The thalamic basis of outcome and cognitive impairment in traumatic brain injury

Abstract

Objective: To understand how, biologically, the acute event of traumatic brain injury gives rise to a longterm disease, we address the relationship between evolving cortical and subcortical brain damage and measures of functional outcome and cognitive functioning at six months post-injury.Methods: Longitudinal analysis of clinical and MRI data collected, in a tertiary neurointensive care setting, in a continuous sample of 157 patients surviving moderate to severe traumatic brain injury between 2000 and 2018. For each patient we collected T1-and T2-weighted MRI data, acutely and at a six-months follow-up, as well as acute measures of injury severity (Glasgow Coma Scale) and follow-up measures of functional impairment (Glasgow Outcome Scale extended), and, in a subset of patients, neuropsychological measures of attention, executive functions, and episodic memory. Results:In the final cohort of 113 subcortical and 92 cortical datasets that survived (blind) quality control, extensive atrophy was observed over the first six months post-injury across the brain.Nonetheless, only atrophy within subcortical regions, particularly in left thalamus, were associated with functional outcome and neuropsychological measures of attention, executive functions, and episodic memory. Furthermore, when brought together in an analytical model, longitudinal brain measurements could distinguish good versus bad outcome with 90% accuracy, whereas acute brain and clinical measurements alone could only achieve 20% accuracy.Interpretation. Despite great injury heterogeneity, secondary thalamic pathology is a measurable minimum common denominator mechanism directly relating biology to clinical measures of outcome and cognitive functioning, potentially linking the acute "event" and the long(er)-term "disease" of TBI.The long-term effects and neurological consequences of moderate-to-severe traumatic brain injury (TBI), including its association with cognitive, emotional, and behavioral dysfunction, are a source of increased concern. 1, 2 According to the TBI Model Systems National Database, of the patients who survive TBI, 22% die within 5 years, 30% suffer cognitive and behavioral declines, 22% show no amelioration, and only 26% demonstrate cognitive and behavioral improvements. 3 Furthermore, TBI patients are known to have increased risk of neurodegenerative disorders and mortality -with the latter potentially secondary to impairments such as executive dysfunction. 4 Gaining a detailed understanding of the relationship between the acute "event" of TBI and its evolving consequences, including cortical and subcortical non-mechanic, time-delayed processes, 5, 6 functional outcomes, 7,8 and cognitive impairment, is paramount for the development of better prognostic models, interventions, 9 and for alleviating the emotional, social, and economic burden of TBI. 10Here, we present a large cohort, longitudinal, study aimed at leveraging conventional clinical magnetic resonance imaging (MRI) data to assess the progression of cortical and subcortical br...

Toward a Global and Reproducible Science for Brain Imaging in Neurotrauma: The ENIGMA Adult Moderate/Severe Traumatic Brain Injury Working Group

“…This is consistent with a subsequent study which found that normobaric hyperoxia may pseudo-normalize the ADC in the cytotoxic rim (Veenith et al, 2014). Acute and early clinical MRI, in conjunction with carefully executed experimental animal studies, can also shed light on the mechanisms underlying msTBI (Lutkenhoff et al, 2019).…”

“…However, this information is less valuable for evaluating patients presenting with less severe injuries or more fine-tuned prognostication of long-term neurobehavioral outcome. Indeed, often individuals with similar indicators of severity and early clinical trajectories experience different outcomes (Bigler et al, 2006;Lutkenhoff et al, 2019). Recovery and community reintegration is further complicated by a number of interacting premorbid, clinical, demographic, and genetic factors (Mollayeva et al, 2019).…”

“…Novel analysis techniques may also help to interpret longitudinal changes as well as help predict ongoing trajectories of change. For example, there is a literature using functional MRI (Crone et al, 2018;Hillary et al, 2014;Rajtmajer et al, 2015;Roy et al, 2016), structural (Lutkenhoff et al, 2013(Lutkenhoff et al, , 2019, and multimodal data (e.g., structural MRI and EEG; Schnakers et al, 2019) to examine recovery in small samples of AMS-TBI during the first year post injury, but we also need more robust methods tailored for more long-term consequences of TBI (Cruz-Haces et al, 2017) which can also handle heterogeneous outcome trajectories. We anticipate that international collaborations, with careful meta-analysis of data from multiple centers, will provide novel avenues for exploring and clarifying chronic and long-term effects of TBI.…”

Toward a global and reproducible science for brain imaging in neurotrauma: the ENIGMA adult moderate/severe traumatic brain injury working group

“…This is consistent with a subsequent study which found that normobaric hyperoxia may pseudo-normalize the ADC in the cytotoxic rim (Veenith et al 2014). Acute and early clinical MRI, in conjunction with carefully executed experimental animal studies, can also shed light on the mechanisms underlying msTBI (Lutkenhoff et al 2019). Moreover, the value of early MRI is not limited to structural scans.…”

“…However, this information is less valuable for evaluating patients presenting with less severe injuries or more fine-tuned prognostication of long-term neurobehavioral outcome. Indeed, often individuals with similar indicators of severity and early clinical trajectories experience different outcomes (Bigler et al 2006;Lutkenhoff et al 2019). Recovery and community re-integration are further complicated by a number of interacting premorbid, clinical, demographic, and genetic factors (Mollayeva et al 2019).…”