We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Comment & Response |

Diffusion Hypoxia and/or Primary Mitochondrial Failure?—Reply ONLINE FIRST

Jonathan P. Coles, PhD1; David K. Menon, PhD1
[+] Author Affiliations
1Division of Anaesthesia, University of Cambridge, Addenbrooke’s Hospital, Cambridge, Cambridgeshire, England
JAMA Neurol. Published online September 12, 2016. doi:10.1001/jamaneurol.2016.3263
Text Size: A A A
Published online


In Reply Lazaridis highlights that while we found evidence of low cerebral blood flow and increased oxygen extraction consistent with ischemia following clinical head injury,1 tissue hypoxia can also result from pathophysiological mechanisms that cannot be explained by macrovascular ischemia with such classic characteristics. Despite comparable perfusion deficits, oxygen extraction is not increased in such regions. We postulate that this may result from an inability to increase the fraction of oxygen extracted from that available due to microvascular occlusion and perivascular edema within the injured brain (diffusion hypoxia). Such pathophysiological mechanisms are distributed heterogeneously across the injured brain, but particularly within the vicinity of brain lesions. Few participants in this cohort underwent monitoring of brain tissue oxygen and microdialysis, and those who did were not placed in the vicinity of regions with relevant pathophysiology. Despite this, flourine 18–labeled fluoromisonidazole trapping is a marker of hypoxia2 and was used in this imaging study to define tissue hypoxia across the whole brain in relation to cerebral blood flow, blood volume, oxygen metabolism, and oxygen extraction fraction. Mitochondrial dysfunction has been found following head injury3 and could contribute to the metabolic derangements that we have shown, particularly in the presence of tissue hypoxia,4 but would not explain the presence of tissue hypoxia per se (and by inference, increased flourine 18–labeled fluoromisonidazole uptake). The predominant finding in this article was that tissue hypoxia can occur in the absence of macrovascular ischemia. This finding may characterize a region of microvascular failure and is a target for future neuroprotective strategies.


Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

First Page Preview

View Large
First page PDF preview





September 12, 2016
Christos Lazaridis, MD
1Division of Neurocritical Care and Vascular Neurology, Department of Neurology, Baylor College of Medicine, Houston, Texas
JAMA Neurol. Published online September 12, 2016.;():. doi:10.1001/jamaneurol.2016.3260.
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

0 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

See Also...