Article (Scientific journals)
Therapies to Restore Consciousness in Patients with Severe Brain Injuries: A Gap Analysis and Future Directions
Edlow, Brian; Sanz, Leandro; Polizzotto, Len et al.
2021In Neurocritical Care, 35, p. 68-85
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Keywords :
coma; consciousness; disorders of consciousness; gap analysis; precision medicine
Abstract :
[en] Background/Objective For patients with disorders of consciousness (DoC) and their families, the search for new therapies has been a source of hope and frustration. Almost all clinical trials in patients with DoC have been limited by small sample sizes, lack of placebo groups, and use of heterogeneous outcome measures. As a result, few therapies have strong evidence to support their use; amantadine is the only therapy recommended by current clinical guidelines, specifically for patients with DoC caused by severe traumatic brain injury. To foster and advance development of consciousness-promoting therapies for patients with DoC, the Curing Coma Campaign convened a Coma Science Work Group to perform a gap analysis. Methods We consider five classes of therapies: (1) pharmacologic; (2) electromagnetic; (3) mechanical; (4) sensory; and (5) regenerative. For each class of therapy, we summarize the state of the science, identify gaps in knowledge, and suggest future directions for therapy development. Results Knowledge gaps in all five therapeutic classes can be attributed to the lack of: (1) a unifying conceptual framework for evaluating therapeutic mechanisms of action; (2) large-scale randomized controlled trials; and (3) pharmacodynamic biomarkers that measure subclinical therapeutic effects in early-phase trials. To address these gaps, we propose a precision medicine approach in which clinical trials selectively enroll patients based upon their physiological receptivity to targeted therapies, and therapeutic effects are measured by complementary behavioral, neuroimaging, and electrophysiologic endpoints. Conclusions This personalized approach can be realized through rigorous clinical trial design and international collaboration, both of which will be essential for advancing the development of new therapies and ultimately improving the lives of patients with DoC.
Research center :
Giga Consciousness-Coma Science Group ; CHU de Liège - Centre du Cerveau²
Disciplines :
Author, co-author :
Edlow, Brian 
Sanz, Leandro   ;  Université de Liège - ULiège > GIGA Consciousness - Coma Science Group
Polizzotto, Len
Pouratian, Nader
Rolston, John
Snider, Samuel
Thibaut, Aurore ;  Université de Liège - ULiège > GIGA > GIGA Consciousness - Coma Science Group ; CHU Liège - Centre Hospitalier Universitaire de Liège > Centre du Cerveau
Stevens, Robert 
Gosseries, Olivia   ;  Université de Liège - ULiège > GIGA Consciousness - Coma Science Group
 These authors have contributed equally to this work.
Language :
Title :
Therapies to Restore Consciousness in Patients with Severe Brain Injuries: A Gap Analysis and Future Directions
Publication date :
08 July 2021
Journal title :
Neurocritical Care
Publisher :
Humana Press, United States
Volume :
Pages :
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
The Curing Coma Campaign
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
FRB - Fondation Roi Baudouin [BE]
Fonds Léon Fredericq [BE]
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