Brian J Scott

All Publications

• 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

• 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. 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