Carlstrom, Lucas P.

2053 Background: Current methods for glioma treatment response assessment are limited. This study aimed to assess the technical and clinical feasibility of molecular profiling using intracranial CSF from patients with gliomas during their disease course. Methods: Adults with gliomas were recruited for longitudinal intracranial CSF collection using 1) Ommaya reservoirs, from which CSF would be sampled on at least two separate occasions, or 2) CSF collection from other clinically indicated CSF access devices, such as ventriculoperitoneal (VP) shunts. Patients were followed until their last visit or present time for ongoing participants. For this initial cfDNA feasibility study, CSF was collected from Ommaya reservoirs in four patients and from an existing VP shunt in one patient. cfDNA was then extracted and analyzed using two sequencing platforms, PredicineCARE for cancer variant profiling and PredicineSCORE for low-pass whole genome sequencing (LP-WGS). This analysis generated genomic aberration profiles and genome-wide copy number burden (CNB) score. Results: Five patients (2 females, 3 males; median age: 40 years, range 32-64 years) underwent longitudinal intracranial CSF collection via Ommaya reservoirs (n=4) or VP shunt (n=1). In total, thirty-five CSF samples were obtained (median volume: 3.80 mL; 0.5-5 mL), with 30 samples (85.7%) yielding sufficient cfDNA for variant profiling and LP-WGS. Our initial findings suggest that tumor fraction increased by 6.28x and 2.87x with radiographic progression in two patients. Tumor fraction decreased by 0.08x and 0.04x in two patients with paired immediate pre-versus-post chemoradiation samples. Despite ongoing pseudoprogression in one patient, tumor fraction decreased to unmeasurable levels from a post-resection baseline of 0.26. Patient-specific tumor-associated variant allelic frequencies (VAFs), including TP53, PTEN, TERT, and CDKN2A/B, decreased within individual patients after resection and chemoradiation. In two patients with isocitrate dehydrogenase (IDH) mutant gliomas, decreasing IDH1 VAF after resection correlated with decreased CSF D-2-hydroxyglutarate (D-2-HG) levels (0.64x and 0.62x, respectively, for the first patient, and 0.01x and 0.07x for the other patient). Both CSF IDH1 VAF and CSF D-2-HG increased in the patient who had radiographic progression (2.56x and 9.21x, respectively). Moreover, CNB decreased below the limit of quantification during treatment and increased above the limit at progression. Conclusions: Longitudinal CSF cfDNA can feasibly be obtained via CSF access devices in patients with gliomas during their disease course. Ongoing studies will evaluate hypotheses generated in this case series regarding how longitudinal CSF cfDNA could be utilized to sensitively detect changes in disease burden. Clinical trial information: NCT04692337 ; NCT04692324 .

Abstract Background Cadaveric dissection remains a preferred and irreplaceable learning modality among neurosurgery residents. We aimed to develop and describe a tiered, quantifiable, and practical curriculum for cranial neurosurgical anatomy education. We report the structure and evaluation of our 2-year pilot study to serve as a suggested guide for other neurosurgery programs. Methods Our Complex Cranial Dissection Program is tailored to the needs of junior-level neurosurgery residents based on their postgraduation years 1 to 4. Dissections are performed in a sequential manner, each of which emphasize a particular set of manual skills and neuroanatomical knowledge. Dissections are scored on a scale of 10 points. The grading was based on specific landmarks and anatomical structures, which need to be exposed, explored, and preserved. Results Out of 16 residents, 14 individuals (87.5%) attended the dissections in the first iteration of the program and 16 individuals (100%) attended the dissections in the second iteration. A total of 17 dissections were performed across all years. In survey feedback about the program, 100% (Year 1) and 94% (Year 2) of residents considered the assigned dissections to be appropriate for their respective training levels. Further, 100% (Year 1) and 94% (Year 2) of residents endorsed that the dissections were important and helpful for their practice prior to similar operating room experiences. Conclusion The development and implementation of structured dissection programs within residency training, along with dedicated staff, and objective feedback serve a crucial role in neurosurgical education to further develop and enhance surgical skills in the operative setting.

Abstract Alpha-gal syndrome (AGS) is an immunoglobulin E–mediated hypersensitivity to galatcose-alpha-1,3-galactose (alpha-gal), a carbohydrate compound present in nonprimate mammalian products. Initial exposure to alpha-gal most often occurs through a tick bite, most commonly the lone star tick in the United States. Repeated exposure to alpha-gal may elicit severe allergic reactions, including anaphylaxis. The allergy restricts dietary intake and may significantly impact perioperative risk, as many medications, anesthetics, and intraoperative surgical products utilize bovine or porcine-derived agents, including those containing magnesium stearate, glycerol, and gelatin. Here, we review the perineurosurgical care of two individuals with AGS and highlight pertinent clinical practices and perioperative management of these patients.

Abstract Introduction Skull base neuroanatomy is traditionally learned through two-dimensional anatomical atlases, which while are of unquestionable value, lack the nuanced association of three-dimensional relationships between fundamental anatomical structures relevant to surgical approaches. Surgically focused step-by-step anatomical dissections can augment trainee learning of complex skull base techniques, particularly multistep and nuanced techniques such as translabyrinthine and transcochlear approaches. Methods Translabyrinthine and transcochlear approaches were performed on six sides of three formalin-fixed latex-injected specimens. The study objective was the completion and photo documentation of the steps involved in the approach in order to provide a comprehensive, intelligible, and anatomically oriented resource for multilevel trainees. Illustrative case examples were prepared to supplement approach dissections. Results The translabyrinthine and transcochlear approaches offer unique lateral windows through the temporal bone into the posterior fossa, providing excellent access to pathology at the petrous apex, internal auditory canal, Meckel's cave, and anterolateral brainstem. The transcochlear approach, which is an anterior extension of the translabyrinthine, particularly provides excellent exposure of the prepontine region and clivus. Important surgical considerations include patient position, temporal bone drilling and identification of critical landmarks, dural opening and identification of neurovascular structures, and reconstruction/closure techniques. Conclusion The translabyrinthine and transcochlear approaches are fundamental techniques for lateral skull base and posterior fossa pathologies. Both approaches are hearing-sacrificing but often require minimal to no cerebellar retraction and deliver unique visualization of prepontine neurovascular structures. This step-by-step approach guide provides a unique practical and high-yield surgically oriented learning resource for neurosurgery and otolaryngology trainees.

AbstractHemifacial spasm is a neuromuscular disorder caused by compression of the facial nerve at the nerve root entry zone, often due to ectatic or aberrant vasculature. Pathologic compression of the nerve–brainstem interface results in involuntary, paroxysmal contractions of ipsilateral facial muscles that may cause considerable impairments in quality of life. For those with severe symptoms, have positive imaging demonstrating vascular compression, or who fail other management modalities,1 2 3 4 microvascular decompression offers potential definitive treatment.5 6 Traditionally, nonabsorbable packing agent is used to pack between the nerve and offending vascular structure. However, for large and more complex arterial structures, simple nonabsorbable padding is often not sufficient.In this operative video, we demonstrate microvascular decompression for intractable hemifacial spasm in a 52-year-old female using a specialized sling tacked to the petrous dura for management of a large, ectatic vertebral artery. Following a standard left retrosigmoid craniotomy, an atheromatous ectatic vertebral artery was identified. We fashioned a bovine pericardium sling around the vessel and used a permanent aneurysm clip to secure it to an incision portion of petrous dura. We subsequently identified potential additional facial nerve root compression by anterior inferior cerebellar artery (AICA) and posterior inferior cerebellar artery (PICA) branches, which were elevated and secured using Teflon felt packing. Following elevation of all three vessels, the lateral spread response resolved. At 2 weeks postoperatively, the patient reported substantial relief in her hemifacial spasms and endorsed highly improved quality of life.

Abstract Cerebrospinal fluid (CSF) is emerging as an abundant source of candidate biomarkers, including proteins, for gliomas. Longitudinal CSF access may enable insights into treatment response and resistance. To that end, we have established a growing biobank of CSF samples, many of which have been obtained longitudinally via CSF access devices, such as Ommaya reservoirs, through our ongoing biomarker discovery clinical trials (NCT04692337, 04692324). We have previously presented our initial data demonstrating a conserved proteomic signature of HGG that decreased with resection and increased with recurrence. Since then, samples have been acquired throughout individual patients’ treatment course toward our goal of identifying CSF-derived biomarkers of treatment response. CSF samples obtained prior to, during, and throughout treatment underwent global proteomics analysis via the SomaScan® assay by Somalogic. Fold-changes for each protein were calculated between different timepoints and ranked for each comparison of interest. Treatment with pembrolizumab alone results in increased IL-23 (5.01x), IL-12 (4.25x), lymphocyte activation gene 3 protein (LAG3) (3.26x), and granzyme A (2.93x), suggesting potential for combination with multiple agents. Chemoradiation, with or without pembrolizumab, consistently downregulated NAD kinase, acetyl CoA transferase, and Bcl-2 and upregulated proteins related to neuronal signaling, such as neurexins and cerebellins, in addition to LAG-3, suggesting potential for synergy between chemoradiation and anti-LAG-3 antibodies currently in clinical trials. Interestingly, pembrolizumab and chemoradiation decreased MMP-12 and MMP-9 abundance as compared to chemoradiation alone (0.25x vs. 18.5x; 0.54x vs. 4.99x). Finally, bevacizumab treatment consistently increased VEGF-A (7.32x), VEGF-B (2.21x), and MMP-3 (2.99x) abundance, while decreasing the presence of our previously reported plasma-associated protein signature in CSF. In conclusion, the global CSF proteome can be longitudinally accessed to evaluate response to standard-of-care and experimental therapies. Further studies are ongoing to identify signatures of therapeutic resistance and to assess the impact of novel immunotherapeutic combinations on the CSF proteome.

OBJECTIVE The authors report a single-surgeon experience with anterior clinoid meningiomas (ACMs) and propose a novel scoring system to predict visual outcomes based on preoperative risk factors. METHODS A cohort study of all ACMs that were surgically treated by a single surgeon between 2003 and 2021 was performed. Visual function was assessed by an ophthalmologist pre- and postoperatively. Based on the combination of visual fields and visual acuity, 4 visual grades were described. Favorable visual outcomes were defined as mild visual deficit or intact vision postoperatively. Unfavorable visual outcomes were defined as a severe or moderate visual deficit. Predictors of unfavorable visual outcomes were identified using multivariable logistic regression analysis. A scoring system was then created using the resulting β coefficient. A receiver operating characteristic curve analysis was performed to identify a cutoff point on the grading score for stratifying patients at risk for unfavorable visual outcomes. RESULTS Fifty-two patients met all inclusion criteria. Twenty-five (48%) patients presented with intact vision, and 27 (51%) presented with some visual dysfunction. Postoperative favorable visual outcomes were achieved in 39 patients (75%). Among the 27 patients presenting with visual dysfunction, 14 (52%) experienced improvement after surgery. No new visual deficits were observed among the 25 patients with intact vision at baseline. Nine patients (17%) had a reversible complication. Multivariable analysis showed that severe preoperative visual deficit (OR 13.03, 95% CI 2.64–64.39; p = 0.002), radiographic evidence of optic nerve (ON) encasement (OR 4.20, 95% CI 1.06–16.61; p = 0.04), intraoperative evidence of ON invasion (OR 17.31, 95% CI 2.91–102.86; p = 0.002), an average ganglion cell layer thickness of ≤ 70 µm (OR 21.54, 95% CI 2.94–159.04; p = 0.003), and an average retinal nerve fiber layer thickness of ≤ 80 µm (OR 13.68, 95% CI 1.91–98.00; p = 0.009) were associated with unfavorable visual outcome. The predictive score included the following factors: abnormal optical coherence tomography (OCT) findings, radiographic evidence of ON encasement by the tumor, and severe preoperative visual deficit. A score ≥ 4 of 6 points was demonstrated to be the cutoff associated with unfavorable visual outcome, with a sensitivity of 80%, specificity of 88%, positive predictive value of 80%, negative predictive value of 88%, and area under the curve of 0.847 (95% CI 0.674–1.0; p = 0.003). CONCLUSIONS The authors have designed a practical and novel scoring system to predict visual outcomes in patients with ACMs. This scoring system may guide preoperative discussions with patients and timely surgical intervention to yield optimal visual function outcomes. Although most patients have excellent neurosurgical outcomes, severe baseline visual deficits, ON encasement, and characteristic OCT abnormalities are associated with unfavorable visual function after ACM resection.