Neurocritical care
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Cerebral edema and intracranial hypertension are major contributors to unfavorable prognosis in traumatic brain injury (TBI). Local epigenetic changes, particularly in DNA methylation, may influence gene expression and thus host response/secondary injury after TBI. It remains unknown whether DNA methylation in the central nervous system is associated with cerebral edema severity or intracranial hypertension post TBI. We sought to identify epigenome-wide DNA methylation patterns associated with these forms of secondary injury after TBI. ⋯ We report a novel potential relationship between intracranial hypertension after TBI and an acute, nonsustained reduction in DNA methylation at cg22111818 in the RGMA gene. To our knowledge, this is the largest EWAS in severe TBI. Our findings are further strengthened by previous findings that RGMA modulates axonal repair in other central nervous system disorders, but a role in intracranial hypertension or TBI has not been previously identified. Additional work is warranted to validate and extend these findings, including assessment of its possible role in risk stratification, identification of novel druggable targets, and ultimately our ability to personalize therapy in TBI.
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Abstraction of critical data from unstructured radiologic reports using natural language processing (NLP) is a powerful tool to automate the detection of important clinical features and enhance research efforts. We present a set of NLP approaches to identify critical findings in patients with acute ischemic stroke from radiology reports of computed tomography (CT) and magnetic resonance imaging (MRI). ⋯ Our study demonstrates robust performance and external validity of a core NLP tool kit for identifying both categorical and continuous outcomes of ischemic stroke from unstructured radiographic text data. Medically tailored NLP methods have multiple important big data applications, including scalable electronic phenotyping, augmentation of clinical risk prediction models, and facilitation of automatic alert systems in the hospital setting.
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The Curing Coma Campaign (CCC) is a multidisciplinary global initiative focused on evaluation, diagnosis, treatment, research, and prognostication for patients who are comatose due to any etiology. To support this mission, the CCC Ethics Working Group conducted a survey of CCC collaborators to identify the ethics priorities of the CCC and the variability in priorities based on country of practice. ⋯ Collaborators of the CCC considered clinical care, diagnostic definitions, and clinical research the top ethics priorities of the CCC. These priorities should be considered as the CCC explores ways to improve evaluation, diagnosis, treatment, research, and prognostication of patients with coma and associated disorders of consciousness. There is some variability in ethics priorities based on country of practice.
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Observational Study
Predicting Clinical Outcomes 7-10 Years after Severe Traumatic Brain Injury: Exploring the Prognostic Utility of the IMPACT Lab Model and Cerebrospinal Fluid UCH-L1 and MAP-2.
Severe traumatic brain injury (TBI) is a major contributor to disability and mortality in the industrialized world. Outcomes of severe TBI are profoundly heterogeneous, complicating outcome prognostication. Several prognostic models have been validated for acute prediction of 6-month global outcomes following TBI (e.g., morbidity/mortality). In this preliminary observational prognostic study, we assess the utility of the International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) Lab model in predicting longer term global and cognitive outcomes (7-10 years post injury) and the extent to which cerebrospinal fluid (CSF) biomarkers enhance outcome prediction. ⋯ Although preliminary, results suggest that existing prognostic models, including models with incorporation of CSF markers, may be applied to predict outcome of severe TBI years after injury. Continued research is needed examining early predictors of longer-term outcomes following TBI to identify potential targets for clinical trials that could impact long-ranging functional and cognitive outcomes.
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Pregabalin (PGB) is an effective adjunctive treatment for focal epilepsy and acts by binding to the alpha2-delta subunit of voltage-gated calcium channels to reduce excitatory neurotransmitter release. Limited data exist on its use in the neurocritical care setting, including cyclic seizures-a pattern of recurrent seizures occurring at nearly regular intervals. Although the mechanism underpinning cyclic seizures remains elusive, spreading excitation linked to spreading depolarizations may play a role in seizure recurrence and periodicity. PGB has been shown to increase spreading depolarization threshold; hence, we hypothesized that the magnitude of antiseizure effect from PGB is more pronounced in patients with cyclic versus noncyclic seizures in a critically ill cohort with recurrent seizures. ⋯ PGB was associated with a relative reduction in seizure burden in neurocritically ill patients with recurrent seizures, especially those with cyclic seizures, and may be considered in the therapeutic arsenal for refractory seizures. Whether this effect is mediated via modulation of spreading depolarization requires further study.