Prognostic and Diagnostic Utility of Serum Biomarkers in Pediatric Traumatic Brain Injury.

Traumatic brain injury (TBI) remains a major cause of morbidity and death among the pediatric population. Timely diagnosis, however, remains a complex task because of the lack of standardized methods that permit its accurate identification. The aim of this study was to determine whether serum levels of brain injury biomarkers can be used as a diagnostic and prognostic tool in this pathology. This prospective, observational study collected and analyzed the serum concentration of neuronal injury biomarkers at enrollment, 24h and 48h post-injury, in 34 children ages 0-18 with pTBI and 19 healthy controls (HC). Biomarkers included glial fibrillary acidic protein (GFAP), neurofilament protein L (NfL), ubiquitin-C-terminal hydrolase (UCH-L1), S-100B, tau and tau phosphorylated at threonine 181 (p-tau181). Subjects were stratified by admission Glasgow Coma Scale score into two categories: a combined mild/moderate (GCS 9-15) and severe (GCS 3-8). Glasgow Outcome Scale-Extended (GOS-E) Peds was dichotomized into favorable (≤4) and unfavorable (≥5) and outcomes. Data were analyzed utilizing Prism 9 and R statistical software. The findings were as follows: 15 patients were stratified as severe TBI and 19 as mild/moderate per GCS. All biomarkers measured at enrollment were elevated compared with HC. Serum levels for all biomarkers were significantly higher in the severe TBI group compared with HC at 0, 24, and 48h. The GFAP, tau S100B, and p-tau181 had the ability to differentiate TBI severity in the mild/moderate group when measured at 0h post-injury. Tau serum levels were increased in the mild/moderate group at 24h. In addition, NfL and p-tau181 showed increased serum levels at 48h in the aforementioned GCS category. Individual biomarker performance on predicting unfavorable outcomes was measured at 0, 24, and 48h across different GOS-E Peds time points, which was significant for p-tau181 at 0h at all time points, UCH-L1 at 0h at 6-9 months and 12 months, GFAP at 48h at 12 months, NfL at 0h at 12 months, tau at 0h at 12 months and S100B at 0h at 12 months. We concluded that TBI leads to increased serum neuronal injury biomarkers during the first 0-48h post-injury. A biomarker panel measuring these proteins could aid in the early diagnosis of mild to moderate pTBI and may predict neurological outcomes across the injury spectrum.

The current landscape of immunotherapy for pediatric brain tumors.

Pediatric central nervous system tumors are the most common solid malignancies in childhood, and aggressive therapy often leads to long-term sequelae in survivors, making these tumors challenging to treat. Immunotherapy has revolutionized prospects for many cancer types in adults, but the intrinsic complexity of treating pediatric patients and the scarcity of clinical studies of children to inform effective approaches have hampered the development of effective immunotherapies in pediatric settings. Here, we review recent advances and ongoing challenges in pediatric brain cancer immunotherapy, as well as considerations for efficient clinical translation of efficacious immunotherapies into pediatric settings.

Robotically Steered Needles: A Survey of Neurosurgical Applications and Technical Innovations.

This paper surveys both the clinical applications and main technical innovations related to steered needles, with an emphasis on neurosurgery. Technical innovations generally center on curvilinear robots that can adopt a complex path that circumvents critical structures and eloquent brain tissue. These advances include several needle-steering approaches, which consist of tip-based, lengthwise, base motion-driven, and tissue-centered steering strategies. This paper also describes foundational mathematical models for steering, where potential fields, nonholonomic bicycle-like models, spring models, and stochastic approaches are cited. In addition, practical path planning systems are also addressed, where we cite uncertainty modeling in path planning, intraoperative soft tissue shift estimation through imaging scans acquired during the procedure, and simulation-based prediction. Neurosurgical scenarios tend to emphasize straight needles so far, and span deep-brain stimulation (DBS), stereoelectroencephalography (SEEG), intracerebral drug delivery (IDD), stereotactic brain biopsy (SBB), stereotactic needle aspiration for hematoma, cysts and abscesses, and brachytherapy as well as thermal ablation of brain tumors and seizure-generating regions. We emphasize therapeutic considerations and complications that have been documented in conjunction with these applications.

Tactile Skill-Based Neurosurgical Simulators Are Effective and Inexpensive.

BACKGROUND: Regulations limit residency work hours and operating time, limiting the amount of hands-on surgical training. To develop alternative hands-on training, many programs teach surgical skills in laboratories and workshops with the use of simulators. The expense of computer simulators and lack of replication of the manual skills and tactile feedback of surgery limit their usefulness. We have developed 2 replicable simulators constructed from low-cost materials, which allow residents to practice the manual skills required in key portions of minimally invasive lumbar decompression and Chiari decompression surgeries. The objective was to review the efficacy of our lumbar and Chiari decompression simulators in improving resident and medical student surgical skills. METHODS: Resident and medical student participants completed one or both simulators 10 times. The lumbar decompression simulations were evaluated by the length of time participants blocked the field of view and by the number of times they lost control of the drill. Chiari decompression simulations were evaluated by the length of time to complete the simulation and by the regularity of their sutures. RESULTS: After 10 attempts, participants of the lumbar decompression simulator decreased the amount of time blocking the field of view by 52% and decreased the number of times they lost control of the drill by 69%. Participants of the Chiari decompression simulator decreased their suturing time by 56% and improved the regularity of their sutures. CONCLUSIONS: The simple and inexpensive simulators evaluated in this study were shown to improve the speed, quality of work, and comfort level of the participants.

Medial axis segmentation of cranial nerves using shape statistics-aware discrete deformable models.

PURPOSE: We propose a segmentation methodology for brainstem cranial nerves using statistical shape model (SSM)-based deformable 3D contours from T2 MR images. METHODS: We create shape models for ten pairs of cranial nerves. High-resolution T2 MR images are segmented for nerve centerline using a 1-Simplex discrete deformable 3D contour model. These segmented centerlines comprise training datasets for the shape model. Point correspondence for the training dataset is performed using an entropy-based energy minimization framework applied to particles located on the centerline curve. The shape information is incorporated into the 1-Simplex model by introducing a shape-based internal force, making the deformation stable against low resolution and image artifacts. RESULTS: The proposed method is validated through extensive experiments using both synthetic and patient MRI data. The robustness and stability of the proposed method are experimented using synthetic datasets. SSMs are constructed independently for ten pairs (CNIII-CNXII) of brainstem cranial nerves using ten non-pathological image datasets of the brainstem. The constructed ten SSMs are assessed in terms of compactness, specificity and generality. In order to quantify the error distances between segmented results and ground truths, two metrics are used: mean absolute shape distance (MASD) and Hausdorff distance (HD). MASD error using the proposed shape model is 0.19 ± 0.13 (mean ± std. deviation) mm and HD is 0.21 mm which are sub-voxel accuracy given the input image resolution. CONCLUSION: This paper described a probabilistic digital atlas of the ten brainstem-attached cranial nerve pairs by incorporating a statistical shape model with the 1-Simplex deformable contour. The integration of shape information as a priori knowledge results in robust and accurate centerline segmentations from even low-resolution MRI data, which is essential in neurosurgical planning and simulations for accurate and robust 3D patient-specific models of critical tissues including cranial nerves.

Isolated Traumatic Diastasis of the Clival Synchondroses without Clival Fracture.

Traumatic clival fractures in the pediatric population are associated with high mortality rates. In our previously reported series, a subset of clival fractures were associated with traumatic diastasis of the surrounding clival synchondroses. Herein, we describe a pediatric case of an isolated traumatic diastasis of the clival synchondroses without clival fracture with significant injury to neurovascular structures. To our knowledge this is the first report to describe this entity. Careful radiological attention should be made towards the clival synchondroses in crushing head injuries to best tailor screening for cerebrovascular injury even in the absence of clival fractures.

Predictors of mortality in children with myelomeningocele and symptomatic Chiari type II malformation.

OBJECTIVE Chiari malformation type II (CM-II) in myelomeningocele is associated with a significant rate of mortality and poor outcome. Death is frequently heralded by the onset or progression of neurological symptoms. The authors sought to identify predictors of poor outcome and mortality within the myelomeningocele population at Children's Hospital of Pittsburgh. METHODS A retrospective chart and radiology review was performed on all infants who underwent primary closure of a myelomeningocele defect at Children's Hospital of Pittsburgh between the years of 1995 and 2015. Preoperative symptoms and signs leading to CM-II decompression, as well as operative details and postoperative changes in these symptoms and signs, were investigated in detail and correlated to outcome. Poor outcome was defined as death, stridor, or ventilator dependence. Deceased patients were separately assessed within this subgroup. RESULTS Thirty-two (21%) of 153 patients were found to have symptomatic CM-II. Of the 32 patients meeting inclusion criteria, 12 (38%) had poor outcomes. Eight patients (25%) died since initial presentation; 5 of these patients (16% of the overall cohort) died within the 1st year of life and 3 (9%) died during adolescence. Seven (88%) of the 8 patients who died had central apnea on presentation (p = 0.001) and 7 (44%) of the 16 patients who developed symptoms in the first 3 months of life died, compared with 1 (6.3%) of 16 who developed symptoms later in childhood (p = 0.04). The median Apgar score at 1 minute was 4.5 for patients who died and 8 for surviving patients (p = 0.006). The median diameter of the myelomeningocele defect was 5.75 cm for patients who died and 5 for those who survived (p = 0.01). The anatomical level of defect trended toward higher levels in patients who died, with 4 patients in that group having an anatomical level at L-2 or higher compared with 5 of the surviving patients (p = 0.001). The median initial head circumference for the 5 patients dying in the 1st year of life was 41.5 cm, versus 34 cm for all other patients (p = 0.01). CONCLUSIONS CM-II in spina bifida is associated with a significant mortality rate even when surgical intervention is performed. Death is more frequent in symptomatic patients presenting prior to 1 year of age. Late deaths are associated with symptom progression despite aggressive surgical and medical intervention. In this patient cohort, death was more likely in patients with symptomatic presentation during the first 3 months of life, low Apgar scores, large myelomeningocele defects, early central apnea, and large head circumference at birth.

MRI-Based Medial Axis Extraction and Boundary Segmentation of Cranial Nerves Through Discrete Deformable 3D Contour and Surface Models.

This paper presents a segmentation technique to identify the medial axis and the boundary of cranial nerves. We utilize a 3-D deformable one-simplex discrete contour model to extract the medial axis of each cranial nerve. This contour model represents a collection of two-connected vertices linked by edges, where vertex position is determined by a Newtonian expression for vertex kinematics featuring internal and external forces, the latter of which include attractive forces toward the nerve medial axis. We exploit multiscale vesselness filtering and minimal path techniques in the medial axis extraction method, which also computes a radius estimate along the path. Once we have the medial axis and the radius function of a nerve, we identify the nerve surface using a two-simplex deformable model, which expands radially and can accommodate any nerve shape. As a result, the method proposed here combines the benefits of explicit contour and surface models, while also achieving a cornerstone for future work that will emphasize shape statistics, static collision with other critical structures, and tree-shape analysis.