Post-anoxic quantitative MRI changes may predict emergence from coma and functional outcomes at discharge

Abstract

Background Traditional predictors of neurological prognosis after cardiac arrest are unreliable after targeted temperature management. Absence of pupillary reflexes remains a reliable predictor of poor outcome. Diffusion-weighted imaging has emerged as a potential predictor of recovery, and here we compare imaging characteristics to pupillary exam. Methods We identified 69 patients who had MRIs within seven days of arrest and used a semi-automated algorithm to perform quantitative volumetric analysis of apparent diffusion coefficient (ADC) sequences at various thresholds. Area under receiver operating characteristic curves (ROC-AUC) were estimated to compare predictive values of quantitative MRI with pupillary exam at days 3, 5 and 7 post-arrest, for persistence of coma and functional outcomes at discharge. Cerebral Performance Category scores of 3–4 were considered poor outcome. Results Excluding patients where life support was withdrawn, ≥2.8% diffusion restriction of the entire brain at an ADC of ≤650 × 10−6 m2/s was 100% specific and 68% sensitive for failure to wake up from coma before discharge. The ROC-AUC of ADC changes at ≤450 × 10−6 mm2/s and ≤650 × 10−6 mm2/s were significantly superior in predicting failure to wake up from coma compared to bilateral absence of pupillary reflexes. Among survivors, >0.01% of diffusion restriction of the entire brain at an ADC ≤450 × 10−6 m2/s was 100% specific and 46% sensitive for poor functional outcome at discharge. The ROC curve predicting poor functional outcome at ADC ≤450 × 10−6 mm2/s had an AUC of 0.737 (0.574–0.899, p = 0.04). Conclusion Post-anoxic diffusion changes using quantitative brain MRI may aid in predicting persistent coma and poor functional outcomes at hospital discharge.

Independent Functional Outcomes after Prolonged Coma following Cardiac Arrest: A Mechanistic Hypothesis

“…Perhaps most importantly, our findings in conjunction with emerging clinical trials of neuroimaging markers of structural integrity in post–cardiac arrest comatose patients also support the broad use of structural imaging protocols (including MRIs) in such patients. Lack of neuroimaging evidence for overwhelming neuronal injury in persistently comatose patients should prompt a vigorous attempt to promote brain activation and aggressive treatment of ongoing seizures or other varying persistent functional abnormalities seen after cardiac arrest.…”

“…66,67 Lastly, ketogenic diet is increasingly used as an effective treatment for refractory seizures in adults, 68 another treatment modality thought to alter metabolic substrate availability even though the basic underlying mechanism is not completely understood. 69,70 Perhaps most importantly, our findings in conjunction with emerging clinical trials of neuroimaging markers of structural integrity in post-cardiac arrest comatose patients 17,18 also support the broad use of structural imaging protocols (including MRIs) in such patients. Lack of neuroimaging evidence for overwhelming neuronal injury in persistently comatose patients should prompt a vigorous attempt to promote brain activation and aggressive treatment of ongoing seizures or other varying persistent functional abnormalities seen after cardiac arrest.…”

“…However, following the widespread use of TTM, an increasing number of reports describe unexpected recoveries despite evidence of poor prognostic markers . In addition, a lack of imaging‐based evidence of anoxic cortical or white matter injuries after cardiac arrest may portend better outcomes, even in patients remaining in coma for more than 7 days . The poorly characterized physiological protective factors related to TTM suggest the possibility that in comatose post–cardiac arrest patients with wide preservation of cerebral structure, some negative predictive markers may only indicate a sustained abnormal state of global neuronal functions without permanent loss of potential to recover integrative cerebral functions.…”

Targeted Temperature Management and Multimodality Monitoring of Comatose Patients After Cardiac Arrest

“…Brain areas most susceptible to hypoxic-anoxic injury include the cerebral cortex and deep brain nuclei that include the caudate, basal ganglia and thalamus. Diffusion restriction involving these areas, characterized by hyperintensity on diffusion-weighted imaging (DWI) and hypointensity on apparent diffusion coefficient (ADC) images, predicts poor outcome with high specificity ( 85 , 87 , 88 ). In a study correlating MRI findings with neuron-specific enolase, a biomarker with high prognostic value, levels >33 μg/ml after CA was associated with extensive DWI changes in both deep nuclei and the cortex ( 89 ).…”

“…These patients had invariably poor outcome. More recently, quantitative measures of diffusion restriction burden on MRI has been proposed to standardize post-CA prognostication ( 86 , 87 , 90 , 91 ); however, the most appropriate thresholds have not been established. In one multi-centered study, an ADC value <650 × 10 −6 m 2 /s in ≥10% of the total brain volume independently predicted poor outcome with a specificity of 91% (95% CI 75–98) and sensitivity of 72% (95% CI 61–80), with >22% of brain volume needed to achieve 100% specificity ( 90 ).…”