Directed and acyclic synaptic connectivity in the human layer 2-3 cortical microcircuit.

The computational capabilities of neuronal networks are fundamentally constrained by their specific connectivity. Previous studies of cortical connectivity have mostly been carried out in rodents; whether the principles established therein also apply to the evolutionarily expanded human cortex is unclear. We studied network properties within the human temporal cortex using samples obtained from brain surgery. We analyzed multineuron patch-clamp recordings in layer 2-3 pyramidal neurons and identified substantial differences compared with rodents. Reciprocity showed random distribution, synaptic strength was independent from connection probability, and connectivity of the supragranular temporal cortex followed a directed and mostly acyclic graph topology. Application of these principles in neuronal models increased dimensionality of network dynamics, suggesting a critical role for cortical computation.

Local Field Potentials Predict Motor Performance in Deep Brain Stimulation for Parkinson's Disease.

BACKGROUND: Deep brain stimulation (DBS) is an effective treatment option for patients with Parkinson's disease (PD). However, clinical programming remains challenging with segmented electrodes. OBJECTIVE: Using novel sensing-enabled neurostimulators, we investigated local field potentials (LFPs) and their modulation by DBS to assess whether electrophysiological biomarkers may facilitate clinical programming in chronically implanted patients. METHODS: Sixteen patients (31 hemispheres) with PD implanted with segmented electrodes in the subthalamic nucleus and a sensing-enabled neurostimulator were included in this study. Recordings were conducted 3 months after DBS surgery following overnight withdrawal of dopaminergic medication. LFPs were acquired while stimulation was turned OFF and during a monopolar review of both directional and ring contacts. Directional beta power and stimulation-induced beta power suppression were computed. Motor performance, as assessed by a pronation-supination task, clinical programming and electrode placement were correlated to directional beta power and stimulation-induced beta power suppression. RESULTS: Better motor performance was associated with stronger beta power suppression at higher stimulation amplitudes. Across directional contacts, differences in directional beta power and the extent of stimulation-induced beta power suppression predicted motor performance. However, within individual hemispheres, beta power suppression was superior to directional beta power in selecting the contact with the best motor performance. Contacts clinically activated for chronic stimulation were associated with stronger beta power suppression than non-activated contacts. CONCLUSIONS: Our results suggest that stimulation-induced ß power suppression is superior to directional ß power in selecting the clinically most effective contact. In sum, electrophysiological biomarkers may guide programming of directional DBS systems in PD patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Lesion-symptom mapping of language impairments in people with brain tumours: The influence of linguistic stimuli.

People with tumours in specific brain sites might face difficulties in tasks with different linguistic material. Previous lesion-symptom mapping studies (VLSM) demonstrated that people with tumours in posterior temporal regions have more severe linguistic impairments. However, to the best of our knowledge, preoperative performance and lesion location on tasks with different linguistic stimuli have not been examined. In the present study, we performed VLSM on 52 people with left gliomas to examine whether tumour distribution differs depending on the tasks of the Aachen Aphasia Test. The VLSM analysis revealed that single-word production (e.g. object naming) was associated with the inferior parietal lobe and that compound and sentence production were additionally associated with posterior temporal gyri. Word repetition was affected in people with tumours in inferior parietal areas, whereas sentence repetition was the only task to be associated with frontal regions. Subcortically, word and sentence production were found to be affected in people with tumours reaching the arcuate fasciculus, and compound production was primarily associated with tumours affecting the inferior longitudinal and inferior fronto-occipital fasciculus. Our work shows that tasks with linguistic stimuli other than single-word naming (e.g. compound and sentence production) relate to additional cortical and subcortical brain areas. At a clinical level, we show that tasks that target the same processes (e.g. repetition) can have different neural correlates depending on the linguistic stimuli used. Also, we highlight the importance of left temporoparietal areas.

Thoracolumbar Instrumentation Surgery in Patients with Parkinson's Disease: A Case-Control Study.

BACKGROUND: With increasing prevalence of Parkinson's disease (PD), instrumentation surgery of the thoracolumbar spine of PD patients grows in importance. Poor operative results with high rates of revision surgery have been reported. The goal of this study was to compare the biomechanical complications of thoracolumbar instrumentation surgery of patients with and without PD. METHODS: In a retrospective case-control study, we compared 16 PD patients with a matched cohort of 104 control patients regarding the following postinstrumentation complications: (1) adjacent joint disease, (2) material failure, and (3) material loosening. Also, we compared the spinal bone density, which is the main prognostic criteria for failed instrumentation surgery, between the groups. RESULTS: We found the rate of material revision to be significantly higher in PD patients (43.8 vs. 13.5%, p = 0.008, odds ratio (OR) = 5.0). Furthermore, the indications for revision surgery differed between the groups, with more hardware failures in the PD group and more adjacent segment degeneration in the control group. PD patients profited from modern operation techniques (percutaneous instrumentation and CT-navigated screw implantation). Hospitalization was significantly longer for PD patients (20.2 ± 15.1 vs. 14.1 ± 8.9 days, p = 0.03). CONCLUSION: PD patients exhibit challenging biomechanical demands on instrumenting the spine. Besides osteoporosis, especially sagittal imbalance, gait disturbance, and altered muscle tone may be contributive. PD patients may particularly profit from navigated and less invasive surgical techniques.

Role of interhemispheric connectivity in recovery from postoperative supplementary motor area syndrome in glioma patients.

OBJECTIVE: Surgical resection of gliomas involving the supplementary motor area (SMA) frequently results in SMA syndrome, a symptom complex characterized by transient akinesia and mutism. Because the factors influencing patient functional outcomes after surgery remain elusive, the authors investigated network-based predictors in a multicentric cohort of glioma patients. METHODS: The participants were 50 patients treated for glioma located in the SMA at one of the three centers participating in the study. Postoperative functional outcomes (motor deficits, mutism) and duration of symptoms were assessed during hospitalization. Long-term outcome was assessed 3 months after surgery. MRI-based lesion-symptom mapping was performed to estimate the severity of gray matter damage and white matter disconnection. RESULTS: The median duration of acute symptoms was 3 days (range 1-42 days). Long-term deficits involving fine motor movements and speech were found at follow-up in 27 patients (54%). Disconnection of the central callosal fibers was associated with prolonged acute symptoms (p < 0.05). Postoperative mutism was significantly related to disconnection severity of the left frontopontine tract, frontal aslant tract, cingulum, and corticostriatal tract (p < 0.05). Disconnection of midposterior callosal fibers and lesion loads within the left medial Brodmann area 4 were associated with long-term motor deficits (p < 0.05). CONCLUSIONS: This study provides evidence for the pathophysiology and predictive factors of postoperative SMA syndrome by demonstrating the relation of the disconnection of callosal fibers with prolonged symptom duration (central segment) and long-term motor deficits (midposterior segment). These data may be useful for presurgical risk assessment and adequate consultation for patients prior to undergoing resection of glioma located within the SMA region.

Deep brain stimulation in Early Onset Parkinson's disease.

Introduction: Subthalamic Deep Brain Stimulation (STN-DBS) is a safe and well-established therapy for the management of motor symptoms refractory to best medical treatment in patients with Parkinson's disease (PD). Early intervention is discussed especially for Early-onset PD (EOPD) patients that present with an age of onset ≤ 45-50 years and see themselves often confronted with high psychosocial demands. Methods: We retrospectively assessed the effect of STN-DBS at 12 months follow-up (12-MFU) in 46 EOPD-patients. Effects of stimulation were evaluated by comparison of disease-specific scores for motor and non-motor symptoms including impulsiveness, apathy, mood, quality of life (QoL), cognition before surgery and in the stimulation ON-state without medication. Further, change in levodopa equivalent dosage (LEDD) after surgery, DBS parameter, lead localization, adverse and serious adverse events as well as and possible additional clinical features were assessed. Results: PD-associated gene mutations were found in 15% of our EOPD-cohort. At 12-MFU, mean motor scores had improved by 52.4 ± 17.6% in the STIM-ON/MED-OFF state compared to the MED-OFF state at baseline (p = 0.00; n = 42). These improvements were accompanied by a significant 59% LEDD reduction (p < 0.001), a significant 6.6 ± 16.1 points reduction of impulsivity (p = 0.02; n = 35) and a significant 30 ± 50% improvement of QoL (p = 0.01). At 12-MFU, 9 patients still worked full- and 6 part-time. Additionally documented motor and/or neuropsychiatric features decreased from n = 41 at baseline to n = 14 at 12-MFU. Conclusion: The present study-results demonstrate that EOPD patients with and without known genetic background benefit from STN-DBS with significant improvement in motor as well as non-motor symptoms. In line with this, patients experienced a meaningful reduction of additional neuropsychiatric features. Physicians as well as patients have an utmost interest in possible predictors for the putative DBS outcome in a cohort with such a highly complex clinical profile. Longitudinal monitoring of DBS-EOPD-patients over long-term intervals with standardized comprehensive clinical assessment, accurate phenotypic characterization and documentation of clinical outcomes might help to gain insights into disease etiology, to contextualize genomic information and to identify predictors of optimal DBS candidates as well as those in danger of deterioration and/or non-response in the future.

A noninvasive method to quantify the impairment of spinal motion ability in Parkinson's disease.

PURPOSE: There is a high demand on spinal surgery in patients with Parkinson's disease (PD) but the results are sobering. Although detailed clinical and radiological diagnostics were carried out with great effort and expense, the biodynamic properties of the spine of PD patients have never been considered. We propose a noninvasive method to quantify the impairment of motion abilities in patients with PD. METHODS: We present an analytical cross-sectional study of 21 patients with severe PD. All patients underwent a biodynamic assessment during a standardized movement-choreography. Thus, individual spinal motion profiles of each patient were objectively assessed and compared with a large comparative cohort of individuals without PD. Moreover, clinical scores to quantify motor function and lumbar back pain were collected and X-ray scans of the spine in standing position were taken and analysed. RESULTS: Biodynamic measurement showed that 36.9% of the assessed motions of all PD patients were severely impaired. Men were generally more functionally impaired than women, in 52% of all motion parameters. The neurological and radiological diagnostics recorded pathological values, of which UPDRS-III ON correlated with findings of the biodynamics assessment (R = 0.52, p = 0.02). CONCLUSIONS: The decision to operate on a PD patient's spine is far-reaching and requires careful consideration. Neurological and radiological scores did not correlate with the biodynamics of the spine. The resulting motion profile could be used as individual predictive factor to estimate whether patients are eligible for spinal surgery or alternative therapies.

Correlation of Tumor Pathology with Fluorescein Uptake and MRI Contrast-Enhancement in Stereotactic Biopsies.

The utilization of fluorescein-guided biopsies has recently been discussed to improve and expedite operative techniques in the detection of tumor-positive tissue, as well as to avoid making sampling errors. In this study, we aimed to report our experience with fluorescein-guided biopsies and elucidate distribution patterns in different histopathological diagnoses in order to develop strategies to increase the efficiency and accuracy of this technique. We report on 45 fluorescence-guided stereotactic biopsies in 44 patients (15 female, 29 male) at our institution from March 2016 to March 2021, including 25 frame-based stereotactic biopsies and 20 frameless image-guided biopsies using VarioGuide®. A total number of 347 biopsy samples with a median of 8 samples (range: 4-18) per patient were evaluated for intraoperative fluorescein uptake and correlated to definitive histopathology. The median age at surgery was 63 years (range: 18-87). Of the acquired specimens, 63% were fluorescein positive. Final histopathology included glioblastoma (n = 16), B-cell non-Hodgkin lymphoma (n = 10), astrocytoma, IDH-mutant WHO grade III (n = 6), astrocytoma, IDH-mutant WHO grade II (n = 1), oligodendroglioma, IDH-mutant and 1p/19q-codeleted WHO grade II (n = 2), reactive CNS tissue/inflammation (n = 4), post-transplantation lymphoproliferative disorder (PTLD; n = 2), ependymoma (n = 1), infection (toxoplasmosis; n = 1), multiple sclerosis (n = 1), and metastasis (n = 1). The sensitivity for high-grade gliomas was 85%, and the specificity was 70%. For contrast-enhancing lesions, the specificity of fluorescein was 84%. The number needed to sample for contrast-enhancing lesions was three, and the overall number needed to sample for final histopathological diagnosis was five. Interestingly, in the astrocytoma, IDH-mutant WHO grade III group, 22/46 (48%) demonstrated fluorescein uptake despite no evidence for gadolinium uptake, and 73% of these were tumor-positive. In our patient series, fluorescein-guided stereotactic biopsy increases the likelihood of definitive neuropathological diagnosis, and the number needed to sample can be reduced by 50% in contrast-enhancing lesions.

The genomic and transcriptional landscape of primary central nervous system lymphoma.

Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Molecular drivers of PCNSL have not been fully elucidated. Here, we profile and compare the whole-genome and transcriptome landscape of 51 CNS lymphomas (CNSL) to 39 follicular lymphoma and 36 DLBCL cases outside the CNS. We find recurrent mutations in JAK-STAT, NFkB, and B-cell receptor signaling pathways, including hallmark mutations in MYD88 L265P (67%) and CD79B (63%), and CDKN2A deletions (83%). PCNSLs exhibit significantly more focal deletions of HLA-D (6p21) locus as a potential mechanism of immune evasion. Mutational signatures correlating with DNA replication and mitosis are significantly enriched in PCNSL. TERT gene expression is significantly higher in PCNSL compared to activated B-cell (ABC)-DLBCL. Transcriptome analysis clearly distinguishes PCNSL and systemic DLBCL into distinct molecular subtypes. Epstein-Barr virus (EBV)+ CNSL cases lack recurrent mutational hotspots apart from IG and HLA-DRB loci. We show that PCNSL can be clearly distinguished from DLBCL, having distinct expression profiles, IG expression and translocation patterns, as well as specific combinations of genetic alterations.

High Frequency of Low-Virulent Microorganisms Detected by Sonication of Implanted Pulse Generators: So What?

INTRODUCTION: Deep brain stimulation (DBS) has become a well-established treatment modality for a variety of conditions over the last decades. Multiple surgeries are an essential part in the postoperative course of DBS patients if nonrechargeable implanted pulse generators (IPGs) are applied. So far, the rate of subclinical infections in this field is unknown. In this prospective cohort study, we used sonication to evaluate possible microbial colonization of IPGs from replacement surgery. METHODS: All consecutive patients undergoing IPG replacement between May 1, 2019 and November 15, 2020 were evaluated. The removed hardware was investigated using sonication to detect biofilm-associated bacteria. Demographic and clinical data were analyzed. RESULTS: A total of 71 patients with a mean (±SD) of 64.5 ± 15.3 years were evaluated. In 23 of these (i.e., 32.4%) patients, a positive sonication culture was found. In total, 25 microorganisms were detected. The most common isolated microorganisms were Cutibacterium acnes (formerly known as Propionibacterium acnes) (68%) and coagulase-negative Staphylococci (28%). Within the follow-up period (5.2 ± 4.3 months), none of the patients developed a clinical manifest infection. DISCUSSIONS/CONCLUSIONS: Bacterial colonization of IPGs without clinical signs of infection is common but does not lead to manifest infection. Further larger studies are warranted to clarify the impact of low-virulent pathogens in clinically asymptomatic patients.

Clinical implementation of a 3D4K-exoscope (Orbeye) in microneurosurgery.

Exoscopic surgery promises alleviation of physical strain, improved intraoperative visualization and facilitation of the clinical workflow. In this prospective observational study, we investigate the clinical usability of a novel 3D4K-exoscope in routine neurosurgical interventions. Questionnaires on the use of the exoscope were carried out. Exemplary cases were additionally video-documented. All participating neurosurgeons (n = 10) received initial device training. Changing to a conventional microscope was possible at all times. A linear mixed model was used to analyse the impact of time on the switchover rate. For further analysis, we dichotomized the surgeons in a frequent (n = 1) and an infrequent (n = 9) user group. A one-sample Wilcoxon signed rank test was used to evaluate, if the number of surgeries differed between the two groups. Thirty-nine operations were included. No intraoperative complications occurred. In 69.2% of the procedures, the surgeon switched to the conventional microscope. While during the first half of the study the conversion rate was 90%, it decreased to 52.6% in the second half (p = 0.003). The number of interventions between the frequent and the infrequent user group differed significantly (p = 0.007). Main reasons for switching to ocular-based surgery were impaired hand-eye coordination and poor depth perception. The exoscope investigated in this study can be easily integrated in established neurosurgical workflows. Surgical ergonomics improved compared to standard microsurgical setups. Excellent image quality and precise control of the camera added to overall user satisfaction. For experienced surgeons, the incentive to switch from ocular-based to exoscopic surgery greatly varies.

Reduction in wound healing complications and infection rate by lumbar CSF drainage after decompressive hemicraniectomy.

OBJECTIVE: Wound healing disorders and surgical site infections are the most frequently encountered complications after decompressive hemicraniectomy (DHC). Subgaleal CSF accumulation causes additional tension of the scalp flap and increases the risk of wound dehiscence, CSF fistula, and infection. Lumbar CSF drainage might relieve subgaleal CSF accumulation and is often used when a CSF fistula through the surgical wound appears. The aim of this study was to investigate if early prophylactic lumbar drainage might reduce the rate of postoperative wound revisions and infections after DHC. METHODS: The authors retrospectively analyzed 104 consecutive patients who underwent DHC from January 2019 to May 2021. Before January 2020, patients did not receive lumbar drainage, whereas after January 2020, patients received lumbar drainage within 3 days after DHC for a median total of 4 (IQR 2-5) days if the first postoperative CT scan confirmed open basal cisterns. The primary endpoint was the rate of severe wound healing complications requiring surgical revision. Secondary endpoints were the rate of subgaleal CSF accumulations and hygromas as well as the rate of purulent wound infections and subdural empyema. RESULTS: A total of 31 patients died during the acute phase; 34 patients with and 39 patients without lumbar drainage were included for the analysis of endpoints. The predominant underlying pathology was malignant hemispheric stroke (58.8% vs 66.7%) followed by traumatic brain injury (20.6% vs 23.1%). The rate of surgical wound revisions was significantly lower in the lumbar drainage group (5 [14.7%] vs 14 [35.9%], p = 0.04). A stepwise linear regression analysis was used to identify potential covariates associated with wound healing disorder and reduced them to lumbar drainage and BMI. One patient was subject to paradoxical herniation. However, the patient's symptoms rapidly resolved after lumbar drainage was discontinued, and he survived with only moderate deficits related to the primary disease. There was no significant difference in the rate of radiological herniation signs. The median lengths of stay in the ICU were similar, with 12 (IQR 9-23) days in the drainage group compared with 13 (IQR 11-23) days in the control group (p = 0.21). CONCLUSIONS: In patients after DHC and open basal cisterns on postoperative CT, lumbar drainage appears to be safe and reduces the rate of surgical wound revisions and intracranial infection after DHC while the risk for provoking paradoxical herniation is low early after surgery.

Transcranial versus Direct Cortical Stimulation for Motor-Evoked Potentials during Resection of Supratentorial Tumors under General Anesthesia (The TRANSEKT-Trial): Study Protocol for a Randomized Controlled Trial.

BACKGROUND: Monitoring of motor function during surgery for supratentorial tumors under general anesthesia applies either transcranial electrical stimulation (TES) or direct cortical stimulation (DCS) to elicit motor-evoked potentials. To date, there is no guideline that favor one method over the other. Therefore, we designed this randomized study to compare between both methods regarding the prediction of postoperative motor deficits and extent of tumor resection. METHODS: This is a multicenter (six centers in Germany and one in Switzerland), double blind, parallel group, exploratory, randomized controlled clinical trial. Patients without or with mild paresis, who are scheduled for surgical resection of motor-eloquent brain tumors under general anesthesia will be randomized to surgical resection under TES or surgical resection under DCS. The primary endpoint is sensitivity and specificity in prognosis of motor function 7 days after surgery. The main secondary endpoint is the extent of tumor resection. The study is planned to include 120 patients within 2 years. DISCUSSION: The present exploratory study should compare TES and DCS regarding sensitivity and specificity in predicting postoperative motor deficit and extent of tumor resection to calculate the required number of patients in a confirmatory trial to test the superiority of one method over the other.

Preoperative nTMS and Intraoperative Neurophysiology - A Comparative Analysis in Patients With Motor-Eloquent Glioma.

BACKGROUND: The resection of a motor-eloquent glioma should be guided by intraoperative neurophysiological monitoring (IOM) but its interpretation is often difficult and may (unnecessarily) lead to subtotal resection. Navigated transcranial magnetic stimulation (nTMS) combined with diffusion-tensor-imaging (DTI) is able to stratify patients with motor-eloquent lesion preoperatively into high- and low-risk cases with respect to a new motor deficit. OBJECTIVE: To analyze to what extent preoperative nTMS motor risk stratification can improve the interpretation of IOM phenomena. METHODS: In this monocentric observational study, nTMS motor mapping with DTI fiber tracking of the corticospinal tract was performed before IOM-guided surgery for motor-eloquent gliomas in a prospectively collected cohort from January 2017 to October 2020. Descriptive analyses were performed considering nTMS data (motor cortex infiltration, resting motor threshold (RMT), motor evoked potential (MEP) amplitude, latency) and IOM data (transcranial MEP monitoring, intensity of monopolar subcortical stimulation (SCS), somatosensory evoked potentials) to examine the association with the postoperative motor outcome (assessed at day of discharge and at 3 months). RESULTS: Thirty-seven (56.1%) of 66 patients (27 female) with a median age of 48 years had tumors located in the right hemisphere, with glioblastoma being the most common diagnosis with 39 cases (59.1%). Three patients (4.9%) had a new motor deficit that recovered partially within 3 months and 6 patients had a persistent deterioration (9.8%). The more risk factors of the nTMS risk stratification model (motor cortex infiltration, tumor-tract distance (TTD) ≤8mm, RMTratio <90%/>110%) were detected, the higher was the risk for developing a new postoperative motor deficit, whereas no patient with a TTD >8mm deteriorated. Irreversible MEP amplitude decrease >50% was associated with worse motor outcome in all patients, while a MEP amplitude decrease ≤50% or lower SCS intensities ≤4mA were particularly correlated with a postoperative worsened motor status in nTMS-stratified high-risk cases. No patient had postoperative deterioration of motor function (except one with partial recovery) when intraoperative MEPs remained stable or showed only reversible alterations. CONCLUSIONS: The preoperative nTMS-based risk assessment can help to interpret ambiguous IOM phenomena (such as irreversible MEP amplitude decrease ≤50%) and adjustment of SCS stimulation intensity.

Optical Characterization of Sodium Fluorescein In Vitro and Ex Vivo.

OBJECTIVE: The utilization of fluorescein-guided biopsies and resection has been recently discussed as a suitable strategy to improve and expedite operative techniques for the resection of central nervous system (CNS) tumors. However, little is known about the optical properties of sodium fluorescein (NaFl) in human tumor tissue and their potential impact on ex vivo analyses involving fluorescence-based methods. METHODS: Tumor tissue was obtained from a study cohort of an observational study on the utilization of fluorescein-guided biopsy and resection (n=5). The optical properties of fluorescein-stained tissue were compared to the optical features of the dye in vitro and in control samples consisting of tumor tissue of high-grade glioma patients (n=3) without intravenous (i.v.) application of NaFl. The dye-exposed tumor tissues were used for optical measurements to confirm the detectability of NaFl emission ex vivo. The tissue samples were fixed in 4%PFA, immersed in 30% sucrose, embedded in Tissue-Tek OCT compound, and cut to 10 µm cryosections. Spatially resolved emission spectra from tumor samples were recorded on representative slides with a Confocal Laser Scanning Microscope FV1000 (Olympus GmbH, Hamburg, Germany) upon excitation with λexc = 488 nm. RESULTS: Optical measurements of fluorescein in 0.9% sodium chloride (NaCl) under in vitro conditions showed an absorption maximum of λmax abs = 479 nm as detected with spectrophotometer Specord 200 and an emission peak at λmax em = 538 nm recorded with the emCCD detection system of a custom-made microscope-based single particle setup using a 500 nm long-pass filter. Further measurements revealed pH- and concentration-dependent emission spectra of NaFl. Under ex vivo conditions, confocal laser scanning microscopy of fluorescein tumor samples revealed a slight bathochromic shift and a broadening of the emission band. CONCLUSION: Tumor uptake of NaFl leads to changes in the optical properties - a bathochromic shift and broadening of the emission band - possibly caused by the dye's high pH sensitivity and concentration-dependent reabsorption acting as an inner filter of the dye's emission, particularly in the short wavelength region of the emission spectrum where absorption and fluorescence overlap. Understanding the ex vivo optical properties of fluorescein is crucial for testing and validating its further applicability as an optical probe for intravital microscopy, immunofluorescence localization studies, and flow cytometry analysis.

Risk of Infection after Deep Brain Stimulation Surgery with Externalization and Local-Field Potential Recordings: Twelve-Year Experience from a Single Institution.

INTRODUCTION: Deep brain stimulation (DBS) has been an established surgical procedure in the field of functional neurosurgery for many years. The experimental electrophysiological method of local field potential (LFP) recordings in postsurgically externalized patients has made substantial contributions to the better understanding of pathophysiologies underlying movement disorders. As interest in LFP recordings for the development of improved stimulation strategies increases, this study's aim was to provide evidence concerning safety of this research method, in a major DBS center. METHODS: We retrospectively analyzed incidence and infection characteristics in adult patients who underwent two-staged DBS surgery with temporary externalization of leads in our center between January 2008 and November 2019. We focused on whether patients had participated in LFP recordings, and evaluated incidence of infections at 3 months and 1 year after the surgery based on medical records. Infection rates were compared to major DBS studies and reports focusing on the risk of infection due to externalization of DBS leads. Results were visualized using descriptive statistics. RESULTS: Between January 2008 and November 2019, DBS surgery was performed in 528 patients (389/139 patients in the LFP/non-LFP group), mainly for movement disorders such as Parkinson's disease (308), dystonia (93), and essential tremor (86). Of the patients, 72.9% participated in LFP recordings. The incidence of infections in the acute postsurgical phase (3 months) was 2.46% and did not differ significantly between the LFP group (1.8%) and the non-LFP group (4.32%). The overall incidence after 1 year amounted to 3.6% (19 patients) with no difference between LFP/non-LFP groups. Incidence rates reported in the literature show a large variety (2.6-10%), and the incidence reported here is within the lower range of reported incidences. DISCUSSION/CONCLUSION: This study demonstrates that DBS is a surgical procedure with a low risk of infection in a large patient cohort. Importantly, it shows that LFP recordings do not have a significant effect on the incidence of infections in patients with externalization. With a representative cohort of more than 380 patients participating in LFP-recordings, this underlines LFP as a safe method in research and supports further use of this method, for example, for the development of adaptive stimulation protocols.

Towards a tractography-based risk stratification model for language area associated gliomas.

OBJECTIVES: Injury to major white matter pathways during language-area associated glioma surgery often leads to permanent loss of neurological function. The aim was to establish standardized tractography of language pathways as a predictor of language outcome in clinical neurosurgery. METHODS: We prospectively analyzed 50 surgical cases of patients with left perisylvian, diffuse gliomas. Standardized preoperative Diffusion-Tensor-Imaging (DTI)-based tractography of the 5 main language tracts (Arcuate Fasciculus [AF], Frontal Aslant Tract [FAT], Inferior Fronto-Occipital Fasciculus [IFOF], Inferior Longitudinal Fasciculus [ILF], Uncinate Fasciculus [UF]) and spatial analysis of tumor and tracts was performed. Postoperative imaging and the resulting resection map were analyzed for potential surgical injury of tracts. The language status was assessed preoperatively, postoperatively and after 3 months using the Aachen Aphasia Test and Berlin Aphasia Score. Correlation analyses, two-step cluster analysis and binary logistic regression were used to analyze associations of tractography results with language outcome after surgery. RESULTS: In 14 out of 50 patients (28%), new aphasic symptoms were detected 3 months after surgery. The preoperative infiltration of the AF was associated with functional worsening (cc = 0.314; p = 0.019). Cluster analysis of tract injury profiles revealed two areas particularly related to aphasia: the temporo-parieto-occipital junction (TPO; temporo-parietal AF, middle IFOF, middle ILF) and the temporal stem/peri-insular white matter (middle IFOF, anterior ILF, temporal UF, temporal AF). Injury to these areas (TPO: OR: 23.04; CI: 4.11 - 129.06; temporal stem: OR: 21.96; CI: 2.93 - 164.41) was associated with a higher-risk of persisting aphasia. CONCLUSIONS: Tractography of language pathways can help to determine the individual aphasia risk profile pre-surgically. The TPO and temporal stem/peri-insular white matter were confirmed as functional nodes particularly sensitive to surgical injuries.

Complete or Partial Parent Artery Sacrifice: Effect of Vessel-Occlusion Strategies on Complete Obliteration of Complex Aneurysms.

OBJECTIVE/BACKGROUND: A small number of complex intracranial aneurysms are not amenable to direct clipping strategies or endovascular treatment. In these patients, parent artery sacrifice and bypass revascularization for aneurysm occlusion is an option. There are 3 strategies for parent artery sacrifice: trapping, complete occlusion of the inflow, and outflow segment; proximal occlusion of the inflow vessel; and distal occlusion of the outflow vessel(s). This study aimed to compare these techniques with regard to aneurysm occlusion rates. METHODS: We reviewed our database for cerebral revascularization before parent artery sacrifice to treat cerebral aneurysms. We assessed aneurysm occlusion rates 3 and 12 months after surgery, outcome, and postoperative aneurysm rupture. RESULTS: In total, 121 patients underwent parent artery sacrifice for complex aneurysms; 30% of the parent arteries were trapped, 58% proximally, and 12% distally occluded. Postoperative digital subtraction angiography revealed an aneurysm occlusion rate of 100% after trapping. Proximal occlusion led to early complete aneurysm occlusion in 71% of the cases, 21% occluded during follow-up. The complete occlusion rate was 96%, distal occlusion had an early aneurysm occlusion rate of 40%, 40% occluded during follow-up. Complete aneurysm occlusion rate was only 80%. All 3 techniques resulted in a volume reduction of more than 60% without a significant difference between the groups. The annual aneurysm rupture rate after distal parent artery sacrifice was 15%; there was no rupture after trapping or proximal parent artery sacrifice. CONCLUSIONS: Trapping and proximal parent artery sacrifice seem to be superior to distal parent artery sacrifice regarding occlusion and rupture rates.

The Effects of Deep Brain Stimulation of the Subthalamic Nucleus on Vascular Endothelial Growth Factor, Brain-Derived Neurotrophic Factor, and Glial Cell Line-Derived Neurotrophic Factor in a Rat Model of Parkinson's Disease.

OBJECTIVE: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has evolved as a powerful therapeutic alternative for the treatment of Parkinson's disease (PD). Despite its clinical efficacy, the mechanisms of action have remained poorly understood. In addition to the immediate symptomatic effects, long-term neuroprotective effects have been suggested. Those may be mediated through neurotrophic factors (NFs) like vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF). Here, the impact of DBS on the expression of NFs was analysed in a rat model of PD. METHODS: Unilateral 6-hydroxydopamine (6-OHDA) lesioned rats received DBS in the STN using an implantable microstimulation system, sham DBS in the STN, or no electrode placement. Continuous unilateral STN-DBS (current intensity 50 µA, frequency 130 Hz, and pulse width 52 µs) was conducted for 14 days. Rats were then sacrificed and brains shock frozen. Striata and motor cortices were dissected with a cryostat. Levels of VEGF, BDNF, and GDNF were analysed, both by quantitative PCR and colorimetric ELISA. RESULTS: PCR revealed a significant upregulation of only BDNF mRNA in the ipsilateral striata of the DBS group, when compared to the sham-stimulated group. There was no significant increase in VEGF mRNA or GDNF mRNA. ELISA analysis showed augmentations of BDNF, VEGF, as well as GDNF protein in the ipsilateral striata after DBS compared to sham stimulation. In the motor cortex, significant increases after DBS were observed for BDNF only, not for the other 2 NFs. CONCLUSIONS: The upregulation of trophic factors induced by STN-DBS may participate in its long-term therapeutic efficacy and potentially neuroprotective effects.