Delayed Postoperative Intracerebral Hemorrhage Associated With Oral Multikinase Inhibitor Therapy for Cancer: A Case Report.

Regorafenib is a multikinase inhibitor with anti-vascular endothelial growth factor receptor (VEGF) activity used as an antiangiogenic agent for metastatic colorectal cancer treatment and has been studied as a potential therapeutic agent for several other cancer treatments. Adverse reactions commonly reported with the use of regorafenib and similar oral multikinase inhibitors include hemorrhage, gastrointestinal fistulas, hypertension, and incomplete wound healing. We report a case of a 59-year-old man with metastatic colorectal adenocarcinoma post-colostomy on regorafenib treatment presenting to the emergency department with altered mental status. MRI showed a left frontoparietal mass, which was resected with a left frontal craniotomy. Postoperative MRI showed a resection cavity without significant hemorrhage. He had been prescribed regorafenib preceding his hospitalization, which was continued after admission before surgery and on postoperative day 1. Thirty-two hours after surgery, the patient exhibited sudden right-sided facial droop and right arm weakness. Imaging revealed an acute intraparenchymal hemorrhage within and adjacent to the tumor resection bed, which was managed conservatively. The patient was subsequently discharged to an inpatient rehabilitation facility. The unusual timing of the hemorrhage suggests that the hemorrhage was due to adverse effects of regorafenib. Patients undergoing neurosurgery should have regorafenib discontinued in preparation for surgery. Similar management should be considered for other anti-VEGF medications to avoid serious complications.

Availability and utilization of molecular testing for primary central nervous system tumors among US hospitals.

Advanced molecular testing has increasingly become an integral component for accurate diagnosis of central nervous system (CNS) tumors. We sought to establish the current state of molecular testing availability and approaches for the diagnosis of CNS tumors in US hospitals that conduct high volumes of CNS tumor resections. We distributed a 16-item survey inquiring about molecular testing approaches for CNS tumors to 115 neuropathologists at US hospitals with neurosurgery residency programs. Thirty-five neuropathologists (30.4%) responded to the survey, all of whom indicated their institutions perform molecular testing on CNS tumor tissue. The most commonly offered tests were MGMT methylation profiling and next-generation sequencing. Fourteen respondents (40%) indicated that their institution is able to test for and report all of the molecular alterations included in our survey. Nine (25.7%) respondents indicated that molecular testing is performed as standard of care for all patients with resected CNS tumors. Our results suggest that even in academic hospitals with a high volume of CNS tumor resections, molecular testing for these tumors is limited. Continued initiatives are necessary to expand the availability of molecular testing for CNS tumors to ensure diagnostic accuracy and guide targeted therapy.

Hemimegalencephaly: A Systematic Comparison of Functional and Anatomic Hemispherectomy for Drug-Resistant Epilepsy.

BACKGROUND AND OBJECTIVES: Hemimegalencephaly (HME) is a rare diffuse malformation of cortical development characterized by unihemispheric hypertrophy, drug-resistant epilepsy (DRE), hemiparesis, and developmental delay. Definitive treatment for HME-related DRE is hemispheric surgery through either anatomic (AH) or functional hemispherectomy (FH). This individual patient data meta-analysis assessed seizure outcomes of AH and FH for HME with pharmacoresistant epilepsy, predictors of Engel I, and efficacy of different FH approaches. METHODS: PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature were searched from inception to Jan 13th, 2023, for primary literature reporting seizure outcomes in >3 patients with HME receiving AH or FH. Demographics, neurophysiology findings, and Engel outcome at the last follow-up were extracted. Postsurgical seizure outcomes were compared through 2-tailed t -test and Fisher exact test. Univariate and multivariate Cox regression analyses were performed to identify independent predictors of Engel I outcome. RESULTS: Data from 145 patients were extracted from 26 studies, of which 89 underwent FH (22 vertical, 33 lateral), 47 underwent AH, and 9 received an unspecified hemispherectomy with a median last follow-up of 44.0 months (FH cohort) and 45.0 months (AH cohort). Cohorts were similar in preoperative characteristics and at the last follow-up; 77% (n = 66) of the FH cohort and 81% (n = 38) and of the AH cohort were Engel I. On multivariate analysis, only the presence of bilateral ictal electroencephalography abnormalities (hazard ratio = 11.5; P = .002) was significantly associated with faster time-to-seizure recurrence. A number-needed-to-treat analysis to prevent 1 additional case of posthemispherectomy hydrocephalus reveals that FH, compared with AH, was 3. There was no statistical significance for any differences in time-to-seizure recurrence between lateral and vertical FH approaches (hazard ratio = 2.59; P = .101). CONCLUSION: We show that hemispheric surgery is a highly effective treatment for HME-related DRE. Unilateral ictal electroencephalography changes and using the FH approach as initial surgical management may result in better outcomes due to significantly lower posthemispherectomy hydrocephalus probability. However, larger HME registries are needed to further delineate the predictors of seizure outcomes.

Seizure outcomes in children with Sturge-Weber syndrome undergoing epilepsy surgery: An individual participant data meta-analysis.

BACKGROUND: A subpopulation of patients with Sturge-Weber syndrome (SWS) develop medically intractable epilepsy. There is a paucity of literature on preoperative factors that predict postoperative seizure outcomes in these patients. An individual participant data meta-analysis (IPDMA) was performed to discern preoperative variables associated with favorable seizure outcomes in pediatric SWS patients undergoing epilepsy surgery. METHODS: PubMed, Cochrane, Web of Science, and Scopus were independently queried following PRISMA guidelines. Studies that reported seizure outcomes in individual pediatric SWS patients were selected. Preoperative demographic variables and disease characteristics were recorded and evaluated in a time-to-event fashion via Cox regression and Kaplan-Meier analysis with log-rank test. RESULTS: A total of 18 studies with 108 patients were included for meta-analysis. Median age at seizure onset was 4.5 months, and 85 patients (78.7%) were seizure-free at last follow-up (median: 72 months). On multivariable Cox regression, no variables were independent predictors of post-operative seizure freedom duration, including the extent of hemispheric resection. There were also no differences in time-to-seizure recurrence on Kaplan-Meier analysis when comparing those treated with hemispheric surgery and those with less than hemispheric surgery (p = 0.52). CONCLUSION: This IPDMA showed that both resective and hemispheric epilepsy surgery achieve favorable and comparable seizure outcomes in pediatric SWS patients. The best available evidence using IPD suggests that resective surgery may be an appropriate alternative to hemispheric epilepsy surgery in well-selected patients. Prospective multi-institutional studies with greater follow-up are warranted to further investigate predictors of seizure outcome in pediatric SWS patients.

Thyroid hormone receptor beta mutations alter photoreceptor development and function in Danio rerio (zebrafish).

We investigate mutations in trß2, a splice variant of thrb, identifying changes in function, structure, and behavior in larval and adult zebrafish retinas. Two N-terminus CRISPR mutants were identified. The first is a 6BP+1 insertion deletion frameshift resulting in a truncated protein. The second is a 3BP in frame deletion with intact binding domains. ERG recordings of isolated cone signals showed that the 6BP+1 mutants did not respond to red wavelengths of light while the 3BP mutants did respond. 6BP+1 mutants lacked optomotor and optokinetic responses to red/black and green/black contrasts. Both larval and adult 6BP+1 mutants exhibit a loss of red-cone contribution to the ERG and an increase in UV-cone contribution. Transgenic reporters show loss of cone trß2 activation in the 6BP+1 mutant but increase in the density of cones with active blue, green, and UV opsin genes. Antibody reactivity for red-cone LWS1 and LWS2 opsin was absent in the 6BP+1 mutant, as was reactivity for arrestin3a. Our results confirm a critical role for trß2 in long-wavelength cone development.