Brain Death Cannot Be Determined by Imaging, Study Shows

 

• CT perfusion and angiography failed to meet sensitivity and specificity thresholds to determine brain death.
• Neither should be used as standalone tests to establish death by neurologic criteria, the researchers said.
• If used as supportive evidence, findings must be weighed against clinical assessments to minimize false-positives.

CT perfusion and CT angiography did not meet sensitivity and specificity thresholds of 98% to determine death by neurologic criteria (commonly referred to as brain death), a cohort study showed.

Qualitative brainstem CT perfusion had a sensitivity of 98.5% and a specificity of 74.4%, and quantitative brainstem CT perfusion was not diagnostically accurate, reported Michaël Chassé, MD, PhD, of the Centre Hospitalier de l'Université de Montréal, and co-authors. Qualitative whole-brain CT perfusion showed a sensitivity of 93.6% and a specificity of 92.3%.

CT angiography sensitivity ranged from 75.5% to 87.3%, and specificity ranged from 89.7% to 91.0%, the researchers reported in JAMA Neurologyopens in a new tab or window. The findings were also presented at the Critical Care Reviews Meetingopens in a new tab or window in Belfast, Ireland.

"Neither CT perfusion nor CT angiography met the prespecified threshold of greater than 98% for both sensitivity and specificity. Consequently, they should not be used as standalone tests to establish death by neurologic criteria," Chassé and colleagues wrote.

"However, they may offer supportive evidence in situations where the bedside examination is incomplete or confounded, but their findings must be weighed against a thorough clinical assessment to minimize false-positive determinations," they added.

Brain death occurs in people who have sustained catastrophic brain injury with no evidence of function of the brain as a whole, a state that must be permanent according to current guidelinesopens in a new tab or window. False-negative brain death criteria may prolong futile organ support, and false-positive criteria may lead to an erroneous declaration of death, the researchers noted.

"Although clinical evaluation forms the cornerstone of death by neurologic criteria, its validity can be influenced by confounding factors, such as the effects of sedative medications, traumatic injuries to the skull, or severe metabolic derangements," they wrote. "In these circumstances, death by neurologic criteria guidelines recommend additional ancillary investigation to determine the absence of brain blood flow or perfusion."

CT angiography visualizes blood flow within large cerebral vessels, and CT perfusion assesses tissue-level microvascular perfusion. "Importantly, neither technique measures neuronal function itself, which is what is assessed clinically or with functional tests, such as electroencephalography or evoked potentials," Chassé and co-authors pointed out.

In 2023, the American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society, and Society of Critical Care Medicine issued joint updated brain death guidelinesopens in a new tab or window, noting that while CT angiography has been used with increasing frequency to assist with brain death diagnoses, "available data demonstrate a lack of validation and the potential for false positives."

The World Brain Death Projectopens in a new tab or window also proposed international guidelines recently, saying ancillary tests like CT perfusion and CT angiography needed further study.

Chassé and colleagues studied 282 patients with a mean age of 57.8 years in 15 Canadian intensive care units from 2017 to 2021; nearly half (47%) were female. They included consecutive, critically ill adults with a Glasgow Coma Scale (GCS) score of 3 and no confounding factors who were at high risk of death by neurologic criteria. (The GCS ranges from 3 to 15, with 3 being the worst score and 15 the best.)

Causes of brain injury included hemorrhagic stroke in 53% of patients, anoxic brain injury in 21%, traumatic brain injury in 14%, ischemic stroke in 5%, infection in 1%, and tumor in 0.4%. Ultimately, 204 patients (72%) were declared dead by standardized clinical criteria.

The researchers assessed contrast-enhanced brain CT perfusion with CT angiography reconstructions performed within 2 hours of a blinded, standardized clinical brain death exam. Clinical assessments occurred a median of 64.5 minutes after ancillary testing.

CT perfusion and CT angiography images were interpreted independently by two experienced neuroradiologists blinded to all clinical information, including results from the clinical exam. "Interrater reliability was excellent for all ancillary tests," Chassé and co-authors said: κ ranged from 0.81 to 0.84.

Fourteen patients (5%) experienced minor adverse events, and no serious adverse events occurred.

The study had several limitations, Chassé and colleagues acknowledged. "We used the clinical determination of death by neurologic criteria as the reference standard, which, although widely accepted, has known limitations," they wrote.

Most imaging was performed within the first few days of injury, and whether accuracy would be similar later -- after patients may have had prolonged life-sustaining therapies -- is unknown, they added.

Disclosures

This work was funded by the Canadian Institutes of Health Research.

Chassé reported receiving grants from the Canadian Institutes of Health Research during the conduct of the study. Co-authors reported receiving grants and fees from other groups and having diagnostic patents.

Primary Source

JAMA Neurology

Source Reference: opens in a new tab or windowChassé M, et al "Computed tomography perfusion and angiography for death by neurologic criteria" JAMA Neurol 2025; DOI: 10.1001/jamaneurol.2025.2375.

https://www.medpagetoday.com/neurology/generalneurology/116076