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Background: Neuromuscular instability of the lumbar spine resulting from impaired motor control and degeneration of the multifidus muscle is a known root cause of refractory chronic low back pain (LBP). An implantable neurostimulation system that aims to restore multifidus motor control by stimulating the L2 medial branch of the dorsal ramus thereby relieving pain and reducing disability has demonstrated clinically significant benefits in the clinical trial setting. The 1-year results of a single-site real-world cohort study are presented., Methods: This study recruited 44 consecutive patients with refractory, predominantly nociceptive axial chronic LBP, evidence of multifidus dysfunction, and no surgical indications or history of surgical intervention for chronic LBP. Each patient was implanted with a neurostimulation device. Pain (numeric rating scale), disability (Oswestry Disability Index), and quality of life (5-level EuroQol 5-Dimension) outcomes were collected at baseline and 3, 6, and 12 months after activation., Results: Statistically significant improvements in pain, disability, and quality of life from baseline were seen at all assessment time points. At 12 months after activation, mean ± standard error of the mean numeric rating scale score was reduced from 7.6 ± 0.2 to 3.9 ± 0.4 (P < 0.001), Oswestry Disability Index score was reduced from 43.0 ± 2.8 to 25.8 ± 3.9 (P < 0.001), and 5-level EuroQol 5-Dimension index improved from 0.504 ± 0.034 to 0.755 ± 0.039 (P < 0.001). No lead migrations were observed. One patient required revision due to lead fracture., Conclusions: Restorative neurostimulation is a new treatment option for well-selected patients with refractory chronic LBP. Clinically meaningful improvements in pain, disability, and quality of life demonstrated in routine clinical practice are consistent with published results of controlled trials., (Copyright © 2022 Elsevier Inc. All rights reserved.)

To exploit the potential of virtual reality (VR) in medicine, the input devices must be selected carefully due to their different benefits. In this work, input devices for common interaction tasks in medical VR planning and training are compared. Depending on the specific purpose, different requirements exist. Therefore, an appropriate trade-off between meeting task-specific requirements and having a widely applicable device has to be found. We focus on two medical use cases, liver surgery planning and craniotomy training, to cover a broad medical domain. Based on these, relevant input devices are compared with respect to their suitability for performing precise VR interaction tasks. The devices are standard VR controllers, a pen-like VR Ink, data gloves and a real craniotome, the medical instrument used for craniotomy. The input devices were quantitatively compared with respect to their performance based on different measurements. The controllers and VR Ink performed significantly better than the remaining two devices regarding precision. Qualitative data concerning task load, cybersickness, and usability and appropriateness of the devices were assessed. Although no device stands out for both applications, most participants preferred using the VR Ink, followed by the controller and finally the data gloves and craniotome. These results can guide the selection of an appropriate device for future medical VR applications., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Brain metastases frequently occur during the course of disease in patients suffering from lung cancer. Occasionally, neurological symptoms caused by brain metastases (BM) might represent the first sign of systemic tumor disease (so called precocious metastases), leading to the detection of the primary lung tumor. The biological basis of precocious BM is largely unknown, and treatment options are not well established for this subgroup of patients. Therefore, we retrospectively analyzed 33 patients (24 non-small cell lung cancer (NSCLC)), 9 small cell lung cancer (SCLC)) presenting with precocious BM focusing on molecular alterations potentially relevant for the tumor's biology and treatment. We found five FGFR1 amplifications (4 adenocarcinoma, 1 SCLC) among 31 analyzed patients (16.1%), eight MET amplifications among 30 analyzed tumors (7 NSCLC, 1 SCLC; 26.7%), three EGFR mutations within 33 patients (all adenocarcinomas, 9.1%), and five KRAS mutations among 32 patients (all adenocarcinomas; 15.6%). No ALK, ROS1 or RET gene rearrangements were detected. Our findings suggest that patients with precocious BM of lung cancer harbor EGFR mutations, MET amplifications or FGFR1 amplifications as potential targeted treatment options., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: The application of acetylsalicylic acid (ASA) represents high evidence in the aging society due to primary and secondary prevention in cardiovascular disease and stroke. However, this presents a challenge for neurosurgeons in terms of preoperative and postoperative management of care. This study aimed to analyze the risk of bleeding by applying ASA before lumbar spinal surgery., Methods: Retrospective analysis of medical records of 3051 patients was performed from 2008 to 2018 who underwent lumbar surgery at our institution. The risk of postoperative hemorrhage was compared in patients treated with ASA versus patients without ASA treatment. Additionally, the relationship between discontinuation of ASA preoperatively (≥7 days) or no previous history of ASA versus continuation with ASA (<7 days) on postoperative hemorrhage was analyzed., Results: Postoperative hemorrhagic were observed in 2.1% (n = 63) of all lumbar operations. In 421 patients, the effect of ASA (<7 days) was still persistent at the time of surgery (ASA impact group). Of these, 12 (2.85%) patients had a hemorrhage. No significant differences were found in comparison to the No ASA impact group (p = 0.272). Sex (p = 0.003), hypertension (p = 0.015), recurrent surgery (p = 0.001) and use of hemostatic agents (p = 0.023) had a significant impact on postoperative hemorrhage., Conclusion: The continuation of ASA medication is not associated with increased risk of postoperative hemorrhage after spinal surgery. However, sex, hypertension, recurrent surgery and the use of hemostatic agents under continued ASA treatment were found to be associated with an increased risk of hemorrhage., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: The study explores microscope integrated optical coherence tomography (OCT) as a intraoperative imaging technique to delineate the microstructural composition of human dura mater cranialis and underlying leptomeninges for surgical guidance., Methods: OCT volume scans, light microscopic pictures and light microscopic videos of the dura mater were acquired in patients (n = 20) with indication for craniotomy. OCT volume scans and corresponding light microscopic data were analyzed post procedural. Thickness of anatomical structures was measured during this phase., Results: OCT scanning of the human cranial dura mater was feasible during microsurgical dissection. A discrimination of the endosteal and inner meningeal layer of the cranial dura mater was possible in 70 % (n = 14) of the patients. Transdural OCT scans could further demonstrate subdural anatomical structures: subdural space 10 % (n = 2), subarachnoid space in 35 % (n = 7), arachnoid vessels in 80 % (n = 16) and brain cortex in 90 % (n = 16) of the patients. Orthogonal distance measurement was possible. The cranial dura mater showed a mean depth of 216 μm, the endosteal layer of 120 μm and the inner meningeal layer of 132 μm. Imaging quality of the dural segment was high - approaching spatial resolution of histopathology. Imaging quality of subdural segments was lower and demonstrated A-line artifacts in 45 % (n = 7)., Conclusion: These results illustrate - for the first time - strengths and weaknesses of three dimensional microscope integrated OCT as an in vivo imaging method of the human cranial dura mater, underlying leptomeninges and human brain cortex as a surgical guidance tool. OCT imaging of the cranial dura mater showed extensive details. Transdural imaging of subdural micro anatomical structures was possible, but showed lower image quality with intermittent A-line artifacts. OCT stated the first intraoperative imaging tool to measure the depth of micro anatomical structures with a high spatial resolution of 7,5 μm., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Ruptured middle cerebral artery (MCA) aneurysms are one of the causes of subarachnoid (SAH) or intracerebral hemorrhage (ICH) but the factors associated with the bleeding type are unknown. The aim of the study was to analyze the association of the morphological variations of the Sylvian fissure (SF) and vascular parameters on occurrence of different bleeding patterns in patients with ruptured MCA aneurysms., Patients and Methods: The data of consecutive 202 patients with ruptured MCA aneurysm of two centers were included for analysis. Patients were divided into three groups: Group 1 with SAH, Group 2 with accompanying ICH and Group 3 with intrasylvian hemorrhage (ISH). The SF was divided into five types according to the previously described classification. Analyzed vascular parameters were aneurysm size, localization, presence of a daughter aneurysm, shape, and angulation of the aneurysm sac., Results: A total of 202 patients (141 female, 61 male, mean age 52.4 yr) were included in this study. 67 patients (33.2%) had a SAH, 122 (60.4%) an ICH and 13 (6.4%) presented with ISH. Statistical analysis showed a significant association of narrow and twisted SF types 4 and 5 (p < 0.001) and temporal angulation of the aneurysm (p = 0.030) for occurrence of ICH. All other vascular parameters showed no significant association for any kind of hemorrhage., Conclusion: Our results allow the conclusion that the complex SF types 4 and 5, as well as the temporal angulation of the aneurysm sac are associated with the occurrence of ICH in ruptured MCA aneurysms., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2019. Published by Elsevier B.V.)

Objectives: Brain arteriovenous malformations (bAVM) are rare vascular lesions. Recent observations challenge the congenital nature of these lesions. The underlying cellular and molecular mechanisms associated with dynamic changes of bAVM still remain unclear. The objective of this study was to explore the potential role of COL4A2 (Collagen alpha-2(IV)) in the pathophysiology of bAVM., Patients and Methods: Expression and localization of COL4A2 were analyzed on tissue microarrays from bAVM patients (n = 60) by immunohistochemistry. Correlations between COL4A2 levels and clinical parameters were examined with Pearson's test for normally- distibuted or Spearman's Rho for not normally distributed data. Comparison between different clinical parameters was performed using t-test, non-parametric Mann-Whitney U test or Kruskal- Wallis test. Fisher's exact test was used for categorical data., Results: COL4A2 was mainly expressed beneath the endothelium of vessels in the tunica media of bAVM. This pattern of expression indicates the basement membrane of the vessel walls. High levels of COL4A2 expression correlated with the age at surgery of patients (p = 0.005; R = 0.393; Spearman's Rho). The age at surgery in young (17-25 years) and old patients (55-76 years) showed a linear correlation; a greater variance of COL4A2 expression was observed in the age group between 26-54 years., Conclusion: This study reports for the first time the expression of COL4A2 in bAVM and suggests a potential role of COL4A2 in bAVM pathophysiology. These findings contribute to a better understanding of the microenvironment of bAVM and may foster the development of improved therapeutic strategies for this disease., (Copyright © 2019. Published by Elsevier B.V.)

Objective: After a decompressive craniectomy (DC), a cranioplasty (CP) is often performed in order to improve neurosurgical outcome and cerebral blood circulation. But even though the performance of a CP subsequent to a DC has become routine medical practice, patients can in fact develop many complications from the surgery that could prolong hospitalization and lead to unfavorable prognoses. This study investigates one of the most frequent complications, bone flap infection, in order to identify prognostic factors of its development., Patients and Methods: In this single-center study, we have retrospectively examined 329 CPs performed between 2002 and 2017. Multiple categorical and metric parameters (e.g., timing of CP, bone flap material, specific laboratory signs of infection and reason for DC) were analyzed applying unadjusted and multivariable testing., Results: Bone flap infection occurred in 24 patients (7.3%). A CP performed more than six months after a DC is associated with a significantly increased risk of infection (OR = 0.308 [0.118; 0.803], p = 0.016). However, with CPs performed after twelve months, the incidence decreases, but without provable statistical impact. In addition, bone flap infection is strongly related to the neurological outcome and the material used for the skull implant, with the use of synthetic bone flaps leading to a marked increase in the rate of infection (p < 0.001)., Conclusions: This study supports the hypothesis that the risk of infection is higher the longer the elapsed time between DC and CP, especially if more than six months. Based on our results, the best DC-CP time frame for keeping the infection rate low is performing the CP within the first six months after the DC. In the event that the CP cannot be performed within the first six months, a CP performed twelve months or more after the DC seems to have a favorable outcome as well., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: Cerebral arterio-venous malformations (AVM) are considered congenital lesions, emerging as an important cause of haemorrhagic stroke in children. The potential influence of age on clinical presentation and angio-architecture have been analysed extensively in the last years. Yet, comparative studies comprising ascending age groups may be limited in their conclusions, especially when comparing young children and adults. It is the aim of this study to evaluate characteristic clinical and angiographic features of AVM within a paediatric subgroup and their correlation to age at presentation., Patients and Methods: Between 1990-2015, 46 children harbouring AVMs were treated at our institution. Clinical presentation, radiological data, treatment strategies and outcome were evaluated retrospectively., Results: Of 46 consecutive patients, 18 were male and 28 female patients. Mean age was 11.6±4.3years, ranging from 2 to 17 years. 35 patients (76%) presented with haemorrhage. Seizures were found in 6 patients (13%) and progressive or transient focal neurological deficits in 4 individuals (9%). There was one incidental patient, only. Mean age of children presenting with haemorrhage was significantly lower as compared to those without a history of intracranial bleeding (p=0.1). The size of the AVM was small (n=27, 59%), corresponding a grade I AVM in the majority of patients (N=28, 61%). 41 patients (89%) underwent treatment of their AVM by an interdisciplinary approach achieving complete elimination of the lesion in 34 patients (83%). 34 patients (83%) showed at least a favourable outcome (mRS≤2) at last follow-up. An excellent recovery (mRS 0-1) was noted in 28 patients (68%)., Conclusion: From our data we suggest that patients' age impacts the clinical presentation. Particularly young children seem to bear a higher risk for haemorrhage from their AVM. Treatment of paediatric AVMs can be achieved safely in experienced hands with a high rate of complete elimination and good clinical outcome., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Objective: Brain arteriovenous malformations (bAVM) are severe conditions that can cause severe neurologic deficits and mortality. The underlying cellular and molecular mechanisms associated with bAVM growth and rupture remain unclear. The objective of this study was to explore the potential role of PLOD2 (procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2) in the pathophysiology of bAVM., Methods: Expression and localization of PLOD2 were analyzed on tissue microarrays from patients with bAVM (n = 60) by immunohistochemistry. Correlations between PLOD2 levels and clinical parameters were examined with a Pearson test or Spearman rank correlation coefficient. Comparison between different clinical parameters was performed using a t test or nonparametric Mann-Whitney U test. A Fisher exact test was used for categorical data., Results: PLOD2 was mainly expressed within the tunica media of the blood vessels. High levels of PLOD2 expression correlated with bAVM size (linear regression, P = 0.0083, R 2 =0.158). Small bAVM showed a higher frequency of hemorrhage compared with large ones (P = 0.001). Although PLOD2 was not directly associated with bAVM hemorrhage, high PLOD2-expressing bAVM had a lower frequency of hemorrhage compared with low or medium PLOD2-expressing bAVM (25% vs. 63% and 75%, respectively)., Conclusions: This study reports for the first time the expression of PLOD2 in bAVM and suggests a potential role of PLOD2 in bAVM pathophysiology. These findings contribute to an better understanding of the microenvironment of bAVM and may foster the development of improved therapeutic strategies for this disease., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to analyze our clinical and neurological results of surgically treated patients suffering from cervical spondylodiscitis with focusing particularly on the surgical methods used and to review the literature., Patients and Methods: We present a series of 21 patients operated with cervical spondylodiscitis between 1998 and 2011. Basic demographic data, comorbidities, the radiological segments involved, the surgical strategy with special consideration of the material used and the clinical outcome were evaluated retrospectively., Results: The mean age of 6 female and 12 male patients was 65 years (range 28-89 years). The mean follow-up was 3.7 years ranging between 4 weeks and 9 years. The leading symptom was neurological deficits rather than pain. The segments C 5/6 (n=8) and C 6/7 (n=7) were most frequently involved. Different surgical methods depending on the location, anatomical and pathological condition and extension of the lesion were performed., Conclusion: In conclusion, cervical spondylodiscitis could effectively be treated in the presented patient cohort by surgical decompression, debridement and PMMA or bone graft implants followed by long term antibiotic therapy. The presented surgical reconstruction technique with PMMA might be a feasible alternative to the use of bone graft or cages. The promising clinical results warrant future prospective studies to further investigate this technique., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: Dens fractures are common cervical injuries in advanced aged patients. The presented study was undertaken to analyze the clinical results and risks of surgically treated patients with dens fractures over 70 years., Methods: Data of 28 patients (17 female, 11 male) over 70 years treated from September 2004 to October 2009 were recorded. Clinical and radiological parameters were obtained including type of fracture, associated cervical and/or other injuries, comorbidities, symptoms, neurological condition, surgical strategy, postoperative course and complications., Results: 89% were in a good neurological condition before surgery (ASIA E or D). In most cases, surgery was performed at an early stage after trauma (21 patients within 5 days). Ventral screw fixation was the preferred surgical strategy (64%). A slight worsening of neurological functions immediately after operation was only seen in one patient. Five patients died in the early and 2 in the late postoperative course which means a treatment mortality of 25%. Among the surviving patients two had general medical complications., Conclusion: Type II dens fractures are a common fracture of elderly patients. Our results are good concerning the neurological functions. Surgical and general medical complications were acceptable. However, the study also underlines that mortality rate is high and therefore treatment options should be well-considered in this high risk group., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Introduction: Brain metastases (BM) commonly occur in patients with metastatic malignant melanoma (MM). Prognosis is poor even with maximal therapy. The aim of the current study was to retrospectively evaluate patients with BM of MM who were treated neurosurgically with respect to clinical presentation, recurrent disease, survival and factors affecting survival., Patients and Methods: Thirty-four patients (19f/15m) with BM of MM were treated in our hospital between 2000 and 2010. Patient data were analysed, survival was examined using Kaplan-Meier-estimates and factors affecting prognosis were evaluated using uni- and multivariate analysis., Results: Twenty-two patients (64.7%) had a single BM, whereas twelve patients (35.3%) revealed two or more lesions. Median survival for patients with a single BM was 13.0 months (95%-CI 9.3-16.7 months), this was significantly (p=0.014) better than for patients with two or more BM (median 5.0, 95%-CI 3.4-14.6 months). Nineteen patients (55.9%) developed an intracranial relapse after microsurgical resection of a first lesion. Patients with an isolated intracerebral relapse survived significantly (p=0.003) longer than those with systemic progression (median 6.0, 95%-CI 0.0-15.3 months vs median 3.0, 95%-CI 1.7-4.3 months). Similarly, patients with a high performance status showed significantly (p=0.001) prolonged survival (median 7.0, 95%-CI 0.0-19.9 months vs median 1.0, 95%-CI 0.0-2.2 months). Eleven out of nineteen patients (57.9%) underwent either another microsurgical resection (n=6) or stereotactic radiosurgery (n=5). These patients remained on a high performance status even after aggressive therapy., Discussion: Even though the prognosis for patients with BM of MM is generally poor, patients with a single BM can benefit from microsurgical resection. However, there is a high risk of intracranial relapse. In selected patients with a good performance status and recurrent intracranial disease, recurrent local therapy can be justified and useful., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: To describe the interdisciplinary surgical approach in spheno-orbital meningiomas and to evaluate the operative results regarding resectability and functional outcome., Patients and Methods: A series of 16 patients underwent surgical resection of spheno-orbital meningiomas followed by bony reconstruction. Four patients presented with a recurrent meningioma and had undergone surgical resection previously. Radical tumour removal was attempted in all cases, although no aggressive effort was made to remove tumour tissue infiltrating the cavernous sinus or soft tissues deep in the orbit to avoid severe functional disturbances. All patients but one were female (mean age 53 years). Mean follow-up period was 68 months (range 4-155 months)., Results: The leading symptom was proptosis in 14 patients, accompanied in 7 cases by progressive visual impairment. Surgical resection was thought to have been complete in 11 patients (69%) and incomplete in 5 (31%). Residual tumour was deliberately left when there was infiltration of the cavernous sinus (n = 4), the pterygopalatine fossa (n = 2) and/or the deep intraorbital soft tissues (n = 1). Tumour recurrence was observed in 9 patients, among whom were 6 patients with an initially "completely" resected meningioma. Eight patients underwent re-operation. Complete resection was achieved in 3 of these latter patients with an isolated exclusively intraorbital tumour manifestation., Conclusion: By means of combined skull base approaches, spheno-orbital meningiomas are grossly resected totally with a long-term survival free of recurrence and an acceptable quality of life. In some cases, deliberate subtotal tumour resection is useful to avoid severe neurological damage with sufficient tumour control and a valuable progression-free survival.

Objectives: The aim of this study was to evaluate the prognostic value of intraoperative aneurysm rupture (IAR) in patients with subarachnoid hemorrhage (SAH) undergoing surgery for cerebral aneurysms., Patients and Methods: Between July 1997 and April 2000, 292 consecutive patients were admitted to our institution with SAH due to ruptured intracranial aneurysms. Of these, 169 patients were treated surgically according to standard microsurgical procedures and were included in this study. Mean age was 47 years. Initial clinical state was graded according to the classification of Hunt and Hess (HH). Outcome was classified according to the Glasgow Outcome Scale as favorable (grades IV and V) and unfavorable (grades I-III). Outcome of patients with intraoperative ruptured and non-ruptured aneurysms was analyzed in correlation to the preoperative clinical state and with respect to the time of surgery and to aneurysm localization., Results: Different rupture rates were observed with respect to the localization of the aneurysm: anterior circulation (n=69) 39.1%, middle cerebral artery (n=46) 34.8%, internal carotid artery (n=48) 31.2%, and posterior circulation (n=6) 16.7%. Patients with HH-grades I-III showed a favorable outcome in 72.2% (61 of 84 patients) without intraoperative rupture and in 71.7% (33 of 46 patients) with intraoperative aneurysm rupture. The corresponding values for patients with HH-grades IV/V were: favorable outcome in 34.6% (9 of 26 patients) and 23.1% (3 of 13 patients), respectively. Poor initial clinical condition (HH IV and V) as well as the initial Fisher grades III and IV were strongly associated with poor clinical outcome., Conclusions: Intraoperative aneurysm rupture has no impact on the outcome, neither in patients with good initial condition nor for poor grades patients.