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Supplementary Methods. Supplementary Table S1: Baseline characteristics of PCNSL Patients. Supplementary Table S2: Baseline characteristics of SCNSL patients. Supplementary Table S3: Corticosteroid use. Supplementary Table S4: Genes with Recurrent Mutations in PCNSL (non-aSHM). Supplementary Table S5: Genes that are targeted by aSHM in PCNSL. Supplementary Table S6: Comparison of mutation prevalence in current PCNSL genomic landscape analysis (red) with prior studies in PCNSL and DLBCL. Supplementary Table S7: Gene set enrichment analysis of CD79B-mutant PCNSLs compared to CD79B-wildtype PCNSLs. Supplementary Figure S1: Ibrutinib concentrations in Cerebrospinal Fluid (CSF). Supplementary Figure S2: Comparison of mutation frequencies in PCNSL and DLBCL outside the CNS. Supplementary Figure S3: Cell-of-origin (COO) Markers in PCNSL. Supplementary Figure S4: CD79B-mutant PCNSL xenograft models. Supplementary Figure S5: Comparison of PCNSL cells with non-CNS DLBCL cell lines. Supplementary Figure S6: Inhibition of individual PI3K isoforms does not induce cell death in CD79B-mutant PCNSL cells. Supplementary Figure S7: In-vitro effects of ibrutinib on CD79B-mutant PCNSL cells.

IntroductionCerebral aneurysms located along the internal carotid artery at the origin of the ophthalmic artery can be treated through open surgery or endovascular technique. The former affords more certainty of aneurysm obliteration, while the latter poses less risk to vision. Flow diversion is an increasingly accepted treatment for side-wall carotid aneurysms, although location at the branch point of the ophthalmic artery is known to moderate occlusion outcomes.Case presentationWe present a case of a middle-aged female patient with a morphologically irregular 4-mm ophthalmic artery aneurysm (OphA) and a smaller superior hypophyseal artery (SHA) aneurysm whose successful and uncomplicated obliteration by flow diversion with adjunctive coiling was predicted via a balloon test occlusion (BTO). BTO was employed prior to stent placement to confirm a) ophthalmic artery distal collateralization with external carotid artery (ECA) branches and b) preserved arterial flow in the retina visualized via fundoscopy. At 1 year following angiography, the patient had no postoperative deficits and benefitted from complete occlusion of the OphA and SHA.ConclusionOphAs constitute a complex surgical disease that is historically associated with high visual morbidity. We present a novel advanced endovascular technique of BTO followed by flow diversion with adjunctive coiling that successfully obliterated an OphA while preserving vision.

Background While it is thought that Borden Type I intracranial dural arteriovenous fistula (dAVF) have a benign clinical course, their management remains controversial. Methods A comparative meta-analysis was completed to evaluate the outcomes of intervention verses observation of Borden Type I intracranial dAVF. Outcome measures included: grade progression, worsening symptoms, death due to dAVF, permanent complications other than death, functional independence (mRS 0–2), and rate of death combined with permanent complication, were evaluated. Risk differences (RD) were determined using a random effects model. Results Three comparative studies combined with the authors’ institutional experience resulted in a total of 469 patients, with 279 patients who underwent intervention and 190 who were observed. There was no significant difference in dAVF grade progression between the intervention and observation arms, 1.8% vs. 0.7%, respectively (RD: 0.01, 95% CI: −0.02 to 0.04, P = 0.49), or in symptom progression occurring in 31/279 (11.1%) intervention patients and 11/190 (5.8%) observation patients (RD: 0.03, CI: −0.02 to 0.09, P = 0.28). There was also no significant difference in functional independence on follow up. However, there was a significantly higher risk of dAVF related death, permanent complication from either intervention or dAVF related ICH or stroke in the intervention group (11/279, 3.9%) compared to the observation group (0/190, 0%) (RD: 0.04, CI: 0.1 to 0.06, P = 0.007). Conclusion Intervention of Borden Type I dAVF results in a higher risk of death or permanent complication, which should be strongly considered when deciding on management of these lesions.

Introduction: Hospitals have improved stroke thrombolysis times through rigorous assessment of care delays. While mobile stroke units (MSU) expedite intravenous thrombolysis for acute ischemic stroke, the same rigor has not been applied to this novel setting. Methods: We reviewed all cases of intravenous tissue plasminogen activator (tPA) administration onboard our mobile stroke unit in Rochester, NY since its inception in 2019. The dispatch timeline was divided into six intervals: (1) drive time, (2) onboarding time, (3) HCT collection, (4) HCT reading, (5) decision time, and (6) tPA administration. Cases in which tPA was delayed due to medical contraindications or inability to obtain consent were not included in the analysis. Results: The mean ± SD total time between MSU dispatch and tPA was 42 ± 8.4 min (range: 26-60 min; N = 53). The longest interval was (1) drive time (between dispatch and arrival, 12.0 ± 4.7 min). However, the inter-case variation was greatest in (5) decision time (between HCT reading and treatment decision, 6.3 ± 6.2 min). After ranking cases by total time, the interval that had the widest variance between the first and fourth quartiles was decision time (2.45x). The other intervals varied by a factor of 1.50x for (6) tPA administration and less than 1.00x for the other four intervals. Decision time was the interval most closely correlated with total time (Spearman’s ρ = 0.46; p = 0.00051), which was reduced in our second year of operation (38.8 from 44.6 minutes; Mann-Whitney, Z = 2.38, p = 0.02). Decision time was negatively correlated with time since inception of the MSU (Spearman’s ρ = -0.29, p = 0.037), suggesting that improvements in decision time drove improvements in overall thrombolysis time. Conclusion: The largest driver of variation in total time from emergency alert to tPA administration is provider decision time in our MSU program. This observation should be investigated in other settings but may ultimately inform MSU training and staffing.

Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with NF-κB. The role of BTK in primary central nervous system (CNS) lymphoma (PCNSL) is unknown. We performed a phase I clinical trial with ibrutinib, the first-in-class BTK inhibitor, for patients with relapsed or refractory CNS lymphoma. Clinical responses to ibrutinib occurred in 10 of 13 (77%) patients with PCNSL, including five complete responses. The only PCNSL with complete ibrutinib resistance harbored a mutation within the coiled-coil domain of CARD11, a known ibrutinib resistance mechanism. Incomplete tumor responses were associated with mutations in the B-cell antigen receptor–associated protein CD79B. CD79B-mutant PCNSLs showed enrichment of mammalian target of rapamycin (mTOR)-related gene sets and increased staining with PI3K/mTOR activation markers. Inhibition of the PI3K isoforms p110α/p110δ or mTOR synergized with ibrutinib to induce cell death in CD79B-mutant PCNSL cells. Significance: Ibrutinib has substantial activity in patients with relapsed or refractory B-cell lymphoma of the CNS. Response rates in PCNSL were considerably higher than reported for diffuse large B-cell lymphoma outside the CNS, suggesting a divergent molecular pathogenesis. Combined inhibition of BTK and PI3K/mTOR may augment the ibrutinib response in CD79B-mutant human PCNSLs. Cancer Discov; 7(9); 1018–29. ©2017 AACR. See related commentary by Lakshmanan and Byrd, p. 940. This article is highlighted in the In This Issue feature, p. 920

Common causes of chronic suppurative otitis media (CSOM) include persistence of acute otitis media, cholesteatoma, and eustachian tube dysfunction. We describe a patient who presented with CSOM of several years duration refractory to medical management. Ultimately, a dental abscess was found on computed tomography (CT) to be the source of concurrent ipsilateral maxillary sinusitis and mastoiditis. Extraction of the molar abscess resulted in complete resolution of her CSOM and need to be on antibiotics. To our knowledge, this is the first report of an odontogenic cause of chronic suppurative otitis media.

Background: Primary Ewing’s sarcoma (ES) is typically seen within the long bones, vertebrae, or pelvis. Uncommonly, it can be found within the cranium among the rarest locations for primary ES are the skull base, in particular, the petroclival bone. Case Description: The patient is a 68-year-old female with past medical history of Stage III breast cancer who presented with severe retro-orbital headache and diplopia due to a cranial nerve VI palsy. Magnetic resonance imaging (MRI) revealed a mass at the left petroclival bone with extension into the adjacent left petrous apex and into the posterior aspect of the left cavernous sinus proximal to the carotid artery. The patient subsequently underwent an endoscopic transsphenoidal biopsy. Pathological and molecular analysis supported a diagnosis of ES. The patient then underwent neoadjuvant chemotherapy and radiotherapy. At 12 month-follow-up, her petroclival ES demonstrated significant interval decrease in size on MRI surveillance imaging. Conclusions: This is the third case of primary ES of the petroclival bone to be reported in the literature. In this patient, management consisted of surgical incisional biopsy followed by adjuvant radiation and chemotherapy. Knowledge and awareness of this type of tumor is important for the skull base surgeon.