Intraoperative radiotherapy after neurosurgical resection of brain metastases as institutional standard treatment- update of the oncological outcome form a single center cohort after 117 procedures.

PURPOSE: Stereotactic radiotherapy (SRT) is the predominant method for the irradiation of resection cavities after resection of brain metastases (BM). Intraoperative radiotherapy (IORT) with 50 kV x-rays is an alternative way to irradiate the resection cavity focally. We have already reported the outcome of our first 40 IORT patients treated until 2020. Since then, IORT has become the predominant cavity treatment in our center due to patients´ choice. METHODS: We retrospectively analyzed the outcomes of all patients who underwent resection of BM and IORT between 2013 and August 2023 at Augsburg University Medical Center (UKA). RESULTS: We identified 105 patients with 117 resected BM treated with 50 kV x-ray IORT. Median diameter of the resected metastases was 3.1 cm (range 1.3 - 7.0 cm). Median applied dose was 20 Gy. All patients received standardized follow-up (FU) including three-monthly MRI of the brain. Mean FU was 14 months, with a median MRI FU for patients alive of nine months. Median overall survival (OS) of all treated patients was 18.2 months (estimated 1-year OS 57.7%). The observed local control (LC) rate of the resection cavity was 90.5% (estimated 1-year LC 84.2%). Distant brain control (DC) was 61.9% (estimated 1-year DC 47.9%). Only 16.2% of all patients needed WBI in the further course of disease. The observed radio necrosis rate was 2.6%. CONCLUSION: After 117 procedures IORT still appears to be a safe and appealing way to perform cavity RT after neurosurgical resection of BM with low toxicity and excellent LC.

Hydrocephalus, cerebral vasospasm, and delayed cerebral ischemia following non-aneurysmatic spontaneous subarachnoid hemorrhages: an underestimated problem.

Non-aneurysmal subarachnoid hemorrhage (NASAH) is rare and mostly benign. However, complications such as cerebral vasospasm (CV), delayed cerebral ischemia (DCI), or post-hemorrhagic hydrocephalus (HC) may worsen the prognosis. The aim of this study was to evaluate the rate of these complications comparing perimesencephalic (PM) and non-perimesencephalic (NPM) SAH. Monocentric, retrospective analysis of patients diagnosed with NASAH from 01/2010 to 01/2021. Diagnosis was set only if vascular pathologies were excluded in at least one digital subtraction angiography, and NASAH was confirmed by cranial computed tomography (cCT) or lumbar puncture (LP). One hundred patients (62 female) with a mean age of 54.9 years (27-84) were identified. Seventy-three percent had a World Federation of Neurological Surgeons (WFNS) grading scale score I, while 9% were WFNS score IV or V at the time of admission. SAH was diagnosed by cCT in 86%, in 14% by lumbar puncture. Twenty-five percent necessitated short-term CSF diversion by extraventricular drainage or lumbar drainage, whereof 7 suffered from long-term HC treated with ventriculoperitoneal shunting (VPS). One patient without a short-term CSF drainage developed long-term HC. Ten percent developed CV, four of whom received intraarterial spasmolysis. Radiological DCI was diagnosed in 2%; none of these correlated with CV. Despite a mortality of 3% occurring solely in NPM SAH, the analyzed complication rate was comparable in both groups. We observed post-hemorrhagic complications in 35% of cases during the first 3 weeks after bleeding, predominantly in patients with NPM SAH. For this reason, close observation and cranial imaging within this time may be indicated not to overlook these complications.

How to avoid pneumocephalus in deep brain stimulation surgery? Analysis of potential risk factors in a series of 100 consecutive patients.

BACKGROUND: Accuracy of lead placement is the key to success in deep brain stimulation (DBS). Precise anatomic stereotactic planning usually is based on stable perioperative anatomy. Pneumocephalus due to intraoperative CSF loss is a common procedure-related phenomenon which could lead to brain shift and targeting inaccuracy. The aim of this study was to evaluate potential risk factors of pneumocephalus in DBS surgery. METHODS: We performed a retrospective single-center analysis in patients undergoing bilateral DBS. We quantified the amount of pneumocephalus by postoperative CT scans and corrected the data for accompanying brain atrophy by an MRI-based score. Automated computerized segmentation algorithms from a dedicated software were used. As potential risk factors, we evaluated the impact of trephination size, the number of electrode tracks, length of surgery, intraoperative blood pressure, and brain atrophy. RESULTS: We included 100 consecutive patients that underwent awake DBS with intraoperative neurophysiological testing. Systolic and mean arterial blood pressure showed a substantial impact with an inverse correlation, indicating that lower blood pressure is associated with higher volume of pneumocephalus. Furthermore, the length of surgery was clearly correlated to pneumocephalus. CONCLUSION: Our analysis identifies intraoperative systolic and mean arterial blood pressure as important risk factors for pneumocephalus in awake stereotactic surgery.

Intraventricular neuroepithelial tumors: surgical outcome, technical considerations and review of literature.

BACKGROUND: Intraventricular neuroepithelial tumors (IVT) are rare lesions and comprise different pathological entities such as ependymomas, subependymomas and central neurocytomas. The treatment of choice is neurosurgical resection, which can be challenging due to their intraventricular location. Different surgical approaches to the ventricles are described. Here we report a large series of IVTs, its postoperative outcome at a single tertiary center and discuss suitable surgical approaches. METHODS: We performed a retrospective chart review at a single tertiary neurosurgical center between 03/2009-05/2019. We included patients that underwent resection of an IVT emphasizing on surgical approach, extent of resection, clinical outcome and postoperative complications. RESULTS: Forty five IVTs were resected from 03/2009 to 05/2019, 13 ependymomas, 21 subependymomas, 10 central neurocytomas and one glioependymal cyst. Median age was 52,5 years with 55.6% (25) male and 44.4% (20) female patients. Gross total resection was achieved in 93.3% (42/45). 84.6% (11/13) of ependymomas, 100% (12/21) of subependymomas, 90% (9/10) of central neurocytomas and one glioependymal cyst were completely removed. Postoperative rate of new neurological deficits was 26.6% (12/45). Postoperative new permanent cranial nerve deficits occurred in one case with 4th ventricle subependymoma and one in 4th ventricle ependymoma. Postoperative KPSS was 90% (IR 80-100). 31.1% of the patients improved in KPSS, 48.9% remained unchanged and 20% declined. Postoperative adverse events rate was 20.0%. Surgery-related mortality was 2.2%. The rate of shunt/cisternostomy-dependent hydrocephalus was 13.3% (6/45). 15.4% of resected ependymomas underwent adjuvant radiotherapy. Mean follow-up was 26,9 (±30.1) months. CONCLUSION: Our surgical findings emphasize satisfactory complete resection throughout all entities. Surgical treatment can remain feasible, if institutional experience is given. Satisfying long-term survival and cure is possible by complete removal. Gross total resection should always be performed under function-remaining aspects due to mostly benign or slow growing nature of IVTs. Further data is needed to evaluate standard of care and alternative therapy options in rare cases of tumor recurrence or in case of patient collective not suitable for operative resection.

Early reduced dopaminergic tone mediated by D3 receptor and dopamine transporter in absence epileptogenesis.

OBJECTIVE: In Genetic Absence Epilepsy Rats From Strasbourg (GAERSs), epileptogenesis takes place during brain maturation and correlates with increased mRNA expression of D3 dopamine receptors (D3R). Whether these alterations are the consequence of seizure repetition or contribute to the development of epilepsy remains to be clarified. Here, we addressed the involvement of the dopaminergic system in epilepsy onset in GAERSs. METHODS: Experiments were performed using rats at different stages of brain maturation from three strains according to their increasing propensity to develop absence seizures: nonepileptic control rats (NECs), Wistar Hannover rats, and GAERSs. Changes in dopaminergic neurotransmission were investigated using different behavioral and neurochemical approaches: autoradiography of D3R and dopamine transporter, single photon emission computed tomographic imaging, acute and chronic drug effects on seizure recordings (dopaminergic agonists and antagonists), quinpirole-induced yawns and dopamine synaptosomal uptake, microdialysis, brain tissue monoamines, and brain-derived neurotrophic factor quantification. RESULTS: Autoradiography revealed an increased expression of D3R in 14-day-old GAERSs, before absence seizure onset, that persists in adulthood, as compared to age-matched NECs. This was confirmed by increased yawns, a marker of D3R activity, and increased seizures when animals were injected with quinpirole at low doses to activate D3R. We also observed a concomitant increase in the expression and activity of the dopamine transporter in GAERSs before seizure onset, consistent with both lowered dopamine basal level and increased phasic responses. SIGNIFICANCE: Our data show that the dopaminergic system is persistently altered in GAERSs, which may contribute not only to behavioral comorbidities but also as an etiopathogenic factor in the development of epilepsy. The data suggest that an imbalanced dopaminergic tone may contribute to absence epilepsy development and seizure onset, as its reversion by a chronic treatment with a dopamine stabilizer significantly suppressed epileptogenesis. Our data suggest a potential new target for antiepileptic therapies and/or improvement of quality of life of epileptic patients.

Introduction of a self-holding retractor for optimized abdominal visualization in ventriculoperitoneal shunt surgery: first experiences at a single center.

OBJECTIVE: Ventriculoperitoneal shunt implantation is a common procedure in general neurosurgery. The patient population is often fragile, ranging from elderly to pediatric patients, and avoidance of perioperative complication is of utmost importance. Abdominal catheter dislocation has been found to be a common cause for early shunt dysfunction and needs to be avoided by optimal visualization of the abdominal catheter insertion zone. Here, we introduce a self-holding wound retractor system Alexis® and demonstrate its use for abdominal shunt surgery in a series of patients. METHODS: We explain the use of the Alexis® self-holding wound retractor during open ventriculoperitoneal shunt surgery in a series of 16 patients operated at our institution. RESULTS: The self-holding retractor consists of two polymer rings connected by a polymer membrane. The deep ring is easily placed on the internal fascia of the straight muscle and circular retraction is achieved by twisting the upper ring. Free hand working can then be performed by a single surgeon with good abdominal exposure. No case of abdominal dislocation or infection occurred in our series, although no properly powered statistical analysis can be performed regarding the sample size. CONCLUSION: We demonstrate the Alexis® Wound Retractor, which is an easy tool for optimal visualization of the abdominal catheter insertion zone. We believe it can facilitate surgical practice of shunt surgery, especially in obese patients.

Incidence, depth, and severity of surgical site infections after neurosurgical interventions.

BACKGROUND: Today, there are only few reports on the incidence of surgical site infections (SSIs) in neurosurgery. The objective of this work was to determine the rate of SSI at a tertiary neurosurgical department for benchmarking purpose. METHODS: Data of consecutive patients undergoing neurosurgical treatment between January 2013 and December 2016 were prospectively entered into a registry. SSIs were diagnosed according to the 2017 Centers for Disease Control and Prevention criteria, with severity graded according to the Clavien-Dindo grade (CDG). We analyzed type and length of surgery (LOS), time to SSI, responsible microorganisms, and its association with the functional status (Karnofsky Performance Status = KPS). RESULTS: Of n = 5463 procedures, a SSI occurred in n = 106 (1.94%). The highest rates of SSI occurred after vascular (3.4%) and cerebrospinal fluid (CSF) diversion procedures (3%), as well as after procedures performed to treat a previous complication (2.9%). There was no difference in LOS across procedures with and without SSI. The median time between the index procedure and SSI was 15.5 days. SSIs were most frequently diagnosed after hospital discharge (55%). The most common microorganisms were coagulase-negative staphylococci, Staphylococcus aureus, and Escherichia coli. In 62.3% of cases, SSI required invasive treatment (surgical revision). Patients with SSI in the in- and out-patient setting (SSI occurring after hospital discharge) presented both with a median KPS of 80. CONCLUSIONS: The current report provides an overview on SSI in a contemporary, unselected, large series of patients undergoing modern neurosurgical care for benchmarking purposes. The overall rate of SSI was about 2%, but subpopulations with higher risks were identified where additional measures could be taken to prevent SSI and monitor patients at risk more closely for SSI.

Comparison of Sitting versus Nonsitting Position for the Resection of Brain Metastases in the Posterior Fossa in a Contemporary Cohort.

BACKGROUND: For surgery of brain metastases, good immediate postoperative functional outcome is of utmost importance. Improved functional status can enable further oncologic therapies and adverse events might delay them. Pros and cons of either sitting or prone positioning for resective surgery of the posterior fossa are debated, but contemporary data on direct postoperative outcome are rare. The aim of our study was to compare the functional outcome and adverse events of surgery for brain metastases in the sitting versus the nonsitting position in the direct postoperative setting. METHODS: We retrospectively compared surgery of metastases located in the posterior fossa over a 3-year period in two level-A neurosurgical centers. Center 1 performed surgery exclusively in the sitting, while center 2 performed surgery only in the nonsitting position. RESULTS: Worse functional outcome (Karnofsky performance scale) and functional deterioration were seen in the "sitting" group. We found significantly more "sitting" patients to deteriorate to a KPS score of ≤60%. In this study, treating patients with brain metastases in the sitting position resulted in a number needed to harm (NNH) of 2.3 and was associated with worse outcome and more adverse events. CONCLUSION: Therefore, we recommend the nonsitting position for surgery of brain metastases of the posterior fossa.

Continuous and Unconstrained Tremor Monitoring in Parkinson's Disease Using Supervised Machine Learning and Wearable Sensors.

Background: Accurately assessing the severity and frequency of fluctuating motor symptoms is important at all stages of Parkinson's disease management. Contrarily to time-consuming clinical testing or patient self-reporting with uncertain reliability, recordings with wearable sensors show promise as a tool for continuously and objectively assessing PD symptoms. While wearables-based clinical assessments during standardised and scripted tasks have been successfully implemented, assessments during unconstrained activity remain a challenge. Methods: We developed and implemented a supervised machine learning algorithm, trained and tested on tremor scores. We evaluated the algorithm on a 67-hour database comprising sensor data and clinical tremor scores for 24 Parkinson patients at four extremities for periods of about 3 hours. A random 25% subset of the labelled samples was used as test data, the remainder as training data. Based on features extracted from the sensor data, a Support Vector Machine was trained to predict tremor severity. Due to the inherent imbalance in tremor scores, we applied dataset rebalancing techniques. Results: Our classifier demonstrated robust performance in detecting tremor events with a sensitivity of 0.90 on the test-portion of the resampled dataset. The overall classification accuracy was high at 0.88. Conclusion: We implemented an accurate classifier for tremor monitoring in free-living environments that can be trained even with modestly sized and imbalanced datasets. This advancement offers significant clinical value in continuously monitoring Parkinson's disease symptoms beyond the hospital setting, paving the way for personalized management of PD, timely therapeutic adjustments, and improved patient quality of life.

Direct subthalamic nucleus stimulation influences speech and voice quality in Parkinson's disease patients.

BACKGROUND: DBS of the subthalamic nucleus (STN) considerably ameliorates cardinal motor symptoms in PD. Reported STN-DBS effects on secondary dysarthric (speech) and dysphonic symptoms (voice), as originating from vocal tract motor dysfunctions, are however inconsistent with rather deleterious outcomes based on post-surgical assessments. OBJECTIVE: To parametrically and intra-operatively investigate the effects of deep brain stimulation (DBS) on perceptual and acoustic speech and voice quality in Parkinson's disease (PD) patients. METHODS: We performed an assessment of instantaneous intra-operative speech and voice quality changes in PD patients (n = 38) elicited by direct STN stimulations with variations of central stimulation features (depth, laterality, and intensity), separately for each hemisphere. RESULTS: First, perceptual assessments across several raters revealed that certain speech and voice symptoms could be improved with STN-DBS, but this seems largely restricted to right STN-DBS. Second, computer-based acoustic analyses of speech and voice features revealed that both left and right STN-DBS could improve dysarthric speech symptoms, but only right STN-DBS can considerably improve dysphonic symptoms, with left STN-DBS being restricted to only affect voice intensity features. Third, several subareas according to stimulation depth and laterality could be identified in the motoric STN proper and close to the associative STN with optimal (and partly suboptimal) stimulation outcomes. Fourth, low-to-medium stimulation intensities showed the most optimal and balanced effects compared to high intensities. CONCLUSIONS: STN-DBS can considerably improve both speech and voice quality based on a carefully arranged stimulation regimen along central stimulation features.