Metabolomic profile of cerebrospinal fluid from patients with diffuse gliomas.

BACKGROUND: Diffuse gliomas are among the most common brain tumors in adults and are associated with a dismal prognosis, especially in patients with glioblastoma. To date, tumor tissue acquisition is mandatory for conclusive diagnosis and therapeutic decision-making. In this study, we aimed to identify possible diagnostic and prognostic biomarkers in cerebrospinal fluid (CSF) and blood. METHODS: During glioma surgery at our institution, CSF and blood samples were collected from patients. Subsequently, targeted metabolomics analysis was used to detect and quantify circulating metabolites. The metabolome profiles of glioma patients were compared with those of patients in a control group who had undergone neurosurgery for other entities, such as nonglial tumors or hydrocephalus, and were correlated with established glioma diagnostic molecular markers. RESULTS: In this study, a total of 30 glioma patients were included, along with a control group of 21 patients without glioma. Serum metabolomic analysis did not detect any significant differences between the groups, whereas CSF-metabolome analysis revealed increased levels of six metabolites in glioma patients. Among these, the most pronounced differences were found for the biogenic amine putrescine (p = 0.00005). p-Cresol sulfate was identified as a potential CSF marker for determining isocitrate dehydrogenase (IDH) status in glioma patients (p = 0.0037). CONCLUSION: CSF-metabolome profiling, unlike blood profiling, shows promise as a diagnostic tool for glioma patients with the potential to assign molecular subtypes. The next step will involve a larger multicenter study to validate these findings, with the ultimate objective of integrating CSF metabolomics analysis into clinical practice.

The safety and utility of the semi-sitting position for clipping of posterior circulation aneurysms.

BACKGROUND: The semi-sitting position offers advantages for surgeries in the posterior cranial fossa. However, data on its safety and effectiveness for clipping aneurysms in the posterior cerebral circulation are limited. This retrospective cohort study evaluates the safety and effectiveness of using the semi-sitting position for these surgeries. METHODS: We conducted a retrospective study of 17 patients with posterior cerebral circulation aneurysms who underwent surgical clipping in the semi-sitting position in the Department of Neurosurgery at Hannover Medical School over a 10-year period. RESULTS: The mean age at surgery was 62 years (range, 31 to 75). Fourteen patients were admitted with subarachnoid hemorrhage and 3 patients had incidental aneurysmas. Fifteen patients had PICA aneurysms, and two had aneurysms of the vertebral artery and the superior cerebellar artery, respectively. The median diameter of the aneurysms was 5 mm (range 3-17 mm). Intraoperative venous air embolism (VAE) occurred in 4 patients, without affecting the surgical or clinical course. VAE was associated with a mild decrease of EtCO2 levels in 3 patients and in 2 patients a decrease of blood pressure occurred which was managed effectively. Surgical procedures proceeded as planned in all instances. There were no complications secondary to VAE. Two patients died secondary to respiratory problems (not related to VAE), and one patient was lost to follow-up. Eleven of fourteen patients were partially or completely independent (Barthel index between 60 and 100) at a median follow-up duration of 13.5 months (range, 3-103 months). CONCLUSION: The semi-sitting position is a safe and effective technique for the surgical clipping of aneurysms in the posterior cerebral circulation. The incidence of VAE is comparable to that seen in tumor surgery. However, it is crucial for the surgical and anesthesiological team to be familiar with potential complications and to react immediately in case of an occurrence of VAE.

Extended Long-Term Outcome After Conservative Decompressive Microsurgery and Routine Adjuvant Fractionated Stereotactic Radiotherapy for Symptomatic Cavernous Sinus Meningiomas.

BACKGROUND AND OBJECTIVES: Cavernous sinus meningiomas (CSM) pose one of the most difficult to treat subgroup of skull base meningiomas. The purpose of this study was to evaluate the efficacy of an interdisciplinary treatment approach for symptomatic CSM which incorporated conservative function preserving microsurgery and routine adjuvant fractionated stereotactic radiotherapy (FSRT). METHODS: A homogenous group of patients with symptomatic primary CSM with extracavernous extension was treated between 2005 and 2012. All patients were available for a minimum follow-up of 5 years. Clinical follow-up included detailed examination of oculomotor deficits, visual status, and endocrinologic function. Radiologic follow-up was conducted by tumor volumetry. RESULTS: Overall, 23 patients were included in this study (78.3% women; median age 58 years). Diplopia was the most common presenting symptom, followed by headache and visual disturbances. Surgical morbidity was low (3/23; 13%). FSRT was applied after a median of 2 months after surgery. At a median clinical follow-up of 113 months, 70.45% of the presenting symptoms had improved, 25% remained unchanged, and in 2 cases (4.54%), worsening occurred. Overall tumor regression was evident in 19/21 World Health Organization 1 and in 1/2 of World Health Organization 2 CSM, respectively, at a median radiological follow-up of 103 months. CONCLUSION: Our findings demonstrate the efficacy of an interdisciplinary treatment approach for symptomatic primary CSM with extracavernous extension with decompression of neurovascular elements followed by FSRT. Precise preoperative planning and intraoperative decision making in combination with routine postoperative radiotherapy can achieve excellent tumor control, improve neurologic function, and minimize long-term morbidity.

Brain Metastases from Thyroid Carcinoma: Prognostic Factors and Outcomes.

Intracranial metastases from thyroid cancer are rare. Although the prognosis of thyroid cancer patients is generally favorable, the prognosis of patients with intracranial metastases from thyroid cancer has been considered unfavorable owing to lower survival rates among such patients compared to those without intracranial involvement. Many questions about their management remain unclear. The aim of the present study was to analyze the characteristics, treatment modalities, and outcomes of patients with brain metastases from thyroid cancer. Among 4320 patients with thyroid cancer recorded in our institutional database over a 30-year period, the data of 20 patients with brain metastasis were retrospectively collected and analyzed. The clinical characteristics, histological type of primary cancer and metastatic brain tumor, additional previous distant metastasis, treatment modalities, locations and characteristics on radiologic findings, time interval between the first diagnosis of primary thyroid cancer and brain metastasis, and survival were analyzed. Among our patient cohort, the mean age at initial diagnosis was 59.3 ± 14.1 years, and at the manifestation of diagnosis of cerebral metastasis, the mean age was found to be 64.8 ± 14.9 years. The histological types of primary thyroid cancer were identified as papillary in ten patients, follicular in seven, and poorly differentiated carcinoma in three. The average interval between the diagnosis of thyroid cancer and brain metastasis was 63.4 ± 58.4 months (range: 0-180 months). Ten patients were identified as having a single intracranial lesion, and ten patients were found to have multiple lesions. Surgical resection was primarily performed in fifteen patients, and whole-brain radiotherapy, radiotherapy, or tyrosine kinase inhibitors were applied in the remaining five patients. The overall median survival time was 15 months after the diagnosis of BMs from TC (range: 1-252 months). Patients with thyroid cancer can develop brain metastasis even many years after the diagnosis of the primary tumor. The results of our study demonstrate increased overall survival in patients younger than 60 years of age at the time of diagnosis of brain metastasis. There was no difference in survival between patients with brain metastasis from papillary carcinoma and those with follicular thyroid carcinoma.

A Pragmatic Review on Spinal Cord Stimulation Therapy for Parkinson's Disease Gait Related Disorders: Gaps and Controversies.

BACKGROUND: Parkinson's Disease (PD) is a progressive neurological disorder that results in potentially debilitating mobility deficits. Recently, spinal cord stimulation (SCS) has been proposed as a novel therapy for PD gait disorders. The highest levels of evidence remain limited for SCS. OBJECTIVES: In this systematic review and narrative synthesis, the literature was searched using combinations of key phrases indicating spinal cord stimulation and PD. METHODS: We included pre-clinical studies and all published clinical trials, case reports, conference abstracts as well as protocols for ongoing clinical trials. Additionally, we included trials of SCS applied to atypical parkinsonism. RESULTS: A total of 45 human studies and trials met the inclusion criteria. Based on the narrative synthesis, a number of knowledge gaps and future avenues of potential research were identified. This review demonstrated that evidence for SCS is currently not sufficient to recommend it as an evidence-based therapy for PD related gait disorders. There remain challenges and significant barriers to widespread implementation, including issues regarding patient selection, effective outcome selection, stimulation location and mode, and in programming parameter optimization. Results of early randomized controlled trials are currently pending. SCS is prone to placebo, lessebo and nocebo as well as blinding effects which may impact interpretation of outcomes, particularly when studies are underpowered. CONCLUSION: Therapies such as SCS may build on current evidence and be shown to improve specific gait features in PD. Early negative trials should be interpreted with caution, as more evidence will be required to develop effective methodologies in order to drive clinical outcomes.

Head movement dynamics in dystonia: a multi-centre retrospective study using visual perceptive deep learning.

Dystonia is a neurological movement disorder characterised by abnormal involuntary movements and postures, particularly affecting the head and neck. However, current clinical assessment methods for dystonia rely on simplified rating scales which lack the ability to capture the intricate spatiotemporal features of dystonic phenomena, hindering clinical management and limiting understanding of the underlying neurobiology. To address this, we developed a visual perceptive deep learning framework that utilizes standard clinical videos to comprehensively evaluate and quantify disease states and the impact of therapeutic interventions, specifically deep brain stimulation. This framework overcomes the limitations of traditional rating scales and offers an efficient and accurate method that is rater-independent for evaluating and monitoring dystonia patients. To evaluate the framework, we leveraged semi-standardized clinical video data collected in three retrospective, longitudinal cohort studies across seven academic centres. We extracted static head angle excursions for clinical validation and derived kinematic variables reflecting naturalistic head dynamics to predict dystonia severity, subtype, and neuromodulation effects. The framework was also applied to a fully independent cohort of generalised dystonia patients for comparison between dystonia sub-types. Computer vision-derived measurements of head angle excursions showed a strong correlation with clinically assigned scores. Across comparisons, we identified consistent kinematic features from full video assessments encoding information critical to disease severity, subtype, and effects of neural circuit interventions, independent of static head angle deviations used in scoring. Our visual perceptive machine learning framework reveals kinematic pathosignatures of dystonia, potentially augmenting clinical management, facilitating scientific translation, and informing personalized precision neurology approaches.

Reducing radiation exposure and costs: CT body scout views with an enhanced protocol versus conventional radiography after shunt surgery.

OBJECTIVE: Ventriculoperitoneal shunt implantation has become standard treatment for cerebrospinal fluid diversion, besides endoscopic third ventriculostomy for certain indications. Postoperative X-ray radiography series of skull, chest and abdomen combined with cranial CT are obtained routinely in many institutions to document the shunt position and valve settings in adult patients. Measures to reduce postoperative radiation exposure are needed, however, there is only limited experience with such efforts. Here, we aim to compare routine postoperative cranial CT plus conventional radiography series (retrospective arm) with cranial CT and body scout views only (prospective arm) concerning both diagnostic quality and radiation exposure. PATIENTS AND METHODS: After introduction of an enhanced CT imaging protocol, routine skull and abdomen radiography was no longer obtained after VP shunt surgery. The image studies of 25 patients with routine postoperative cranial CT and conventional radiography (retrospective arm of study) were then compared to 25 patients with postoperative cranial CT and CT body scout views (prospective arm of study). Patient demographics such as age, sex and primary diagnosis were collected. The image quality of conventional radiographic images and computed tomography scout views images were independently analyzed by one neurosurgeon and one neuroradiologist. RESULTS: There were no differences in quality assessments according to three different factors determined by two independent investigators for both groups. There was a statistically significant difference, however, between the conventional radiography series group and the CT body scout view imaging group with regard to radiation exposure. The effective dose estimation calculation yielded a difference of 0.05 mSv (two-tailed t-test, p = 0.044) in favor of CT body scout view imaging. Furthermore, the new enhanced protocol resulted in a reduction of cost and the use of human resources. CONCLUSION: CT body scout view imaging provides sufficient imaging quality to determine shunt positioning and valve settings. With regard to radiation exposure and costs, we suggest that conventional postoperative shunt series may be abandoned.

External ventricular drainage in pediatric patients: indications, management, and shunt conversion rates.

PURPOSE: Placement of an external ventricular drainage (EVD) is one of the most frequent procedures in neurosurgery, but it has specific challenges and risks in the pediatric population. We here investigate the indications, management, and shunt conversion rates of an EVD. METHODS: We retrospectively analyzed the data of a consecutive series of pediatric patients who had an EVD placement in the Department of Neurosurgery at Hannover Medical School over a 12-year period. A bundle approach was introduced to reduce infections. Patients were categorized according to the underlying pathology in three groups: tumor, hemorrhage, and infection. RESULTS: A total of 126 patients were included in this study. Seventy-two were male, and 54 were female. The mean age at the time of EVD placement was 5.2 ± 5.0 years (range 0-17 years). The largest subgroup was the tumor group (n = 54, 42.9%), followed by the infection group (n = 47, 37.3%), including shunt infection (n = 36), infected Rickham reservoir (n = 4), and bacterial or viral cerebral infection (n = 7), and the hemorrhage group (n = 25, 19.8%). The overall complication rate was 19.8% (n = 25/126), and the total number of complications was 30. Complications during EVD placement were noted in 5/126 (4%) instances. Complications during drainage time were infection in 9.5% (12 patients), dysfunction in 7.1% (9 patients), and EVD dislocation in 3.2% (4 patients). The highest rate of complications was seen in the hemorrhage group. There were no long-term complications. Conversion rates into a permanent shunt system were 100% in previously shunt-dependent patients. Conversion rates were comparable in the tumor group (27.7%) and in the hemorrhage group (32.0%). CONCLUSION: EVD placement in children is an overall safe and effective option in children. In order to make further progress, carefully planned prospective and if possible randomized studies are needed controlling for multivariable aspects.

Hearing loss in juvenile rats leads to excessive play fighting and hyperactivity, mild cognitive deficits and altered neuronal activity in the prefrontal cortex.

Background: In children, hearing loss has been associated with hyperactivity, disturbed social interaction, and risk of cognitive disturbances. Mechanistic explanations of these relations sometimes involve language. To investigate the effect of hearing loss on behavioral deficits in the absence of language, we tested the impact of hearing loss in juvenile rats on motor, social, and cognitive behavior and on physiology of prefrontal cortex. Methods: Hearing loss was induced in juvenile (postnatal day 14) male Sprague-Dawley rats by intracochlear injection of neomycin under general anesthesia. Sham-operated and non-operated hearing rats served as controls. One week after surgery auditory brainstem response (ABR) measurements verified hearing loss or intact hearing in sham-operated and non-operated controls. All rats were then tested for locomotor activity (open field), coordination (Rotarod), and for social interaction during development in weeks 1, 2, 4, 8, 16, and 24 after surgery. From week 8 on, rats were trained and tested for spatial learning and memory (4-arm baited 8-arm radial maze test). In a final setting, neuronal activity was recorded in the medial prefrontal cortex (mPFC). Results: In the open field deafened rats moved faster and covered more distance than sham-operated and non-operated controls from week 8 on (both p < 0.05). Deafened rats showed significantly more play fighting during development (p < 0.05), whereas other aspects of social interaction, such as following, were not affected. Learning of the radial maze test was not impaired in deafened rats (p > 0.05), but rats used less next-arm entries than other groups indicating impaired concept learning (p < 0.05). In the mPFC neuronal firing rate was reduced and enhanced irregular firing was observed. Moreover, oscillatory activity was altered, both within the mPFC and in coherence of mPFC with the somatosensory cortex (p < 0.05). Conclusions: Hearing loss in juvenile rats leads to hyperactive behavior and pronounced play-fighting during development, suggesting a causal relationship between hearing loss and cognitive development. Altered neuronal activities in the mPFC after hearing loss support such effects on neuronal networks outside the central auditory system. This animal model provides evidence of developmental consequences of juvenile hearing loss on prefrontal cortex in absence of language as potential confounding factor.

Somatosensory evoked potentials recorded from DBS electrodes: the origin of subcortical N18.

The different peaks of somatosensory-evoked potentials (SEP) originate from a variety of anatomical sites in the central nervous system. The origin of the median nerve subcortical N18 SEP has been studied under various conditions, but the exact site of its generation is still unclear. While it has been claimed to be located in the thalamic region, other studies indicated its possible origin below the pontomedullary junction. Here, we scrutinized and compared SEP recordings from median nerve stimulation through deep brain stimulation (DBS) electrodes implanted in various subcortical targets. We studied 24 patients with dystonia, Parkinson's disease, and chronic pain who underwent quadripolar electrode implantation for chronic DBS and recorded median nerve SEPs from globus pallidus internus (GPi), subthalamic nucleus (STN), thalamic ventral intermediate nucleus (Vim), and ventral posterolateral nucleus (VPL) and the centromedian-parafascicular complex (CM-Pf). The largest amplitude of the triphasic potential of the N18 complex was recorded in Vim. Bipolar recordings confirmed the origin to be close to Vim electrodes (and VPL/CM-Pf) and less close to STN electrodes. GPi recorded only far-field potentials in unipolar derivation. Recordings from DBS electrodes located in different subcortical areas allow determining the origin of certain subcortical SEP waves more precisely. The subcortical N18 of the median nerve SEP-to its largest extent-is generated ventral to the Vim in the region of the prelemniscal radiation/ zona incerta.

Assessing the feasibility of the transmastoid infralabyrinthine approach without decompression of the jugular bulb to the extradural part of the petrous apex and petroclival junction prior to surgery.

BACKGROUND AND OBJECTIVE: This study aims to define specific measurements on cranial high-resolution computed tomography (HRCT) images prior to surgery to prove the feasibility of the navigated transmastoid infralabyrinthine approach (TI-A) without rerouting of the facial nerve (FN) and decompression of the jugular bulb (JB) in accessing the extradural-intrapetrous part of petrous bone lesions located at the petrous apex and petroclival junction. MATERIALS AND METHODS: Vertical and horizontal distances of the infralabyrinthine space were measured on cranial HRCT images prior to dissection. Subsequently, the area of access was measured on dissected human cadaveric specimens. Infralabyrinthine access to the extradural part of the petrous apex and petroclival junction was evaluated on dissected specimens by two independent raters. Finally, the vertical and horizontal distances were correlated with the area of access. RESULTS: Fourteen human cadaveric specimens were dissected bilaterally. In 54% of cases, the two independent raters determined appropriate access to the petrous apex and petroclival junction. A highly significant positive correlation (r = 0.99) was observed between the areas of access and the vertical distances. Vertical distances above 5.2 mm were considered to permit suitable infralabyrinthine access to the extradural area of the petrous apex and petroclival junction. CONCLUSIONS: Prior to surgery, vertical infralabyrinthine distances on HRCT images above 5.2 mm provide suitable infralabyrinthine access to lesions located extradurally at the petrous apex and petroclival junction via the TI-A without rerouting of the FN and without decompression of the JB.

Large-Scale Screening: Phenotypic and Mutational Spectrum in Isolated and Combined Dystonia Genes.

BACKGROUND: Pathogenic variants in several genes have been linked to genetic forms of isolated or combined dystonia. The phenotypic and genetic spectrum and the frequency of pathogenic variants in these genes have not yet been fully elucidated, neither in patients with dystonia nor with other, sometimes co-occurring movement disorders such as Parkinson's disease (PD). OBJECTIVES: To screen >2000 patients with dystonia or PD for rare variants in known dystonia-causing genes. METHODS: We screened 1207 dystonia patients from Germany (DysTract consortium), Spain, and South Korea, and 1036 PD patients from Germany for pathogenic variants using a next-generation sequencing gene panel. The impact on DNA methylation of KMT2B variants was evaluated by analyzing the gene's characteristic episignature. RESULTS: We identified 171 carriers (109 with dystonia [9.0%]; 62 with PD [6.0%]) of 131 rare variants (minor allele frequency <0.005). A total of 52 patients (48 dystonia [4.0%]; four PD [0.4%, all with GCH1 variants]) carried 33 different (likely) pathogenic variants, of which 17 were not previously reported. Pathogenic biallelic variants in PRKRA were not found. Episignature analysis of 48 KMT2B variants revealed that only two of these should be considered (likely) pathogenic. CONCLUSION: This study confirms pathogenic variants in GCH1, GNAL, KMT2B, SGCE, THAP1, and TOR1A as relevant causes in dystonia and expands the mutational spectrum. Of note, likely pathogenic variants only in GCH1 were also found among PD patients. For DYT-KMT2B, the recently described episignature served as a reliable readout to determine the functional effect of newly identified variants. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Task design for crowdsourced glioma cell annotation in microscopy images.

Crowdsourcing has been used in computational pathology to generate cell and cell nuclei annotations for machine learning. Herein, we broaden its scope to the previously unsolved challenging task of glioma cell detection. This requires multiplexed immunofluorescence microscopy due to diffuse invasiveness and exceptional similarity between glioma cells and reactive astrocytes. In four pilot experiments, we iteratively developed a task design enabling high-quality annotations by crowdworkers on Amazon Mechanical Turk. We applied majority or weighted vote and validated them against ground truth in the final setting. On the base of a YOLO convolutional neural network architecture, we used these consensus labels for training with different image representations regarding colors, intensities, and immmunohistochemical marker combinations. A crowd of 712 workers defined aggregated point annotations in 235 images with an average [Formula: see text] score of 0.627 for majority vote. The networks resulted in acceptable [Formula: see text] scores up to 0.69 for YOLOv8 on average and indicated first evidence for transferability to images lacking tumor markers, especially in IDH-wildtype glioblastoma. Our work confirms feasibility of crowdsourcing to generate labels suitable for training of machine learning tools in the challenging and clinically relevant use case of glioma microenvironment.

Outcomes of Unilateral Pallidotomy in Focal and Hemidystonia Cases: A Single-Blind Cohort Study.

BACKGROUND: The role of deep brain stimulation in the treatment of dystonia has been widely documented. However, there is limited literature on the outcome of lesioning surgery in unilateral dystonia. OBJECTIVE: We restrospectively reviewed our cases of focal and hemidystonia undergoing unilateral Pallidotomy at our institute to evaluate the short-term and long-term outcome. METHODS: Patients who underwent radiofrequency lesioning of GPi for unilateral dystonia between 1999 and 2019 were retrospectively reviewed. All patients were evaluated using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Dystonia Disability Scale (DDS) preoperatively at the short term follow-up (<1 year) and at long-term follow-up (2-7.5 years). Video recordings performed at these time points were independently reviewed by a blinded movement disorders specialist. RESULTS: Eleven patients were included for analysis. The preoperative, short-term, and long-term follow-up motor BFMDRS and DDS scores were 15.5 (IQR [interquartile range]: 10.5, 23.75) and 10.5 (IQR: 6.0, 14.5); 3.0 (IQR: 1.0, 6.0, P = 0.02) and 3.0 (IQR: 3.0, 8.0, P = 0.016); and 14.25 (IQR: 4.0, 20.0, P = 0.20) and 10.5 (IQR: 2.0, 15.0, P = 0.71) respectively. For observers B, the BFMDRS scores at the same time points were 19 (IQR: 12.5, 27.0), 7.5 (IQR: 6.0, 15.0, P = 0.002), and 21 (IQR: 7.0, 22.0, P = 0.65) respectively. The improvement was statistically significant for all observations at short-term follow-up but not at long-term follow-up. CONCLUSION: Pallidotomy is effective for hemidystonia or focal dystonia in the short term. Continued benefit was seen in the longer term in some patients, whereas others worsened. Larger studies may be able to explain this in future.

Surgical site infections after glioblastoma surgery: boon or bane?

BACKGROUND: Surgical site infections (SSIs) are among the most common postoperative complications. Glioblastoma multiforme is the most frequent malignant brain tumor with a dismal prognosis despite combined treatment. The effect of SSIs on the course of glioblastoma patients has not been fully clarified since available data are limited and partially contradictory. The aim of this study is to investigate the impact of SSIs on the course of patients with glioblastoma. METHODS: The medical records of all patients undergoing surgery for glioblastoma between 2010 and 2020 in our institution were scanned and those with surgical site infections after glioblastoma resection were identified and compared to an age-matched control group. Overall survival and progression-free survival were the primary endpoints followed by the number of hospitalizations and the length of stay in hospital. RESULTS: Out of 305 patients undergoing surgery for glioblastoma, 38 patients with postoperative surgical site infection after resection were identified and 15 (5 men and 10 women aged between 9 and 72) were included in this study. 23 patients were excluded. The control group consisted of 30 age-matched patients without SSI (18 men and 12 women). There were no significant differences in median overall survival. Progression-free survival was higher in the SSI group. The number of hospitalizations and the length of stay were significantly higher in the SSI group. CONCLUSION: Our data suggest that SSIs might reduce early recurrences without affecting overall survival. Furthermore, they might decrease health-related quality of life by doubling the total length of hospital stay.

Vagus nerve stimulation for the treatment of narcolepsy.

BACKGROUND AND OBJECTIVE: No study on neurostimulation in narcolepsy is available until now. Arousal- and wake-promoting effects of vagus nerve stimulation (VNS) have been demonstrated in animal experiments and are well-known as side effects of VNS therapy in epilepsy and depression. The objective was to evaluate the therapeutic effect of VNS on daily sleepiness and cataplexies in narcolepsy. METHODS: In our open-label prospective comparative study, we included narcolepsy patients who were treated with VNS because of depression or epilepsy and compared them to controls without narcolepsy treated with VNS for depression or epilepsy (18 patients in each group, aged 31.5 ± 8.2 years). We evaluated daily sleepiness (Epworth Sleepiness Scale, ESS) and the number of cataplexies per week before the implantation of VNS and at three and six month follow-ups. RESULTS: Compared to baseline (ESS: 15.9 ± 2.5) patients with narcolepsy showed a significant improvement on ESS after three months (11.2 ± 3.3, p < 0.05) and six months (9.6 ± 2.8, p < 0.001) and a trend to reduction of cataplexies. No significant ESS-improvement was observed in patients without narcolepsy (14.9 ± 3.9, 13.6 ± 3.7, 13.2 ± 3.5, p = 0.2 at baseline, three and six months, correspondingly). Side effects did not differ between the study groups. CONCLUSION: In this first evaluation of VNS in narcolepsy, we found a significant improvement of daily sleepiness due to this type of neurostimulation. VNS could be a promising non-medical treatment in narcolepsy.

Does Temporary Externalization of Electrodes After Deep Brain Stimulation Surgery Result in a Higher Risk of Infection?

OBJECTIVES: Deep brain stimulation (DBS) is a well-established surgical therapy for movement disorders that comprises implantation of stimulation electrodes and a pacemaker. These procedures can be performed separately, leaving the possibility of externalizing the electrodes for local field potential recording or testing multiple targets for therapeutic efficacy. It is still debated whether the temporary externalization of DBS electrodes leads to an increased risk of infection. We therefore aimed to assess the risk of infection during and after lead externalization in DBS surgery. MATERIALS AND METHODS: In this retrospective study, we analyzed a consecutive series of 624 DBS surgeries, including 266 instances with temporary externalization of DBS electrodes for a mean of 6.1 days. Patients were available for follow-up of at least one year, except in 15 instances. In 14 patients with negative test stimulation, electrodes were removed. All kinds of infections related to implantation of the neurostimulation system were accounted for. RESULTS: Overall, infections occurred in 22 of 624 surgeries (3.5%). Without externalization of electrodes, infections were noted after 7 of 358 surgeries (2.0%), whereas with externalization, 15 of 252 infections were found (6.0%). This difference was significant (p = 0.01), but it did not reach statistical significance when comparing groups within different diagnoses. The rate of infection with externalized electrodes was highest in psychiatric disorders (9.1%), followed by Parkinson's disease (7.3%), pain (5.7%), and dystonia (5.5%). The duration of the externalization of the DBS electrodes was comparable in patients who developed an infection (6.1 ± 3.1 days) with duration in those who did not (6.0 ± 3.5 days). CONCLUSIONS: Although infection rates were relatively low in our study, there was a slightly higher infection rate when DBS electrodes were externalized. On the basis of our results, the indication for electrode externalization should be carefully considered, and patients should be informed about the possibility of a higher infection risk when externalization of DBS electrodes is planned.

Favorable combinations of antiseizure medication with vagus nerve stimulation to improve health-related quality of life in patients with epilepsy.

BACKGROUND: Vagus nerve stimulation (VNS) is a non-pharmacological treatment of refractory epilepsy, which also has an antidepressive effect. The favorable combinations of VNS with specific mechanisms of action of antiseizure medication (ASM) on mood and health-related quality of life (HrQol) have not yet been studied. The objective was to identify favourable combinations of specific ASMs with VNS for the HrQoL and depression in refractory epilepsy. METHODS: We performed an observational study including patients with refractory epilepsy and an implanted VNS (N = 151). In the first 24 months after VNS implantation, all patients were on stable ASM therapy. We used the standardized questionnaires QOLIE10, EQVAS and EQ5D to evaluate HrQoL as well as the Beck Depression Inventory (BDI). Multiple regression analysis was performed to evaluate the synergistic combinations of ASM with VNS for HrQoL. RESULTS: At the year-two follow-up (N = 151, age 45.2 ± 17.0 years), significant improvement (p < 0.05) in BDI scores was found for combination of VNS with SV2A modulators (58.4 %) or AMPA antagonists (44.4 %). A significant increase of HrQoL by at least 30 % (p < 0.05) was measured for a combination of VNS with SV2A modulators (brivaracetam, levetiracetam) or slow sodium channel inhibitors (eslicarbazepine, lacosamide). CONCLUSION: The results of our study suggests a favorable effect of the combination of SV2A modulators or slow sodium channel inhibitors with VNS on the HrQoL in comparison to other ASMs. Besides the possible synergistic effects on the seizure frequency, the amelioration of behavioral side effects of SV2A modulators by VNS is an important factor of HrQoL-improvement in these combinations.

Subthalamic Nucleus Deep Brain Stimulation Restores Motor and Sensorimotor Cortical Neuronal Oscillatory Activity in the Free-Moving 6-Hydroxydopamine Lesion Rat Parkinson Model.

OBJECTIVES: Enhanced beta oscillations in cortical-basal ganglia (BG) thalamic circuitries have been linked to clinical symptoms of Parkinson's disease. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces beta band activity in BG regions, whereas little is known about activity in cortical regions. In this study, we investigated the effect of STN DBS on the spectral power of oscillatory activity in the motor cortex (MCtx) and sensorimotor cortex (SMCtx) by recording via an electrocorticogram (ECoG) array in free-moving 6-hydroxydopamine (6-OHDA) lesioned rats and sham-lesioned controls. MATERIALS AND METHODS: Male Sprague-Dawley rats (250-350 g) were injected either with 6-OHDA or with saline in the right medial forebrain bundle, under general anesthesia. A stimulation electrode was then implanted in the ipsilateral STN, and an ECoG array was placed subdurally above the MCtx and SMCtx areas. Six days after the second surgery, the free-moving rats were individually recorded in three conditions: 1) basal activity, 2) during STN DBS, and 3) directly after STN DBS. RESULTS: In 6-OHDA-lesioned rats (N = 8), the relative power of theta band activity was reduced, whereas activity of broad-range beta band (12-30 Hz) along with two different subbeta bands, that is, low (12-30 Hz) and high (20-30 Hz) beta band and gamma band, was higher in MCtx and SMCtx than in sham-lesioned controls (N = 7). This was, to some extent, reverted toward control level by STN DBS during and after stimulation. No major differences were found between contacts of the electrode grid or between MCtx and SMCtx. CONCLUSION: Loss of nigrostriatal dopamine leads to abnormal oscillatory activity in both MCtx and SMCtx, which is compensated by STN stimulation, suggesting that parkinsonism-related oscillations in the cortex and BG are linked through their anatomic connections.