Evidence map›Paper›PMID 34236624›Full record

ArticleNeurocritical care2021

Therapies to Restore Consciousness in Patients with Severe Brain Injuries: A Gap Analysis and Future Directions.

Brian L Edlow, Leandro R D Sanz, Len Polizzotto, Nader Pouratian, John D Rolston, Samuel B Snider, Aurore Thibaut, Robert D Stevens, Olivia Gosseries, Curing Coma Campaign and its contributing members

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurocritical care, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed, 3 pooled it
14.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

71 citing papers in PubMed, 3 syntheses or guidelines pooled it, 125 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. Trial
  7. Review
  8. Article
  9. Ethical Considerations in Transcranial Focused Ultrasound Neuromodulation for Disorders of Consciousness.Neuromodulation : journal of the International Neuromodulation Society · 2026
    Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Frontal Disorders and Consciousness: A Review.Current neurology and neuroscience reports · 2025
    Review
  19. Article
  20. Article

11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 7 institutions in 2 countries.

Brian L Edlow *Center for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 175 Cambridge Street - Suite 300, Boston, MA, 02114, USA. bedlow@mgh.harvard.edu.ORCID http://orcid.org/0000-0001-7235-8456
Leandro R D Sanz *Coma Science Group, GIGA-Consciousness, GIGA, University of Liege, Liege, Belgium.
Len PolizzottoDepartment of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, USA.
Nader PouratianDepartment of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
John D RolstonDepartments of Neurosurgery and Biomedical Engineering, University of Utah, Salt Lake City, UT, USA.
Samuel B SniderDepartment of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Aurore ThibautComa Science Group, GIGA-Consciousness, GIGA, University of Liege, Liege, Belgium.
Robert D Stevens *Departments of Anesthesiology and Critical Care Medicine, Radiology, and Neurology and Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Olivia Gosseries *Coma Science Group, GIGA-Consciousness, GIGA, University of Liege, Liege, Belgium.
Curing Coma Campaign and its contributing members
University of Liège · BEUniversity of Utah · USBrigham and Women's Hospital · USHarvard University · USJohns Hopkins University · USUniversity of California, Los Angeles · USWorcester Polytechnic Institute · US

Funding

The Late Effects of TBI (LETBI) Study: Injury Patterns and Biological Markers of Post-Traumatic NeurodegenerationRF1NS115268 · NINDS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Kristen Dams-O'Connor · 2019 to 2026
$10.3M
A Connectome-Based Clinical Trial Platform to Promote Early Recovery of Consciousness after Traumatic ComaDP2HD101400 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI EDLOW, BRIAN L. · 2019 to 2019
$2.5M
Patient-Specific Modeling and Network Perturbation to Enhance the Predictability of Direct Cortical Stimulation for EpilepsyK23NS114178 · NINDS · UNIVERSITY OF UTAH · PI ROLSTON, JOHN D · 2019 to 2023
$961k
Brainstem Connectome Mapping to Guide Targeted Stimulant Therapy in Patients with Traumatic ComaR21NS109627 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI EDLOW, BRIAN L. · 2019 to 2020
$480k
NICHD NIH HHS DP2 HD101400NINDS NIH HHS K23 NS114178NINDS NIH HHS R21 NS109627NINDS NIH HHS RF1 NS115268
6 · The paper itself

Abstract

BACKGROUND/

objectiveFor 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.

methodsWe 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.

resultsKnowledge 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.

conclusionsThis 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.

Indexed as

Brain Injuries, TraumaticConsciousnessComaConsciousness DisordersHumansNeuroimagingComaConsciousnessDisorders of consciousnessGap analysisPrecision medicine

Identifiers

PMID34236624
PMCPMC8266715
OpenAlexW3181074154

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.