Improving advanced intraoperative MRI methods during pediatric neurosurgery.

Advanced intraoperative MR images (ioMRI) acquired during the resection of pediatric brain tumors could offer additional physiological information to preserve healthy tissue. With this work, we aimed to develop a protocol for ioMRI with increased sensitivity for arterial spin labeling (ASL) and diffusion MRI (dMRI), optimized for patient positioning regularly used in the pediatric neurosurgery setting. For ethical reasons, ASL images were acquired in healthy adult subjects that were imaged in the prone and supine position. After this, the ASL cerebral blood flow (CBF) was quantified and compared between both positions. To evaluate the impact of the RF coils setups on image quality, we compared different setups (two vs. four RF coils) by looking at T1-weighted (T1w) signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), as well as undertaking a qualitative evaluation of T1w, T2w, ASL, and dMR images. Mean ASL CBF did not differ between the surgical prone and supine positions in any of the investigated regions of interest or the whole brain. T1w SNR (gray matter: p = 0.016, 34% increase; white matter: p = 0.016, 32% increase) and CNR were higher (p = 0.016) in the four versus two RF coils setups (18.0 ± 1.8 vs. 13.9 ± 1.8). Qualitative evaluation of T1w, T2w, ASL, and dMR images resulted in acceptable to good image quality and did not differ statistically significantly between setups. Only the nonweighted diffusion image maps and corticospinal tract reconstructions yielded higher image quality and reduced susceptibility artifacts with four RF coils. Advanced ioMRI metrics were more precise with four RF coils as the standard deviation decreased. Taken together, we have investigated the practical use of advanced ioMRI during pediatric neurosurgery. We conclude that ASL CBF quantification in the surgical prone position is valid and that ASL and dMRI acquisition with two RF coils can be performed adequately for clinical use. With four versus two RF coils, the SNR of the images increases, and the sensitivity to artifacts reduces.

Robotic alignment system Cirq (Brainlab) for navigated brain tumor biopsies in children.

INTRODUCTION: The Cirq robotic alignment system (Brainlab, Munich, Germany) is a manually adjustable electronic arm with a robotic alignment module on its distal end, enabling the neurosurgeon to automatically and accurately align surgical instruments to a preoperatively planned trajectory. In this study, we share our first experiences and results using Cirq for intracranial tumor biopsy in children. METHODS: From May 2021 until October 2022, all consecutive patients that underwent a brain tumor biopsy using Cirq were included and compared to a historical cohort of patients biopsied with the non-robotic system Varioguide (Brainlab, Munich, Germany). Patient-related data, tumor-related data, and surgery-related data were collected. Registration accuracy was calculated for different patient-to-image registration methods. Pre- and postoperative images were fused, and entry error, target error, and angulation error were calculated. RESULTS: Thirty-seven patients, aged 1-19 years, were included (14 with Cirq and 23 with Varioguide). An integrated histopathological and molecular diagnosis was acquired in all cases. Patient-to-image registration was significantly more accurate when based on bone screw fiducials combined with intraoperative CT, as compared to surface matching or skin fiducials. The target error (Euclidian distance) was 5.3 mm for Cirq as compared to 8.3 mm for Varioguide, but this was not statistically significant. Entry error and angulation error were also not significantly different between both groups. CONCLUSION: Intracranial biopsy with the Cirq robotic system is feasible and safe, and its accuracy does not differ from the Varioguide system.

Navigated intraoperative ultrasound in pediatric brain tumors.

PURPOSE: The aim of this study was to evaluate the diagnostic value and accuracy of navigated intraoperative ultrasound (iUS) in pediatric oncological neurosurgery as compared to intraoperative magnetic resonance imaging (iMRI). METHODS: A total of 24 pediatric patients undergoing tumor debulking surgery with iUS, iMRI, and neuronavigation were included in this study. Prospective acquisition of iUS images was done at two time points during the surgical procedure: (1) before resection for tumor visualization and (2) after resection for residual tumor assessment. Dice similarity coefficients (DSC), Hausdorff distances 95th percentiles (HD95) and volume differences, sensitivity, and specificity were calculated for iUS segmentations as compared to iMRI. RESULTS: A high correlation (R = 0.99) was found for volume estimation as measured on iUS and iMRI before resection. A good spatial accuracy was demonstrated with a median DSC of 0.72 (IQR 0.14) and a median HD95 percentile of 4.98 mm (IQR 2.22 mm). The assessment after resection demonstrated a sensitivity of 100% and a specificity of 84.6% for residual tumor detection with navigated iUS. A moderate accuracy was observed with a median DSC of 0.58 (IQR 0.27) and a median HD95 of 5.84 mm (IQR 4.04 mm) for residual tumor volumes. CONCLUSION: We found that iUS measurements of tumor volume before resection correlate well with those obtained from preoperative MRI. The accuracy of residual tumor detection was reliable as compared to iMRI, indicating the suitability of iUS for directing the surgeon's attention to areas suspect for residual tumor. Therefore, iUS is considered as a valuable addition to the neurosurgical armamentarium. TRIAL REGISTRATION NUMBER AND DATE: PMCLAB2023.476, February 12th 2024.

Cerebrospinal fluid leakage after intradural spinal surgery in children.

PURPOSE: This study aimed to establish the incidence of CSF leakage in children and associated complications after intradural spinal surgery in three tertiary neurosurgical referral centers and to describe the treatment strategies applied. METHODS: Patients of 18 years or younger who underwent intradural spinal surgery between 2015 and 2021 in three tertiary neurosurgical referral centers were included. Patients who died or were lost to follow-up within six weeks after surgery were excluded. The primary outcome measure was CSF leakage within six weeks after surgery, defined as leakage of CSF through the skin. Secondary outcome measures included the presence of pseudomeningocele (PMC), meningitis, and surgical site infection (SSI). RESULTS: We included a total of 75 procedures, representing 66 individual patients. The median age in this cohort was 5 (IQR = 0-13 years. CSF leakage occurred in 2.7% (2/75) of procedures. It occurred on days 3 and 21 after the index procedure, respectively. One patient was treated with a pressure bandage and an external lumbar drain on day 4 after diagnosis of the leak, and the other was treated with wound revision surgery on day 1 after the leak occurred. In total, 1 patient developed a PMC without a CSF leak which was treated with wound revision surgery. SSI occurred in 10.7%, which included both cases of CSF leak. CONCLUSIONS: CSF leakage after intradural spinal surgery in the pediatric population is relatively rare (2.7%). Nevertheless, the clinical consequences with respect to secondary complications such as infection and the necessity for invasive treatment are serious.

Cerebrospinal fluid leakage after cranial surgery in the pediatric population-a systematic review and meta-analysis.

BACKGROUND: Cerebrospinal fluid (CSF) leakage is a common complication after neurosurgical intervention. It is associated with substantial morbidity and increased healthcare costs. The current systematic review and meta-analysis aim to quantify the incidence of cerebrospinal fluid leakage in the pediatric population and identify its risk factors. METHODS: The authors followed the PRISMA guidelines. The Embase, PubMed, and Cochrane database were searched for studies reporting CSF leakage after intradural cranial surgery in patients up to 18 years old. Meta-analysis of incidences was performed using a generalized linear mixed model. RESULTS: Twenty-six articles were included in this systematic review. Data were retrieved of 2929 patients who underwent a total of 3034 intradural cranial surgeries. Surprisingly, only four of the included articles reported their definition of CSF leakage. The overall CSF leakage rate was 4.4% (95% CI 2.6 to 7.3%). The odds of CSF leakage were significantly greater for craniectomy as opposed to craniotomy (OR 4.7, 95% CI 1.7 to 13.4) and infratentorial as opposed to supratentorial surgery (OR 5.9, 95% CI 1.7 to 20.6). The odds of CSF leakage were significantly lower for duraplasty use versus no duraplasty (OR 0.41 95% CI 0.2 to 0.9). CONCLUSION: The overall CSF leakage rate after intradural cranial surgery in the pediatric population is 4.4%. Risk factors are craniectomy and infratentorial surgery. Duraplasty use is negatively associated with CSF leak. We suggest defining a CSF leak as "leakage of CSF through the skin," as an unambiguous definition is fundamental for future research.

Neurocognitive changes after awake surgery in glioma patients: a retrospective cohort study.

PURPOSE: Deficits in neurocognitive functioning (NCF) frequently occur in glioma patients. Both treatment and the tumor itself contribute to these deficits. In order to minimize the harmful effects of surgery, an increasing number of patients undergo awake craniotomy. To investigate whether we can indeed preserve cognitive functioning after state-of-the art awake surgery and to identify factors determining postoperative NCF, we performed a retrospective cohort study. METHODS: In diffuse glioma (WHO grade 2-4) patients undergoing awake craniotomy, we studied neurocognitive functioning both pre-operatively and 3-6 months postoperatively. Evaluation covered five neurocognitive domains. We performed analysis of data on group and individual level and evaluated the value of patient-, tumor- and treatment-related factors for predicting change in NCF, using linear and logistic regression analysis. RESULTS: We included 168 consecutive patients. Mean NCF-scores of psychomotor speed and visuospatial functioning significantly deteriorated after surgery. The percentage of serious neurocognitive impairments (- 2 standard deviations) increased significantly for psychomotor speed only. Tumor involvement in the left thalamus predicted a postoperative decline in NCF for the domains overall-NCF, executive functioning and psychomotor speed. An IDH-wildtype status predicted decline for overall-NCF and executive functioning. CONCLUSIONS: In all cognitive domains, except for psychomotor speed, cognitive functioning can be preserved after awake surgery. The domain of psychomotor speed seems to be most vulnerable to the effects of surgery and early postoperative therapies. Cognitive performance after glioma surgery is associated with a combination of structural and biomolecular effects from the tumor, including IDH-status and left thalamic involvement.

Incisional CSF leakage after intradural cranial surgery in children: incidence, risk factors, and complications.

OBJECTIVE: The risk of cerebrospinal fluid (CSF) leakage after cranial surgery and its associated complications in children are unclear because of variable definitions and the lack of multicenter studies. In this study, the authors aimed to establish the incidence of CSF leakage after intradural cranial surgery in the pediatric population. In addition, they evaluated potential risk factors and complications related to CSF leakage in the pediatric population. METHODS: The authors performed an international multicenter retrospective cohort study in three tertiary neurosurgical referral centers. Included were all patients aged 18 years or younger who had undergone cranial surgery to reach the subdural space during the period between 2015 and 2021. Patients who died or were lost to follow-up within 6 weeks after surgery were excluded. The primary outcome measure was the incidence of CSF leakage, defined as leakage through the skin, within 6 weeks after surgery. Univariable and multivariable logistic regression analyses were performed to identify risk factors for and complications related to CSF leakage. RESULTS: In total, 759 procedures were identified, performed in 687 individual patients. The incidence of CSF leakage was 7.5% (95% CI 5.7%-9.6%). In the multivariate model, independent risk factors for CSF leakage were hydrocephalus (OR 4.5, 95% CI 2.2-8.9) and craniectomy (OR 7.6, 95% CI 3.0-19.5). Patients with CSF leakage had higher odds of pseudomeningocele (5.7, 95% CI 3.0-10.8), meningitis (21.1, 95% CI 9.5-46.8), and surgical site infection (7.4, 95% CI 2.6-20.8) than patients without leakage. CONCLUSIONS: CSF leakage risk in children after cranial surgery, which is comparable to the risk reported in adults, is an event of major concern and has a serious clinical impact.

Advanced intraoperative MRI in pediatric brain tumor surgery.

Introduction: In the pediatric brain tumor surgery setting, intraoperative MRI (ioMRI) provides "real-time" imaging, allowing for evaluation of the extent of resection and detection of complications. The use of advanced MRI sequences could potentially provide additional physiological information that may aid in the preservation of healthy brain regions. This review aims to determine the added value of advanced imaging in ioMRI for pediatric brain tumor surgery compared to conventional imaging. Methods: Our systematic literature search identified relevant articles on PubMed using keywords associated with pediatrics, ioMRI, and brain tumors. The literature search was extended using the snowball technique to gather more information on advanced MRI techniques, their technical background, their use in adult ioMRI, and their use in routine pediatric brain tumor care. Results: The available literature was sparse and demonstrated that advanced sequences were used to reconstruct fibers to prevent damage to important structures, provide information on relative cerebral blood flow or abnormal metabolites, or to indicate the onset of hemorrhage or ischemic infarcts. The explorative literature search revealed developments within each advanced MRI field, such as multi-shell diffusion MRI, arterial spin labeling, and amide-proton transfer-weighted imaging, that have been studied in adult ioMRI but have not yet been applied in pediatrics. These techniques could have the potential to provide more accurate fiber tractography, information on intraoperative cerebral perfusion, and to match gadolinium-based T1w images without using a contrast agent. Conclusion: The potential added value of advanced MRI in the intraoperative setting for pediatric brain tumors is to prevent damage to important structures, to provide additional physiological or metabolic information, or to indicate the onset of postoperative changes. Current developments within various advanced ioMRI sequences are promising with regard to providing in-depth tissue information.

Radiological differences between subtypes of WHO 2016 grade II-III gliomas: a systematic review and meta-analysis.

BACKGROUND: Isocitrate dehydrogenase (IDH) mutation and 1p/19q-codeletion are oncogenetic alterations with a positive prognostic value for diffuse gliomas, especially grade II and III. Some studies have suggested differences in biological behavior as reflected by radiological characteristics. In this paper, the literature regarding radiological characteristics in grade II and III glioma subtypes was systematically evaluated and a meta-analysis was performed. METHODS: Studies that addressed the relationship between conventional radiological characteristics and IDH mutations and/or 1p/19q-codeletions in newly diagnosed, grade II and III gliomas of adult patients were included. The "3-group analysis" compared radiological characteristics between the WHO 2016 glioma subtypes (IDH-mutant astrocytoma, IDH-wildtype astrocytoma, and oligodendroglioma), and the "2-group analysis" compared radiological characteristics between 1p/19q-codeleted gliomas and 1p/19q-intact gliomas. RESULTS: Fourteen studies (3-group analysis: 670 cases, 2-group analysis: 1042 cases) were included. IDH-mutated astrocytomas showed more often sharp borders and less frequently contrast enhancement compared to IDH-wildtype astrocytomas. 1p/19q-codeleted gliomas had less frequently sharp borders, but showed a heterogeneous aspect, calcification, cysts, and edema more frequently. For the 1p/19q-codeleted gliomas, a sensitivity of 96% was found for heterogeneity and a specificity of 88.1% for calcification. CONCLUSIONS: Significant differences in conventional radiological characteristics exist between the WHO 2016 glioma subtypes, which may reflect differences in biological behavior. However, the diagnostic value of the independent radiological characteristics is insufficient to reliably predict the molecular genetic subtype.

Epilepsy surgery provides new insights in retinotopic organization of optic radiations. A systematic review.

PURPOSE OF REVIEW: Visual field defects (VFDs) produced by temporal lobe resections provide valuable information on the retinotopic organization of the optic radiations. The results of this systematic review of the literature will be translated into a revised--and evidence-based--map of the retinotopic anatomy of the anterior optic radiations. RECENT FINDINGS: Recent studies provide best evidence by combining automatic static perimetry and modern imaging techniques. VFDs occur in 83% of patients undergoing temporal lobectomy. There is a significant correlation between size of resection and amount of VFD. Most defects appear incongruous. Macular involvement is seen in more than 50% of cases. The inferolateral defect border is of a sloping nature and sometimes crosses the horizontal meridian. On the basis of these findings, the classical theory on the retinotopic anatomy of the optic radiation should be revised. SUMMARY: This article systematically reviews the literature on VFDs after temporal lobe resection. Frequency, size, congruity, macular involvement and defect borders are related to size of resection. The classical theory on the retinotopic organization of the anterior optic radiations should be revised.

Interrelationships between molecular subtype, anatomical location, and extent of resection in diffuse glioma: a systematic review and meta-analysis.

BACKGROUND: The introduction of the 2016 WHO Classification of Tumors of the Central Nervous System has resulted in tumor groupings with improved prognostic value for diffuse glioma patients. Molecular subtype, primarily based on IDH-mutational status and 1p/19q-status, is a strong predictor of survival. It is unclear to what extent this finding may be mediated by differences in anatomical location and surgical resectability among molecular subgroups. Our aim was to elucidate possible correlations between (1) molecular subtype and anatomical location and (2) molecular subtype and extent of resection. METHODS: We performed a systematic review of literature searching for studies on molecular subtype in relation to anatomical location and extent of resection. Only original data concerning adult participants suffering from cerebral diffuse glioma were included. Studies adopting similar outcomes measures were included in our meta-analysis. RESULTS: In the systematic analysis for research questions 1 and 2, totals of 20 and 9 studies were included, respectively. Study findings demonstrated that IDH-mutant tumors were significantly more frequently located in the frontal lobe and less often in the temporal lobe compared with IDH-wildtype gliomas. Within the IDH-mutant group, 1p/19q-codeleted tumors were associated with more frequent frontal and less frequent temporal localization compared with 1p/19q-intact tumors. In IDH-mutant gliomas, greater extent of resection was achieved than in IDH-wildtype tumors. CONCLUSIONS: Genetic profile of diffuse cerebral glioma influences their anatomical location and seems to affect tumor resectability.

Tumor-related neurocognitive dysfunction in patients with diffuse glioma: a retrospective cohort study prior to antitumor treatment.

BACKGROUND: Impairments in neurocognitive functioning (NCF) frequently occur in glioma patients. Both the tumor and its treatment contribute to these impairments. We aimed to quantify NCF in glioma patients before treatment and to investigate which factors influence NCF. METHODS: We performed a retrospective cohort study in diffuse glioma patients according to STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) criteria. All patients had undergone neuropsychological assessment as part of routine clinical care, before awake surgery. We studied "overall NCF" and NCF in 5 neurocognitive domains separately. For "overall NCF" and per domain, we performed analyses at 2 different levels of outcome measures: (1) group level: mean cognitive functioning of the study sample, and (2) individual level: the percentage of impaired patients. We performed multivariable logistic regression analyses to investigate which factors were associated with the occurrence of cognitive impairments. RESULTS: From our cohort of glioma patients (2010-2016), 168 patients met all the inclusion criteria. All cognitive domains were significantly affected at the group level. The percentages of neurocognitive impairments (-2SD) were highest for Executive Functioning, Psychomotor Speed, and Memory (26.5%, 23.2%, and 19.3%, respectively). Patients with high-grade glioma were affected more severely than patients with low-grade glioma. Tumor volume, isocitrate dehydrogenase status, WHO grade, and histology were associated with the occurrence of domain-specific impairments. CONCLUSIONS: Cognitive impairment occurs in the majority of treatment-naive glioma patients. The domains Executive Functioning, Speed, and Memory are involved most frequently. These impairments in NCF are explained not only by tumor location and volume, but also by other (biological) mechanisms.