A survey of preferences and expectations for surgical interventions targeting atonic seizures in Lennox-Gastaut syndrome.

PURPOSE: To assess preferences and outcome expectations for vagus nerve stimulation (VNS) and corpus callosotomy (CC) surgeries in the treatment of atonic seizure in Lennox-Gastaut syndrome (LGS). METHODS: A total of 260 surveys were collected from patients are caregivers of LGS patients via Research Electronic Data Capture (REDCap). RESULTS: Respondents reported an average acceptable atonic seizure reduction rate of 55.9% following VNS and 74.7% following CC. 21.3% (n = 50) were willing to be randomized. Respondents reported low willingness for randomization and a higher seizure reduction expectation with CC. CONCLUSION: Our findings guide surgical approaches for clinicians to consider patient preference in order to design future studies comparing effectiveness between these two procedures.

The Utility of Responsive Neurostimulation for the Treatment of Pediatric Drug-Resistant Epilepsy.

Drug-resistant epilepsy (DRE) has a strongly negative impact on quality of life, as well as the development of pediatric patients. Surgical treatments have evolved over time, including more invasive craniotomies for resection or disconnection. More recently, neuromodulation techniques have been employed as a less invasive option for patients. Responsive neurostimulation (RNS) is the first closed-loop technology that allows for both treatment and device data collection, which allows for an internal assessment of the efficacy of treatment. This novel technology has been approved in adults and has been used off label in pediatrics. This review seeks to describe this technology, its history, and future directions.

Minimally invasive modification of the Goel-Harms atlantoaxial fusion technique: a case series and illustrative guide.

OBJECTIVE: The Goel-Harms atlantoaxial screw fixation technique for the treatment of atlantoaxial instability and unstable odontoid fractures is reliable and reproducible for a variety of anatomies. The drawbacks of the technique are the potential for significant bleeding from the C2 nerve root venous plexus and the risks associated with posterior midline exposure and retraction, such as pain and wound complications. The authors developed a minimally invasive surgical (MIS) modification of the Goel-Harms technique using intra-articular grafting to facilitate placement of percutaneous lateral mass and pars screws with extended tabs for minimally invasive subfascial rod placement. The objective of this study was to present the authors' first series of 5 patients undergoing minimally invasive modification in comparison with 51 patients undergoing open atlantoaxial fusion. METHODS: A retrospectiveanalysis of patient comorbid conditions, blood loss, length of surgery, and length of stay was performed on patients undergoing Goel-Harms instrumented fusion (GHIF) for unstable odontoid fractures performed between 2016 and 2021. RESULTS: Patients undergoing the minimally invasive procedure showed significantly less blood loss than those undergoing the open atlantoaxial fusion procedure, with a median blood loss of 30 ml compared with 150 ml using the open technique (p < 0.01). The patients showed no significant differences in length of stay (2 days for MIS vs 4 days for open atlantoaxial fusion, p = 0.25). There were no significant differences in length of surgery for MIS, but a possible trend toward increased operative duration (234 vs 151 minutes, p = 0.112). CONCLUSIONS: In this small pilot study, it was shown that MIS-GHIF can be performed with decreased blood loss in atlantoaxial instability and odontoid fractures. This technique may allow for greater and safer application of the procedure in the elderly and infirm.

Association Between Patient Perception of Surgeons and Color of Scrub Attire.

This survey study involves asking participants about their opinions on positive and negative character traits of male and female clinicians dressed in 4 different colors of scrub suits.

Risk factors for proximal junctional kyphosis after pediatric spinal deformity surgery with halo gravity traction.

PURPOSE: To determine risk factors for proximal junctional kyphosis (PJK) in pediatric patients with scoliosis undergoing halo gravity traction (HGT) prior to posterior spinal fusion (PSF). METHODS: Data from consecutive patients who underwent PSF after HGT with 2-year follow-up were retrospectively collected from a single center. Patients were divided into two groups: PJK vs. no PJK. RESULTS: Twenty-five patients (age 13.6 ± 3.1 years) underwent HGT for a mean of 42 ± 37 days. Eight patients (32%) developed radiographic PJK and 1 (4%) developed proximal junctional failure. PJK patients had greater loss of cervical lordosis (-17.4 ± 23.2 vs. 2.7 ± 16.2°, p < 0.05), greater increase in lumbar lordosis (9.3 ± 19.5 vs. -2.8 ± 12.8°; p = 0.034) during traction, and smaller overall major coronal curve angle correction (-16.8 ± 30.6 vs. -36.6 ± 16.4°; p = 0.026). From postoperative to last follow-up, PJK patients had a greater increase in upper end vertebrae (UEV) slope (3.3 ± 7.8 vs. -4.0 ± 7.7°; p = 0.004). Selection of UIV based on which vertebra was most level either pre-traction or in-traction was not associated with PJK development (p > 0.05). CONCLUSION: In-traction radiographic changes of decreased cervical lordosis, decreased major coronal curve, increased lumbar lordosis, and disruption of cervical sagittal balance at last follow-up may have implications for level selection and risk of PJK.

Pediatric Neurosurgery in Primary Care: Masses of the Scalp and Skull in Children.

There are a wide variety of scalp and skull lesions that can affect the pediatric population, many of which are first encountered by primary care physicians. The differential consists of a broad range of more common congenital lesions, sequelae of trauma, and vascular anomalies, to very rare neoplastic processes. It is important to understand signs and symptoms that may indicate whether a lesion may be benign versus life threatening, what imaging studies are appropriate and how to interpret them, and when to seek referrals to specialists.

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.

Potential utility of FLAIR in MRI-negative Cushing's disease.

OBJECTIVE Accurate presurgical localization of microadenomas in Cushing's disease (CD) leads to improved remission rates and decreased adverse events. Volumetric gradient recalled echo (3D-GRE) MRI detects pituitary microadenomas in CD in up to 50%-80% cases as a focus of hypointensity due to delayed contrast wash-in. The authors have previously reported that postcontrast FLAIR imaging may be useful in detecting otherwise MRI-negative pituitary microadenomas as foci of hyperintensity. This reflects theoretically complementary imaging of microadenomas due to delayed contrast washout. The authors report on the diagnostic accuracy and clinical utility of FLAIR imaging in the detection of microadenomas in patients with CD. METHODS The authors prospectively analyzed imaging findings in 23 patients (24 tumors) with biochemically proven CD who underwent transsphenoidal surgery for CD. Preoperatively, the patients underwent pituitary MRI with postcontrast FLAIR and postcontrast 3D-GRE sequences. RESULTS Postcontrast FLAIR hyperintensity was detected in macroadenomas, and in 3D-GRE-positive or -negative microadenomas. Overall, 3D-GRE was superior in detecting surgically and histopathologically confirmed, location-concordant microadenomas. Of 24 pituitary adenomas, 18 (75%; sensitivity 82%, positive predictive value 95%) were found on 3D-GRE, and 13 (50% [1 was false positive]; sensitivity 55%, positive predictive value 92%) were correctly identified on FLAIR. The stand-alone specificity of 3D-GRE and FLAIR was similar (50%). These results confirm the superiority of 3D-GRE as a stand-alone imaging modality. The authors then tested the utility of FLAIR as a complementary tool to 3D-GRE imaging. All 5 patients with negative 3D-GRE MRI displayed a distinct focus of FLAIR enhancement. Four of those 5 cases (80%) had location-concordant positive histopathological results and achieved postsurgical biochemical remission. The remaining patient was not cured, because resection did not include the region of FLAIR hyperintensity. CONCLUSIONS This study suggests that delayed microadenoma contrast washout may be detected as FLAIR hyperintensity in otherwise MRI-negative CD cases. The authors propose adding postcontrast FLAIR sequences to complement 3D-GRE for surgical planning in patients with CD. Clinical trial registration no.: NIH protocol 03-N-0164, NCT00060541 (clinicaltrials.gov).

Somatostatin receptor expression on von Hippel-Lindau-associated hemangioblastomas offers novel therapeutic target.

Von Hippel-Lindau (VHL)-associated hemangioblastomas (VHL-HB) arise in the central nervous system (CNS), and are a leading cause of morbidity and mortality in VHL disease. Currently, surgical resection is the most effective way to manage symptomatic VHL-HBs. Surgically unresectable VHL-HBs or those in frail patients are challenging problems. Therapies targeting oncologic and vascular endothelial growth factor (VEGF) pathways have failed to demonstrate tumor control. Our experience and previous reports on VHL-HB avidity to somatostatin analogues suggested somatostatin receptor (SSTR) expression in VHL-HBs, offering an alternative therapeutic strategy. We explored this possibility by demonstrating consistent histologic expression of SSTR1, 2a, 4, and 5 in VHL-HBs. We found that somatostatin analogue octreotide induces apoptosis in VHL-HB stromal cells in a dose-dependent fashion by BAX - caspase-3 pathway unrelated to canonical VHL pathway. When administered to a patient with unresectable symptomatic suprasellar hemangioblastoma, octreotide resulted in tumor volume reduction, symptom stabilization, and tumor cytopenia on repeat 68Ga-DOTA-TATE positron emission tomography (PET) within 6 months, suggesting tumor infarction. We conclude that VHL-HBs harbor multiple SSTR subtypes that offer actionable chemo-therapeutic strategy for management of symptomatic, unresectable tumors by somatostatin analogue therapy.

Simulating vasogenic brain edema using chronic VEGF infusion.

OBJECTIVE To study peritumoral brain edema (PTBE), it is necessary to create a model that accurately simulates vasogenic brain edema (VBE) without introducing a complicated tumor environment. PTBE associated with brain tumors is predominantly a result of vascular endothelial growth factor (VEGF) secreted by brain tumors, and VEGF infusion alone can lead to histological blood-brain barrier (BBB) breakdown in the absence of tumor. VBE is intimately linked to BBB breakdown. The authors sought to establish a model for VBE with chronic infusion of VEGF that can be validated by serial in-vivo MRI and histological findings. METHODS Male Fischer rats (n = 182) underwent stereotactic striatal implantation of MRI-safe brain cannulas for chronic infusion of VEGF (2-20 µg/ml). Following a preinfusion phase (4-6 days), the rats were exposed to VEGF or control rat serum albumin (1.5 µl/hr) for as long as 144 hours. Serial MRI was performed during infusion on a high-field (9.4-T) machine at 12-24, 24-36, 48-72, and 120-144 hours. Rat brains were then collected and histological analysis was performed. RESULTS Control animals and animals infused with 2 µg/ml of VEGF experienced no neurological deficits, seizure activity, or abnormal behavior. Animals treated with VEGF demonstrated a significantly larger volume (42.90 ± 3.842 mm3) of T2 hyper-attenuation at 144 hours when compared with the volume (8.585 ± 1.664 mm3) in control animals (mean difference 34.31 ± 4.187 mm3, p < 0.0001, 95% CI 25.74-42.89 mm3). Postcontrast T1 enhancement in the juxtacanalicular region indicating BBB breakdown was observed in rats undergoing infusion with VEGF. At the later time periods (120-144 hrs) the volume of T1 enhancement (34.97 ± 8.99 mm3) was significantly less compared with the region of edema (p < 0.0001). Histologically, no evidence of necrosis or inflammation was observed with VEGF or control infusion. Immunohistochemical analysis demonstrated astrocyte activation, vascular remodeling, and increased claudin-5 expression in juxtacanalicular regions. Aquaporin-4 expression was increased in both control and VEGF animals in the juxtacanalicular regions. CONCLUSIONS The results of this study show that chronic brain infusion of VEGF creates a reliable model of VBE. This model lacks necrosis and inflammation that are characteristic of previous models of VBE. The model allows for a precise investigation into the mechanism of VBE formation. The authors also anticipate that this model will allow for investigation into the mechanism of glucocorticoid action in abrogating VBE, and to test novel therapeutic strategies targeting PTBE.

Characterization of the blood brain barrier in pediatric central nervous system neoplasms.

OBJECTIVE: The normal blood-brain barrier (BBB) is composed of tight junctions between endothelial cells and surrounding astrocyte foot processes. Breakdown of the physiological astrocyte-endothelial cell relationship occurs in adult metastatic and primary brain tumors. However, the astrocyte-endothelial cell relationship has not been studied in pediatric tumors. MATERIALS AND METHODS: Utilizing specimens from cases of pilocytic astrocytoma (n = 5), medulloblastoma (n = 5), and low-grade diffuse astrocytoma (n = 1), immunofluorescence were performed using primary antibodies against CD31, glial fibrillary acidic protein (GFAP), and aquaporin 4 (AQ4). Clinical, magnetic resonance imaging, operative, and histopathological findings were analyzed. RESULTS: Strongly-enhancing areas of medulloblastoma exhibited complete BBB breakdown with sparse GFAP and AQ4 staining around CD31-positive vessels. Moderately enhancing regions of pilocytic astrocytomas exhibited regions of intact BBB and vasculature surrounded by dense GFAP staining but reduced and disorganized AQ4 staining, suggesting tumor cells could not fulfill physiological BBB support. Non-enhancing low-grade diffuse astrocytoma demonstrated intact BBB with intense peri-microvasculature GFAP and AQ4 staining. AQ4 stained so strongly that AQ4 visualization alone delineated CD31-positive vessels. CONCLUSION: Taken together, BBB breakdown in pediatric tumors corresponds to a loss of normal endothelial cell-astrocyte foot process relationships. Further development of pharmaceutical agents capitalizing on this disrupted BBB is warranted in medulloblastoma and pilocytic astrocytoma. However, BBB integrity remains a challenge in treating low-grade diffuse astrocytoma before progression toward secondary glioblastoma.

Endosphenoidal coil for intraoperative magnetic resonance imaging of the pituitary gland during transsphenoidal surgery.

OBJECTIVE Pituitary MR imaging fails to detect over 50% of microadenomas in Cushing's disease and nearly 80% of cases of dural microinvasion. Surface coils can generate exceptionally high-resolution images of the immediately adjacent tissues. To improve imaging of the pituitary gland, a receive-only surface coil that can be placed within the sphenoid sinus (the endosphenoidal coil [ESC]) during transsphenoidal surgery (TSS) was developed and assessed. METHODS Five cadaver heads were used for preclinical testing of the ESC. The ESC (a double-turn, 12-mm-diameter surface coil made from 1-mm-diameter copper wire) was developed to obtain images in a 1.5-T MR scanner. The ESC was placed (via a standard sublabial TSS approach) on the anterior sella face. Clinical MR scans were obtained using the 8-channel head coil and ESC as the receiver coils. Using the ESC, ultra-high-resolution, 3D, balanced fast field echo (BFFE) and T1-weighted imaging were performed at resolutions of 0.25 × 0.25 × 0.50 mm3 and 0.15 × 0.15 × 0.30 mm3, respectively. RESULTS Region-of-interest analysis indicated a 10-fold increase in the signal-to-noise ratio (SNR) of the pituitary when using the ESC compared with the 8-channel head coil. ESC-related improvements (p < 0.01) in the SNR were inversely proportional to the distance from the ESC tip to the anterior pituitary gland surface. High-resolution BFFE MR imaging obtained using ESC revealed a number of anatomical features critical to pituitary surgery that were not visible on 8-channel MR imaging, including the pituitary capsule, the intercavernous sinus, and microcalcifications in the pars intermedia. These ESC imaging findings were confirmed by the pathological correlation with whole-mount pituitary sections. CONCLUSIONS ESC can significantly improve SNR in the sellar region intraoperatively using current 1.5-T MR imaging platforms. Improvement in SNR can provide images of the sella and surrounding structures with unprecedented resolution. Clinical use of this ESC may allow for MR imaging detection of previously occult pituitary adenomas and identify microscopic invasion of the dura or cavernous sinus.