Seizures are a frequent complication of adult-type diffuse gliomas, and are often difficult to control with medications. Gliomas with mutations in isocitrate dehydrogenase 1 or 2 (IDHmut) are more ...likely than IDH-wild type (IDHwt) gliomas to cause seizures as part of their initial clinical presentation. However, whether IDHmut is also associated with seizures during the remaining disease course, and whether IDHmut inhibitors can reduce seizure risk, are unclear. Clinical multivariable analyses showed that preoperative seizures, glioma location, extent of resection, and glioma molecular subtype (including IDHmut status) all contributed to postoperative seizure risk in adult-type diffuse glioma patients, and that postoperative seizures were often associated with tumor recurrence. Experimentally, the metabolic product of IDHmut, d-2-hydroxyglutarate, rapidly synchronized neuronal spike firing in a seizure-like manner, but only when non-neoplastic glial cells were present. In vitro and in vivo models recapitulated IDHmut glioma-associated seizures, and IDHmut inhibitors currently being evaluated in glioma clinical trials inhibited seizures in those models, independent of their effects on glioma growth. These data show that postoperative seizure risk in adult-type diffuse gliomas varies in large part by molecular subtype, and that IDHmut inhibitors could play a key role in mitigating such risk in IDHmut glioma patients.
•This is a case report of severe diffuse cranial hyperostosis.•Hyperostosis associated with cortical herniation into the posterior fossa.•Chronic herniation of the mesial temporal lobe manifested as ...impaired delayed short-term memory.
This case report discusses an incident of cranial hyperostosis that was discovered after an episode of syncope on imaging. A CT and MRI work-up revealed intracranial volume loss and cerebral herniation into the posterior fossa. Concomitant with the episode of syncope, the patient presented with deficits in delayed short-term memory, which was supported using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) test. As far as we are aware, this is the first report of severe memory dysfunction stemming from chronic herniation of the mesial temporal lobe due to severe hyperostosis. Hyperostosis has been shown to manifest as a wide variety of symptoms, but the delayed short-term memory impairment observed in this case is completely novel.
The authors present the case of a patient who after undergoing craniotomy for glioblastoma resection was found to have gliosarcoma recurrence in the subdural space without intraparenchymal ...recurrence. A 74-year old man originally presented with the first seizure of his life and was found to have a right temporal glioblastoma multiforme. He underwent craniotomy and adjuvant chemotherapy and radiation therapy. Five months later, he presented with what was to be presumed to be a right subdural hematoma found on surveillance imaging. After expanding on repeat imaging, the patient was electively taken for burr hole evacuation, however intraoperatively thickened membranes were encountered leading to craniotomy and resection of lesion with pathology consistent with gliosarcoma. What we describe is novel because not only was there rare subdural spread of previously resected glioblastoma observed, but also transformation to the more aggressive tumor of gliosarcoma. Thus, we add to the body of literature and evidence to the clinical consideration of glioma as a rare cause of non-traumatic subdural collection. Specifically in a population of patients who have already undergone glioma resections, work up of subdural collections should include contrasted MRI beyond CT. The treatment paradigm does not change in this presentation of glioma recurrence. Surgical decompression and resection to alleviate brain compression, followed by adjuvant chemotherapy and radiation.
•We present the case of subdural spread of previously resected glioblastoma.•Patient presented with what was thought to be asymptomatic subdural hematoma.•Final pathology from craniotomy and evacuation was consistent with gliosarcoma.
Seizures are a frequent complication of adult-type diffuse gliomas, and are often difficult to control with medications. Gliomas with mutations in isocitrate dehydrogenase 1 or 2 (IDHmut) are more ...likely than IDH-wild type (IDHwt) gliomas to cause seizures as part of their initial clinical presentation. However, whether IDHmut is also associated with seizures during the remaining disease course, and whether IDHmut inhibitors can reduce seizure risk, are unclear. Clinical multivariable analyses showed that preoperative seizures, glioma location, extent of resection, and glioma molecular subtype (including IDHmut status) all contributed to postoperative seizure risk in adult-type diffuse glioma patients, and that postoperative seizures were often associated with tumor recurrence. Experimentally, the metabolic product of IDHmut, D-2-hydroxyglutarate, rapidly synchronized neuronal spike firing in a seizure-like manner, but only when non-neoplastic glial cells were present. In vitro and in vivo models recapitulated IDHmut glioma-associated seizures, and IDHmut inhibitors currently being evaluated in glioma clinical trials inhibited seizures in those models, independent of their effects on glioma growth. These data show that postoperative seizure risk in adult-type diffuse gliomas varies in large part by molecular subtype, and that IDHmut inhibitors could play a key role in mitigating such risk in IDHmut glioma patients.
Although typically benign, trigeminal schwannomas (TS) may require surgical resection when large or symptomatic and can cause significant morbidity. This study aims to summarize the literature and ...synthesize outcomes following surgical resection of TS. A systematic review was performed according to PRISMA guidelines. Data extracted included patient and tumor characteristics, surgical approaches, and postoperative outcomes. Odds ratios (OR) with corresponding 95% confidence intervals (CI) were used for outcome analysis. The initial search yielded 1838 results, of which 26 studies with 974 patients undergoing surgical resection of TS were included. The mean age was 42.9 years and 58.0% were female. The mean tumor diameter was 4.7 cm, with Samii type A, B, C, and D tumors corresponding to 33.4%, 15.8%, 37.2%, and 13.6%, respectively. Over a mean symptom duration of 29 months, patients presented with trigeminal hypesthesia (58.7%), headache (32.8%), trigeminal motor weakness (22.8%), facial pain (21.3%), ataxia (19.4%), diplopia (18.7%), and visual impairment (12.0%). Surgical approaches included supratentorial (61.4%), infratentorial (15.0%), endoscopic (8.6%), combined/staged (5.3%), and anterior (5.7%) or posterior (4.0%) petrosectomy. Postoperative improvement of facial pain (83.9%) was significantly greater than trigeminal motor weakness (33.0%) or hypesthesia (29.4%). The extent of resection (EOR) was reported as gross total (GTR), near total, and subtotal in 77.7%, 7.7%, and 14.6% of cases, respectively. Over a mean follow-up time of 62.6 months, recurrence/progression was noted in 7.4% of patients at a mean time to recurrence of 44.9 months. Patients with GTR had statistically significantly lower odds of recurrence/progression (OR: 0.07; 95% CI: 0.04–0.15) compared to patients with non-GTR. This systematic review and meta-analysis report patient outcomes following surgical resection of TS. EOR was found to be an important predictor of the risk of recurrence. Facial pain was more likely to improve postoperatively than facial hypesthesia. This work reports baseline rates of post-operative complications across studies, establishing benchmarks for neurosurgeons innovating and working to improve surgical outcomes for TS patients.
Abstract
Tumor-associated epilepsy (TAE) is a frequent complication of diffusely infiltrative gliomas, and impairs quality-of-life. We previously showed that isocitrate dehydrogenase 1 mutant ...(IDHmut) gliomas were associated with preoperative seizures, and that D2HG increased synchronized bursts in cultured neurons (PMID: 28404805). But the mechanism whereby this occurs, whether IDHmut inhibitors can block this, and whether seizure risk varies by IDHmut status post-operatively, are unknown. We discovered that exogenous 3 mM D2HG had a 150% greater effect on the firing rate of cultured mouse cortical neurons when nonneoplastic glia cells were present versus when they were absent (P=0.002). Coculture with patient-derived IDHmut glioma cells increased the firing rate of human cortical neuron/astrocyte spheroids by up to 272%, and the IDHmut inhibitor AG881 reduced the excitatory effect of IDHmut glioma cells on spheroids by 79% (P=0.0008). Using a novel in vivo model of TAE, wherein EEG recordings were taken of immunocompetent mice engrafted with isogenic mouse glioma lines (NRAS/ATRX/TP53mut ± IDHmut), we found that IDHmut gliomas produced 7.6-fold more epileptiform spikes than IDHwt gliomas (P=0.004). RNA-Seq analysis of the peritumoral mouse brain tissue showed that this increase in spikes was associated with significantly increased expression of key genes known to be upregulated in epilepsy, including SLC12A5, THSB1, VEGFA, FOSL2, and SYNPO. Treatment with 5 mg/kg AG881 by daily oral gavage reduced those spikes in IDHmut-engrafted mice by 51% within three days (P=0.027), whereas vehicle control had no effect (P=0.33). Among 247 patients with grade 2–4 adult-type diffuse gliomas, multivariable time-to-event analysis showed that post-operative seizure risk was positively associated with pre-operative seizures, subtotal resection, and IDHmut astrocytoma. Together, these data show that (i) the D2HG product of IDHmut gliomas increases neuronal excitation in a glial-dependent manner; (ii) IDHmut also affects post-operative seizure risk; (iii) IDHmut inhibitors may improve TAE control.
: Placenta accreta spectrum (PAS) disorders are placental conditions associated with significant maternal morbidity and mortality. While antenatal vaginal bleeding in the setting of PAS is common, ...the implications of this on overall outcomes remain unknown. Our primary objective was to identify the implications of antenatal vaginal bleeding in the setting of suspected PAS on both maternal and fetal outcomes.
: We performed a case-control study of patients referred to our PAS center of excellence delivered by cesarean hysterectomy from 2012 to 2022. Subsequently, antenatal vaginal bleeding episodes were quantified, and components of maternal morbidity were assessed. A maternal composite of surgical morbidity was utilized, comprised of blood loss ≥ 2 L, transfusion ≥ 4 units of blood, intensive care unit (ICU) admission, and post-operative length of stay ≥ 4 days.
: During the time period, 135 cases of confirmed PAS were managed by cesarean hysterectomy. A total of 61/135 (45.2%) had at least one episode of bleeding antenatally, and 36 (59%) of these had two or more bleeding episodes. Increasing episodes of antenatal vaginal bleeding were associated with emergent delivery (
< 0.01), delivery at an earlier gestational age (35 vs. 34 vs. 33 weeks,
< 0.01), and increased composite maternal morbidity (76, 84, and 94%,
= 0.03).
: Antenatal vaginal bleeding in the setting of PAS is associated with increased emergent deliveries, earlier gestational ages, and maternal composite morbidity. This important antenatal event may aid in not only counseling patients but also in the coordination of multidisciplinary teams caring for these complex patients.
In this manuscript, we introduce and benchmark Mandalorion v4.1 for the identification and quantification of full-length transcriptome sequencing reads. It further improves upon the already strong ...performance of Mandalorion v3.6 used in the LRGASP consortium challenge. By processing real and simulated data, we show three main features of Mandalorion: first, Mandalorion-based isoform identification has very high precision and maintains high recall even in the absence of any genome annotation. Second, isoform read counts as quantified by Mandalorion show a high correlation with simulated read counts. Third, isoforms identified by Mandalorion closely reflect the full-length transcriptome sequencing data sets they are based on.
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