Ruchira M Jha1,2,3,4,5, Patrick M Kochanek6,7,8,9,10,11. 1. Department of Critical Care Medicine, Room 646A, Scaife Hall, 3550 Terrace Street, Pittsburgh, 15261, PA, USA. jharm3@upmc.edu. 2. Safar Center for Resuscitation Research John G. Rangos Research Center, 6th Floor; 4401 Penn Avenue, Pittsburgh, PA, 15224, USA. jharm3@upmc.edu. 3. Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. jharm3@upmc.edu. 4. Department of Neurological Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. jharm3@upmc.edu. 5. Clinical and Translational Science Institute, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. jharm3@upmc.edu. 6. Department of Critical Care Medicine, Room 646A, Scaife Hall, 3550 Terrace Street, Pittsburgh, 15261, PA, USA. 7. Safar Center for Resuscitation Research John G. Rangos Research Center, 6th Floor; 4401 Penn Avenue, Pittsburgh, PA, 15224, USA. 8. Clinical and Translational Science Institute, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. 9. Department of Anesthesiology, University of Pittsburgh, Pittsburgh, PA, USA. 10. Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. 11. UPMC Children's Hospital of Pittsburgh John G. Rangos Research Center, 6th Floor 4401 Penn Avenue, Pittsburgh, PA, 15224, USA.
Abstract
PURPOSE OF REVIEW: Standard clinical protocols for treating cerebral edema and intracranial hypertension after severe TBI have remained remarkably similar over decades. Cerebral edema and intracranial hypertension are treated interchangeably when in fact intracranial pressure (ICP) is a proxy for cerebral edema but also other processes such as extent of mass lesions, hydrocephalus, or cerebral blood volume. A complex interplay of multiple molecular mechanisms results in cerebral edema after severe TBI, and these are not measured or targeted by current clinically available tools. Addressing these underpinnings may be key to preventing or treating cerebral edema and improving outcome after severe TBI. RECENT FINDINGS: This review begins by outlining basic principles underlying the relationship between edema and ICP including the Monro-Kellie doctrine and concepts of intracranial compliance/elastance. There is a subsequent brief discussion of current guidelines for ICP monitoring/management. We then focus most of the review on an evolving precision medicine approach towards cerebral edema and intracranial hypertension after TBI. Personalization of invasive neuromonitoring parameters including ICP waveform analysis, pulse amplitude, pressure reactivity, and longitudinal trajectories are presented. This is followed by a discussion of cerebral edema subtypes (continuum of ionic/cytotoxic/vasogenic edema and progressive secondary hemorrhage). Mechanisms of potential molecular contributors to cerebral edema after TBI are reviewed. For each target, we present findings from preclinical models, and evaluate their clinical utility as biomarkers and therapeutic targets for cerebral edema reduction. This selection represents promising candidates with evidence from different research groups, overlap/inter-relatedness with other pathways, and clinical/translational potential. We outline an evolving precision medicine and translational approach towards cerebral edema and intracranial hypertension after severe TBI.
PURPOSE OF REVIEW: Standard clinical protocols for treating cerebral edema and intracranial hypertension after severe TBI have remained remarkably similar over decades. Cerebral edema and intracranial hypertension are treated interchangeably when in fact intracranial pressure (ICP) is a proxy for cerebral edema but also other processes such as extent of mass lesions, hydrocephalus, or cerebral blood volume. A complex interplay of multiple molecular mechanisms results in cerebral edema after severe TBI, and these are not measured or targeted by current clinically available tools. Addressing these underpinnings may be key to preventing or treating cerebral edema and improving outcome after severe TBI. RECENT FINDINGS: This review begins by outlining basic principles underlying the relationship between edema and ICP including the Monro-Kellie doctrine and concepts of intracranial compliance/elastance. There is a subsequent brief discussion of current guidelines for ICP monitoring/management. We then focus most of the review on an evolving precision medicine approach towards cerebral edema and intracranial hypertension after TBI. Personalization of invasive neuromonitoring parameters including ICP waveform analysis, pulse amplitude, pressure reactivity, and longitudinal trajectories are presented. This is followed by a discussion of cerebral edema subtypes (continuum of ionic/cytotoxic/vasogenic edema and progressive secondary hemorrhage). Mechanisms of potential molecular contributors to cerebral edema after TBI are reviewed. For each target, we present findings from preclinical models, and evaluate their clinical utility as biomarkers and therapeutic targets for cerebral edema reduction. This selection represents promising candidates with evidence from different research groups, overlap/inter-relatedness with other pathways, and clinical/translational potential. We outline an evolving precision medicine and translational approach towards cerebral edema and intracranial hypertension after severe TBI.
Authors: Kevin N Sheth; Jordan J Elm; Bradley J Molyneaux; Holly Hinson; Lauren A Beslow; Gordon K Sze; Ann-Christin Ostwaldt; Gregory J Del Zoppo; J Marc Simard; Sven Jacobson; W Taylor Kimberly Journal: Lancet Neurol Date: 2016-08-23 Impact factor: 44.182
Authors: John K Yue; Mary J Vassar; Hester F Lingsma; Shelly R Cooper; David O Okonkwo; Alex B Valadka; Wayne A Gordon; Andrew I R Maas; Pratik Mukherjee; Esther L Yuh; Ava M Puccio; David M Schnyer; Geoffrey T Manley Journal: J Neurotrauma Date: 2013-09-24 Impact factor: 5.269
Authors: Marco A Stefani; Rafael Modkovski; Gisele Hansel; Eduardo R Zimmer; Afonso Kopczynski; Alexandre P Muller; Nathan R Strogulski; Marcelo S Rodolphi; Randhall K Carteri; André P Schmidt; Jean P Oses; Douglas H Smith; Luis V Portela Journal: Ann Clin Transl Neurol Date: 2017-05-04 Impact factor: 4.511
Authors: Bridgette D Semple; Linda J Noble-Haeusslein; Major Gooyit; Kayleen G Tercovich; Zhihong Peng; Trung T Nguyen; Valerie A Schroeder; Mark A Suckow; Mayland Chang; Jacob Raber; Alpa Trivedi Journal: PLoS One Date: 2015-11-20 Impact factor: 3.240
Authors: Ruchira M Jha; Anupama Rani; Shashvat M Desai; Sudhanshu Raikwar; Sandra Mihaljevic; Amanda Munoz-Casabella; Patrick M Kochanek; Joshua Catapano; Ethan Winkler; Giuseppe Citerio; J Claude Hemphill; W Taylor Kimberly; Raj Narayan; Juan Sahuquillo; Kevin N Sheth; J Marc Simard Journal: Int J Mol Sci Date: 2021-11-02 Impact factor: 5.923
Authors: Dongjing Liu; Benjamin E Zusman; John R Shaffer; Yunqi Li; Annie I Arockiaraj; Shuwei Liu; Daniel E Weeks; Shashvat M Desai; Patrick M Kochanek; Ava M Puccio; David O Okonkwo; Yvette P Conley; Ruchira M Jha Journal: Neurocrit Care Date: 2022-01-13 Impact factor: 3.532
Authors: Ruchira M Jha; Stefania Mondello; Helen M Bramlett; C Edward Dixon; Deborah A Shear; W Dalton Dietrich; Kevin K W Wang; Zhihui Yang; Ronald L Hayes; Samuel M Poloyac; Philip E Empey; Audrey D Lafrenaye; Hong Q Yan; Shaun W Carlson; John T Povlishock; Janice S Gilsdorf; Patrick M Kochanek Journal: J Neurotrauma Date: 2020-12-18 Impact factor: 5.269
Authors: Ruchira M Jha; Benjamin E Zusman; Ava M Puccio; David O Okonkwo; Matthew Pease; Shashvat M Desai; Matthew Leach; Yvette P Conley; Patrick M Kochanek Journal: JAMA Netw Open Date: 2021-07-01