Cerebrospinal Fluid Leak after Transsphenoidal Surgery: A Systematic Review and Meta-analysis.

Background Cerebrospinal fluid (CSF) leak is widely recognized as a challenging and commonly occurring postoperative complication of transsphenoidal surgery (TSS). The primary objective of this study is to benchmark the current prevalence of CSF leak after TSS in the adult population. Methods The authors followed the PRISMA guidelines. The PubMed, Embase, and Cochrane Library databases were searched for articles reporting CSF leak after TSS in the adult population. Meta-analysis was performed using the Untransformed Proportion metric in OpenMetaAnalyst. For two between-group comparisons a generalized linear mixed model was applied. Results We identified 2,408 articles through the database search, of which 70, published since 2015, were included in this systematic review. These studies yielded 24,979 patients who underwent a total of 25,034 transsphenoidal surgeries. The overall prevalence of postoperative CSF leak was 3.4% (95% confidence interval or CI 2.8-4.0%). The prevalence of CSF leak found in patients undergoing pituitary adenoma resection was 3.2% (95% CI 2.5-4.2%), whereas patients who underwent TSS for another indication had a CSF leak prevalence rate of 7.1% (95% CI 3.0-15.7%) (odds ratio [OR] 2.3, 95% CI 0.9-5.7). Patients with cavernous sinus invasion (OR 3.0, 95% CI 1.1-8.7) and intraoperative CSF leak (OR 5.9, 95% CI 3.8-9.0) have increased risk of postoperative CSF leak. Previous TSS and microscopic surgery are not significantly associated with postoperative CSF leak. Conclusion The overall recent prevalence of CSF leak after TSS in adults is 3.4%. Intraoperative CSF leak and cavernous sinus invasion appear to be significant risk factors for postoperative CSF leak.

Intracranial Meningiomas Decrease in Volume on Magnetic Resonance Imaging After Discontinuing Progestin.

BACKGROUND: The behavior of meningiomas under influence of progestin therapy remains unclear. OBJECTIVE: To investigate the relationship between growth kinetics of intracranial meningiomas and usage of the progestin cyproterone acetate (PCA). METHODS: This study prospectively followed 108 women with 262 intracranial meningiomas and documented PCA use. A per-meningioma analysis was conducted. Changes in meningioma volumes over time, and meningioma growth velocities, were measured on magnetic resonance imaging (MRI) after stopping PCA treatment. RESULTS: Mean follow-up time was 30 (standard deviation [SD] 29) mo. Ten (4%) meningiomas were treated surgically at presentation. The other 252 meningiomas were followed after stopping PCA treatment. Overall, followed meningiomas decreased their volumes by 33% on average (SD 28%). A total of 188 (72%) meningiomas decreased, 51 (20%) meningiomas remained stable, and 13 (4%) increased in volume of which 3 (1%) were surgically treated because of radiological progression during follow-up after PCA withdrawal. In total, 239 of 262 (91%) meningiomas regressed or stabilized during follow-up. Subgroup analysis in 7 women with 19 meningiomas with follow-up before and after PCA withdrawal demonstrated that meningioma growth velocity changed statistically significantly (P = .02). Meningiomas grew (average velocity of 0.25 mm3/day) while patients were using PCA and shrank (average velocity of -0.54 mm3/day) after discontinuation of PCA. CONCLUSION: Ninety-one percent of intracranial meningiomas in female patients with long-term PCA use decrease or stabilize on MRI after stopping PCA treatment. Meningioma growth kinetics change significantly from growth during PCA usage to shrinkage after PCA withdrawal.

Postoperative headache after surgical treatment of cerebellopontine angle tumors: a systematic review.

PURPOSE: Postoperative headache (POH) is a complication that occurs after surgical resection of cerebellopontine angle (CPA) tumors. The two most common surgical approaches are the translabyrinthine (TL), and retrosigmoid (RS) approach. The objective of this systematic review was to investigate whether POH occurs more frequently after RS compared to TL approaches. METHODS: A systematic search was conducted in Cochrane, Pubmed and Embase. Studies were included if POH after CPA tumor removal was reported and both surgical approaches were compared. The methodological quality of the studies was assessed using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. RESULTS: In total, 3,942 unique articles were screened by title and abstract. After the initial screening process 63 articles were screened for relevance to the inquiry, of which seven studies were included. Three studies found no significant difference between both surgical approaches (p = 0.871, p = 0.120, p = 0.592). Three other studies found a lower rate of POH in the TL group compared to the RS group (p = 0.019, p < 0.001, p < 0.001). Another study showed a significantly lower POH rate in the TL group after one and six months (p = 0.006), but not after 1 year (p = 0.6). CONCLUSION: The results of this systematic review show some evidence of a lower rate of POH in favor of the TL approach versus the RS approach for CPA tumor resection. Prospective research studies are needed to further investigate this finding.

Petroclival meningiomas: the risk of post-operative cranial nerve deficits among different surgical approaches-a systematic review and meta-analysis.

BACKGROUND: The surgical resection of petroclival meningiomas (PCMs) remains a challenge. Both the relationship with neurovascular structures and the deep location of the tumor can affect the extent of resection and the rate of post-operative morbidity. METHODS: The authors performed a systematic review and meta-analysis of the literature examining the rate of new cranial nerve (CN) deficits after resection of PCM. A systematic search of two databases was performed for studies published between 1990 and 2018. Random-effect meta-analysis was used to pool the rate of post-operative CN deficits, mortality rate, and rate of radical resection. RESULTS: We included twelve studies and 334 patients harboring PCM. The overall rate of complete resection was 68% (95% CI 57.9-78.2%; p < 0.01; I2 = 83%). The rate of early and late post-operative CN deficits was the following: 3.8 and 2.7% (III CN), 6.6 and 3% (IV), 7.3 and 5.5% (V CN), 8 and 3.6% (VI CN), 8.9 and 8.9%% (VIII), and 4 and 2.7% (IX-XI CNs) (I2 = 0%, and p < 0.01 for all analyses). The risk of post-operative deficit of the IV CN was higher among the petrosal group (7.6%; I2 = 0% vs 2.1%; I2 = 0%), whereas the impairment of VII CN function was higher among retrosigmoid group (16.6%; I2 = 64.6% vs 11.4%; I2 = 52.8%), but it was transient in the majority of cases. CONCLUSIONS: This systematic review and meta-analysis provides a detailed overview of post-operative CN deficits ensuing surgical resection of PCMs. These findings should be acknowledged when counseling patients with PCMs regarding the more appropriate approach for their tumor.

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 exposure visualization and audible distance emission for navigated temporal bone drilling in phantoms.

BACKGROUND: A neuronavigation interface with extended function as compared with current systems was developed to aid during temporal bone surgery. The interface, named EVADE, updates the prior anatomical image and visualizes the bone drilling process virtually in real-time without need for intra-operative imaging. Furthermore, EVADE continuously calculates the distance from the drill tip to segmented temporal bone critical structures (e.g. the sigmoid sinus and facial nerve) and produces audiovisual warnings if the surgeon drills in too close vicinity. The aim of this study was to evaluate the accuracy and surgical utility of EVADE in physical phantoms. METHODOLOGY/PRINCIPAL FINDINGS: We performed 228 measurements assessing the position accuracy of tracking a navigated drill in the operating theatre. A mean target registration error of 1.33±0.61 mm with a maximum error of 3.04 mm was found. Five neurosurgeons each drilled two temporal bone phantoms, once using EVADE, and once using a standard neuronavigation interface. While using standard neuronavigation the surgeons damaged three modeled temporal bone critical structures. No structure was hit by surgeons utilizing EVADE. Surgeons felt better orientated and thought they had improved tumor exposure with EVADE. Furthermore, we compared the distances between surface meshes of the virtual drill cavities created by EVADE to actual drill cavities: average maximum errors of 2.54±0.49 mm and -2.70±0.48 mm were found. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that EVADE gives accurate feedback which reduces risks of harming modeled critical structures compared to a standard neuronavigation interface during temporal bone phantom drilling.

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.

Association of schizophrenia in 22q11.2 deletion syndrome and gray matter volumetric deficits in the superior temporal gyrus.

OBJECTIVE: Individuals with 22q11.2 deletion syndrome are known to be at high risk of developing schizophrenia. Previous imaging studies have provided limited data on the relation of schizophrenia expression in 22q11.2 deletion syndrome to specific regional brain volumetric changes. The authors hypothesized that the main structural brain finding associated with schizophrenia expression in 22q11.2 deletion syndrome, as for schizophrenia in the general population, would be gray matter volumetric deficits, especially in the temporal lobes. METHOD: MR brain images from 29 patients with 22q11.2 deletion syndrome and schizophrenia and 34 comparison subjects with 22q11.2 deletion syndrome and no history of psychosis were analyzed using a voxel-based morphometry method that also yielded volumes for related region-of-interest analyses. The authors compared data from the two groups using an analysis of covariance model correcting for total intracranial volume, age, sex, IQ, and history of congenital cardiac defects. The false discovery rate threshold was set at 0.05 to account for multiple comparisons. RESULTS: Voxel-based morphometry analyses identified significant gray matter reductions in the left superior temporal gyrus (Brodmann's area 22) in the schizophrenia group. There were no significant between-group differences in white matter or CSF volumes. Region-of-interest analyses showed significant bilateral gray matter volume reductions in the temporal lobes and superior temporal gyri in the schizophrenia group. CONCLUSIONS: The structural brain expression of schizophrenia associated with the highly penetrant 22q11.2 deletion involves lower gray matter volumes in temporal lobe regions. These structural MRI findings in a 22q11.2 deletion syndrome form of schizophrenia are consistent with those from studies involving schizophrenia samples from the general population. The results provide further support for 22q11.2 deletion syndrome as a genetic subtype and as a useful neurodevelopmental model of schizophrenia.

Skull base tumor model.

OBJECT: Resident duty-hours restrictions have now been instituted in many countries worldwide. Shortened training times and increased public scrutiny of surgical competency have led to a move away from the traditional apprenticeship model of training. The development of educational models for brain anatomy is a fascinating innovation allowing neurosurgeons to train without the need to practice on real patients and it may be a solution to achieve competency within a shortened training period. The authors describe the use of Stratathane resin ST-504 polymer (SRSP), which is inserted at different intracranial locations to closely mimic meningiomas and other pathological entities of the skull base, in a cadaveric model, for use in neurosurgical training. METHODS: Silicone-injected and pressurized cadaveric heads were used for studying the SRSP model. The SRSP presents unique intrinsic metamorphic characteristics: liquid at first, it expands and foams when injected into the desired area of the brain, forming a solid tumorlike structure. The authors injected SRSP via different passages that did not influence routes used for the surgical approach for resection of the simulated lesion. For example, SRSP injection routes included endonasal transsphenoidal or transoral approaches if lesions were to be removed through standard skull base approach, or, alternatively, SRSP was injected via a cranial approach if the removal was planned to be via the transsphenoidal or transoral route. The model was set in place in 3 countries (US, Italy, and The Netherlands), and a pool of 13 physicians from 4 different institutions (all surgeons and surgeons in training) participated in evaluating it and provided feedback. RESULTS: All 13 evaluating physicians had overall positive impressions of the model. The overall score on 9 components evaluated--including comparison between the tumor model and real tumor cases, perioperative requirements, general impression, and applicability--was 88% (100% being the best possible achievable score where the evaluator strongly agreed with the proposed factor). Individual components had scores at or above 80% (except for 1). The only score that was below 80% was related to radiographic visibility of the model for adequate surgical planning (score of 74%). The highest score was given to usefulness in neurosurgical training (98%). CONCLUSIONS: The skull base tumor model is an effective tool to provide more practice in preoperative planning and technical skills.

Voxel-based morphometry and automated lobar volumetry: the trade-off between spatial scale and statistical correction.

Voxel-based morphometry (VBM) and automated lobar region of interest (ROI) volumetry are comprehensive and fast methods to detect differences in overall brain anatomy on magnetic resonance images. However, VBM and automated lobar ROI volumetry have detected dissimilar gray matter differences within identical image sets in our own experience and in previous reports. To gain more insight into how diverging results arise and to attempt to establish whether one method is superior to the other, we investigated how differences in spatial scale and in the need to statistically correct for multiple spatial comparisons influence the relative sensitivity of either technique to group differences in gray matter volumes. We assessed the performance of both techniques on a small dataset containing simulated gray matter deficits and additionally on a dataset of 22q11-deletion syndrome patients with schizophrenia (22q11DS-SZ) vs. matched controls. VBM was more sensitive to simulated focal deficits compared to automated ROI volumetry, and could detect global cortical deficits equally well. Moreover, theoretical calculations of VBM and ROI detection sensitivities to focal deficits showed that at increasing ROI size, ROI volumetry suffers more from loss in sensitivity than VBM. Furthermore, VBM and automated ROI found corresponding GM deficits in 22q11DS-SZ patients, except in the parietal lobe. Here, automated lobar ROI volumetry found a significant deficit only after a smaller sub-region of interest was employed. Thus, sensitivity to focal differences is impaired relatively more by averaging over larger volumes in automated ROI methods than by the correction for multiple comparisons in VBM. These findings indicate that VBM is to be preferred over automated lobar-scale ROI volumetry for assessing gray matter volume differences between groups.

Nonmaturation of arm arteriovenous fistulas for hemodialysis access: A systematic review of risk factors and results of early treatment.

INTRODUCTION: Arteriovenous fistula (AVF) nonmaturation increases reliance of hemodialysis patients on grafts and catheters, exposing them to associated high complication risks. This systematic review assessed the success rates and complications of therapeutic interventions in arm hemodialysis AVFs experiencing nonmaturation. It also compared the efficacy of preoperative clinical factors (eg, age, gender, race), and preoperatively and postoperatively acquired hemodynamic parameters (eg, arterial diameter or blood flow through the AVF) at stratifying risk of nonmaturation. METHODS: Two independent researchers used a systematic strategy to search literature databases and extract data from articles judged relevant and valid. The evidence base for this review comprised 33 articles, 12 about treatment, and 21 concerning risk stratification. A meta-analysis was performed to calculate summary measures for nonmaturation treatment success and risk stratification efficacy (eg, excess risk and relative risk) of preoperative clinical, preoperative hemodynamic, and postoperative hemodynamic risk factors. RESULTS: The success rate of early endovascular or surgical treatment, defined as the possibility of achieving adequate hemodialysis, averaged 86%, with 1-year primary patencies of 51%, 1-year secondary patencies of 76%, and complication rates of 9.3%, with 5.5% minor complications. Overall, patients with preoperative clinical risk factors had excess nonmaturation risks of 21% (95% confidence interval [CI], 11%-30%) and a relative risk of 1.7 (95% CI, 1.3-2.1). Patients with preoperative hemodynamic risk factors had average estimated excess risks of 24% (95% CI, 15%-33%) and a relative risk of 1.7 (95% CI, 1.4-2.0). Patients with hemodynamic risk factors present shortly after operation had excess nonmaturation risks of 50% (95% CI, 42%-58%) and a relative risk of 4.3 (95% CI, 3.4-5.5). CONCLUSIONS: Patients can be treated effectively for AVF nonmaturation early on, and it is possible to identify those patients at risk of nonmaturation most effectively with an early postoperative assessment of hemodynamic risk factors. Additional research is needed that concentrates on adopting the strategy of early treatment of patients with postoperative risk factors.