Brian J Scott

All Publications

• Rapid Peak Cilta-cel Expansion is Associated with Delayed Neurotoxicity in Multiple Myeloma. Blood Hosoya, H., Velayati, A., Dima, D., Jensen, A., Portuguese, A. J., Hovanky, V., Mikkilineni, L., Peres, L. C., Grajales-Cruz, A. F., Homsy, S., Rana, M. S., Cancilla, J., Patil, S., Sahaf, B., Latchford, T., Freeman, C. L., Scott, B. J., Song, K. W., Castaneda-Puglianini, O. A., Khan, H., Dahiya, S., Locke, F. L., Mackall, C. L., Miklos, D. B., Banerjee, R., Hansen, D. K., Alsina, M., Sidana, S. 2026

  Abstract

  The impact of chimeric antigen receptor (CAR)-T cell expansion and persistence on clinical outcomes and treatment-related morbidity in patients with relapsed/refractory multiple myeloma (RRMM) remains incompletely defined, in part due to limited availability of standardized CAR-T cell quantification assays. We evaluated CAR-T cell kinetics and their association with efficacy and toxicity in RRMM patients treated with idecabtagene vicleucel (ide-cel) or ciltacabtagene autoleucel (cilta-cel). Using a uniform flow cytometry-based platform (N=90; cilta-cel, n=54; ide-cel, n=36), we observed significantly greater CAR-T cell expansion with cilta-cel than with ide-cel (median 106 vs 49 cells/uL). Peak CAR-T cell expansion was associated with clinical response in the ide-cel cohort but not with cilta-cel, where rapid and excessive expansion was instead associated with an increased risk of delayed neurotoxicities (DNTs), a complication with potential long-term functional consequences (median peak 1,009 vs 96 cells/uL). To identify clinically accessible biomarkers of CAR-T cell expansion, we analyzed absolute lymphocyte count (ALC) as a surrogate biomarker in a larger multicenter cohort (N=532; cilta-cel, n=256; ide-cel, n=276). Higher peak ALC was significantly associated with the development of DNTs, particularly Parkinsonism after cilta-cel. A peak ALC ³3000/uL - or ³2500/uL following a daily twofold increase - predicted elevated DNT risk (sensitivity 81%, specificity 59%). Together, these findings delineate distinct expansion-toxicity relationships in cilta-cel and ide-cel therapy, establish ALC as a practical, uniformly available surrogate for CAR-T cell expansion, and define quantitative thresholds that may enable early recognition of patients at risk for DNT, informing preemptive strategies to mitigate morbidity following cilta-cel.

  View details for DOI 10.1182/blood.2025032844

  View details for PubMedID 42418682

• Peripheral Nerve Infiltration by CAR T-cells in a Case of Mononeuritis Multiplex after Ciltacabtagene Autoleucel. Blood cell therapy Hosoya, H., Song, K. W., Dyson, K., Dufort, G., Sahaf, B., Rosenberg, A., Sidana, S., Miklos, D., Vogel, H., Fernandez-Pol, S., Muppidi, S., Scott, B., Mikkilineni, L. 2026; 9 (2): 55-59

  Abstract

  Delayed neurological toxicity, distinct from acute immune effector cell-associated neurotoxicity (ICANS), is an emerging complication of ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-targeting CAR T-cell therapy. Peripheral nerve (PN) involvement has been described as cranial nerve palsies or Guillain-Barré-like syndromes, yet the underlying mechanisms remain poorly defined. We describe a case of asymmetric, immune-mediated multifocal PN involvement, clinically resembling autoimmune, T-cell-mediated mononeuritis multiplex (MNM), occurring after cilta-cel therapy. Several months post-infusion, the patient developed progressive asymmetric sensorimotor neuropathy preceded by bilateral facial nerve palsies. Electrodiagnostic studies confirmed multifocal axonal involvement, and nerve biopsy revealed Wallerian degeneration with CD3+ and CAR+ T-cell infiltration in the absence of BCMA expression on neural tissue. These findings suggest that delayed neurotoxicity may arise from immune-mediated, BCMA-independent mechanisms involving off-target tissue inflammation. Although CAR T-cells were detected within the affected nerve tissue, their pathogenic significance remains unclear and may reflect antigen-independent infiltration, immune activation or secondary bystander recruitment in the setting of immune dysregulation. The patient demonstrated marked neurological recovery following corticosteroids and cyclophosphamide, an immunosuppressive regimen modeled on MNM treatment. This case underscores the importance of comprehensive neurodiagnostic evaluation and early immunosuppression in managing delayed, non-ICANS CAR T-cell neurotoxicity.

  View details for DOI 10.31547/bct-2025-027

  View details for PubMedID 42253352

  View details for PubMedCentralID PMC13237437

• Early Steroid and Anakinra Use to Manage Axicabtagene Ciloleucel Toxicity Reduces the Total Duration of CRS and ICANS. Blood advances Wang, W. L., Lee, D., Cheung, E., Jensen, A., Rana, M. S., Goyal, A., Hamilton, M. P., Ghalehsari, N., Latchford, T., Scott, B. J., Mallampet, J., Heng, E., Khan, H., Zarak, M. S., Lohman, C., Sahaf, B., Sidana, S., Weng, W. K., Smith, M., Bharadwaj, S., Frank, M. J., Miklos, D. B., Dahiya, S. 2026

  Abstract

  Axicabtagene ciloleucel (axi-cel) is an effective CAR-T cell therapy for relapsed or refractory (R/R) large B-cell lymphoma (LBCL). Yet, controlling cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) without compromising therapeutic efficacy remains a difficult challenge. In July 2020, our center adopted a toxicity management protocol modified from Cohort 4 of the registrational ZUMA-1 trial, with earlier steroid use and incorporation of anakinra in toxicity management. To evaluate this change, we conducted a retrospective analysis of patients receiving axi-cel for R/R LBCL in the 3L+ setting from January 2018 through April 2023. The outcomes of interest were toxicity incidence/duration, treatment response, CAR-T expansion, and drug/healthcare utilization. Out of the 195 identified patients, the post-change cohort (N = 103) had higher anakinra (22% vs. 5%) and steroid (88% vs. 71%) usage rates than the comparator cohort (N = 92) without increases in cumulative steroid dose. Overall CRS and ICANS rates were similar, with directionally lower severe (grade 3+) ICANS rates in the post-change cohort. A significant reduction in CRS and ICANS duration was observed with the new protocol (adj. est: -0.93 [95% CI: -1.67, -0.19] days and -2.49 [95% CI: -4.96, -0.03] days, respectively). Day 7 CAR-T expansion was lower in the post-change cohort, possibly due to the earlier steroid use. However, efficacy outcomes, ICU admission rates, and hospitalization length were similar between the cohorts. This study supports earlier intervention for CAR-T toxicities and establishes anakinra as a safe and effective alternative toxicity management drug to tocilizumab.

  View details for DOI 10.1182/bloodadvances.2025019031

  View details for PubMedID 41855506

• Prevalence of Patent Foramen Ovale in Solid Organ Cancer Patients with Embolic Stroke - A Case Series. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Lun, R., Shah, P., Teasdale, B., Zamarud, A., Kraler, L., Lansberg, M., Scott, B., Vora, N., Dowlatshahi, D., Siegal, D. M., Albers, G. W. 2026: 108597

  Abstract

  BACKGROUND: Cancer-associated stroke has become increasingly recognized as a subcategory of embolic stroke of undetermined source (ESUS). Paradoxical embolism through a patent foramen ovale (PFO) is frequently cited as a common stroke mechanism in this population, but its prevalence in an ESUS cohort with newly diagnosed cancer is unknown.OBJECTIVE: To determine the prevalence of PFO in patients with solid organ malignancy and ESUS.METHODS: We searched the Stanford Research Repository for adults with solid organ malignancies who suffered a stroke secondary to an anterior circulation large vessel occlusion within 1 year after their cancer diagnosis. Only subjects who had an echocardiogram with bubble study were included. Chart extraction was completed for clinical/radiographic information. We used descriptive statistics to summarize the data.RESULTS: Fifty-five patients were included. Median time from cancer diagnosis to stroke was 65 days (IQR 11-182). The most common primary cancer site was lung (25.5%); 43.6% had metastases; 21/55 (38.2%) transitioned to comfort care during hospitalization. The prevalence of PFO was 20% (11/55). Paradoxical embolism was identified as a likely mechanism of stroke in 5/11 (45%) patients with PFO based on co-occurring venous thromboembolism (VTE). In 4/5 patients, VTE was asymptomatic and diagnosed based on screening studies at presentation.CONCLUSION: The prevalence of PFO among cancer patients with ESUS was 20%, and there was a high (45%) rate of co-occurring VTE. Given the high rates of asymptomatic detection of VTE identified based on screening ultrasounds, these results could support screening for VTE in this population.

  View details for DOI 10.1016/j.jstrokecerebrovasdis.2026.108597

  View details for PubMedID 41730377

• Developing Comprehensive Strategies for Managing Behaviorally Dysregulated Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS) in Patients Undergoing Chimeric Antigen Receptor (CAR) T cell Therapy Latchford, T. M., Davis, B., Scott, B. J., Dahiya, S., Fishman, D., Lahijani, S. ELSEVIER SCIENCE INC. 2026

  View details for Web of Science ID 001708753600078

• Immunotherapies for Central Nervous System Tumors and their Neurologic Complications. Current neurology and neuroscience reports Song, K. W., Scott, B. J. 2026; 26 (1): 7

  Abstract

  To discuss the landscape of immunotherapy trials for central nervous system (CNS) tumors including immune checkpoint inhibitors, vaccine therapies, oncolytic viruses, and chimeric antigen receptor T-cell therapy as well as explore the corresponding spectrum of neurologic toxicities.As more clinical trials are underway in CNS tumors, we are starting to appreciate both the promise of immunotherapy and current limitations. While a subset of patients demonstrate benefit, immunotherapy trials have not transformed CNS tumor outcomes, which prompts the field to consider next generation therapies and combinatorial approaches. In addition, novel toxicities of CNS immunotherapy are being described such as tumor-inflammation associated neurotoxicity. Immunotherapy in CNS tumor is still in its nascent stages and shows early signs of promise. However, immunotherapeutic approaches in CNS tumors need to account for the unique physiology of the CNS and the corresponding neurologic toxicities that are associated with therapies targeting the CNS. Elucidating both will set the stage for advancement of safe and effective immunotherapy for CNS tumors.

  View details for DOI 10.1007/s11910-025-01477-9

  View details for PubMedID 41484655

  View details for PubMedCentralID 5637314

• SINGLE-CELL LANDSCAPE OF B7H3-CAR T THERAPY IN GLIOMA: MECHANISMS OF RESISTANCE AND SIGNATURES OF LONG-TERM RESPONSE Chen, Y., Song, K., Desai, M., Ehlinger, Z., Daghagh, H., Rietberg, S., Feeney, A., Tanner, K., Dyson, K., Stockdale, B., Dhapola, G., Lohman, C., Patil, S., Kuo, A., Good, Z., Prabhu, S., Kong, K., Egeler, E., Beebe, B., Carr, C., Mahdi, J., Bertrand, S., Iv, M., Threlkeld, Z., Charu, V., Tunuguntla, R., Therkelsen, K., Nagpal, S., Monje, M., Scott, B., Li, G., Lim, M., Sotillo, E., Sahaf, B., Ramakrishna, S., Thomas, R., Mackall, C. OXFORD UNIV PRESS INC. 2025: v13

  View details for DOI 10.1093/neuonc/noaf201.0044

  View details for Web of Science ID 001612039700001

• EVALUATION OF B7-H3 IMMUNOHISTOCHEMISTRY IN HIGH-GRADE GLIOMAS FOR CHIMERIC ANTIGEN RECEPTOR T-CELL PREDICTIVE TESTING Dyson, K., Zuraski, C., Solomon, D., Li, G., Stocksdale, B., Song, K., Mahdi, J., Tanner, K., Bertrand, S., Iv, M., Threlkeld, Z., Ramakrishna, S., Sahaf, B., Egeler, E., Tunuguntla, R., Therkelsen, K., Nagpal, S., Lim, M., Monje, M., Scott, B., Mackall, C., Charu, V., Thomas, R. OXFORD UNIV PRESS INC. 2025: v49-v50

  View details for DOI 10.1093/neuonc/noaf201.0195

  View details for Web of Science ID 001613247800006

• Neurotoxicity in central nervous system tumors treated with CAR T cell therapy: a review. Journal of neuro-oncology Mahdi, J., Gust, J. A., Vitanza, N. A., Scott, B., Monje, M., Ronsley, R. 2025; 176 (1): 60

  View details for DOI 10.1007/s11060-025-05251-2

  View details for PubMedID 41171480

  View details for PubMedCentralID 5996391

• Cellular immunotherapies for central nervous system cancers. Neuro-oncology advances Scott, B. J., Monje, M. 2025; 7 (Suppl 4): iv84-iv94

  Abstract

  Cellular Immunotherapies have transformed therapeutic options for individuals with hematologic malignancies over the past 10 years. There are several distinct types of cellular immunotherapies, each with potential applications to CNS cancers. Here, we review cancer cellular therapeutics for cancers of the brain and spinal cord, focusing on the preclinical and clinical studies that have been done in glioblastoma, diffuse intrinsic pontine glioma/diffuse midline glioma, medulloblastoma and lymphoma involving the central nervous system. Numerous potential therapeutic targets have been identified, and several early clinical trials have demonstrated safety and feasibility of administering CAR T and CAR NK cells for intracranial tumors. Addressing mechanisms of treatment failure, while safely and effectively studying the most promising therapies will advance the treatment landscape for these extremely challenging diseases.

  View details for DOI 10.1093/noajnl/vdaf120

  View details for PubMedID 40933036

  View details for PubMedCentralID PMC12418592

• A phase 1 study of B7H3 CAR-T cells administered intracranially in recurrent glioblastoma. Li, G., Stocksdale, B. R., Song, K., Mahdi, J., Tanner, K., Bertrand, S., Iv, M., Threlkeld, Z., Ramakrishna, S., Sahaf, B., Egeler, E., Charu, V., Tunuguntla, R., Therkelsen, K., Nagpal, S., Lim, M., Monje, M., Scott, B., Mackall, C., Thomas, R. LIPPINCOTT WILLIAMS & WILKINS. 2025: 2018

  View details for DOI 10.1200/JCO.2025.43.16_suppl.2018

  View details for Web of Science ID 001509526200001

• CAR T-cell therapy for gliomas. Current opinion in neurology Song, K. W., Scott, B. J. 2024; 37 (6): 672-681

  Abstract

  To review the landscape of chimeric antigen receptor T-cell (CAR T) therapy for gliomas as seen in recently published trials and discuss on-going challenges with new cancer immunotherapy treatments.Given how CAR T therapy has revolutionized the treatment of several hematologic malignancies, there has been increasing interest in using immunotherapy, and particularly CAR T therapy for gliomas. Within the past decade, several first in human trials have published early patient experiences showing treatment is generally well tolerated but with limited efficacy, which may be improving with newer evolutions in CAR T design to overcome known resistance mechanisms in glioma treatment.CAR T therapy is a promising avenue of treatment for high-grade gliomas, which have a universally poor prognosis as well as limited therapeutics. There are a growing number of CAR T clinical trials for CNS tumors and thus, an understanding of their treatment strategies, toxicity management, and overcoming resistance mechanisms will be important for both clinical practice and to identify areas for future research.

  View details for DOI 10.1097/WCO.0000000000001318

  View details for PubMedID 39498846

• Neurohospitalist Core Competencies. The Neurohospitalist Wold, J. J., Robertson, J., Jeevarajan, J. A., Knox, M. G., Thatikunta, P., Solorzano, G. E., Galetta, K., Dujari, S., Goyal, T., Ehrlich, M. E., Donnelly, J. P., Marriott, E., Mandge, V. A., Dhoot, R. S., Luedke, M. W., Maas, M. B., Yu, M. Y., Toledano, M., Mustafa, R., Palaganas, J. L., Kvam, K., Dugue, R., Meltzer, E., Touma, L., Shah, M. P., Douglas, V. C., Orjuela, K., Scott, B. J., Klein, J. P., Likosky, D. J., Simpson, J. R., Richie, M. B., Dohle, C., Morris, J. G., Gold, C. A. 2024: 19418744241297187

  Abstract

  The Neurohospitalist Core Competencies comprise a set of competency-based learning objectives that encapsulate the knowledge, skills, and attitudes of neurohospitalitists who specialize in the care of hospitalized patients with neurologic conditions. These competencies serve to characterize the rapidly expanding field of neurohospitalist medicine. The 27 chapters are divided into 3 sections entitled: neurological conditions, clinical interventions and interpretation of ancillary studies, and neurohospitalist role in the healthcare system. Each individual learning objective in the chapters describes a specific concept with an action verb to illustrate the behavior that the neurohospitalist exhibits. The individual neurohospitalist may not exhibit mastery in each of the topics included as individual practices vary in scope and practice pattern. A few examples of how the complete set of competencies may be used include in the creation of curricula for neurohospitalist fellowships, to assist in defining the scope of practice of neurohospitalists for administrative leaders of hospitals and departments, and in influencing the direction of further research and quality improvement in the field.

  View details for DOI 10.1177/19418744241297187

  View details for PubMedID 39610897

  View details for PubMedCentralID PMC11600417

• TUMOR INFLAMMATION-ASSOCIATED NEUROTOXICITY (TIAN): A TOXICITY SYNDROME IN PATIENTS TREATED WITH IMMUNOTHERAPY FOR CENTRAL NERVOUS SYSTEM TUMORS Mahdi, J., Dietrich, J., Straathof, K., Roddie, C., Scott, B. J., Davidson, T., Prolo, L., Batchelor, T. T., Campen, C. J., Davis, K. L., Gust, J., Lim, M., Majzner, R. G., Park, J. R., Partap, S., Ramakrishna, S., Richards, R., Schultz, L., Vitanza, N. A., Wang, L. D., Mackall, C. L., Monje, M. OXFORD UNIV PRESS INC. 2024

  View details for DOI 10.1093/neuonc/noae064.384

  View details for Web of Science ID 001252720000574

• Education Research: Educational Outcomes Associated With the Introduction of a Neurohospitalist Program. Neurology. Education Dujari, S., Scott, B. J., Gold, C. A., Weng, Y., Kvam, K. A. 2024; 3 (2): e200131

  Abstract

  Background and Objectives: As the prevalence of the neurohospitalist (NH) practice model grows, understanding its effect on trainee education is imperative. We sought to determine the impact of an academic NH program on neurology resident evaluations of faculty teaching.Methods: We performed a retrospective study of faculty teaching evaluations before and after the implementation of a full-time NH service. Primary outcomes were neurology resident evaluations of faculty teaching, which were compared in the pre-NH period (August 2010-July 2014) vs the post-NH period (August 2016-July 2018). In a secondary analysis, we used the difference-in-difference approach to analyze the effect of introducing the NH service on resident evaluation of faculty teaching compared with stroke and neurocritical care faculty controls. We performed an additional descriptive analysis of medical student evaluation of faculty teaching and described Residency In-service Training Exam scores and Accreditation Council for Graduate Medical Education (ACGME) resident survey data before and after the intervention.Results: There were 368 resident and 360 medical student evaluations of faculty teaching during the study period. Compared to the pre-NH period, the post-NH period had significantly higher resident evaluations of faculty teaching in 19 of 27 questions of faculty teaching, across 5 of the 6 ACGME core competencies. Within the competencies of patient care, practice-based learning and improvement, and systems-based practice, the NH teaching faculty were rated significantly higher across all questions. In the difference-in-difference model, resident evaluations of faculty teaching following the implementation of the NH service remained significantly improved compared with controls in teaching evidence-based medicine, teaching diagnostic algorithms, and explaining rationale for clinical decisions. Medical student ratings of faculty teaching were unchanged in the pre-NH and the post-NH period.Discussion: Neurology residents may benefit from the clinical expertise of NHs and their ability to teach evidence-based practice and role model systems-based practice. Given the central role NHs may play in trainee education, additional focus on both the local and national levels should be dedicated to further developing the teaching skills of NHs.

  View details for DOI 10.1212/NE9.0000000000200131

  View details for PubMedID 39359890

• Education Research: Sustained Implementation of Quality Improvement Practices Is Observed in Early Career Physicians Following a Neurology Resident QI Curriculum. Neurology. Education Xiong, K., Miller-Kuhlmann, R. K., Scott, B. J., He, Z., Dujari, S., Gold, C., Kvam, K. 2024; 3 (2): e200137

  Abstract

  Background and Objectives: The Accreditation Council for Graduate Medical Education and American Board of Psychiatry and Neurology expect engagement in quality improvement (QI) activities for all residents and practicing neurologists. Our neurology residency program instituted an experiential Neurology Residency QI Curriculum in 2015 for all residents. In this study, we aimed to characterize the role of QI engagement in the early-career paths of program graduates.Methods: We distributed an online survey evaluating QI training, scholarship, and leadership (before, during, and after residency training) to all individuals who graduated from our residency program (graduation years 2017-2021). Primary outcomes were QI project leadership or mentorship and QI scholarship (projects, posters, and publications) after residency. Predictors of these outcomes were also evaluated using Fisher exact test.Results: Twenty-nine of 50 graduates (58%) completed the survey. Median time from residency graduation was 3 years. Of the respondents, 14% actively participated in a QI project before residency, 83% during residency, and 48% after graduating. In addition, 41% had led or mentored a QI project and 34% had performed QI scholarship since residency. Fourteen percent of participants held formal roles in QI or patient safety, while 24% received formal full-time equivalents for QI work. Significant predictors (p < 0.05) of QI leadership included older age, time since graduation, rank, and participation in Clinical Effectiveness Leadership Training (CELT-an institutional QI faculty development course). Significant predictors (p < 0.05) of QI scholarship included older age, time since graduation, participation in CELT, and participation in QI scholarship during residency. QI training, participation, and/or project leadership before residency did not predict either QI leadership or scholarship after residency.Discussion: Many neurology residency graduates continued to lead QI projects and produce QI scholarship in the early years after graduation. However, receiving protected time for leadership and academic work in this area is uncommon. Our findings suggest that more infrastructure, including training, career development, and mentorship, can foster neurologists interested in leading in quality and patient safety. In academic models, promotion pathways that support academic advancement for faculty leading in QI are needed.

  View details for DOI 10.1212/NE9.0000000000200137

  View details for PubMedID 39359889

• Clinical Features of Neurotoxicity Following CD19 CAR T-cell Therapy in Mantle Cell Lymphoma. Blood advances Nie, E. H., Su, Y. J., Baird, J. H., Agarwal, N., Bharadwaj, S., Weng, W. K., Smith, M., Dahiya, S., Han, M. H., Dunn, J. E., Kipp, L. B., Miklos, D. B., Scott, B. J., Frank, M. J. 2024

  Abstract

  CD19 chimeric antigen receptor (CAR) T-cell therapy has proven highly effective for treating relapsed/refractory mantle cell lymphoma (MCL). However, immune effector cell-associated neurotoxicity syndrome (ICANS) remains a significant concern. This study aimed to evaluate the clinical, radiological, and laboratory correlatives associated with ICANS development following CD19 CAR T-cell therapy in patients with MCL. All patients (n = 26) who received standard of care brexucabtagene autoleucel until July 2022 at our institution were evaluated. Laboratory and radiographic correlatives including brain magnetic resonance imaging (MRI) and electroencephalogram (EEG) were evaluated to determine the clinical impact of ICANS. Seventeen (65%) patients experienced ICANS after treatment, with a median onset on day 6. Ten (38%) patients experienced severe (≥ grade 3) ICANS. All ICANS patients had antecedent cytokine release syndrome (CRS), but no correlation was observed between ICANS severity and CRS grade. 92% of EEGs revealed interictal changes; no patients experienced frank seizures due to ICANS. 86% of severe ICANS patients with post-infusion brain MRIs demonstrated acute neuroimaging findings not seen on pretreatment MRI. Severe ICANS was also associated with higher rates of cytopenia, coagulopathy, increased cumulative steroid exposure, and prolonged hospitalization. However, severe ICANS did not affect treatment outcomes of patients with MCL. Severe ICANS is frequently associated with a range of post-infusion brain MRI changes and abnormal EEG findings. Longer hospitalization was observed in severe ICANS patients, especially those with abnormal acute MRI or EEG findings, but there was no discernible impact on overall treatment response and survival.

  View details for DOI 10.1182/bloodadvances.2023011896

  View details for PubMedID 38295285

• Neurotoxicity of Cancer Immunotherapies Including CAR T Cell Therapy. Current neurology and neuroscience reports Song, K. W., Scott, B. J., Lee, E. Q. 2023

  Abstract

  To outline the spectrum of neurotoxicity seen with approved immunotherapies and in pivotal clinical trials including immune checkpoint inhibitors, chimeric antigen receptor T-cell therapy, vaccine therapy, and oncolytic viruses.There has been an exponential growth in new immunotherapies, which has transformed the landscape of oncology treatment. With more widespread use of cancer immunotherapies, there have also been advances in characterization of its associated neurotoxicity, research into potential underlying mechanisms, and development of management guidelines. Increasingly, there is also mounting interest in long-term neurologic sequelae. Neurologic complications of immunotherapy can impact every aspect of the central and peripheral nervous system. Early recognition and treatment are critical. Expanding indications for immunotherapy to solid and CNS tumors has led to new challenges, such as how to reliably distinguish neurotoxicity from disease progression. Our evolving understanding of immunotherapy neurotoxicity highlights important areas for future research and the need for novel immunomodulatory therapeutics.

  View details for DOI 10.1007/s11910-023-01315-w

  View details for PubMedID 37938472

  View details for PubMedCentralID 8291304

• TUMOR INFLAMMATION-ASSOCIATED NEUROTOXICITY (TIAN): A TOXICITY SYNDROME IN PATIENTS TREATED WITH IMMUNOTHERAPY FOR CENTRAL NERVOUS SYSTEM TUMORS Mahdi, J., Dietrich, J., Straathof, K., Roddie, C., Scott, B., Davidson, T., Prolo, L., Batchelor, T., Campen, C., Davis, K., Gust, J., Lim, M., Majzner, R., Park, J., Partap, S., Ramakrishna, S., Richards, R., Schultz, L., Vitanza, N., Wang, L., Mackall, C., Monje, M. OXFORD UNIV PRESS INC. 2023

  View details for DOI 10.1093/neuonc/noad073.192

  View details for Web of Science ID 001023504300193

• Tumor inflammation-associated neurotoxicity. Nature medicine Mahdi, J., Dietrich, J., Straathof, K., Roddie, C., Scott, B. J., Davidson, T. B., Prolo, L. M., Batchelor, T. T., Campen, C. J., Davis, K. L., Gust, J., Lim, M., Majzner, R. G., Park, J. R., Partap, S., Ramakrishna, S., Richards, R., Schultz, L., Vitanza, N. A., Wang, L. D., Mackall, C. L., Monje, M. 2023

  Abstract

  Cancer immunotherapies have unique toxicities. Establishment of grading scales and standardized grade-based treatment algorithms for toxicity syndromes can improve the safety of these treatments, as observed for cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) in patients with B cell malignancies treated with chimeric antigen receptor (CAR) T cell therapy. We have observed a toxicity syndrome, distinct from CRS and ICANS, in patients treated with cell therapies for tumors in the central nervous system (CNS), which we term tumor inflammation-associated neurotoxicity (TIAN). Encompassing the concept of 'pseudoprogression,' but broader than inflammation-induced edema alone, TIAN is relevant not only to cellular therapies, but also to other immunotherapies for CNS tumors. To facilitate the safe administration of cell therapies for patients with CNS tumors, we define TIAN, propose a toxicity grading scale for TIAN syndrome and discuss the potential management of this entity, with the goal of standardizing both reporting and management.

  View details for DOI 10.1038/s41591-023-02276-w

  View details for PubMedID 37024595

  View details for PubMedCentralID 7238960

• Multifocal demyelinating leukoencephalopathy and oligodendroglial lineage cell loss with immune effector cell-associated neurotoxicity syndrome (ICANS) following CD19 CAR T-cell therapy for mantle cell lymphoma. Journal of neuropathology and experimental neurology Nie, E. H., Ahmadian, S. S., Bharadwaj, S. N., Acosta-Alvarez, L., Threlkeld, Z. D., Frank, M. J., Miklos, D. B., Monje, M., Scott, B. J., Vogel, H. 2023

  Abstract

  Immune effector cell-associated neurotoxicity syndrome (ICANS) is a prevalent condition seen after treatment with chimeric antigen receptor T-cell (CAR T) therapy and other cancer cell therapies. The underlying pathophysiology and neuropathology of the clinical syndrome are incompletely understood due to the limited availability of brain tissue evaluation from patient cases, and a lack of high-fidelity preclinical animal models for translational research. Here, we present the cellular and tissue neuropathologic analysis of a patient who experienced grade 4 ICANS after treatment with anti-CD19 CAR T therapy for mantle cell lymphoma. Our pathologic evaluation reveals a pattern of multifocal demyelinating leukoencephalopathy associated with a clinical course of severe ICANS. A focused analysis of glial subtypes further suggests region-specific oligodendrocyte lineage cell loss as a potential cellular and pathophysiologic correlate in severe ICANS. We propose a framework for the continuum of neuropathologic changes thus far reported across ICANS cases. Future elucidation of the mechanistic processes underlying ICANS will be critical in minimizing neurotoxicity following CAR T-cell and related immunotherapy treatments across oncologic and autoimmune diseases.

  View details for DOI 10.1093/jnen/nlac121

  View details for PubMedID 36592076

• Continuous EEG monitoring detects nonconvulsive seizure and Ictal-Interictal Continuum abnormalities in moderate to severe ICANS following systemic CAR-T therapy. The Neurohospitalist Satyanarayan, S., Spiegel, J., Hovsepian, D., Markert, M., Thomas, R., Muffly, L., Miklos, D., Graber, K., Scott, B. J. 2023; 13 (1): 53-60

  Abstract

  Immune Cell Effector Associated Neurotoxicity Syndrome (ICANS) is common amongst patients receiving CD19 targeted Chimeric Antigen Receptor T-cell (CAR-T) therapy. The purpose of this study is to characterize the incidence of seizures and ictal-interictal continuum (IIC) abnormalities in patients with ICANS.Retrospective review of consecutive patients treated with axicabtagene ciloleucel (axi-cel) for recurrent high-grade systemic lymphoma at Stanford Medical Center between 2/2016-6/2019. Electronic medical records (EMR) were reviewed for clinical features, treatment information, EEG data, CRS (cytokine release syndrome)/ICANS severity, and clinical outcomes.Fifty-six patients met inclusion criteria. 85.7% of patients developed CRS, and 58.9% developed ICANS. Twenty-eight patients had EEG monitoring, of whom 26 had ICANS. Median duration of EEG monitoring was 30 hours (range .5-126 hours). Four patients (7.1%) had seizures (1 patient had a clinical generalized seizure, 2 patients had clinical and nonconvulsive seizures, and 1 patient had an isolated non-convulsive seizure). Ictal-interictal continuum abnormalities were common, of which generalized periodic discharges (GPDs) with triphasic morphology and GPDs with epileptiform morphology were most frequently seen. Generalized periodic discharges with triphasic wave morphology were found across Grade 2-3 peak ICANS severity, however the majority (86%) of patients with epileptiform GPDs had Grade 3 peak ICANS severity.Among patients receiving axi-cel, seizure occurred in 7.1% of the total cohort, representing 12% of patients with ICANS. Ictal-interictal continuum abnormalities are also seen in patients with ICANS, most commonly GPDs. 75% of patients with seizures had nonconvulsive seizures supporting the use of continuous video EEG monitoring in this population.

  View details for DOI 10.1177/19418744221128852

  View details for PubMedID 36531846

  View details for PubMedCentralID PMC9755619

• Single institution experience with death by neurological criteria/brain death guideline adherence. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Lerner, D. P., Tadevosyan, A., Scott, B. J., Ramineni, A., Bassil, R., Burns, J. D., Russell, J. A. 2022; 108: 25-29

  Abstract

  To determine the effect on adherence to an institutional death by neurological criteria/brain death (DNC/BD) policy of implementation of a standardized DNC/BD checklist in the electronic medical record (EMR).The retrospective study cohort included all patients admitted to our institution who were declared dead by neurologic criteria determined by ICD code (G93.82) between June 2015 and October 2019. Two investigators independently reviewed each case for adherence with institutional policy, and agreement was assessed using unweighted kappa statistics. Patient data and adherence to institutional policy before and after implementation of a standardized DNC/BD checklist were compared.There were 66 patients identified by the initial search and 38 were included in the final analysis, with 19 cases in both the pre- and post- checklist periods. There were no significant differences in age, cause of DNC/BD, time to DNC/BD determination, potential toxic, metabolic, physiologic confounders, or use of ancillary testing. The pre-checklist period adherence was 47.4% (n = 9/19) versus 94.6% (n = 18/19; p = 0.001) in the post-checklist EMR DNC/BD period.Implementation of a standardized EMR checklist substantially improved DNC/BD policy adherence in our institution.This study provides Class IV evidence on the use of standardized EMR checklist to improve death by neurologic criteria/brain death policy adherence.

  View details for DOI 10.1016/j.jocn.2022.11.009

  View details for PubMedID 36577320

• Long-Term Cognitive and Neuropsychiatric Outcomes in Adults Who Have Received Chimeric Antigen Receptor T-Cell (CAR-T) Therapy for Aggressive Lymphoma at Stanford - a Pilot Feasibility Study Scott, B. J., Murray, T., Deutsch, G. K., Lahijani, S., Frank, M. J., Monje, M. AMER SOC HEMATOLOGY. 2022: 5201-5202

  View details for DOI 10.1182/blood-2022-168229

  View details for Web of Science ID 000893223205100

• Continuous EEG monitoring detects nonconvulsive seizure and Ictal-Interictal Continuum abnormalities in moderate to severe ICANS following systemic CAR-T therapy NEUROHOSPITALIST Satyanarayan, S., Spiegel, J., Hovsepian, D., Markert, M., Thomas, R., Muffly, L., Miklos, D., Graber, K., Scott, B. J. 2022

  View details for DOI 10.1177/19418744221128852

  View details for Web of Science ID 000867394200001

• A rare neuromyelitis optica mimic: Primary CNS histiocytic sarcoma. Multiple sclerosis (Houndmills, Basingstoke, England) Rogawski, D. S., Nirschl, J. J., McDonald, J., Nie, E., Schwartz, N. U., Vogel, H., Scott, B. J., Gold, C. A., Kipp, L. B. 2022; 28 (10): 1651-1654

  Abstract

  Primary central nervous system (CNS) histiocytic sarcoma is a rare hematolymphoid malignancy with features of mature histiocytes and carries a poor prognosis. We describe a unique case in which a 50-year-old woman presented with recurrent acute brainstem syndrome, area postrema syndrome, and myelitis with corresponding magnetic resonance imaging (MRI) lesions meeting diagnostic criteria for seronegative neuromyelitis optica spectrum disorder (NMOSD). Despite initial improvement with steroids and plasma exchange, she experienced recurrent symptoms over 10months referable to new and persistently enhancing lesions. At autopsy, neuropathology revealed a diffusely infiltrative primary CNS histiocytic sarcoma. This case represents a rare clinicoradiologic mimic of NMOSD, underscoring the importance of evaluation for infiltrative diseases in cases of atypical seronegative NMOSD.

  View details for DOI 10.1177/13524585221097564

  View details for PubMedID 35876468

• Outcomes of a Neurohospitalist Program at an Academic Medical Center. The Neurohospitalist Gold, C. A., Scott, B. J., Weng, Y., Bernier, E., Kvam, K. A. 2022; 12 (3): 453-462

  Abstract

  The purpose is to determine the impact of an academic neurohospitalist service on clinical outcomes.We performed a retrospective, quasi-experimental study of patients discharged from the general neurology service before (August 2010-July 2014) and after implementation of a full-time neurohospitalist service (August 2016-July 2018) compared to a control group of stroke patients. Primary outcomes were length of stay and 30-day readmission. Using the difference-in-difference approach, the impact of introducing a neurohospitalist service compared to controls was assessed with adjustment of patients' characteristics. Secondary outcomes included mortality, in-hospital complications, and cost.There were 2706 neurology admissions (1648 general; 1058 stroke) over the study period. The neurohospitalist service was associated with a trend in reduced 30-day readmissions (ratio of ORs: .52 [.27, .98], P = .088), while length of stay was not incrementally changed in the difference-in-difference model (-.3 [-.7, .1], P = .18). However, descriptive results demonstrated a significant reduction in mean adjusted LOS of .7 days (4.5 to 3.8 days, P < .001) and a trend toward reduced readmissions (8.9% to 7.6%, P = .42) in the post-neurohospitalist cohort despite a significant increase in patient complexity, shift to higher acuity diagnoses, more emergent admissions, and near quadrupling of observation status patients. Mortality and in-hospital complications remained low, patient satisfaction was stable, and cost was not incrementally changed in the post-neurohospitalist cohort.Implementation of a neurohospitalist service at an academic medical center is feasible and associated with a significant increase in patient complexity and acuity and a trend toward reduced readmissions.

  View details for DOI 10.1177/19418744221083182

  View details for PubMedID 35755235

  View details for PubMedCentralID PMC9214938

• Multifocal demyelinating leukoencephalopathy and oligodendroglial lineage cell loss with CD19 CAR T-cell lymphoma therapy Nie, E., Ahmadian, S., Bharadwaj, S., Acosta-Alvarez, L., Threlkeld, Z., Frank, M., Miklos, D., Born, D., Scott, B., Monje, M., Vogel, H. OXFORD UNIV PRESS INC. 2022: 464

  View details for Web of Science ID 000798368400099

• Primary central nervous system histiocytic sarcoma presenting as neuromyelitis optica Nirschl, J., Rogawski, D., McDonald, J., Nie, E., Schwartz, N., Scott, B., Gratzinger, D., Gold, C., Kipp, L., Vogel, H. OXFORD UNIV PRESS INC. 2022: 491

  View details for Web of Science ID 000798368400189

• Outcomes of a Neurohospitalist Program at an Academic Medical Center NEUROHOSPITALIST Gold, C. A., Scott, B. J., Weng, Y., Bernier, E., Kvam, K. A. 2022

  View details for DOI 10.1177/19418744221083182

  View details for Web of Science ID 000787269900001

• Neuro-Oncologic Emergencies. Neurologic clinics Threlkeld, Z. D., Scott, B. J. 2021; 39 (2): 545–63

  Abstract

  Cancer and cancer therapies have the potential to affect the nervous system in a host of different ways. Cerebral edema, increased intracranial pressure, cerebrovascular events, status epilepticus, and epidural spinal cord compression are among those most often presenting as emergencies. Neurologic side-effects of cancer therapies are often mild, but occasionally result in serious illness. Immunotherapies cause autoimmune-related neurologic side-effects that are generally responsive to immunosuppressive therapies. Emergency management of neuro-oncologic problems benefits from early identification and close collaboration among interdisciplinary team members and patients or surrogate decision-makers.

  View details for DOI 10.1016/j.ncl.2021.01.012

  View details for PubMedID 33896532

• Recurrent Status Epilepticus in the Setting of Chimeric Antigen Receptor (CAR)-T Cell Therapy The Neurohospitalist Reveron-Thornton, R., Scott, B. J., Post, D., Finley Caulfield, A., Werbaneth, K., Hovsepian, D. A., Spiegel, J., Miklos, D., Thomas, R. P., Patel, C. B. 2021: 74-79

  Abstract

  Axicabtagene ciloleucel (AC) is an FDA-approved anti-CD19 autologous chimeric antigen receptor T-cell (CAR-T) therapy for refractory diffuse large B cell lymphoma (DLBCL). While its efficacy in DLBCL has been promising, neurotoxicity remains a significant concern. We present a case of a 22-year-old woman with chemotherapy-refractory DLBCL who exhibited Grade IV neurotoxicity in the setting of sepsis, after undergoing AC infusion. Despite prophylactic levetiracetam given per guidelines,1,2 she experienced a precipitous mental status decline on post-infusion day 8 (D8) followed by hypoxic respiratory failure in the setting of clinical status epilepticus on D11 and nonconvulsive status epilepticus (NCSE) on D18. While neuroimaging was unremarkable, EEG demonstrated diffuse slowing and 2.5-3 Hz generalized periodic discharges consistent with NCSE. Seizures were initially refractory to lorazepam, increasing doses of levetiracetam, and phenobarbital, requiring a midazolam drip titrated to 50-70% burst suppression for resolution. Methylprednisolone and tocilizumab were used to treat neurotoxicity and cytokine release syndrome, respectively. Empiric antibiotics were used for sepsis. After cessation of sedatives on D19, mental status improved to near baseline. PET/CT just prior to discharge showed a complete response of the DLBCL (Deauville 3). She was discharged on D37 with no further seizure activity. Unfortunately, a 3-month interval PET/CT demonstrated disease progression which continued through salvage pembrolizumab eventually leading to death 1.2 years post-CAR-T infusion. This case illustrates the clinical management challenges of a complex and rare neurotoxic side effect of CAR-T cell therapy, namely NCSE following status epilepticus.

  View details for DOI 10.1177/19418744211000980

  View details for PubMedCentralID PMC8689529

• Susceptibility-Weighted Imaging Diagnosis of Cerebral Fat Embolism NEUROHOSPITALIST Burns, J. D., Noujaim, D., Scott, B. J. 2017; 7 (3): 147

  View details for DOI 10.1177/1941874416669284

  View details for Web of Science ID 000457810300010

  View details for PubMedID 28634507

  View details for PubMedCentralID PMC5467812

• Raccoon Roundworm Infection Associated with Central Nervous System Disease and Ocular Disease - Six States, 2013-2015 MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT Sircar, A. D., Abanyie, F., Blumberg, D., Chin-Hong, P., Coulter, K. S., Cunningham, D., Huskins, W., Langelier, C., Reid, M., Scott, B. J., Shirley, D., Babik, J. M., Belova, A., Sapp, S. G. H., McAuliffe, I., Rivera, H. N., Yabsley, M. J., Montgomery, S. P. 2016; 65 (35): 930–33

  Abstract

  Baylisascaris procyonis, predominantly found in raccoons, is a ubiquitous roundworm found throughout North America. Although raccoons are typically asymptomatic when infected with the parasite, the larval form of Baylisascaris procyonis can result in fatal human disease or severe neurologic outcomes if not treated rapidly. In the United States, Baylisascaris procyonis is more commonly enzootic in raccoons in the midwestern and northeastern regions and along the West Coast (1). However, since 2002, infections have been documented in other states (Florida and Georgia) and regions (2). Baylisascariasis is not a nationally notifiable disease in the United States, and little is known about how commonly it occurs or the range of clinical disease in humans. Case reports of seven human baylisascariasis cases in the United States diagnosed by Baylisascaris procyonis immunoblot testing at CDC are described, including review of clinical history and laboratory data. Although all seven patients survived, approximately half were left with severe neurologic deficits. Prevention through close monitoring of children at play, frequent handwashing, and clearing of raccoon latrines (communal sites where raccoons defecate) are critical interventions in curbing Baylisascaris infections. Early treatment of suspected cases is critical to prevent permanent sequelae.

  View details for DOI 10.15585/mmwr.mm6535a2

  View details for Web of Science ID 000383311600002

  View details for PubMedID 27608169

• A Neurohospitalist Discharge Clinic Shortens the Transition From Inpatient to Outpatient Care NEUROHOSPITALIST Shah, M., Douglas, V., Scott, B., Josephson, S. 2016; 6 (2): 64–69

  Abstract

  Medicine hospitalist programs have effectively incorporated hospitalist-run discharge clinics into clinical practice to help bridge the vulnerable transition periods after hospital discharge. A neurohospitalist discharge clinic would similarly allow continuity with the inpatient provider while addressing challenges in the coordination of neurologic care. We anticipated that this would afford a greater total number of patients to be seen and at a shorter interval.The number of posthospital discharge patients who were seen in general continuity per month in the 6 months prior to establishment of neurohospitalist discharge clinic and those seen over 1 full calendar year 6 months after clinic began was compared by reviewing medical records. Average length of time between discharge from hospital and first clinic visit was compared between patients seen in general neurology continuity clinic and those seen in discharge clinic.There was a significant increase in the average number of postdischarge visits per month after initiation of neurohospitalist discharge clinic compared to prior (16.1 visits vs 10.5 visits, P = .001). Patients were seen significantly sooner after hospitalization in discharge clinic (35.9 ± 4.3 days) compared to those seen in general continuity clinic during the same time epoch (57.6 ± 4.1 days; p < 0.001).Creation of a neurohospitalist discharge clinic was effective in increasing posthospital discharge follow-up frequency and shortening duration of time to follow-up.

  View details for DOI 10.1177/1941874415618707

  View details for Web of Science ID 000457809800003

  View details for PubMedID 27053983

  View details for PubMedCentralID PMC4802776

• Leptomeningeal metastasis in breast cancer - a systematic review ONCOTARGET Scott, B. J., Oberheim-Bush, N. A., Kesari, S. 2016; 7 (4): 3740–47

  Abstract

  There is limited data on the impact of specific patient characteristics, tumor subtypes or treatment interventions on survival in breast cancer LM.A systematic review was conducted to assess the impact of hormone receptor and HER-2 status on survival in breast cancer LM. A search for clinical studies published between 1/1/2007 and 7/1/2012 and all randomized-controlled trials was performed. Survival data from all studies are reported by study design (prospective trials, retrospective cohort studies, case studies).A total of 36 studies with 851 LM breast cancer subjects were identified. The majority (87%) were treated with intrathecal chemotherapy. Pooled median overall survival ranged from 14.9-18.1 weeks depending on study type. Breast cancer LM survival (15 weeks) was longer than other solid tumor LM 8.3 weeks and lung cancer LM 8.7 weeks, but shorter than LM lymphoma (15.4 versus 24.2 weeks). The impact of hormone receptor and HER-2 status on survival could not be determined.A median overall survival of 15 weeks in prospective studies of breast cancer LM provides a historical comparison for future LM breast cancer trials. Other outcomes including the impact of molecular status on survival could not be determined based on available studies.

  View details for DOI 10.18632/oncotarget.5911

  View details for Web of Science ID 000369952400008

  View details for PubMedID 26543235

  View details for PubMedCentralID PMC4826166

• Neuro-Oncologic Emergencies SEMINARS IN NEUROLOGY Scott, B. J. 2015; 35 (6): 675–82

  Abstract

  Cancer can have diverse and widespread effects on the nervous system. Knowledge of the most common characteristic mechanisms by which cancer impacts the nervous system enables prompt diagnosis and appropriate management. Here, a variety of neuro-oncologic emergencies are reviewed. Mass effect, status epilepticus, pituitary apoplexy, and metastatic epidural spinal cord compression are emergencies that arise from direct effects of central nervous system neoplasms. Limbic encephalitis may result in hospitalization and at times critical illness, and is usually caused by antibody-mediated reactions to neoplasms. Treatment-related neuro-oncologic emergencies from the effects of radiation and chemotherapy in severe cases may also result in medical emergencies.

  View details for DOI 10.1055/s-0035-1564684

  View details for Web of Science ID 000365345900010

  View details for PubMedID 26595868

• Concurrent intrathecal methotrexate and liposomal cytarabine for leptomeningeal metastasis from solid tumors: a retrospective cohort study JOURNAL OF NEURO-ONCOLOGY Scott, B. J., van Vugt, V. A., Rush, T., Brown, T., Chen, C. C., Carter, B. S., Schwab, R., Fanta, P., Helsten, T., Bazhenova, L., Parker, B., Pingle, S., Saria, M. G., Brown, B. D., Piccioni, D. E., Kesari, S. 2014; 119 (2): 361–68

  Abstract

  Leptomeningeal metastasis (LM) from solid tumors is typically a late manifestation of systemic cancer with limited survival. Randomized trials comparing single agent intrathecal methotrexate to liposomal cytarabine have shown similar efficacy and tolerability. We hypothesized that combination intrathecal chemotherapy would be a safe and tolerable option in solid tumor LM. We conducted a retrospective cohort study of combination IT chemotherapy in solid tumor LM at a single institution between April 2010 and July 2012. In addition to therapies directed at active systemic disease, each subject received IT liposomal cytarabine plus IT methotrexate with dexamethasone premedication. Patient characteristics, survival outcomes and toxicities were determined by systematic chart review. Thirty subjects were treated during the study period. The most common cancer types were breast 15 (50 %), glioblastoma 6 (20 %), and lung 5 (17 %). Cytologic clearance was achieved in 6 (33 %). Median non-glioblastoma overall survival was 30.2 weeks (n = 18; range 3.9-73.4), and did not differ significantly by tumor type. Median time to neurologic progression was 7 weeks (n = 8; range 0.9-57), with 10 subjects (56 %) experiencing death from systemic disease without progression of LM. Age less than 60 was associated with longer overall survival (p = 0.01). Six (21 %) experienced grade III toxicities during treatment, most commonly meningitis 2 (7 %). Combination IT chemotherapy was feasible in this small retrospective cohort. Prospective evaluation is necessary to determine tolerability, the impact on quality of life and neurocognitive outcomes or any survival benefit when compared to single agent IT chemotherapy.

  View details for DOI 10.1007/s11060-014-1486-2

  View details for Web of Science ID 000341184500015

  View details for PubMedID 24942463

• Recurrent Syncope Due to Refractory Cerebral Venous Sinus Thrombosis and Transient Elevations of Intracranial Pressure NEUROHOSPITALIST Larimer, P., McDermott, M. W., Scott, B. J., Shih, T. T., Poisson, S. N. 2014; 4 (1): 18–21

  Abstract

  Chronic paroxysmal intracranial hypertension leading to syncope is a phenomenon not reported previously in patients with refractory cerebral venous sinus thrombosis. We report a case of paroxysmal intracranial hypertension leading to syncopal episodes in a patient with idiopathic autoimmune hemolytic anemia and venous sinus thrombosis. This case demonstrates that intermittent elevations in intracranial pressure can lead to syncope in patients with venous sinus thrombosis and emphasizes the importance of considering this potentially treatable etiology of syncopal episodes.

  View details for DOI 10.1177/1941874413493183

  View details for Web of Science ID 000457807600004

  View details for PubMedID 24381706

  View details for PubMedCentralID PMC3869304

• Headache and Focal Neurologic Deficits in a 37-Year-Old Woman JAMA NEUROLOGY Ayodele, M. O., Pekmezci, M., Aghi, M. K., Scott, B. J. 2013; 70 (11): 1445–49

  Abstract

  A 37-year-old woman presented with progressively worsening headache. She had no headache history, and initial evaluation revealed hydrocephalus of unclear etiology. A ventriculoperitoneal shunt was placed with improvement. However, her headache returned and she developed neurologic deficits. Imaging studies demonstrated multiple cystic lesions in the posterior fossa. Serum and cerebrospinal fluid studies were unrevealing and a biopsy of the cystic lesions was performed. The clinical approach, differential diagnosis, and neuropathological findings are discussed.

  View details for DOI 10.1001/jamaneurol.2013.3933

  View details for Web of Science ID 000330117000018

  View details for PubMedID 24081305

• CXCL13 plus interleukin 10 is highly specific for the diagnosis of CNS lymphoma. Blood Rubenstein, J. L., Wong, V. S., Kadoch, C., Gao, H., Barajas, R., Chen, L., Josephson, S. A., Scott, B., Douglas, V., Maiti, M., Kaplan, L. D., Treseler, P. A., Cha, S., Hwang, J. H., Cinque, P., Cyster, J. G., Lowell, C. 2013; 121 (23): 4740-4748

  Abstract

  Establishing the diagnosis of focal brain lesions in patients with unexplained neurologic symptoms represents a challenge. The goal of this study is to provide evidence supporting functional roles for CXC chemokine ligand (CXCL)13 and interleukin (IL)-10 in central nervous system (CNS) lymphomas and to evaluate the utility of each as prognostic and diagnostic biomarkers. We demonstrate for the first time that elevated CXCL13 concentration in cerebrospinal fluid (CSF) is prognostic and that CXCL13 and CXCL12 mediate chemotaxis of lymphoma cells isolated from CNS lymphoma lesions. Expression of the activated form of Janus kinase 1 supported a role for IL-10 in prosurvival signaling. We determined the concentration of CXCL13 and IL-10 in CSF of CNS lymphoma patients and control cohorts including inflammatory and degenerative neurologic disease in a multicenter study involving 220 patients. Bivariate elevated CXCL13 plus IL-10 was 99.3% specific for primary and secondary CNS lymphoma, with sensitivity significantly greater than reference standard CSF tests. These results identify CXCL13 and IL-10 as potentially important biomarkers of CNS lymphoma that merit further evaluation and support incorporation of CXCL13 and IL-10 into diagnostic algorithms for the workup of focal brain lesions in which lymphoma is a consideration.

  View details for DOI 10.1182/blood-2013-01-476333

  View details for PubMedID 23570798

  View details for PubMedCentralID PMC3674672

• A Systematic Approach to the Diagnosis of Suspected Central Nervous System Lymphoma JAMA NEUROLOGY Scott, B. J., Douglas, V. C., Tihan, T., Rubenstein, J. L., Josephson, S. 2013; 70 (3): 311–19

  Abstract

  Central nervous system (CNS) lymphoma can present a diagnostic challenge. Currently, there is no consensus regarding what presurgical evaluation is warranted or how to proceed when lesions are not surgically accessible. We conducted a review of the literature on CNS lymphoma diagnosis (1966 to October 2011) to determine whether a common diagnostic algorithm can be generated. We extracted data regarding the usefulness of brain and body imaging, serum and cerebrospinal fluid (CSF) studies, ophthalmologic examination, and tissue biopsy in the diagnosis of CNS lymphoma. Contrast enhancement on imaging is highly sensitive at the time of diagnosis: 98.9% in immunocompetent lymphoma and 96.1% in human immunodeficiency virus-related CNS lymphoma. The sensitivity of CSF cytology is low (2%-32%) but increases when combined with flow cytometry. Cerebrospinal fluid lactate dehydrogenase isozyme 5, β2-microglobulin, and immunoglobulin heavy chain rearrangement studies have improved sensitivity over CSF cytology (58%-85%) but have only moderate specificity (85%). New techniques of proteomics and microRNA analysis have more than 95% specificity in the diagnosis of CNS lymphoma. Positive CSF cytology, vitreous biopsy, or brain/leptomeningeal biopsy remain the current standard for diagnosis. A combined stepwise systematic approach outlined here may facilitate an expeditious, comprehensive presurgical evaluation for cases of suspected CNS lymphoma.

  View details for DOI 10.1001/jamaneurol.2013.606

  View details for Web of Science ID 000316804400004

  View details for PubMedID 23319132

  View details for PubMedCentralID PMC4135394

• The Effect of a Neurohospitalist Service on Outcomes at an Academic Medical Center Neurology Douglas, V. C., Scott, B. J., Berg, G., Freeman, D. W., Josephson, S. A. 2012; 79 (10)
• Bevacizumab salvage therapy following progression in high-grade glioma patients treated with VEGF receptor tyrosine kinase inhibitors NEURO-ONCOLOGY Scott, B. J., Quant, E. C., McNamara, M. B., Ryg, P. A., Batchelor, T. T., Wen, P. Y. 2010; 12 (6): 603–7

  Abstract

  Agents targeting the vascular endothelial growth factor (VEGF) pathway are being used with increasing frequency in patients with recurrent high-grade glioma. The effect of more than one antiangiogenic therapy given in succession has not been established. We reviewed the efficacy of bevacizumab, a VEGF-A monoclonal antibody, in patients who progressed following prior therapy with VEGF receptor tyrosine kinase inhibitors (R-TKi). Seventy-three patients with recurrent high-grade gliomas received VEGF R-TKi (cediranib, sorafenib, pazopanib, or sunitinib) as part of phase I or II clinical trials. Twenty-four of these patients with glioblastoma progressed and received bevacizumab-containing regimens immediately after R-TKi. Those who stopped R-TKi therapy for reasons other than disease progression, or received a treatment that did not include bevacizumab, were excluded from the analysis. The efficacy of bevacizumab-containing regimens in these 24 patients was evaluated. During R-TKi therapy, 6 of 24 patients (25%) had a partial response (PR) to treatment. The 6-month progression-free survival (APF6) was 16.7% and median time-to-progression (TTP) was 14.3 weeks. Grade III/IV toxicities were seen in 13 of 24 patients (54%). Subsequently with bevacizumab salvage therapy, 5 of 24 patients (21%) had a PR, the APF6 was 12.5%, and the median TTP was 8 weeks. Five of 24 patients had grade III/IV toxicities (21%). The median overall survival (OS) from the start of R-TKi therapy was 9.2 months (range: 2.8-34.1+), whereas the median OS after bevacizumab was 5.2 months (range: 1.3-28.9+). Bevacizumab retains modest activity in high-grade glioma patients who progress on R-TKi. However, the APF6 of 12.5% in this cohort of patients indicates that durable tumor control is not achieved for most patients.

  View details for DOI 10.1093/neuonc/nop073

  View details for Web of Science ID 000278817700010

  View details for PubMedID 20156808

  View details for PubMedCentralID PMC2940643