Metabolic alterations in meningioma reflect the clinical course.

BACKGROUND: Meningiomas are common brain tumours that are usually defined by benign clinical course. However, some meningiomas undergo a malignant transformation and recur within a short time period regardless of their World Health Organization (WHO) grade. The current study aimed to identify potential markers that can discriminate between benign and malignant meningioma courses. METHODS: We profiled the metabolites from 43 patients with low- and high-grade meningiomas. Tumour specimens were analyzed by nuclear magnetic resonance analysis; 270 metabolites were identified and clustered with the AutoPipe algorithm. RESULTS: We observed two distinct clusters marked by alterations in glycine/serine and choline/tryptophan metabolism. Glycine/serine cluster showed significantly lower WHO grades and proliferation rates. Also progression-free survival was significantly longer in the glycine/serine cluster. CONCLUSION: Our findings suggest that alterations in glycine/serine metabolism are associated with lower proliferation and more recurrent tumours. Altered choline/tryptophan metabolism was associated with increases proliferation, and recurrence. Our results suggest that tumour malignancy can be reflected by metabolic alterations, which may support histological classifications to predict the clinical outcome of patients with meningiomas.

Navigated Deep Brain Stimulation Surgery: Evaluating the Combined Use of a Frame-Based Stereotactic System and a Navigation System.

Deep brain stimulation (DBS) is a complex surgical procedure that requires detailed anatomical knowledge. In many fields of neurosurgery navigation systems are used to display anatomical structures during an operation to aid performing these surgeries. In frame-based DBS, the advantage of visualization has not yet been evaluated during the procedure itself. In this study, we added live visualization to a frame-based DBS system, using a standard navigation system and investigated its accuracy and potential use in DBS surgery. As a first step, a phantom study was conducted to investigate the accuracy of the navigation system in conjunction with a frame-based approach. As a second step, 5 DBS surgeries were performed with this combined approach. Afterwards, 3 neurosurgeons and 2 neurologists with different levels of experience evaluated the potential use of the system with a questionnaire. Moreover, the additional personnel, costs and required set up time were noted and compared to 5 consecutive standard procedures. In the phantom study, the navigation system showed an inaccuracy of 2.1 mm (mean SD 0.69 mm). In the questionnaire, a mean of 9.4/10 points was awarded for the use of the combined approach as a teaching tool, a mean of 8.4/10 for its advantage in creating a 3-dimensional (3-D) map and a mean of 8/10 points for facilitating group discussions. Especially neurosurgeons and neurologists in training found it useful to better interpret clinical results and side effects (mean 9/10 points) and neurosurgeons appreciated its use to better interpret microelectrode recordings (mean 9/10 points). A mean of 6/10 points was awarded when asked if the benefits were worth the additional efforts. Initially 2 persons, then one additional person was required to set up the system with no relevant added time or costs. Using a navigation system for live visualization during frame-based DBS surgery can improve the understanding of the complex 3-D anatomy and many aspects of the procedure itself. For now, we would regard it as an excellent teaching tool rather than a necessity to perform DBS surgeries.

Do directional deep brain stimulation leads rotate after implantation?

BACKGROUND: The two middle contacts of directional leads (d-leads) for deep brain stimulation are split into three segments, allowing current steering toward desired axial directions. To facilitate programming, their final orientation needs to be reliably determined. However, it is currently unclear whether d-leads rotate after implantation. Our objective was to assess the degree of d-lead rotation after implantation. METHODS: We retrospectively analyzed d-lead orientation on intraoperative X-rays, postoperative CT scans (latencies to surgery: 108-189 min postoperatively), and rotational fluoroscopies (4-9 days postoperatively) for a consecutive series of 32 implanted d-leads. For five d-leads, a CT scan with a mean follow-up of 57 days (range 28-182) was available. All d-leads were implanted with the marker facing anterior and the intention to hit an "iron sight" (ISi) on the X-ray, indicating anterior orientation (i.e., 0° ± 6°). RESULTS: In nine d-leads, an ISi was visible on the final X-ray; median orientation was 1.5° (range 0.5-6.0°) at the first follow-up CT, confirming anterior orientation. In d-leads without ISi or where ISi was not evaluable, the median rotation was 15.5° (9.5-35.0°) and 26.5° (5.5-62.0°), respectively. The orientation of the initial CT was comparable with the orientation determined by the postoperative rotational fluoroscopy and second CT in all d-lead groups. CONCLUSION: D-lead orientation does not change within the first week after implantation. We provide first indications that d-lead orientation remains stable for several weeks after surgery. Determination of lead orientation using marker-based X-ray alone seems too imprecise; adding the ISi method can increase determination of intraoperative orientation.

Tremor and Quality of Life in Patients With Advanced Essential Tremor Before and After Replacing Their Standard Deep Brain Stimulation With a Directional System.

OBJECTIVES: Patients with essential tremor treated with thalamic deep brain stimulation may experience increased tremor with the progression of their disease. Initially, this can be counteracted with increased stimulation. Eventually, this may cause unwanted side-effects as the circumferential stimulation from a standard ring contact spreads into adjacent regions. Directional leads may offer a solution to this clinical problem. We aimed to compare the ability of a standard and a directional system to reduce tremor without side-effects and to improve the quality of life for patients with advanced essential tremor. MATERIALS AND METHODS: Six advanced essential tremor patients with bilateral thalamic deep brain stimulation had their standard system replaced with a directional system. Tremor rating scale scores were prospectively evaluated before and after the replacement surgery. Secondary analyses of quality of life related to tremor, voice, and general health were assessed. RESULTS: There was a significantly greater reduction in tremor without side-effects (p = 0.017) when using the directional system. There were improvements in tremor (p = 0.031) and voice (p = 0.037) related quality of life but not in general health for patients using optimized stimulation settings with the directional system compared to the standard system. CONCLUSIONS: In this cohort of advanced essential tremor patients who no longer had ideal tremor reduction with a standard system, replacing their deep brain stimulation with a directional system significantly improved their tremor and quality of life. Up-front implantation of directional deep brain stimulation leads may provide better tremor control in those patients who progress at a later time point.

Radiation exposure of a mobile 3D C-arm with large flat-panel detector for intraoperative imaging and navigation - an experimental study using an anthropomorphic Alderson phantom.

BACKGROUND: Intraoperative 3-dimensional (3D) navigation is increasingly being used for pedicle screw placement. For this purpose, dedicated mobile 3D C-arms are capable of providing intraoperative fluoroscopy-based 3D image data sets. Modern 3D C-arms have a large field of view, which suggests a higher radiation exposure. In this experimental study we therefore investigate the radiation exposure of a new mobile 3D C-arm with large flat-panel detector to a previously reported device with regular flat-panel detector on an Alderson phantom. METHODS: We measured the radiation exposure of the Vision RFD 3D (large 30 × 30 cm detector) while creating 3D image sets as well as standard fluoroscopic images of the cervical and lumbar spine using an Alderson phantom. The dosemeter readings were then compared with the radiation exposure of the previous model Vision FD Vario 3D (smaller 20 × 20 cm detector), which had been examined identically in advance and published elsewhere. RESULTS: The larger 3D C-arm induced lower radiation exposures at all dosemeter sites in cervical 3D scans as well as at the sites of eye lenses and thyroid gland in lumbar 3D scans. At ​​male and especially female gonads in lumbar 3D scans, however, the larger 3D C-arm showed higher radiation exposures compared with the smaller 3D C-arm. In lumbar fluoroscopic images, the dosemeters near/in the radiation field measured a higher radiation exposure using the larger 3D C-arm. CONCLUSIONS: The larger 3D C-arm offers the possibility to reduce radiation exposures for specific applications despite its larger flat-panel detector with a larger field of view. However, due to the considerably higher radiation exposure of the larger 3D C-arm during lumbar 3D scans, the smaller 3D C-arm is to be recommended for short-distance instrumentations (mono- and bilevel) from a radiation protection point of view. The larger 3D C-arm with its enlarged 3D image set might be used for long instrumentations of the lumbar spine. From a radiation protection perspective, the use of the respective 3D C-arm should be based on the presented data and the respective application.

Deep Brain Stimulation for Spasmodic Dysphonia: A Blinded Comparison of Unilateral and Bilateral Stimulation in Two Patients.

Deep brain stimulation (DBS) is a promising new therapy for patients with spasmodic dysphonia (SD). The preliminary results from our randomized controlled trial showed good clinical effects with unilateral left thalamic stimulation in 6 right- handed patients. This suggests that the pathological process underpinning SD may have a "hemisphere dominant" pathway. We describe 2 patients with concurrent essential tremor and SD who had previously undergone bilateral thalamic DBS for their limb tremor. Both patients experienced an unanticipated improvement of their SD symptoms. One patient was right-handed, and the other was mixed left-handed. To investigate the amount of SD improvement following DBS therapy in each hemisphere, 4 different settings were tested: both sides on, left side on, right side on, and both sides off. Both patients most improved following bilateral stimulation. There was, however, a powerful unilateral benefit in both patients with only a small additional benefit from bilateral stimulation. The right-handed patient improved most with left-hemisphere stimulation whereas the mixed left-handed patient improved most with right hemisphere stimulation. There was some discrepancy between the two tests applied in the second patient reflecting the known difficulties to evaluate vocal symptom improvement in SD. We discuss the possible correlation of handedness and speech hemisphere dominance as well as the need for more reliable tests to measure SD severity. Ultimately, we recommend a bilateral approach for future studies, using a patient perception test as the primary outcome and functional imaging to further investigate the correlation of handedness and the amount of hemisphere dominance in SD.

Defining the Anatomy of the Vagus Nerve and Its Clinical Relevance for the Neurosurgical Treatment of Glossopharyngeal Neuralgia.

The neurosurgical treatment of glossopharyngeal neuralgia includes microvascular decompression or rhizotomy of the nerve. When considering open section of the glossopharyngeal nerve, numerous authors have recommended additional sectioning of the 'upper rootlets' of the vagus nerve because these fibers can occasionally carry the pain fibers causing the patient's symptoms. Sacrifice of vagus nerve rootlets, however, carries the potential risk of dysphagia and dysphonia. In this study, the anatomy and physiology of the vagus nerve rootlets are characterized to provide guidance for surgical decision-making. Twelve patients who underwent posterior fossa craniotomy with intraoperative electrophysiological monitoring of the vagus nerve rootlets were included in this study. In the 7 patients with glossopharyngeal neuralgia, the clinical outcomes and complications were further analyzed. In half of the patients, electrophysiological data demonstrated pure sensory function in the rostral rootlet(s) of the vagus nerve and motor responses in its caudal rootlets. This orientation of the vagus nerve, with some pure sensory function in its most rostral rootlet(s), was defined as Type A. In the other half of patients, all vagus nerve rootlets (including the most rostral) had motor responses. This was defined as Type B. The surgical strategy was guided by whether the patient had a Type A or Type B vagus nerve. For those with Type B, no vagus nerve rootlets were sacrificed. None of the patients with glossopharyngeal neuralgia developed any permanent neurological deficits. We recommend intraoperative electrophysiological testing of the vagus nerve rootlets. If the testing reveals motor innervation in the rostral vagal rootlet (Type B), that rootlet may be decompressed but should not be sectioned to avoid a motor complication. Patients with pure sensory innervation of the rostral rootlet(s) (Type A) can have decompression or section of those rootlets without complication.

Coughing as a Side Effect of Deep Brain Stimulation due to Peripheral Stimulation of the Vagus Nerve: Case Report.

The authors describe how severe coughing and breathing issues were caused by a deep brain stimulation (DBS) system due to current induction in the adjacent vagus nerve. A 57-year-old man with Parkinson's disease (PD) who received bilateral subthalamic nucleus DBS presented with coughing and breathing difficulty when his DBS system was activated. The intensity of coughing was directly related to the amount of stimulation. When the DBS system was turned off, his cough resolved immediately. A system check revealed no radiographic abnormalities and all electrode impedances were within the normal range. We hypothesize that the coughing was caused by an induced electromagnetic stimulation of the vagus nerve from the extensions, which were running in close proximity to the nerve in the neck. Since the patient could not tolerate the coughing at stimulation settings required to ameliorate his PD symptoms, we ultimately exchanged the extensions and moved them further away from the vagus nerve. This resulted in immediate, complete, and continuous relief of the patient's symptoms.

Combination of CT angiography and MRI in surgical planning of deep brain stimulation.

PURPOSE: For safe deep brain stimulation (DBS) planning, an accurate visualization and localization of vessels is mandatory. Contrast enhanced (ce) MRI depicts both arteries and veins. Computed tomography angiography (CTA) detects arteries with high geometric accuracy. We routinely combine both modalities for DBS planning. METHODS: A total of 222 trajectories in a consecutive series of 113 patients who underwent DBS operations were included. In all trajectories, the number of veins and arteries in a 10-mm diameter around the planned trajectory were counted in a ceMRI and a CTA. If a vessel was visible in both modalities, the distance was measured. RESULTS: A total of 370 vessels were counted. Two hundred forty vessels (65%) were visible in both modalities. With 134 of the vessels, we detected a difference of the vessel's location with an average distance of 1.24 mm (SD 0.58). Eighty vessels (22%) were visible only in the ceMRI, 50 vessels (13%) only in the CTA. We had four bleedings (1.8% per lead) of which one was symptomatic (0.45%). CONCLUSION: The majority of vessels were visible in both modalities; however, in more than half of these cases, the location was not identical. Here, the location in the CTA can be regarded as the ground truth. Moreover, both the CTA and the ceMRI depicted vessels not seen in the other imaging modality. We therefore assume that the combination of both imaging modalities for DBS planning increases the chance to detect vascular conflicts along the trajectory, thus reducing the risk of intracranial bleeding.

Development of a Standardized Cranial Phantom for Training and Optimization of Functional Stereotactic Operations.

BACKGROUND: In recent years, simulations based on phantom models have become increasingly popular in the medical field. In the field of functional and stereotactic neurosurgery, a cranial phantom would be useful to train operative techniques, such as stereo-electroencephalography (SEEG), to establish new methods as well as to develop and modify radiological techniques. In this study, we describe the construction of a cranial phantom and show examples for it in stereotactic and functional neurosurgery and its applicability with different radiological modalities. METHODS: We prepared a plaster skull filled with agar. A complete operation for deep brain stimulation (DBS) was simulated using directional leads. Moreover, a complete SEEG operation including planning, implantation of the electrodes, and intraoperative and postoperative imaging was simulated. RESULTS: An optimally customized cranial phantom is filled with 10% agar. At 7°C, it can be stored for approximately 4 months. A DBS and an SEEG procedure could be realistically simulated. Lead artifacts can be studied in CT, X-ray, rotational fluoroscopy, and MRI. CONCLUSIONS: This cranial phantom is a simple and effective model to simulate functional and stereotactic neurosurgical operations. This might be useful for teaching and training of neurosurgeons, establishing operations in a new center and for optimization of radiological examinations.

Polyglobulia in patients with hemangioblastomas is related to tumor size but not to serum erythropoietin.

BACKGROUND: Hemangioblastomas are associated with elevated hemoglobin (Hb) levels (polyglobulia), which is associated with a higher risk for cerebral stroke, cardiac infarction and pulmonary embolism. The pathomechanism of polyglobulia remains unclear and different theories have been postulated. Among those are elevated serum erythropoietin (EPO) levels caused by secretion of the tumor or associated tumor cyst. METHODS: To elucidate the pathomechanism, we systematically investigated the relation between polyglobulia, serum EPO level, size of the solid tumor and associated cyst in hemangioblastomas. We prospectively evaluated hemoglobin and EPO levels in a series of 33 consecutive patients operated on hemangioblastomas in our center. We measured the size of the solid tumor and associated cyst in magnetic resonance imaging. Statistical evaluations were performed using the Fisher's exact test and student's t-test. RESULTS: As a result five patients had elevated hemoglobin levels. Only one of these had an elevated serum EPO level. Of 26 patients with normal hemoglobin levels, 4 patients had elevated EPO levels.Patients with low or normal hemoglobin levels (84%) had an average tumor size of 0.8 cm3, which differed significantly from patients with elevated hemoglobin levels (16%), who had an average solid tumor size of 8.0 cm3 (p < 0.05). We did not observe a significant correlation between EPO levels or polyglobulia and associated cysts. CONCLUSIONS: We therefore conclude that in contrast to previous case reports and interpretations, our data show no correlation between polyglobulia and EPO levels or associated cysts in patients with hemangioblastomas. In fact, it is the size of the solid tumor that correlates with polyglobulia.The study was retrospectively registered in the German Clinical Trial Registry on 10 July 2014; Trial registration: DRKS00006310.

Accidental Durotomy in Minimally Invasive Transforaminal Lumbar Interbody Fusion: Frequency, Risk Factors, and Management.

PURPOSE: To assess the frequency, risk factors, and management of accidental durotomy in minimally invasive transforaminal lumbar interbody fusion (MIS TLIF). METHODS: This single-center study retrospectively investigates 372 patients who underwent MIS TLIF and were mobilized within 24 hours after surgery. The frequency of accidental durotomies, intraoperative closure technique, body mass index, and history of previous surgery was recorded. RESULTS: We identified 32 accidental durotomies in 514 MIS TLIF levels (6.2%). Analysis showed a statistically significant relation of accidental durotomies to overweight patients (body mass index ≥ 25 kg/m(2); P = 0.0493). Patient age older than 65 years tended to be a positive predictor for accidental durotomies (P = 0.0657). Mobilizing patients on the first postoperative day, we observed no durotomy-associated complications. CONCLUSIONS: The frequency of accidental durotomies in MIS TLIF is low, with overweight being a risk factor for accidental durotomies. The minimally invasive approach seems to minimize durotomy-associated complications (CSF leakage, pseudomeningocele) because of the limited dead space in the soft tissue. Patients with accidental durotomy can usually be mobilized within 24 hours after MIS TLIF without increased risk. The minimally invasive TLIF technique might thus be beneficial in the prevention of postoperative immobilization-associated complications such as venous thromboembolism. This trial is registered with DRKS00006135.

Minimally Invasive Technique for PMMA Augmentation of Fenestrated Screws.

PURPOSE: To describe the minimally invasive technique for cement augmentation of cannulated and fenestrated screws using an injection cannula as well as to report its safety and efficacy. METHODS: A total of 157 cannulated and fenestrated pedicle screws had been cement-augmented during minimally invasive posterior screw-rod spondylodesis in 35 patients from January to December 2012. Retrospective evaluation of cement extravasation and screw loosening was carried out in postoperative plain radiographs and thin-sliced triplanar computed tomography scans. RESULTS: Twenty-seven, largely prevertebral cement extravasations were detected in 157 screws (17.2%). None of the cement extravasations was causing a clinical sequela like a new neurological deficit. One screw loosening was noted (0.6%) after a mean follow-up of 12.8 months. We observed no cementation-associated complication like pulmonary embolism or hemodynamic insufficiency. CONCLUSIONS: The presented minimally invasive cement augmentation technique using an injection cannula facilitates convenient and safe cement delivery through polyaxial cannulated and fenestrated screws during minimally invasive screw-rod spondylodesis. Nevertheless, the optimal injection technique and design of fenestrated screws have yet to be identified. This trial is registered with German Clinical Trials DRKS00006726.

PEEK cages versus PMMA spacers in anterior cervical discectomy: comparison of fusion, subsidence, sagittal alignment, and clinical outcome with a minimum 1-year follow-up.

PURPOSE: To compare radiographic and clinical outcomes after anterior cervical discectomy in patients with cervical degenerative disc disease using PEEK cages or PMMA spacers with a minimum 1-year follow-up. METHODS: Anterior cervical discectomy was performed in 107 patients in one or two levels using empty PEEK cages (51 levels), Sulcem PMMA spacers (49 levels) or Palacos PMMA spacers (41 levels) between January, 2005 and February, 2009. Bony fusion, subsidence, and sagittal alignment were retrospectively assessed in CT scans and radiographs at follow-up. Clinical outcome was measured using the VAS, NDI, and SF-36. RESULTS: Bony fusion was assessed in 65% (PEEK cage), 57% (Sulcem), and 46% (Palacos) after a mean follow-up of 2.5 years. Mean subsidence was 2.3-2.6 mm without significant differences between the groups. The most pronounced loss of lordosis was found in PEEK cages (-4.1°). VAS was 3.1 (PEEK cage), 3.6 (Sulcem), and 2.7 (Palacos) without significant differences. Functional outcome in the PEEK cage and Palacos group was superior to the Sulcem group. CONCLUSIONS: The substitute groups showed differing fusion rates. Clinical outcome, however, appears to be generally not correlated with fusion status or subsidence. We could not specify a superior disc substitute for anterior cervical discectomy. This trial is registered with DRKS00003591.

Optic nerve and chiasm hemangioblastomas in von Hippel-Lindau disease: report of 12 cases and review of the literature.

Introduction: Optic nerve and chiasm hemangioblastomas are rare tumors, occurring sporadically or in the context of von Hippel-Lindau (VHL) disease. They have only been portrayed in isolated case reports and small cohorts. Their natural history and therapeutic strategies are only scarcely described. To better characterize these rare tumors, we retrospectively analyzed an optic nerve and chiasm hemangioblastoma series of 12 VHL patients. By combining our own experience to a review of all known cases in literature, we intended to create treatment recommendations for optic nerve and chiasm hemangioblastomas in VHL patients. Methods: We reviewed two electronic databases in the hospitals of our senior authors, searching for VHL patients with optic nerve or chiasm hemangioblastomas. Clinical data were summarized. Tumor size and growth rate were measured on contrast enhanced MRI. Comparable data were collected by literature review of all available cases in VHL patients (Pubmed, Trip, Google and Google Scholar). Results: Of 269 VHL patients, 12 had optic nerve or chiasm hemangioblastomas. In 10 of 12 patients, tumors were diagnosed upon annual ophthalmoscopic/MRI screening. Of 8 patients who were asymptomatic at diagnosis, 7 showed absent or very slow annual progression, without developing significant vision impairment. One patient developed moderate vision impairment. Two symptomatic patients suffered from rapid tumor growth and progressive vision impairment. Both underwent late-stage surgery, resulting in incomplete resection and progressive vision impairment. One patient presented with acute vision field loss. A watchful-waiting approach was adopted because the hemangioblastoma was ineligible for vision-sparing surgery. One patient developed progressive vision impairment after watchful waiting. In the literature we found 45 patient cases with 48 hemangioblastomas. Discussion: When optic nerve and chiasm hemangioblastomas are diagnosed, we suggest annual MRI follow-up as long as patients do not develop vision impairment. If tumors grow fast, threaten the contralateral eye, or if patients develop progressive vision deficiency; surgical resection must be considered because neurological impairment is irreversible, and resection of large tumors carries a higher risk of further visual decline.

Laser Interstitial Thermal Therapy in a Large Thalamic Glioma with Long-Term Remission: A Case Report.

INTRODUCTION: Thalamic gliomas pose a particular therapeutic challenge as complete resection is rarely achieved due to the deep and eloquent location. Laser interstitial thermal therapy (LITT) may provide a valuable management option for deep-seated gliomas that are not accessible with open surgery. CASE PRESENTATION: A 57-year-old woman presented with a rapidly progressive large thalamic glioblastoma. Opting for full ablation, we selected a challenging trajectory to maximize the possibility of full ablation. At 2.4 cm in diameter, the tumour was larger than recommended for LITT; nevertheless, three laser ablations along a single trajectory resulted in macroscopic ablation without complications. Adjuvant radio-chemotherapy was started soon after surgery without radiological recurrence 1.5 years after the initial surgery. CONCLUSION: This case demonstrates the potential when thalamic tumours are managed with timely LITT treatment and meticulous trajectory planning. Moreover, it highlights the need for close interdisciplinary management with neurosurgeons, neuropathologists, neuroradiologists, and neurooncologists.

Sequence variations in the von Hippel-Lindau tumor suppressor gene in patients with intracranial aneurysms.

BACKGROUND: The rupture of intracranial aneurysms leads to subarachnoid hemorrhage, which is often associated with poor outcome. Preventive treatment of unruptured intracranial aneurysms is possible and recommended. However, the lack of candidate genes precludes identifying patients at risk by genetic analyses. We observed intracranial aneurysms in 2 patients with von Hippel-Lindau (VHL) disease and the known disease-causing mutation c.292T > C (p.Tyr98His) in the VHL tumor suppressor gene. This study investigates whether the VHL gene is a possible candidate gene for aneurysm formation. METHODS: Patients with intracranial aneurysms admitted to our department between 2006 and 2009 were enrolled. The peripheral leukocyte DNA of 200 patients was investigated for sequence variations in the VHL gene using denaturing high performance liquid chromatography. Peripheral leukocyte DNA of 100 randomly sampled probands was investigated as a control group. The allelic frequencies of sequence variations between both groups were compared using the Fisher exact test. RESULTS: Fourteen of 200 patients with intracranial aneurysms had sequence variations at 6 different loci in the VHL gene. In contrast, no sequence variations were identified in 100 probands in the control group (P = 0.0062). However, none of the single-sequence variations had a statistically significant difference in the allelic frequencies compared to the control group. CONCLUSIONS: There is accumulating evidence for a genetic basis of aneurysm development. Our investigations lead to the conclusion that the VHL gene is potentially involved in the formation of intracranial aneurysms in a subset of patients. Additional candidate genes need to be identified in order to develop sensitive genetic screening for at-risk patients.

The Impact of Implementing a Radiation-Sparing Protocol for Percutaneous Kyphoplasty-A Prospective Dosemetric Study.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: The purpose of this prospective study was to evaluate a protocol for radiation-sparing kyphoplasty by assessing dosemetrically recorded radiation exposures to both patient and surgeon. METHODS: This prospective clinical study examines the radiation exposure to patient and surgeon during single-level kyphoplasty in 32 thoracolumbar osteoporotic vertebral body fractures (12 OF 2, 9 OF 3, 11 OF 4 types) using a radiation aware surgical protocol between May 2017 and November 2019. The radiation exposure was measured at different locations using film, eye lens and ring dosemeters. Dose values are reported under consideration of lower detection limits of each dosemeter type. RESULTS: A high proportion of dosemeter readings was below the lower detection limits, especially for the surgeon (>90%). Radiation exposure to the surgeon was highest at the unprotected thyroid gland (0.053 ± 0.047 mSv), however only slightly above the lower detection limit of dosemeters (0.044 mSv). Radiation exposure to the patient was highest at the chest (0.349 ± 0.414 mSv) and the gonad (0.186 ± 0.262 mSv). Fluoroscopy time, dose area product and number of fluoroscopic images were 46.0 ± 17.9 sec, 124 ± 109 cGy×cm2, and 35 ± 13 per kyphoplasty, respectively. Back pain significantly improved from 6.8 ± 1.6 to 2.5 ± 1.7 on the numeric rating scale on the first postoperative day (P < 0.0001). CONCLUSIONS: The implementation of a strict intraoperative radiation protection protocol allows for safely performed kyphoplasty with ultra-low radiation exposure for the patient and surgeon without exceeding the annual occupational dose limits. TRIAL REGISTRATION: The study was registered in the German Clinical Trials Register (DRKS00011908, registration date 16/05/2017).

Sweet spots of standard and directional leads in patients with refractory essential tremor: white matter pathways associated with maximal tremor improvement.

OBJECTIVE: In patients with essential tremor (ET) treated with standard deep brain stimulation (sDBS) whose ET had progressed and who no longer received optimal benefit from sDBS, directional deep brain stimulation (dDBS) may provide better tremor control. Current steering may provide better coverage of subcortical structures related to tremor control in patients with ET and significant progression without optimal response to sDBS. METHODS: This study included 6 patients with ET initially treated with sDBS whose tremor later progressed and who then underwent reimplantation with dDBS to optimize their tremor control. To investigate the differences in the local effects of sDBS and dDBS, the authors generated the volume of tissue activation (VTA) to calculate the sweet spots associated with the best possible tremor control with no side effects. Then, to investigate the anatomical structures associated with maximal tremor control, the white matter pathways of the posterior subthalamic areas (PSAs) were generated and their involvement with the sDBS and dDBS sweet spots was calculated. RESULTS: Tremor improvement was significantly better with dDBS (68.4%) than with sDBS (48.7%) (p = 0.017). The sDBS sweet spot was located within the ventral intermediate nucleus, whereas the sweet spot of the dDBS was mainly located within the PSA. The sweet spots of both sDBS and dDBS involved a similar portion of the cerebellothalamic pathway. However, the dDBS had greater involvement of the pallidofugal pathways than the sDBS. CONCLUSIONS: In patients with ET treated with sDBS who later had ET progression, dDBS provided better tremor control, which was related to directionality and a more ventral position. The involvement of both the cerebellothalamic and pallidofugal pathways obtained with dDBS is associated with additional improvement over the sDBS.

Posterior Fossa Approaches Using the Leksell Vantage Frame with a Virtual Planning Approach in a Series of 10 Patients-Feasibility, Accuracy, and Pitfalls.

The open-face design of the Leksell Vantage frame provides many advantages. However, its more rigid, contoured design offers less flexibility than other frames. This is especially true for posterior fossa approaches. This study explores whether these limitations can be overcome by tailored frame placement using a virtual planning approach. The posterior fossa was accessed in ten patients using the Leksell Vantage frame. Frame placement was planned with the Brainlab Elements software, including a phantom-based (virtual) pre-operative planning approach. A biopsy was performed in all patients; in four, additional laser ablation surgery was performed. The accuracy of virtual frame placement was compared to actual frame placement. The posterior approach was feasible in all patients. In one case, the trajectory had to be adjusted; in another, the trajectory was switched from a right- to a left-sided approach. Both cases showed large deviations from the initially planned frame placement. A histopathological diagnosis was achieved in all patients. The new Leksell Vantage frame can be used to safely target the posterior fossa with a high diagnostic success rate and accuracy. Frame placement needs to be well-planned and executed. This can be facilitated using specific software solutions as demonstrated.