved study from 2005. The PathFinder (Prosurgics, UK) is a neurosurgical robotic system with 6 degrees of freedom. It uses a fiducial system that is automatically detectable by the planning software and a camera system embedded in the robot's head. The registration procedure was performed automatically by photographing the fiducials from different angles. The robot then aligns its end-effector and tool holder along the specified path for the surgeon to pass the probe to the target. We recruited 37 consecutive patients to test the application accuracy and consistency of the system using three different fiducial fixation mechanisms: a double adhesive fixed to the skin, an ECG lead dot fixed to the skin, and a registration plate fixed to the skull. RESULTS: Out of 37 consecutive patients, 17 were males and 20 were females, with a mean age of 46.6 years. The procedures were: transsphenoidal in 8, malignant tumour biopsies in 3 and resections in 5, benign tumour excisions in 6 and functional procedures in 15 [6 bilateral deep-brain stimulations (DBSs) of the subthalamic nucleus for Parkinson's disease, 3 bilateral anterior cingulotomies for depression, 3 bilateral DBSs of the ventral intermediate nucleus of the thalamus for tremor and 3 depth electrodes during epilepsy surgery]. We tested a total of 140 targets with an average of 3-4 targets per patient. The mean application accuracy was less than 1 mm and the application accuracy was consistent in all targets in the same patient. CONCLUSIONS: This robotic system was very accurate and consistent in practice as long as the robot had achieved acceptable registration.

Gamma knife thalamotomy for multiple sclerosis tremor.

BACKGROUND: Some patients with MS suffer from disabling tremor. Improvement with medical treatment is modest, at best. Stereotactic surgery targeting the vim nucleus of the thalamus has been successful in alleviating MS tremor. Gamma knife radiosurgery represents a minimally invasive alternative to radiofrequency lesioning and DBS that can provide improvement in patients suffering from essential and parkinsonian tremor. We reviewed our experience with GK thalamotomy in the management of six consecutive patients suffering from disabling MS tremor. METHODS: The median age at the time of radiosurgery was 46 years (range, 31 to 57 years). Intention tremor had been present for a median of three years (range 8 months to 12 years). One 4-mm isocenter was used to deliver a median maximum dose of 140 Gy (range, 130-150 Gy) to the vim nucleus of the thalamus opposite the side of the most disabling tremor. Clinical outcome was assessed using the Fahn-Tolosa-Marin scale. RESULTS: The median follow-up was 27.5 months (range, 5-46 months). All patients experienced improvement in tremor after a median latency period of 2.5 months. More improvement was noted in tremor amplitude than in writing and drawing ability. In four patients, the tremor reduction led to functional improvement. One patient suffered from transient contralateral hemiparesis, which resolved after brief corticosteroid administration. No other complication was seen. CONCLUSION: Gamma knife radiosurgical thalamotomy is effective as a minimally invasive alternative to stereotactic surgery for the palliative treatment of disabling MS tremor.

Computerized posturography balance assessment of patients with bilateral ventralis intermedius nuclei deep brain stimulation.

Bilateral ventralis intermedius nuclei (Vim) deep brain stimulation (DBS) improves tremor in patients with both essential tremor (ET) and Parkinson's disease (PD). In each condition, patients have individually noted both subjective improvement and worsening in balance. Computerized posturography (CP) is able to quantify some aspects of balance. Twenty-one patients (8 with PD and 13 with ET) with bilateral Vim DBS were recruited to undergo randomized-order identical CP testing (EquiTest system) while their DBS devices were both activated and deactivated. One PD patient could not complete any OFF assessment and is not included. Three PD patients could not tolerate portions of the OFF testing. Overall, sensory organization testing was improved by DBS activation in conditions that involved quiet standing with eyes open with no motion of the support surface, or with sway-referenced support surface motion, but worsened during quiet standing with eyes closed only in ET patients. Falls lessened with activation in ET patients. Motor control testing was not changed. Bilateral Vim DBS activation mostly improved balance, but may modestly worsen other specific features.

Chronic deep brain stimulation of subthalamic and anterior thalamic nuclei for controlling refractory partial epilepsy.

OBJECTIVES: Experimental data and case reports of intractable epilepsy patients treated with deep brain stimulation (DBS) of the internal nuclei suggest a considerable anticonvulsant effect. We intended to describe the results of DBS on subthalamic nuclei and anterior thalamic nuclei (STN and ATN) from our patients and to evaluate the long-term efficiency and safety of DBS for controlling intractable epilepsy. METHODS: Six patients with refractory epilepsy and inadequate for surgery were implanted with DBS electrodes (3 in STN and 3 in ATN, respectively), switched on after a week of insertion followed by chronological observation. Seizure counts were monitored and compared with pre-implantation baseline. RESULTS: There was significant clinical improvement in respect of reduction of seizure frequency as well as the alleviation of ictal severity in almost patients. The mean reduction in seizure frequency was 62.3% (49.1% from STN vs. 75.4% from ATN). Except one patient (patient 3) with accidental infection on the right anterior chest, no complication or withdrawal of DBS was seen during our study. CONCLUSION: DBS on STN and ATN demonstrated their clear efficiency and relative safety comparable or superior to previous studies during long term follow-up. Subsequent, well designed studies warrant the further increase of the knowledge about antiepileptic effect of DBS.

Functional stereotactic surgery for treatment of cervical dystonia: review of the experience from the lesional era.

BACKGROUND: Functional stereotactic neurosurgery has been rediscovered as a powerful tool to treat various manifestations of medically refractory dystonia. The purpose of this study was to provide the first systematic review of previous experience with thalamic and basal ganglia surgery in the treatment of cervical dystonia (CD). METHODS: A comprehensive review of the literature published between 1950 and 1990 was performed. In addition, data from an unpublished doctoral thesis on 162 patients with CD operated on by Mundinger between 1972 and 1986 were analyzed. RESULTS: Overall, there is published documentation of experience with more than 300 patients with CD who underwent functional stereotactic surgery between the late 1950s and the early 1980s. In general, amelioration of CD was achieved in about 50-70% of patients in most studies. Bilateral surgery generally provided better outcomes than unilateral surgery. Postoperative benefit was reported to become evident only after a delay in several studies. Some reports demonstrated sustained benefit after follow-up of more than 5 years. Bilateral procedures, in particular bilateral thalamotomies, were clearly associated with a higher rate of postoperative side effects, such as dysarthria, dysphagia and ataxia, ranging from 20 to 70%. In the first decade after its introduction, thalamotomy was the preferred procedure. Later, the subthalamic area was targeted more frequently in order to affect pallidal outflow. Experience with targeting the pallidum proper was limited. Functional stereotactic surgery for CD was abandoned in the late 1970s for several reasons, including the general decline in movement disorder surgery at that time, the introduction of selective peripheral denervation and the widespread and beneficial use of botulinum toxin soon thereafter. CONCLUSIONS: Functional stereotactic surgery for treatment of CD has a rich history. There are several lessons to be learned from review of earlier experience. Contemporary techniques have led to a significant improvement in the benefit to risk ratio, in particular regarding bilateral surgery.