Skip to main content
AAN.com

Abstract

Background and Objectives

Perihematomal edema (PHE) contributes to poor outcome after deep intraparenchymal hemorrhage (IPH), which is characterized by neuroinflammation and an influx of peripherally derived innate immune cells. We previously identified soluble ST2 (sST2) as a candidate for immune-mediated secondary brain injury. Leveraging prospectively collected cohorts from 2 centers, we sought to determine whether sST2 was associated with functional outcome, PHE, and the immune response following IPH.

Methods

Patients with deep IPH were enrolled within 36 hours of ictus, and blood was collected for sST2 and immune cell measurement. Hematoma volume and PHE were measured on serial CT scans. Good outcome was defined as a modified Rankin Scale score of 0–3 at 90 days. Linear mixed-effects models were used to analyze the relationship between sST2 and PHE over time. Flow cytometry was used to identify shifts in immune cell populations associated with sST2. Immunohistochemistry of human brain tissue was used to identify ST2-expressing cells in the perihematomal region.

Results

The 55 included patients had a median admission Glasgow Coma Scale score of 14 (interquartile range [IQR] 9–15), an intracerebral hemorrhage (ICH) score of 1 (IQR 1–2), and a hematoma volume of 8.6 mL (IQR 3.4–13.8 mL). Receiver operating curve analysis found the sST2 level to be predictive of poor outcome with an area under the curve of 0.763 (95% CI 0.632–0.894) and Youden optimum cut point of 61.8 ng/mL (p < 0.001). sST2 remained an independent predictor after adjustment for ICH score (adjusted odds ratio 2.53, 95% CI 1.03–6.19, p = 0.042). Measurement of PHE found those patients with high sST2 to have greater edema volume over time (β = 1.07, 95% CI 0.51–1.63, p < 0.001). High sST2 was associated with a shift toward an innate peripheral immune response (monocytes and natural killer cells; 68.6% ± 5.1% vs 47.5% ± 4.0%; p = 0.003).

Discussion

Our findings demonstrate that elevated sST2 links the peripheral innate immune response to PHE volume and outcome after IPH. This knowledge is relevant to future studies that seek to identify patients with IPH at highest risk for immune-mediated injury or limit injury through targeted interventions.

Get full access to this article

View all available purchase options and get full access to this article.

References

1.
Zahuranec DB, Lisabeth LD, Sánchez BN, et al. Intracerebral hemorrhage mortality is not changing despite declining incidence. Neurology. 2014;82(24):2180-2186.
2.
Hanley DF, Lane K, McBee N, et al. Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial. Lancet. 2017;389(10069):603-611.
3.
Hanley DF, Thompson RE, Rosenblum M, et al. Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial. Lancet. 2019;393(10175):1021-1032.
4.
Alrahbi S, Alaraimi R, Alzaabi A, Gosselin S. Intensive blood-pressure lowering in patients with acute cerebral hemorrhage. Can J Emerg Med. 2018;20(2):256-259.
5.
Anderson CS, Heeley E, Huang Y, et al. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med. 2013;368(25):2355-2365.
6.
Selim M, Foster LD, Moy CS, et al. Deferoxamine mesylate in patients with intracerebral haemorrhage (i-DEF): a multicentre, randomised, placebo-controlled, double-blind phase 2 trial. Lancet Neurol. 2019;18(5):428-438.
7.
Babu R, Bagley JH, Di C, Friedman AH, Adamson C. Thrombin and hemin as central factors in the mechanisms of intracerebral hemorrhage–induced secondary brain injury and as potential targets for intervention. Neurosurg Focus. 2012;32(4):E8.
8.
Urday S, Kimberly WT, Beslow LA, et al. Targeting secondary injury in intracerebral haemorrhage: perihaematomal oedema. Nat Rev Neurol. 2015;11(2):111-122.
9.
Grunwald Z, Beslow LA, Urday S, et al. Perihematomal edema expansion rates and patient outcomes in deep and lobar intracerebral hemorrhage. Neurocrit Care. 2017;26(2):205-212.
10.
Murthy SB, Urday S, Beslow LA, et al. Rate of perihaematomal oedema expansion is associated with poor clinical outcomes in intracerebral haemorrhage. J Neurol Neurosurg Psychiatry. 2016;87(11):1169-1173.
11.
Murthy SB, Moradiya Y, Dawson J, et al. Perihematomal edema and functional outcomes in intracerebral hemorrhage: influence of hematoma volume and location. Stroke. 2015;46(11):3088-3092.
12.
Wang J. Preclinical and clinical research on inflammation after intracerebral hemorrhage. Prog Neurobiol. 2010;92(4):463-477.
13.
Zhou Y, Wang Y, Wang J, Anne Stetler R, Yang QW. Inflammation in intracerebral hemorrhage: from mechanisms to clinical translation. Prog Neurobiol. 2014;115(183):25-44.
14.
Hammond MD, Ai Y, Sansing LH. Gr1+ macrophages and dendritic cells dominate the inflammatory infiltrate 12 h after experimental intracerebral hemorrhage. Transl Stroke Res. 2012;3(S1):s125-s131.
15.
Hammond MD, Taylor RA, Mullen MT, et al. CCR2+Ly6Chi inflammatory monocyte recruitment exacerbates acute disability following intracerebral hemorrhage. J Neurosci. 2014;34(11):3901-3909.
16.
Leasure AC, Kuohn LR, Vanent KN, et al. Association of serum IL-6 (interleukin 6) with functional outcome after intracerebral hemorrhage. Stroke. 2021;52(5):1733-1740.
17.
Adeoye O, Walsh K, Woo JG, et al. Peripheral monocyte count is associated with case fatality after intracerebral hemorrhage. J Stroke Cerebrovasc Dis. 2014;23(2):e107-e111.
18.
Walsh KB, Sekar P, Langefeld CD, et al. Monocyte count and 30-day case fatality in intracerebral hemorrhage. Stroke. 2015;46(8):2302-2304.
19.
Wolcott Z, Batra A, Bevers MB, et al. Soluble ST2 predicts outcome and hemorrhagic transformation after acute stroke. Ann Clin Transl Neurol. 2017;4(8):553-563.
20.
Tian X, Guo Y, Wang X, et al. Serum soluble ST2 is a potential long-term prognostic biomarker for transient ischaemic attack and ischaemic stroke. Eur J Neurol. 2020;27(11):2202-2208.
21.
Hansen C, Sastre C, Wolcott Z, Bevers MB, Kimberly WT. Time-dependent, dynamic prediction of fatty acid-binding protein 4, galectin-3, and soluble ST2 measurement with poor outcome after acute stroke. Int J Stroke. 2020;16(6):660-668.
22.
Bevers MB, Wolcott Z, Bache S, et al. Soluble ST2 links inflammation to outcome after subarachnoid hemorrhage. Ann Neurol. 2019;86(3):384-394.
23.
Schleicher RL, Bevers MB, Rubin DB, et al. Early brain injury and soluble ST2 after nontraumatic subarachnoid hemorrhage. Stroke. 2021;52(8):e494-e496.
24.
Lissak IA, Zafar SF, Westover MB, et al. Soluble ST2 is associated with new epileptiform abnormalities following nontraumatic subarachnoid hemorrhage. Stroke. 2020;51(4):1128-1134.
25.
Sastre C, Bevers MB, Kimberly WT. Role of interleukin-1 receptor-like 1 (ST2) in cerebrovascular disease. Neurocrit Care. 2021;35(3):887-893.
26.
Gao Y, Ma L, Luo CL, et al. IL-33 exerts neuroprotective effect in mice intracerebral hemorrhage model through suppressing inflammation/apoptotic/autophagic pathway. Mol Neurobiol. 2016;54(5):3879-3892.
27.
Rutledge R, Lentz CW, Fakhry S, Hunt J. Appropriate use of the Glasgow Coma Scale in intubated patients: a linear regression prediction of the Glasgow verbal score from the Glasgow eye and motor scores. J Trauma. 1996;41(3):514-522.
28.
Hemphill JC, Bonovich DC, Besmertis L, Manley GT, Johnston SC. The ICH score. Stroke. 2001;32(4):891-897.
29.
Urday S, Beslow LA, Goldstein DW, et al. Measurement of perihematomal edema in intracerebral hemorrhage. Stroke. 2015;46(4):1116-1119.
30.
Zhang R, Wu X, Hu W, et al. Neutrophil-to-lymphocyte ratio predicts hemorrhagic transformation in ischemic stroke: a meta-analysis. Brain Behav. 2019;9(9):e01382.
31.
Lattanzi S, Brigo F, Trinka E, Cagnetti C, Di Napoli M, Silvestrini M. Neutrophil-to-lymphocyte ratio in acute cerebral hemorrhage: a system review. Transl Stroke Res. 2019;10(2):137-145.
32.
Gusdon AM, Gialdini G, Kone G, et al. Neutrophil-lymphocyte ratio and perihematomal edema growth in intracerebral hemorrhage. Stroke. 2017;48(9):2589-2592.
33.
Dziedzic T, Bartus S, Klimkowicz A, Motyl M, Slowik A, Szczudlik A. Intracerebral hemorrhage triggers interleukin-6 and interleukin-10 release in blood. Stroke. 2002;33(9):2334-2335.
34.
Walsh KB, Zhang X, Zhu X, et al. Intracerebral hemorrhage induces inflammatory gene expression in peripheral blood: global transcriptional profiling in intracerebral hemorrhage patients. DNA Cel Biol. 2019;38(7):660-669.
35.
Kakkar R, Lee RT. The IL-33/ST2 pathway: therapeutic target and novel biomarker. Nat Rev Drug Discov. 2008;7(10):827-840.
36.
Shi SX, Shi K, Liu Q. Brain injury instructs bone marrow cellular lineage destination to reduce neuroinflammation. Sci Transl Med. 2021;13(589):eabc7029.
37.
Askenase MH, Goods BA, Beatty HE, et al. Longitudinal transcriptomics define the stages of myeloid activation in the living human brain after intracerebral hemorrhage. Sci Immunol. 2021;6(56):eabd6279.
38.
Hayakawa H, Hayakawa M, Kume A, Tominaga SI. Soluble ST2 blocks interleukin-33 signaling in allergic airway inflammation. J Biol Chem. 2007;282(36):26369-26380.
39.
Xia J, Zhao J, Shang J, et al. Increased IL-33 expression in chronic obstructive pulmonary disease. Am J Physiol Lung Cell Mol Physiol. 2015;308(7):L619-L627.
40.
Beltrán CJ, Núñez LE, Díaz-Jiménez D, et al. Characterization of the novel ST2/IL-33 system in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2010;16(7):1097-1107.
41.
Shimpo M, Morrow DA, Weinberg EO, et al. Serum levels of the interleukin-1 receptor family member ST2 predict mortality and clinical outcome in acute myocardial infarction. Circulation. 2004;109(18):2186-2190.
42.
Weinberg EO, Shimpo M, De Keulenaer GW, et al. Expression and regulation of ST2, an interleukin-1 receptor family member, in cardiomyocytes and myocardial infarction. Circulation. 2002;106(23):2961-2966.
43.
McMurray JJV, Adamopoulos S, Anker SD, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2012;33(14):1787-1847.
44.
Schmitz J, Owyang A, Oldham E, et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity. 2005;23(5):479-490.
45.
Liu X, Hu R, Pei L, et al. Regulatory T cell is critical for interleukin-33-mediated neuroprotection against stroke. Exp Neurol. 2020;328:113233.
46.
Pascual-Reguant A, Bayat Sarmadi J, Baumann C, et al. TH17 cells express ST2 and are controlled by the alarmin IL-33 in the small intestine. Mucosal Immunol. 2017;10(6):1431-1442.
47.
Bourgeois E, Van LP, Samson M, et al. The pro-Th2 cytokine IL-33 directly interacts with invariant NKT and NK cells to induce IFN-gamma production. Eur J Immunol. 2009;39(4):1046-1055.
48.
Ochayon DE, Ali A, Alarcon PC, et al. IL-33 promotes type 1 cytokine expression via p38 MAPK in human NK cells. J Leukoc Biol. 2020;107(4):663-671.
49.
Babic ZM, Zunic FZ, Pantic JM, et al. IL-33 receptor (ST2) deficiency downregulates myeloid precursors, inflammatory NK and dendritic cells in early phase of sepsis. J Biomed Sci. 2018;25(1):56.
50.
Kurowska-Stolarska M, Stolarski B, Kewin P, et al. IL-33 amplifies the polarization of alternatively activated macrophages that contribute to airway inflammation. J Immunol. 2009;183(10):6469-6477.
Letters to the Editor
24 December 2022
Reader Response: Association of Soluble ST2 With Functional Outcome, Perihematomal Edema, and Immune Response After Intraparenchymal Hemorrhage
Binghao Zhao, Neurosurgeon | Peking Union Medical College Hospital
Haosu Wang, Nurse | Henan Medical College
Hao Xing, Neurosurgeon | Peking Union Medical College Hospital
Wenbin Ma, Neurosurgeon | Peking Union Medical College Hospital

Bevers et al. investigated if soluble ST2 (sST2) in the peripheral blood was associated with functional outcome, perihematomal edema (PHE), and immune response following intraparenchymal hemorrhage (IPH).1  The mean age in both the BWH (71 ± 13 yr) and YNHH cohorts (67 ± 14 yr) was high.1 There may be some intracranial immunosuppression and inhibition of immune cell infiltration in the elderly compared to young candidates. 2,3  These disparities could contribute to a biased evaluation of a potential immune response in this population. We suggest the authors consider individual baseline characteristics as a contributing factor in their conclusions.

In addition, it is unclear whether the participants in the two cohorts had other comorbidities. If some of the participants were in poor physical health, they might not be able to survive IPH; they might also have poor prognoses and less functional outcomes than those with relatively good physical status.4,5 The sample size in BWH (N = 29) and YNHH (N = 26) cohorts was not strong enough. We still anticipate prospective studies with longer follow-ups and more participants.

 

References

1. Bevers M, Booraem C, Li K, et al. Association of Soluble ST2 With Functional Outcome, Perihematomal Edema, and Immune Response After Intraparenchymal Hemorrhage. Neurology. Published online December 22, 2022. doi: 10.1212/WNL.0000000000206764

2. Keskin DB, Anandappa AJ, Sun J, et al. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature 2019;565:234-239.

3. Da Mesquita S, Louveau A, Vaccari A, et al. Functional aspects of meningeal lymphatics in ageing and Alzheimer's disease. Nature 2018;560:185-191.

4. Gruneir A, Griffith LE, Fisher K, et al. Increasing comorbidity and health services utilization in older adults with prior stroke. Neurology 2016;87:2091-2098.

5. Appelros P, Matérne M, Jarl G, Arvidsson-Lindvall M. Comorbidity in Stroke-Survivors: Prevalence and Associations with Functional Outcomes and Health. J Stroke Cerebrovasc Dis 2021;30:106000.

Author disclosures are available upon request([email protected]).

Information & Authors

Information

Published In

Neurology®
Volume 100Number 13March 28, 2023
Pages: e1329-e1338
PubMed: 36549913

Publication History

Received: July 6, 2022
Accepted: November 16, 2022
Published online: December 22, 2022
Published in print: March 28, 2023

Permissions

Request permissions for this article.

Disclosure

M.B. Bevers reports funding from NIH K23 NS112474, American Academy of Neurology AI18-0000000062, and the Heitman Neurovascular Research Foundation. C. Booraem, K. Li, A. Sreekrishnan, C. Sastre, G.J. Falcone, and K.N. Sheth report no relevant disclosures. L.H. Sansing reports funding from NIH R21NS088972 and R01NS097728. W.T. Kimberly reports grant support from Biogen, Inc., outside the submitted work, and consulting fees and grant support from NControl Therapeutics, Inc., and has patent 16/486687 pending on sST2; he serves as a scientific advisory board member for Biogen, Inc., and NControl Therapeutics, Inc.; he reports funding from NIH R01 NS099209 and NIH R21 NS120002 and the Heitman Neurovascular Research Foundation. Go to Neurology.org/N for full disclosures.

Study Funding

This study was supported by NIH R01 NS099209 and NIH R21 NS120002 (W.T.K.); NIH K23 NS112474 and American Academy of Neurology AI18-0000000062 (M.B.B.); the Heitman Neurovascular Research Foundation (W.T.K., M.B.B.); and NIH R21NS088972 and R01NS097728 (L.H.S.).

Authors

Affiliations & Disclosures

Matthew B. Bevers, MD, PhD
From the Division of Neurocritical Care (M.B.B., C.B., K.L., A.S.), Brigham and Women's Hospital; Division of Neurocritical Care (C.S., G.J.F., W.T.K.), Center for Genomic Medicine, Massachusetts General Hospital, Boston; and Department of Neurology (K.N.S., L.H.S.), Yale-New Haven Hospital, CT.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
1) Consulting fees from Atlas Ventures<br><br><br><br>Immediate Family Member:<br><br>1) Consulting fees from Gensler
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
1) NINDS K23NS112474, PI, 2020-2025<br><br>2) NINDS R21NS120002, Co-I, 2021-2022<br><br>3) SATURN Trial, NIH StrokeNET U01NS102289, Site-PI, 2020- enrollment <br><br>completion<br><br><br><br>Immediate Family Member:<br><br>1) NIH AHRQ K08HS026008, PI, 2020-2023<br><br>2) NCATS KL2TR002545, PI 2018-2020
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
1) American Academy of Neurology Clinical Research Training Scholarship 2018-<br><br>21<br><br>2) David Heitman Neurovascular Fund 2018-20
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Caroline Booraem, BA
From the Division of Neurocritical Care (M.B.B., C.B., K.L., A.S.), Brigham and Women's Hospital; Division of Neurocritical Care (C.S., G.J.F., W.T.K.), Center for Genomic Medicine, Massachusetts General Hospital, Boston; and Department of Neurology (K.N.S., L.H.S.), Yale-New Haven Hospital, CT.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Karen Li, BBA
From the Division of Neurocritical Care (M.B.B., C.B., K.L., A.S.), Brigham and Women's Hospital; Division of Neurocritical Care (C.S., G.J.F., W.T.K.), Center for Genomic Medicine, Massachusetts General Hospital, Boston; and Department of Neurology (K.N.S., L.H.S.), Yale-New Haven Hospital, CT.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Anirudh Sreekrishnan, MD
From the Division of Neurocritical Care (M.B.B., C.B., K.L., A.S.), Brigham and Women's Hospital; Division of Neurocritical Care (C.S., G.J.F., W.T.K.), Center for Genomic Medicine, Massachusetts General Hospital, Boston; and Department of Neurology (K.N.S., L.H.S.), Yale-New Haven Hospital, CT.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Cristina Sastre, PhD
From the Division of Neurocritical Care (M.B.B., C.B., K.L., A.S.), Brigham and Women's Hospital; Division of Neurocritical Care (C.S., G.J.F., W.T.K.), Center for Genomic Medicine, Massachusetts General Hospital, Boston; and Department of Neurology (K.N.S., L.H.S.), Yale-New Haven Hospital, CT.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
From the Division of Neurocritical Care (M.B.B., C.B., K.L., A.S.), Brigham and Women's Hospital; Division of Neurocritical Care (C.S., G.J.F., W.T.K.), Center for Genomic Medicine, Massachusetts General Hospital, Boston; and Department of Neurology (K.N.S., L.H.S.), Yale-New Haven Hospital, CT.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NIH (grant #P30AG021342, co-investigator, 2021-2022)
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
American Heart Association (grant #817874, principal <br>investigator, 2020-2024).
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Kevin Navin Sheth, MD
From the Division of Neurocritical Care (M.B.B., C.B., K.L., A.S.), Brigham and Women's Hospital; Division of Neurocritical Care (C.S., G.J.F., W.T.K.), Center for Genomic Medicine, Massachusetts General Hospital, Boston; and Department of Neurology (K.N.S., L.H.S.), Yale-New Haven Hospital, CT.
Disclosure
Scientific Advisory Boards:
1.
(1) DSMB for Zoll sponsored study<br>(2) DSMB for Sense<br>(3) Cerovasc<br>(4) Astrocyte<br>(5) Rhaeos<br>(6) CSL
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
Editorial Board, Stroke<br>Editorial Board, Neurosurgery<br>Editorial Board, Annals of Neurology
Patents:
1.
Provisional patent Stroke detection technology<br>Provisional patent for nanoparticle technology
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
Astrocyte
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Bard, Biogen, Hyperfine
Research Support, Government Entities:
1.
(1) NIH U24NS107136, U24NS107215, U01NS106513, <br>RO1NR018335, R01EB031114, R01MD016178, R01NS110721
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
American Heart Association
Stock/stock Options/board of Directors Compensation:
1.
Materials: <br>Astrocyte, Alva, AbbieVie
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
Legal consultant
Lauren H. Sansing, MD, MS
From the Division of Neurocritical Care (M.B.B., C.B., K.L., A.S.), Brigham and Women's Hospital; Division of Neurocritical Care (C.S., G.J.F., W.T.K.), Center for Genomic Medicine, Massachusetts General Hospital, Boston; and Department of Neurology (K.N.S., L.H.S.), Yale-New Haven Hospital, CT.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NIH/NINDS, U01NS113445, PI, 2019-2022<br><br>NIH/NINDS R01NS095993, PI, 2016-2021<br><br>NIH/NINDS R01NS097728, PI, 2016-2021
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
American Heart Association, 19EIA34770133, PI, 2019-2024<br><br>American Heart Association, 2020AHA000BFCHS00199732, PI 2021-2025
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
W. Taylor Kimberly, MD, PhD https://orcid.org/0000-0002-2519-8530
From the Division of Neurocritical Care (M.B.B., C.B., K.L., A.S.), Brigham and Women's Hospital; Division of Neurocritical Care (C.S., G.J.F., W.T.K.), Center for Genomic Medicine, Massachusetts General Hospital, Boston; and Department of Neurology (K.N.S., L.H.S.), Yale-New Haven Hospital, CT.
Disclosure
Scientific Advisory Boards:
1.
(1) Biogen: Scientific Advisory board, funds paid to <br>Massachusetts General Hospital<br>(2) NControl Therapeutics: Scientific Advisory board
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
(1) Biogen: travel to investigator meetings as part of a <br>clinical trial
Editorial Boards:
1.
(1) Neurotherapeutics Journal: Associate Editor
Patents:
1.
(1) U.S. National Phase Application No. 16/486,687, filed <br>August 16, 2019. Methods and composition for treating a brain <br>injury.
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
(1) Biogen: for global co-PI work for the CHARM trial <br>(phase 3 clinical trial), funds paid to Massachusetts <br>General Hospital<br>(2) NControl Therapeutics
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
(1) Biogen: for global co-PI work for the CHARM trial <br>(phase 3 clinical trial), funds paid to Massachusetts <br>General Hospital<br>(2) NControl Therapeutics: for an observational study, funds <br>paid to Massachusetts General Hospital; sST2 knockout rat <br>model
Research Support, Government Entities:
1.
(1) NIH/NINDS, R01 NS099209, PI, 2016-present<br>(2) NIH/NINDS, R21 NSNS120002, PI, 2021-present<br>(3) NIH/NIBIB, R01 EB031114-01A1, MPI, 2022-present<br>(4) NIH/NINDS, R01 NS110721, co-I, 2019-present<br>(5) NIH/NINDS, U01 NS113443, co-I, 2019-present
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
(1) American Heart Association, 20SRG35540018, 2020-<br>2022
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
(1) Woolsey Pharmaceuticals, 2019
Legal Proceedings:
1.
NONE

Notes

Correspondence Dr. Bevers [email protected]
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Submitted and externally peer reviewed. The handling editor was Editor-in-Chief José Merino, MD, MPhil, FAAN.

Metrics & Citations

Metrics

Citations

Download Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.

Cited By
  1. Is Soluble ST2 a Novel Biomarker of Intracerebral Hemorrhage?, Neurology, 100, 13, (599-600), (2023)./doi/10.1212/WNL.0000000000206861
    Abstract
Loading...

View Options

Get Access

Login options

Check if you have access through your login credentials or your institution to get full access on this article.

Personal login Institutional Login
Purchase Options

Purchase this article to get full access to it.

Purchase Access, $39 for 24hr of access

View options

Short Form

View Short Form

Full Text

View Full Text

Full Text HTML

View Full Text HTML

Media

Figures

Other

Tables

Share

Share

Share article link

Share