Distance Control and Virtual Drilling Improves Anatomical Orientation During Anterior Petrosectomy.

BACKGROUND: A combined drill distance control and virtual drilling image guidance feedback method was developed. OBJECTIVE: To investigate whether first-time usage of the proposed method, during anterior petrosectomy (AP), improves surgical orientation and surgical performance. The accuracy of virtual drilling and the clinical practicability of the method were also investigated. METHODS: In a simulated surgical setting using human cadavers, a trial was conducted with 5 expert skull base surgeons from 3 different hospitals. They performed 10 AP approaches, using either the feedback method or standard image guidance. Damage to critical structures was assessed. Operating time, drill cavity sizes, and proximity of postoperative drill cavities to the cochlea and the acoustic meatus, were measured. Questionnaires were obtained postoperatively. Errors in the virtual drill cavities as compared with actual postoperative cavities were calculated. In a clinical setup, the method was used during AP. RESULTS: Surgeons rated their intraoperative orientation significantly better with the feedback method compared with standard image guidance. During the cadaver trial, the cochlea was harmed on 1 occasion in the control group, while surgeons drilled closer to the cochlea and meatus without injuring them in the group using feedback. Virtual drilling under- and overestimation errors were 2.2 ± 0.2 and -3.0 ± 0.6 mm on average. The method functioned properly during the clinical setup. CONCLUSION: The proposed feedback method improves orientation and surgical performance in an experimental setting. Errors in virtual drilling reflect spatial errors of the image guidance system. The feedback method is clinically practicable during AP.

RNA-Sequencing Highlights Inflammation and Impaired Integrity of the Vascular Wall in Brain Arteriovenous Malformations.

Background and Purpose- Interventional treatment of unruptured brain arteriovenous malformations (BAVMs) has become increasingly controversial. Because medical therapy is still lacking, we aimed to obtain insight into the disease mechanisms implicated in BAVMs and to identify potential targets for medical treatment to prevent rupture of a BAVM. Methods- We used next-generation RNA sequencing to identify differential expression on a transcriptome-wide level comparing tissue samples of 12 BAVMs to 16 intracranial control arteries. We identified differentially expressed genes by negative binominal generalized log-linear regression (false discovery rate corrected P<0.05). We selected 10 genes for validation using droplet digital polymerase chain reaction. We performed functional pathway analysis accounting for potential gene-length bias, to establish enhancement of biological pathways involved in BAVMs. We further assessed which Gene Ontology terms were enriched. Results- We found 736 upregulated genes in BAVMs including genes implicated in the cytoskeletal machinery and cell-migration and genes encoding for inflammatory cytokines and secretory products of neutrophils and macrophages. Furthermore, we found 498 genes downregulated including genes implicated in extracellular matrix composition, the binary angiopoietin-TIE system, and TGF (transforming growth factor)-ß signaling. We confirmed the differential expression of top 10 ranked genes. Functional pathway analysis showed enrichment of the protein digestion and absorption pathway (false discovery rate-adjusted P=1.70×10-2). We identified 47 enriched Gene Ontology terms (false discovery rate-adjusted P<0.05) implicated in cytoskeleton network, cell-migration, endoplasmic reticulum, transmembrane transport, and extracellular matrix composition. Conclusions- Our genome-wide RNA-sequencing study points to involvement of inflammatory mediators, loss of cerebrovascular quiescence, and impaired integrity of the vascular wall in the pathophysiology of BAVMs. Our study may lend support to potential receptivity of BAVMs to medical therapeutics, including those promoting vessel maturation, and anti-inflammatory and immune-modifying drugs.

Participation restrictions in patients after surgery for cerebral meningioma.

OBJECTIVES: To examine participation restrictions in patients after surgery for cerebral meningioma and to explore possible determinants of participation. DESIGN: Cross-sectional study. PATIENTS: Patients who had surgery for cerebral meningioma at the University Medical Center Utrecht, The Netherlands, between 2007 and 2009. METHODS: Clinical data were retrieved from medical files, and patients completed a postal questionnaire. Participation restrictions were measured with the Utrecht Scale for Evaluation of Rehabilitation-Participation. RESULTS: Of the 194 eligible patients, 76% (n = 136) participated in this study. Mean time after surgery was 32.6 months (standard deviation 10.6 months). Overall, patients showed favourable levels of participation. Nevertheless, many patients reported one or more problems of participation. Restrictions were most frequently reported regarding household duties, work or education. Twenty-three patients (32.9% of those who were in work before the meningioma) were not able to resume their job after surgery. Dissatisfaction was reported particularly regarding sports or other physical exercise. The presence of cognitive or emotional problems, multiple comorbidities and epilepsy were related to more participation problems. CONCLUSION: Patients who have had surgery for cerebral meningioma experience participation restrictions. The results of this study can be used to identify patients at risk of developing participation problems and to tailor rehabilitation goals.

Benchmarking Distance Control and Virtual Drilling for Lateral Skull Base Surgery.

BACKGROUND: Novel audiovisual feedback methods were developed to improve image guidance during skull base surgery by providing audiovisual warnings when the drill tip enters a protective perimeter set at a distance around anatomic structures ("distance control") and visualizing bone drilling ("virtual drilling"). OBJECTIVE: To benchmark the drill damage risk reduction provided by distance control, to quantify the accuracy of virtual drilling, and to investigate whether the proposed feedback methods are clinically feasible. METHODS: In a simulated surgical scenario using human cadavers, 12 unexperienced users (medical students) drilled 12 mastoidectomies. Users were divided into a control group using standard image guidance and 3 groups using distance control with protective perimeters of 1, 2, or 3 mm. Damage to critical structures (sigmoid sinus, semicircular canals, facial nerve) was assessed. Neurosurgeons performed another 6 mastoidectomy/trans-labyrinthine and retro-labyrinthine approaches. Virtual errors as compared with real postoperative drill cavities were calculated. In a clinical setting, 3 patients received lateral skull base surgery with the proposed feedback methods. RESULTS: Users drilling with distance control protective perimeters of 3 mm did not damage structures, whereas the groups using smaller protective perimeters and the control group injured structures. Virtual drilling maximum cavity underestimations and overestimations were 2.8 ± 0.1 and 3.3 ± 0.4 mm, respectively. Feedback methods functioned properly in the clinical setting. CONCLUSION: Distance control reduced the risks of drill damage proportional to the protective perimeter distance. Errors in virtual drilling reflect spatial errors of the image guidance system. These feedback methods are clinically feasible.

Validation of an automated surveillance approach for drain-related meningitis: a multicenter study.

OBJECTIVE Manual surveillance of healthcare-associated infections is cumbersome and vulnerable to subjective interpretation. Automated systems are under development to improve efficiency and reliability of surveillance, for example by selecting high-risk patients requiring manual chart review. In this study, we aimed to validate a previously developed multivariable prediction modeling approach for detecting drain-related meningitis (DRM) in neurosurgical patients and to assess its merits compared to conventional methods of automated surveillance. METHODS Prospective cohort study in 3 hospitals assessing the accuracy and efficiency of 2 automated surveillance methods for detecting DRM, the multivariable prediction model and a classification algorithm, using manual chart review as the reference standard. All 3 methods of surveillance were performed independently. Patients receiving cerebrospinal fluid drains were included (2012-2013), except children, and patients deceased within 24 hours or with pre-existing meningitis. Data required by automated surveillance methods were extracted from routine care clinical data warehouses. RESULTS In total, DRM occurred in 37 of 366 external cerebrospinal fluid drainage episodes (12.3/1000 drain days at risk). The multivariable prediction model had good discriminatory power (area under the ROC curve 0.91-1.00 by hospital), had adequate overall calibration, and could identify high-risk patients requiring manual confirmation with 97.3% sensitivity and 52.2% positive predictive value, decreasing the workload for manual surveillance by 81%. The multivariable approach was more efficient than classification algorithms in 2 of 3 hospitals. CONCLUSIONS Automated surveillance of DRM using a multivariable prediction model in multiple hospitals considerably reduced the burden for manual chart review at near-perfect sensitivity.

Cognitive and emotional problems in patients after cerebral meningioma surgery.

OBJECTIVES: To determine long-term cognitive complaints and symptoms of depression or anxiety in patients following surgery for a cerebral meningioma, and to examine factors associated with these outcomes. DESIGN: Cross-sectional study. PATIENTS: Patients operated on for a cerebral meningioma in the University Medical Center Utrecht, The Netherlands, between 2007 and 2009. METHODS: Clinical data were retrieved from medical files. Patients completed a postal questionnaire. Cognitive complaints were measured with the Cognitive Failures Questionnaire. A score above 43.5 was defined as presence of cognitive complaints. Anxiety and depressive symptoms were measured with the Hospital Anxiety and Depression Scale, and were considered present if the scale score was ≥ 8. RESULTS: The response rate was 76% (n = 136). Mean time after operation was 32.6 months (standard deviation 10.6 months). Overall, 40% of patients experienced cognitive and/or emotional problems. Thirty-one patients (23%) experienced cognitive complaints, 39 (29%) showed anxiety, and 31 (23%) showed depressive symptoms. Country of birth and previous depression/burn-out were the most important factors. Scores on all outcome measures were related to each other. CONCLUSION: Forty percent of patients experienced cognitive or emotional problems following surgery for a cerebral meningioma. Screening for these problems is therefore important in order to provide patients with the care they require as soon as possible.

Surgical instrument tracking optimizes trans-sphenoidal endoscopic treatment of petrous apex cholesterol granuloma.

During endoscopic trans-sphenoidal treatment of petrous apex cholesterol granuloma, the challenge for the surgeon is to drill the posterior wall of the sphenoid sinus to reach the lesion while attempting to avoid the internal carotid artery (ICA). A refined neuronavigation technique is presented that diminishes bonework needed for exposure and marsupialization, and simultaneously minimizes risks of accidental harm to the ICA. The technique utilizes real-time intraoperative instrument tracking of a drill, enabling safe creation of a direct canal toward the cyst just medial to the paraclival ICA and of a curette for entirely image-guided marsupialization of the cyst's deep areas through the canal.

Automated detection of healthcare associated infections: external validation and updating of a model for surveillance of drain-related meningitis.

OBJECTIVE: Automated surveillance of healthcare-associated infections can improve efficiency and reliability of surveillance. The aim was to validate and update a previously developed multivariable prediction model for the detection of drain-related meningitis (DRM). DESIGN: Retrospective cohort study using traditional surveillance by infection control professionals as reference standard. PATIENTS: Patients receiving an external cerebrospinal fluid drain, either ventricular (EVD) or lumbar (ELD) in a tertiary medical care center. Children, patients with simultaneous drains, <1 day of follow-up or pre-existing meningitis were excluded leaving 105 patients in validation set (2010-2011) and 653 in updating set (2004-2011). METHODS: For validation, the original model was applied. Discrimination, classification and calibration were assessed. For updating, data from all available years was used to optimally re-estimate coefficients and determine whether extension with new predictors is necessary. The updated model was validated and adjusted for optimism (overfitting) using bootstrapping techniques. RESULTS: In model validation, the rate of DRM was 17.4/1000 days at risk. All cases were detected by the model. The area under the ROC curve was 0.951. The positive predictive value was 58.8% (95% CI 40.7-75.4) and calibration was good. The revised model also includes Gram stain results. Area under the ROC curve after correction for optimism was 0.963 (95% CI 0.953- 0.974). Group-level prediction was adequate. CONCLUSIONS: The previously developed multivariable prediction model maintains discriminatory power and calibration in an independent patient population. The updated model incorporates all available data and performs well, also after elaborate adjustment for optimism.

Determination of a facial nerve safety zone for navigated temporal bone surgery.

BACKGROUND: Transtemporal approaches require surgeons to drill the temporal bone to expose target lesions while avoiding the critical structures within it, such as the facial nerve and other neurovascular structures. We envision a novel protective neuronavigation system that continuously calculates the drill tip-to-facial nerve distance intraoperatively and produces audiovisual warnings if the surgeon drills too close to the facial nerve. Two major problems need to be solved before such a system can be realized. OBJECTIVE: To solve the problems of (1) facial nerve segmentation and (2) calculating a safety zone around the facial nerve in relation to drill-tip tracking inaccuracies. METHODS: We developed a new algorithm called NerveClick for semiautomatic segmentation of the intratemporal facial nerve centerline from temporal bone computed tomography images. We evaluated NerveClick's accuracy in an experimental setting of neuro-otologic and neurosurgical patients. Three neurosurgeons used it to segment 126 facial nerves, which were compared with the gold standard: manually segmented facial nerve centerlines. The centerlines are used as a central axis around which a tubular safety zone is built. The zone's thickness incorporates the drill tip tracking errors. The system will warn when the tracked tip crosses the safety zone. RESULTS: Neurosurgeons using NerveClick could segment facial nerve centerlines with a maximum error of 0.44 ± 0.23 mm (mean ± standard deviation) on average compared with manual segmentations. CONCLUSION: Neurosurgeons using our new NerveClick algorithm can robustly segment facial nerve centerlines to construct a facial nerve safety zone, which potentially allows timely audiovisual warnings during navigated temporal bone drilling despite tracking inaccuracies.

Automated detection of external ventricular and lumbar drain-related meningitis using laboratory and microbiology results and medication data.

OBJECTIVE: Monitoring of healthcare-associated infection rates is important for infection control and hospital benchmarking. However, manual surveillance is time-consuming and susceptible to error. The aim was, therefore, to develop a prediction model to retrospectively detect drain-related meningitis (DRM), a frequently occurring nosocomial infection, using routinely collected data from a clinical data warehouse. METHODS: As part of the hospital infection control program, all patients receiving an external ventricular (EVD) or lumbar drain (ELD) (2004 to 2009; n = 742) had been evaluated for the development of DRM through chart review and standardized diagnostic criteria by infection control staff; this was the reference standard. Children, patients dying <24 hours after drain insertion or with <1 day follow-up and patients with infection at the time of insertion or multiple simultaneous drains were excluded. Logistic regression was used to develop a model predicting the occurrence of DRM. Missing data were imputed using multiple imputation. Bootstrapping was applied to increase generalizability. RESULTS: 537 patients remained after application of exclusion criteria, of which 82 developed DRM (13.5/1000 days at risk). The automated model to detect DRM included the number of drains placed, drain type, blood leukocyte count, C-reactive protein, cerebrospinal fluid leukocyte count and culture result, number of antibiotics started during admission, and empiric antibiotic therapy. Discriminatory power of this model was excellent (area under the ROC curve 0.97). The model achieved 98.8% sensitivity (95% CI 88.0% to 99.9%) and specificity of 87.9% (84.6% to 90.8%). Positive and negative predictive values were 56.9% (50.8% to 67.9%) and 99.9% (98.6% to 99.9%), respectively. Predicted yearly infection rates concurred with observed infection rates. CONCLUSION: A prediction model based on multi-source data stored in a clinical data warehouse could accurately quantify rates of DRM. Automated detection using this statistical approach is feasible and could be applied to other nosocomial infections.

Correspondence between altered functional and structural connectivity in the contralesional sensorimotor cortex after unilateral stroke in rats: a combined resting-state functional MRI and manganese-enhanced MRI study.

This study shows a significant correlation between functional connectivity, as measured with resting-state functional magnetic resonance imaging (MRI), and neuroanatomical connectivity, as measured with manganese-enhanced MRI, in rats at 10 weeks after unilateral stroke and in age-matched controls. Reduced interhemispheric functional connectivity between the contralesional primary motor cortex (M1) and ipsilesional sensorimotor cortical regions was accompanied by a decrease in transcallosal manganese transfer from contralesional M1 to the ipsilesional sensorimotor cortex after a large unilateral stroke. Increased intrahemispheric functional connectivity in the contralesional sensorimotor cortex was associated with locally enhanced neuroanatomical tracer uptake, which underlines the strong link between functional and structural reorganization of neuronal networks after stroke.

The sutureless excimer laser assisted non-occlusive anastomosis (SELANA); a feasibility study in a pressurized cadaver model.

OBJECTIVE: To compare intracranial feasibility of the conventional Excimer laser assisted non-occlusive anastomosis (ELANA) with the new experimental sutureless ELANA (SELANA). METHODS: Four pressurized human cadaver heads were bilaterally trepanated, using a combined pterional/pretemporal/transcavernous approach. In each head, seven ELANA anastomoses and seven contralateral SELANA anastomoses were constructed on (1) the proximal PCA/basilar artery (P1 segment/basilar artery; BA), (2) the distal posterior cerebral artery (PCA, P2 segment), (3) the supraclinoidal internal carotid artery (ICA), (4) the ICA bifurcation, (5) the proximal anterior cerebral artery (ACA, A1 segment), (6) the proximal middle cerebral artery (MCA, M1 segment), and (7) the distal MCA (M2 segment). RESULTS: In total, 26 of 28 ELANA anastomoses (93%) and 22 of 28 SELANA anastomoses (79%) could be completed. Two ELANA anastomoses on the BA could not be finished because of limited space. Six SELANA anastomoses could not be attached because the applicator did not facilitate an angulated anastomosis spot. Of the remaining anastomoses, more ELANA (eight) than SELANA (two) anastomoses could not be realized without manipulation of surrounding structures. The SELANA anastomoses were completed significantly faster than the ELANA, mean difference ranging from 11 min on the M2 to 107 min on the P1/BA. CONCLUSION: This comparative study shows potential advantages of the SELANA anastomosis over the ELANA anastomosis because during application, it causes less manipulation of surrounding structures while it is faster and easier. Further preclinical research should be performed in order to improve SELANA feasibility on angulated anastomosis spots and to assess long-term SELANA patency and endothelialization.

Recovery of sensorimotor function after experimental stroke correlates with restoration of resting-state interhemispheric functional connectivity.

Despite the success of functional imaging to map changes in brain activation patterns after stroke, spatiotemporal dynamics of cerebral reorganization in correlation with behavioral recovery remain incompletely characterized. Here, we applied resting-state functional magnetic resonance imaging (rs-fMRI) together with behavioral testing to longitudinally assess functional connectivity within neuronal networks, in relation to changes in associated function after unilateral stroke in rats. Our specific goals were (1) to identify temporal alterations in functional connectivity within the bilateral cortical sensorimotor system and (2) to elucidate the relationship between those alterations and changes in sensorimotor function. Our study revealed considerable loss of functional connectivity between ipsilesional and contralesional primary sensorimotor cortex regions, alongside significant sensorimotor function deficits in the first days after stroke. The interhemispheric functional connectivity restored in the following weeks, but remained significantly reduced up to 10 weeks after stroke in animals with lesions that comprised subcortical and cortical tissue, whereas transcallosal neuroanatomical connections were preserved. Intrahemispheric functional connectivity between primary somatosensory and motor cortex areas was preserved in the lesion border zone and moderately enhanced contralesionally. The temporal pattern of changes in functional connectivity between bilateral primary motor and somatosensory cortices correlated significantly with the evolution of sensorimotor function scores. Our study (1) demonstrates that poststroke loss and recovery of sensorimotor function is associated with acute deterioration and subsequent retrieval of interhemispheric functional connectivity within the sensorimotor system and (2) underscores the potential of rs-fMRI to assess spatiotemporal characteristics of functional brain reorganization that may underlie behavioral recovery after brain injury.

Effectiveness of neuronavigation in resecting solitary intracerebral contrast-enhancing tumors: a randomized controlled trial.

OBJECT: The goal of this study was to assess the impact of neuronavigation on the cytoreductive treatment of solitary contrast-enhancing intracerebral tumors and outcomes of this treatment in cases in which neuronavigation was preoperatively judged to be redundant. METHODS: The authors conducted a prospective randomized study in which 45 patients, each harboring a solitary contrast-enhancing intracerebral tumor, were randomized for surgery with or without neuronavigation. Peri- and postoperative parameters under investigation included the following: duration of the procedure; surgeon's estimate of the usefulness of neuronavigation; quantification of the extent of resection, determined using magnetic resonance imaging; and the postoperative course, as evaluated by neurological examinations, the patient's quality-of-life self-assessment, application of the Barthel index and the Karnofsky Performance Scale score, and the patient's time of death. The mean amount of residual tumor tissue was 28.9% for standard surgery (SS) and 13.8% for surgery involving neuronavigation (SN). The corresponding mean amounts of residual contrast-enhancing tumor tissue were 29.2 and 24.4%, respectively. These differences were not significant. Gross-total removal (GTR) was achieved in five patients who underwent SS and in three who underwent SN. Median survival was significantly shorter in the SN group (5.6 months compared with 9 months, unadjusted hazard ratio = 1.6); however, this difference may be attributable to the coincidental early death of three patients in the SN group. No discernible important effect on the patients' 3-month postoperative course was identified. CONCLUSIONS: There is no rationale for the routine use of neuronavigation to improve the extent of tumor resection and prognosis in patients harboring a solitary enhancing intracerebral lesion when neuronavigation is not already deemed advantageous because of the size or location of the lesion.

Toward functional neuronavigation: implementation of functional magnetic resonance imaging data in a surgical guidance system for intraoperative identification of motor and language cortices. Technical note and illustrative case.

In recent years, surgical navigation systems have become equipped to allow incorporation of data such as functional neuronavigation data. Functional magnetic resonance (fMR) imaging is a noninvasive modality that demonstrates various brain functions. Although still in an experimental stage, fMR imaging is a promising tool for mapping of motor and language functions. One advantage is that it can be implemented in presurgical imaging protocols and is therefore potentially widely available in general neurosurgical practice. In this paper the integration of fMR imaging and surgical navigation is described, and the potential advantages and pitfalls of its application in clinical practice are discussed.