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We appreciate the comments of Rady and Verheijde (1) and are grateful for the opportunity to clarify certain aspects of our recently published article in Critical Care Medicine (2). Opposite to a current view suggesting that standard MRI T1-weightened sequences are not precise enough to early detect brain structural anomalies in this setting, we demonstrated that anoxic comatose patients displayed significantly extensive cortical and subcortical brain volumes atrophy compared with matched controls, providing new insights into the brain structural impact of anoxic/hypoxic insult related to cardiac arrest (CA), and paving the way for the use of this innovative neuroimaging tools in CA survivors neuroprognostication. It is worth noting that despite these promising results, we have never suggested that quantitative MRI morphometry should be used in isolation as a prognosticator for post-CA patients, but rather advocated for their use in conjunction with other prognostic variables available, as currently recommended in this challenging setting (3).
Rady and Verheijde (1) raise concerns about to which extent the structural anomalies that we have observed, are specifically related to the anoxic-ischemic brain insult. It should be noted that, as a variant to most of the studies in the field (3), we have carefully controlled and matched patients and control groups, on age and sex. Nevertheless, we agree that additional variable as cultural level or previous cognitive decline—both well-known brain atrophy associated factors—were not controlled in the current study and would need to be specifically addressed. Furthermore, we confirm that we have exclusively observed a dissociated pattern of atrophy between cortical and subcortical structures on the patients group, suggesting a specific vulnerability/adaptability of cortical/subcortical structures towards CA-related brain injury. Concerning our colleague’s suggestion of recording and comparing structural MRI of the same subjects, before and after CA, we consider that ethical and feasibility issues (i.e., CA yearly occurrence rate of about 50–110 per 100,000 people worldwide) (2) would render this approach impracticable.
Finally, our colleagues put into the light the crucial issue of the “gold standard” methods that should be used to test potential neuroimaging-derived predictors in this setting. It is worth noting that we have used blinded assessment of outcomes, which were performed 1 year after the coma onset, using a standardized and validated scale (Glasgow Outcome Scale-Extended) (4). We think that complementary clinical scoring tools, which more accurately discriminate the full span of acquired disorders of consciousness (e.g., Coma Recovery Scale-Revised) (5), could be used instead. Nevertheless, we disagree with the idea of employing additional neuroimaging surrogates (e.g., transcranial magnetic stimulation) to validate novel neuroprognostication methods (e.g., structural MRI). We suggest that such a combination of techniques could be better suited to 1) increase the understanding of the pathophysiologic mechanisms underpinning functional/structural changes induced by severe brain injury and further elucidating the neural substrates of consciousness and 2) ultimately provide clinically useful multimodal batteries of test, validated against robust behavioral data.
Innovations in the recordings and processing of neuroimaging have produced a cornucopia of possibilities to assess the structure and function of the brain in patients with acquired disorders of consciousness. But even if further large-scale validation studies are required, the novelty of these approaches should not impede us to assess their usefulness in this defiant setting, where pervasive nihilism (6) prevail, and patients are frequently viewed through an end-of-life prism, leaving them marginalized from the evolving fruits of neuroscience.
Dr. Silva has disclosed that he does not have any potential conflicts of interest.
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