Stereotactic frame-based biopsy of infratentorial lesions via the suboccipital-transcerebellar approach with the Zamorano-Duchovny stereotactic system-a retrospective analysis of 79 consecutive cases.

OBJECTIVE: Lesions of the posterior fossa (brainstem and cerebellum) are challenging in diagnosis and treatment due to the fact that they are often located eloquently and total resection is rarely possible. Therefore, frame-based stereotactic biopsies are commonly used to asservate tissue for neuropathological diagnosis and further treatment determination. The aim of our study was to assess the safety and diagnostic success rate of frame-based stereotactic biopsies for lesions in the posterior fossa via the suboccipital-transcerebellar approach. METHODS: We performed a retrospective database analysis of all frame-based stereotactic biopsy cases at our institution since 2007. The aim was to identify all surgical cases for infratentorial lesion biopsies via the suboccipital-transcerebellar approach. We collected clinical data regarding outcomes, complications, diagnostic success, radiological appearances, and stereotactic trajectories. RESULTS: A total of n = 79 cases of stereotactic biopsies for posterior fossa lesions via the suboccipital-transcerebellar approach (41 female and 38 male) utilizing the Zamorano-Duchovny stereotactic system were identified. The mean age at the time of surgery was 42.5 years (± 23.3; range, 1-87 years). All patients were operated with intraoperative stereotactic imaging (n = 62 MRI, n = 17 CT). The absolute diagnostic success rate was 87.3%. The most common diagnoses were glioma, lymphoma, and inflammatory disease. The overall complication rate was 8.7% (seven cases). All patients with complications showed new neurological deficits; of those, three were permanent. Hemorrhage was detected in five of the cases having complications. The 30-day mortality rate was 7.6%, and 1-year survival rate was 70%. CONCLUSIONS: Our data suggests that frame-based stereotactic biopsies with the Zamorano-Duchovny stereotactic system via the suboccipital-transcerebellar approach are safe and reliable for infratentorial lesions bearing a high diagnostic yield and an acceptable complication rate. Further research should focus on the planning of safe trajectories and a careful case selection with the goal of minimizing complications and maximizing diagnostic success.

Repeat surgery of recurrent glioma for molecularly informed treatment in the age of precision oncology: A risk-benefit analysis.

PURPOSE: Surgery for recurrent glioma provides cytoreduction and tissue for molecularly informed treatment. With mostly heavily pretreated patients involved, it is unclear whether the benefits of repeat surgery outweigh its potential risks. METHODS: Patients receiving surgery for recurrent glioma WHO grade 2-4 with the goal of tissue sampling for targeted therapies were analyzed retrospectively. Complication rates (surgical, neurological) were compared to our institutional glioma surgery cohort. Tissue molecular diagnostic yield, targeted therapies and post-surgical survival rates were analyzed. RESULTS: Between 2017 and 2022, tumor board recommendation for targeted therapy through molecular diagnostics was made for 180 patients. Of these, 70 patients (38%) underwent repeat surgery. IDH-wildtype glioblastoma was diagnosed in 48 patients (69%), followed by IDH-mutant astrocytoma (n = 13; 19%) and oligodendroglioma (n = 9; 13%). Gross total resection (GTR) was achieved in 50 patients (71%). Tissue was processed for next-generation sequencing in 64 cases (91%), and for DNA methylation analysis in 58 cases (83%), while immunohistochemistry for mTOR phosphorylation was performed in 24 cases (34%). Targeted therapy was recommended in 35 (50%) and commenced in 21 (30%) cases. Postoperatively, 7 patients (11%) required revision surgery, compared to 7% (p = 0.519) and 6% (p = 0.359) of our reference cohorts of patients undergoing first and second craniotomy, respectively. Non-resolving neurological deterioration was documented in 6 cases (10% vs. 8%, p = 0.612, after first and 4%, p = 0.519, after second craniotomy). Median survival after repeat surgery was 399 days in all patients and 348 days in GBM patients after repeat GTR. CONCLUSION: Surgery for recurrent glioma provides relevant molecular diagnostic information with a direct consequence for targeted therapy under a reasonable risk of postoperative complications. With satisfactory postoperative survival it can therefore complement a multi-modal glioma therapy approach.

Deep learning aided preoperative diagnosis of primary central nervous system lymphoma.

The preoperative distinction between glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL) can be difficult, even for experts, but is highly relevant. We aimed to develop an easy-to-use algorithm, based on a convolutional neural network (CNN) to preoperatively discern PCNSL from GBM and systematically compare its performance to experienced neurosurgeons and radiologists. To this end, a CNN-based on DenseNet169 was trained with the magnetic resonance (MR)-imaging data of 68 PCNSL and 69 GBM patients and its performance compared to six trained experts on an external test set of 10 PCNSL and 10 GBM. Our neural network predicted PCNSL with an accuracy of 80% and a negative predictive value (NPV) of 0.8, exceeding the accuracy achieved by clinicians (73%, NPV 0.77). Combining expert rating with automated diagnosis in those cases where experts dissented yielded an accuracy of 95%. Our approach has the potential to significantly augment the preoperative radiological diagnosis of PCNSL.

The molecular diagnostic yield of frame-based stereotactic biopsies in the age of precision neuro-oncology: a cross-sectional study.

PURPOSE: With the increasing role of molecular genetics in the diagnostics of intracranial tumors, delivering sufficient representative tissue for such analyses is of paramount importance. This study explored the rate of successful diagnosis after frame-based stereotactic biopsies of intracranial lesions. METHODS: Consecutive patients undergoing frame-based stereotactic biopsies in 2020 and 2021 were included in this retrospective analysis. Cases were classified into three groups: conclusive, diagnosis with missing molecular genetics (MG) data, and inconclusive neuropathological diagnosis. RESULTS: Of 145 patients, a conclusive diagnosis was possible in n = 137 cases (94.5%). For 3 cases (2.0%), diagnosis was established with missing MG data. In 5 cases (3.5%), an inconclusive (tumor) diagnosis was met. Diagnoses comprised mainly WHO 4 glioblastomas (n = 73, 56%), CNS lymphomas (n = 23, 16%), inflammatory diseases (n = 14, 10%), and metastases (n = 5, 3%). Methylomics were applied in 49% (n = 44) of tumor cases (panel sequencing in n = 28, 30% of tumors). The average number of specimens used for MG diagnostics was 5, while the average number of specimens provided was 15. In a univariate analysis, insufficient DNA was associated with an inconclusive diagnosis or a diagnosis with missing MG data (p < 0.001). Analyses of planned and implemented trajectories of cases with diagnosis with missing MG data or inconclusive diagnosis (n = 8) revealed that regions of interest were reached in almost all cases (n = 7). CONCLUSION: Although stereotactic frame-based biopsies deliver a limited amount of tissue, they bear high histopathological and molecular genetic diagnostic yields. Given the proven surgical precision of the planned biopsy trajectories, optimizing surveyed lesion regions could help improve the rate of conclusive diagnoses.

Routine ICU admission after brain tumor surgery: retrospective validation and critical appraisal of two prediction scores.

BACKGROUND: Routine admission to an intensive care unit (ICU) following brain tumor surgery has been a common practice for many years. Although this practice has been challenged by many authors, it has still not changed widely, mainly due to the lack of reliable data for preoperative risk assessment. Motivated by this dilemma, risk prediction scores for postoperative complications following brain tumor surgery have been developed recently. In order to improve the ICU admission policy at our institution, we assessed the applicability, performance, and safety of the two most appropriate risk prediction scores. METHODS: One thousand consecutive adult patients undergoing elective brain tumor resection within 19 months were included. Patients with craniotomy for other causes, i.e., cerebral aneurysms and microvascular decompression, were excluded. The decision for postoperative ICU-surveillance was made by joint judgment of the operating surgeon and the anesthesiologist. All data and features relevant to the scores were extracted from clinical records and subsequent ICU or neurosurgical floor documentation was inspected for any postoperative adverse events requiring ICU admission. The CranioScore derived by Cinotti et al. (Anesthesiology 129(6):1111-20, 5) and the risk assessment score of Munari et al. (Acta Neurochir (Wien) 164(3):635-641, 15) were calculated and prognostic performance was evaluated by ROC analysis. RESULTS: In our cohort, both scores showed only a weak prognostic performance: the CranioScore reached a ROC-AUC of 0.65, while Munari et al.'s score achieved a ROC-AUC of 0.67. When applying the recommended decision thresholds for ICU admission, 64% resp. 68% of patients would be classified as in need of ICU surveillance, and the negative predictive value (NPV) would be 91% for both scores. Lowering the thresholds in order to increase patient safety, i.e., 95% NPV, would lead to ICU admission rates of over 85%. CONCLUSION: Performance of both scores was limited in our cohort. In practice, neither would achieve a significant reduction in ICU admission rates, whereas the number of patients suffering complications at the neurosurgical ward would increase. In future, better risk assessment measures are needed.

Choice of Implantable Pulse Generators for Deep Brain Stimulation: An Overview of Clinical Practice.

INTRODUCTION: The success of deep brain stimulation (DBS) treatment depends on several factors, including proper patient selection, accurate electrode placement, and adequate stimulation settings. Another factor that may impact long-term satisfaction and therapy outcomes is the type of implantable pulse generator (IPG) used: rechargeable or non-rechargeable. However, there are currently no guidelines on the choice of IPG type. The present study investigates the current practices, opinions, and factors DBS clinicians consider when choosing an IPG for their patients. METHODS: Between December 2021 and June 2022, we sent a structured questionnaire with 42 questions to DBS experts of two international, functional neurosurgery societies. The questionnaire included a rating scale where participants could rate the factors influencing their choice of IPG type and their satisfaction with certain IPG aspects. Additionally, we presented four clinical case scenarios to assess preference of choice of IPG-type in each case. RESULTS: Eighty-seven participants from 30 different countries completed the questionnaire. The three most relevant factors for IPG choice were "existing social support," "cognitive status," and "patient age." Most participants believed that patients valued avoiding repetitive replacement surgeries more than the burden of regularly recharging the IPG. Participants reported that they implanted the same amount of rechargeable as non-rechargeable IPGs for primary DBS insertions and 20% converted non-rechargeable to rechargeable IPGs during IPG replacements. Most participants estimated that rechargeable was the more cost-effective option. CONCLUSION: This present study shows that the decision-making of the choice of IPG is very individualized. We identified the key factors influencing the physician's choice of IPG. Compared to patient-centric studies, clinicians may value different aspects. Therefore, clinicians should rely not only on their opinion but also counsel patients on different types of IPGs and consider the patient's preferences. Uniform global guidelines on IPG choice may not represent regional or national differences in the healthcare systems.

Deep brain stimulation of the nucleus accumbens in treatment-resistant alcohol use disorder: a double-blind randomized controlled multi-center trial.

Treatment resistance in alcohol use disorders (AUD) is a major problem for affected individuals and for society. In the search of new treatment options, few case studies using deep brain stimulation (DBS) of the nucleus accumbens have indicated positive effects in AUD. Here we report a double-blind randomized controlled trial comparing active DBS ("DBS-EARLY ON") against sham stimulation ("DBS-LATE ON") over 6 months in n = 12 AUD inpatients. This 6-month blind phase was followed by a 12-month unblinded period in which all patients received active DBS. Continuous abstinence (primary outcome), alcohol use, alcohol craving, depressiveness, anxiety, anhedonia and quality of life served as outcome parameters. The primary intention-to-treat analysis, comparing continuous abstinence between treatment groups, did not yield statistically significant results, most likely due to the restricted number of participants. In light of the resulting limited statistical power, there is the question of whether DBS effects on secondary outcomes can nonetheless be interpreted as indicative of an therapeutic effect. Analyses of secondary outcomes provide evidence for this, demonstrating a significantly higher proportion of abstinent days, lower alcohol craving and anhedonia in the DBS-EARLY ON group 6 months after randomization. Exploratory responder analyses indicated that patients with high baseline alcohol craving, depressiveness and anhedonia responded to DBS. The results of this first randomized controlled trial are suggestive of beneficial effects of DBS in treatment-resistant AUD and encourage a replication in larger samples.

A single-center, open-label trial on convenience and complications of rechargeable implantable pulse generators for spinal cord stimulation: The Recharge Pain Trial.

Rechargeable implantable pulse generators (r-IPGs) have been available for spinal cord stimulation (SCS) claiming to offer a longer service life but demanding continuous monitoring and regular recharging by the patients. The aim of the study (DRKS00021281; Apr 7th, 2020) was to assess the convenience, safety, and acceptance of r-IPGs and their effect on patient lives under long-term therapy. Standardized questionnaires were sent to all chronic pain patients with a r-IPG at the time of trial. Primary endpoint was the overall convenience of the charging process on an ordinal scale from "very hard" (1 point) to "very easy" (5 points). Secondary endpoints were charge burden (min/week), rates of user confidence and complications (failed recharges, interruptions of therapy). Endpoints were analyzed for several subgroups. Data sets n = 40 (42% return rate) were eligible for analysis. Patient age was 57.2 ± 12.6 (mean ± standard deviation) years with the r-IPG being implanted for 52.1 ± 32.6 months. The overall convenience of recharging was evaluated as "easy" (4 points). The charge burden was 112.7 ± 139 min/week. 92% of the patients felt confident recharging the neurostimulator. 37.5% of patients reported failed recharges. 28.9% of patients experienced unintended interruptions of stimulation. Subgroup analysis only showed a significant impact on overall convenience for different models of stimulators (p < 0.05). Overall, SCS patients feel confident handling a r-IPG at high rates of convenience and acceptable effort despite high rates of usage-related complications. Further technical improvements for r-IPGs are needed.

Recharge PSYCH: A Study on Rechargeable Implantable Pulse Generators in Deep Brain Stimulation for Psychiatric Disorders.

BACKGROUND: Rechargeable implantable pulse generators (r-IPGs) for deep brain stimulation (DBS) promise longer battery life and fewer replacement surgeries versus non-rechargeable systems. Long-term data on the effects of recharging in patients who received DBS for psychiatric indications is limited. The Recharge PSYCH trial is the first study that included DBS patients with psychiatric disorders treated with different r-IPG models. METHODS: Standardized questionnaires were sent to all psychiatric DBS patients with an r-IPG implanted at the time of the study. The primary endpoint was convenience of recharging. Secondary endpoints were rate of user confidence and rate of usage-related complications, as well as charge burden (defined as minutes per week needed to recharge). RESULTS: Data sets of n = 21 patients were eligible for data analysis. At the time of the survey patients were implanted with the r-IPG for a mean 31.8 ± 22.4 months. Prior to being implanted with an r-IPG, patients had undergone a median of 3 IPG replacements. The overall convenience of the charging process was rated as "easy" with a median of 8.0 out of 10.0 points. 33.3% of patients experienced situations in which the device could not be successfully recharged. In 38.1% of patients, therapy with the r-IPG was interrupted unintentionally. The average charge burden was 286 ± 22.4 minutes per week. CONCLUSIONS: Patients with psychiatric disorders rated the recharging process as "easy", but with a significantly higher charge burden and usage-related complication rates compared to published data on movement disorder DBS patients.

Questionnaire-based approach to evaluate the convenience of rechargeable extracorporeal pulse generators for wireless spinal cord stimulation.

Spinal cord stimulation (SCS) has been utilized for more than 50 years to treat refractory neuropathic pain. Currently, SCS systems with fully implantable pulse generators (IPGs) represent the standard. New wireless extracorporeal SCS (wSCS) devices without IPGs promise higher levels of comfort and convenience for patients. However, to date there are no studies on how charging and using this wSCS system affects patients and their therapy. This study is the first questionnaire-based survey on this topic focusing on patient experience. The trial was a single arm, open-label and mono-centric phase IV study. Standardized questionnaires were sent to all patients with a wSCS device in use at the time of trial. The primary endpoint was the convenience of the charging and wearing process scored on an ordinal scale from "very hard" (1) to "very easy" (5). Secondary endpoints included time needed for charging, the duration of stimulation per day and complication rates. Questionnaires of 6 out of 9 patients were returned and eligible for data analysis. The mean age of patients was 61.3 ± 6.7 (± SD) years. The duration of therapy was 20.3 ± 15.9 months (mean ± SD). The mean duration of daily stimulation was 17 ± 5.9 h (mean ± SD). n = 5 patients rated the overall convenience as "easy" (4) and n = 3 patients evaluated the effort of the charging process and wearing of the wSCS device as "low" (4). n = 5 patients considered the wearing and charging process as active participation in their therapy. n = 5 patients would choose an extracorporeal device again over a conventional SCS system. Early or late surgical complications did not occur in this patient collective. Overall, patients felt confident using extracorporeal wSCS devices without any complications. Effort to maintain therapy with this system was rated as low.

The use of quantitative pupillometry in patients with pituitary tumors: a technical note.

BACKGROUND: Pituitary tumors may cause compression of the optic chiasm, resulting in decreased visual acuity. Therefore, decompression of the optic chiasm is a major goal of surgical treatment in such patients. Quantitative pupillometry has been used in various clinical settings for assessing the optic system but has not been applied in patients with pituitary tumors. This study aimed to evaluate the potential of this technique to improve treatment modalities in patients undergoing surgical resection of pituitary tumors. METHOD: Pupillometry using the automated NPi 200® Pupillometer was performed in seven patients who underwent surgical resection of large pituitary tumors at the University of Heidelberg in 2018. The neurological pupil index (NPi) was assessed preoperatively and postoperatively, and correlations with visual acuity and magnetic resonance imaging (MRI) findings regarding optic chiasm compression were determined. RESULTS: All patients experienced visual disturbance due to a large pituitary tumor. The NPi was < 4.0 in all patients in at least one pupil. Intraoperative MRI demonstrated successful decompression of the optic chiasm in all cases. Postoperatively, the NPi values increased, and this increase was correlated with improved visual acuity. CONCLUSIONS: We found that quantitative pupillometry can detect optic chiasm compression in patients with pituitary tumors. Furthermore, postoperative improvement of NPi values may indicate sufficient decompression of the optic chiasm. Further studies are warranted to substantiate the granularity of this technique to gain valuable information for patients with pituitary tumors who are indicated for surgery.

Wireless Subcutaneous Trigeminal Nerve Field Stimulation for Refractory Trigeminal Pain: A Single Center Experience.

INTRODUCTION: Subcutaneous trigeminal nerve field stimulation (sTNFS) is a neuromodulatory treatment for neuropathic trigeminal pain with the ability to reduce the intensity and frequency of pain attacks. However, hardware issues including lead migration, skin erosion, infection, so-called pocket pain at the site of the implanted neurostimulator are reported. Implantable wireless neurostimulation technology promises not only an even less invasive sTNFS treatment and thinner and more flexible electrodes better suited for facial implants, but also provides further advantages such as lack of an implantable neurostimulator and 3T magnetic resonance imaging compatibility. MATERIAL AND METHODS: All patients who had received trial stimulation with a partially implantable sTNFS system were analyzed for ICHD-3 (3rd edition of the International Classification of Headache Disorders) diagnosis, success of trial stimulation, pre- and postoperative pain intensity, frequency of attacks, complications, and side-effects of sTNFS. RESULTS: All patients (N = 3) responded to sTNFS (≥50% pain reduction) during the trial period. According to ICHD-3, N = 2 of the patients were classified with trigeminal neuralgia (TN) with concomitant persistent facial pain and N = 1 patient with multiple sclerosis associated TN. The time of the test period was 44 ± 31.24 days (mean ± SD). The average daily duration of stimulation per patient amounted 2.5 ± 2.2 hours (range 1-5). The pain intensity (defined on a visual analog scale) was reduced by 80% ± 17% (mean ± SD). Reduction or cessation in pain medication was observed in all patients. No surgical complications occurred in the long-term follow-up period of 18.84 ± 6 (mean ± SD) months. CONCLUSION: The partially implantable sTNFS device seems to be safe, effective, and reliable. Compared to conventional devices, the equipment is not limited to the length of trial stimulation. Furthermore, the daily stimulation duration was much shorter compared to previous reports.

Mapping autonomic, mood and cognitive effects of hypothalamic region deep brain stimulation.

Because of its involvement in a wide variety of cardiovascular, metabolic and behavioural functions, the hypothalamus constitutes a potential target for neuromodulation in a number of treatment-refractory conditions. The precise neural substrates and circuitry subserving these responses, however, are poorly characterized to date. We sought to retrospectively explore the acute sequelae of hypothalamic region deep brain stimulation and characterize their neuroanatomical correlates. To this end we studied-at multiple international centres-58 patients (mean age: 68.5 ± 7.9 years, 26 females) suffering from mild Alzheimer's disease who underwent stimulation of the fornix region between 2007 and 2019. We catalogued the diverse spectrum of acutely induced clinical responses during electrical stimulation and interrogated their neural substrates using volume of tissue activated modelling, voxel-wise mapping, and supervised machine learning techniques. In total 627 acute clinical responses to stimulation-including tachycardia, hypertension, flushing, sweating, warmth, coldness, nausea, phosphenes, and fear-were recorded and catalogued across patients using standard descriptive methods. The most common manifestations during hypothalamic region stimulation were tachycardia (30.9%) and warmth (24.6%) followed by flushing (9.1%) and hypertension (6.9%). Voxel-wise mapping identified distinct, locally separable clusters for all sequelae that could be mapped to specific hypothalamic and extrahypothalamic grey and white matter structures. K-nearest neighbour classification further validated the clinico-anatomical correlates emphasizing the functional importance of identified neural substrates with area under the receiving operating characteristic curves between 0.67 and 0.91. Overall, we were able to localize acute effects of hypothalamic region stimulation to distinct tracts and nuclei within the hypothalamus and the wider diencephalon providing clinico-anatomical insights that may help to guide future neuromodulation work.

Wireless, remote solution for home fetal and maternal heart rate monitoring.

BACKGROUND: Access to prenatal care can be challenging due to physician shortages and rural geography. The multiple prenatal visits performed to collect basic fetal measurements lead to significant patient burden as well. The standard of care tools for fetal monitoring, external fetal heart rate monitoring with cardiotocography, as used today, must be applied by a medical professional in a healthcare setting. Novel tools to enable a remote and self-administered fetal monitoring solution would significantly alleviate some of the current barriers to care. OBJECTIVE: To compare maternal and fetal heart rate monitoring data obtained by 'Invu system' (a wireless, wearable, self-administered, fixed-location device containing passive electrical and acoustic sensors) to cardiotocography, toward a true remote fetal monitoring solution. MATERIALS AND METHODS: A prospective, open-label, multicenter study evaluated concurrent use of Invu and cardiotocography in pregnant women, aged 18 to 50 years, with singleton pregnancies ≥32+0 weeks' gestation (NCT03504189). Simultaneous recording sessions from Invu and cardiotocography lasted for ≥30 minutes. Data from the 8 electrical sensors and 4 acoustic sensors in the Invu belt were acquired, digitized, and sent wirelessly for analysis by an algorithm on cloud-based servers. The algorithm validates the data, preprocesses the data to remove noise, detects heartbeats independently from the two data sources (electrical and acoustic), and fuses the detected heartbeat arrays to calculate fetal heart rate (FHR) and maternal heart rate (MHR). The primary performance endpoint was Invu FHR limit of agreement within ± 10 beats per minute (bpm) of FHR measured with cardiotocography. RESULTS: A total of 147 women were included in the study analysis. The mean (SD) maternal age was 31.8 ±6.9 years, and the mean gestational age was 37.7 ±2.3 weeks. There was a highly significant correlation between FHR measurements from Invu and cardiotocography (r = 0.92; P<0.0001). The 95% limits of agreement for the difference, the range within which most differences between the two measurements will lie, were -8.84 bpm to 8.24 bpm. Invu measurements of MHR were also very similar to cardiotocography and were highly significantly correlated (r = 0.97; P<0.0001). No adverse events were reported during the study. CONCLUSION: Although captured by very different methods, the FHR and MHR outputs wirelessly obtained by the Invu system through passive methods were very similar to those obtained by the current standard of care. The limits of agreement for FHR measured by Invu were within a clinically acceptable ± 8 bpm of cardiotocography FHR. The Invu device uses passive technology to allow for safe, non-invasive and convenient monitoring of patients in the clinic and remotely. Further work should investigate how remote perinatal monitoring could best address some of the recent challenges seen with prenatal care and maternal and fetal outcomes. CLINICAL TRIAL INFORMATION: Registration date: April 20, 2018; First participant enrollment: February 28, 2018; ClinicalTrials.gov registration NCT03504189; https://clinicaltrials.gov/ct2/show/NCT03504189.

Modifying the progression of Alzheimer's and Parkinson's disease with deep brain stimulation.

At times of an aging population and increasing prevalence of neurodegenerative disorders, effective medical treatments remain limited. Therefore, there is an urgent need for new therapies to treat Alzheimer's disease (AD). Deep brain stimulation (DBS) is thought to address the neuronal network dysfunction of this disorder and may offer new therapeutic options. Preliminary evidence suggests that DBS of the fornix may have effects on cognitive decline, brain glucose metabolism, hippocampal volume and cortical grey matter volume in certain patients with mild AD. Rodent studies have shown that increase of cholinergic neurotransmitters, hippocampal neurogenesis, synaptic plasticity and reduction of amyloid plaques are associated with DBS. Currently a large phase III study of fornix DBS is assessing efficacy in patients with mild AD aged 65 years and older. The Nucleus basalis of Meynert has also been explored in a phase I study in of mild to moderate AD and was tolerated well regardless of the lack of benefit. Being an established therapy for Parkinson's Disease (PD), DBS may exert some disease-modifying traits rather than being a purely symptomatic treatment. There is evidence of dopaminergic neuroprotection in animal models and some suggestion that DBS may influence the natural progression of the disorder. Neuromodulation may possibly have beneficial effects on course of different neurodegenerative disorders compared to medical therapy alone. For dementias, functional neurosurgery may provide an adjunctive option in patient care. This article is part of the special issue entitled 'The Quest for Disease-Modifying Therapies for Neurodegenerative Disorders'.

A Wireless Neuroprosthesis for Patients with Drug-refractory Epilepsy: A Proof-of-Concept Study.

Objective Acute or protracted cortical recording may be necessary for patients with drug-refractory epilepsy to identify the ictogenic regions before undergoing resection. Currently, these invasive recording techniques present certain limitations, one of which is the need for cables connecting the recording electrodes placed in the intracranial space with external devices displaying the recorded electrocorticographic signals. This equates to a direct connection between the sterile intracranial space with the non-sterile environment. Due to the increasing likelihood of infections with time, subdural grids are typically removed a few days after implantation, a limiting factor in localizing the epileptogenic zone if seizures are not frequent enough to be captured within this time-frame. Furthermore, patients are bound to stay in the hospital, connected by the wires to the recording device, thus increasing substantially the treatment costs. To address some of the current shortcomings of invasive monitoring, we developed a neuroprosthesis made of a subdural silicone grid connected to a wireless transmitter allowing prolonged electrocorticografic recording and direct cortical stimulation. This device consists of a silicone grid with 128-platinum/iridium contacts, connected to an implantable case providing wireless recording and stimulation. The case also houses a wirelessly rechargeable battery for chronic long-term implants. We report the results of the first human proof-of-concept trial for wireless transmission of electrocorticographic recordings using a device suited for long-term implantation in three patients with drug-refractory epilepsy.  Methods Three patients with medically refractory epilepsy underwent the temporary intraoperative placement of the subdural grid connected to the wireless device for recording and transmission of electrocorticographic signals for a duration of five minutes before the conventional recording electrodes were placed or the ictal foci were resected. Results Wireless transmission of brain signals was successfully achieved. The wireless electrocorticographic signal was judged of excellent quality by a blinded neurophysiologist. Conclusions This preliminary experience reports the first successful placement of a wireless electrocorticographic recording device in humans. Long-term placement for prolonged wireless electrocorticographic recording in epilepsy patients will be the next step.

A multicenter, open-label, controlled trial on acceptance, convenience, and complications of rechargeable internal pulse generators for deep brain stimulation: the Multi Recharge Trial.

OBJECTIVE: Rechargeable neurostimulators for deep brain stimulation have been available since 2008, promising longer battery life and fewer replacement surgeries compared to non-rechargeable systems. Long-term data on how recharging affects movement disorder patients are sparse. This is the first multicenter, patient-focused, industry-independent study on rechargeable neurostimulators. METHODS: Four neurosurgical centers sent a questionnaire to all adult movement disorder patients with a rechargeable neurostimulator implanted at the time of the trial. The primary endpoint was the convenience of the recharging process rated on an ordinal scale from "very hard" (1) to "very easy" (5). Secondary endpoints were charge burden (time spent per week on recharging), user confidence, and complication rates. Endpoints were compared for several subgroups. RESULTS: Datasets of 195 movement disorder patients (66.1% of sent questionnaires) with Parkinson's disease (PD), tremor, or dystonia were returned and included in the analysis. Patients had a mean age of 61.3 years and the device was implanted for a mean of 40.3 months. The overall convenience of recharging was rated as "easy" (4). The mean charge burden was 122 min/wk and showed a positive correlation with duration of therapy; 93.8% of users felt confident recharging the device. The rate of surgical revisions was 4.1%, and the infection rate was 2.1%. Failed recharges occurred in 8.7% of patients, and 3.6% of patients experienced an interruption of therapy because of a failed recharge. Convenience ratings by PD patients were significantly worse than ratings by dystonia patients. Caregivers recharged the device for the patient in 12.3% of cases. Patients who switched from a non-rechargeable to a rechargeable neurostimulator found recharging to be significantly less convenient at a higher charge burden than did patients whose primary implant was rechargeable. Age did not have a significant impact on any endpoint. CONCLUSIONS: Overall, patients with movement disorders rated recharging as easy, with low complication rates and acceptable charge burden.

Evaluation of three automatic brain vessel segmentation methods for stereotactical trajectory planning.

BACKGROUND AND OBJECTIVE: Stereotactical procedures require exact trajectory planning to avoid blood vessels in the trajectory path. Innovation in imaging and image recognition techniques have facilitated the automatic detection of blood vessels during the planning process and may improve patient safety in the future. To assess the feasibility of a vessel detection and warning system using currently available imaging and vessel segmentation techniques. METHODS: Image data were acquired from post-contrast, isovolumetric T1-weighted sequences (T1CE) and time.-of-flight MR angiography at 3T or 7T from a total of nine subjects. Vessel segmentation by a combination of a vessel-enhancement filter with subsequent level-set segmentation was evaluated using three different methods (Vesselness, FastMarching and LevelSet) in 45 stereotactic trajectories. Segmentation results were compared to a gold-standard of manual segmentation performed jointly by two human experts. RESULTS: The LevelSet method performed best with a mean interclass correlation coefficient (ICC) of 0.76 [0.73, 0.81] compared to the FastMarching method with ICC 0.70 [0.67, 0.73] respectively. The Vesselness algorithm achieved clearly inferior overall performance with a mean ICC of 0.56 [0.53, 0.59]. The differences in mean ICC between all segmentation methods were statistically significant (p < 0.001 with post-hoc p < 0.026). The LevelSet method performed likewise good in MPRAGE and 3T-TOF images and excellent in 7T-TOF image data. The negative predictive value (NPV) was very high (>97%) for all methods and modalities. Positive predictive values (PPV) were found in the overall range of 65-90% likewise depending on algorithm and modality. This pattern reflects the disposition of all segmentation methods - in case of misclassification - to produce preferentially false-positive than false-negative results. In a clinical setting, two to three potential collision warnings would be given per trajectory on average with a PPV of around 50%. CONCLUSIONS: It is feasible to integrate a clinically meaningful vessel detection and collision warning system into stereotactical planning software. Both, T1CE and MRA sequences are suitable as image data for such an application.

Acute 5 Hz deep brain stimulation of the lateral habenula is associated with depressive-like behavior in male wild-type Wistar rats.

BACKGROUND: Chronic high frequency Deep Brain Stimulation (DBS) of the Lateral Habenula (LHb) has been applied in clinical case studies to treat patients with treatment resistant depression. LHb neurons in models of depression were found to have a preferred firing frequency in the theta band. The aim of this study was to determine differential behavioral effects of acute high- and theta band-frequency DBS and whether bilateral DBS electrode insertion may be associated with a lesional effect. METHODS: Adult male Wistar rats were implanted with bilateral LHb DBS electrodes and randomly assigned to 100 Hz, 5 Hz or sham stimulation (n = 8 per group). Rats were tested against a control group (n = 8) in a battery of behavioral paradigms. RESULTS: No differences between groups were found with regards to locomotor activity in the open field test or anhedonia-like behavior in the novelty suppressed feeding paradigm. 100 Hz stimulation was associated with increased exploratory behavior in the elevated plus maze. In the forced swim test, 5 Hz stimulation was associated with significantly decreased latency to and increased duration of immobility, whereas 100 Hz stimulation significantly increased latency to immobility. No significant behavioral differences between sham stimulation and control group animals were detected. CONCLUSION: Acute theta band frequency DBS in the LHb is associated with depressive-like behavior in wild-type male Wistar rats. This was likely not mediated by a general decrease in locomotor activity or a lesional effect after electrode implantation.