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Neuroimmune activation is associated with neurological outcome in anoxic and traumatic coma.

ABSTRACT: The pathophysiological underpinnings of critically disrupted brain connectomes resulting in coma are poorly understood. Inflammation is potentially an important but still undervalued factor. Here, we present a first-in-human prospective study using the 18-kDa translocator protein (TSPO) radioligand 18F-DPA714 for PET imaging to allow in vivo neuroimmune activation quantification in patients with coma (n = 17) following either anoxia or traumatic brain injuries in comparison with age- and sex-matched controls. Our findings yielded novel evidence of an early inflammatory component predominantly located within key cortical and subcortical brain structures that are putatively implicated in consciousness emergence and maintenance after severe brain injury (i.e. mesocircuit and frontoparietal networks). We observed that traumatic and anoxic patients with coma have distinct neuroimmune activation profiles, both in terms of intensity and spatial distribution. Finally, we demonstrated that both the total amount and specific distribution of PET-measurable neuroinflammation within the brain mesocircuit were associated with the patient's recovery potential. We suggest that our results can be developed for use both as a new neuroprognostication tool and as a promising biometric to guide future clinical trials targeting glial activity very early after severe brain injury.

SUBMITTER: Sarton B

PROVIDER: S-EPMC10994537 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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Neuroimmune activation is associated with neurological outcome in anoxic and traumatic coma.

Sarton Benjamine B Tauber Clovis C Fridman Estéban E Péran Patrice P Riu Beatrice B Vinour Hélène H David Adrian A Geeraerts Thomas T Bounes Fanny F Minville Vincent V Delmas Clément C Salabert Anne-Sophie AS Albucher Jean François JF Bataille Benoit B Olivot Jean Marc JM Cariou Alain A Naccache Lionel L Payoux Pierre P Schiff Nicholas N Silva Stein S

Brain : a journal of neurology 20240401 4

The pathophysiological underpinnings of critically disrupted brain connectomes resulting in coma are poorly understood. Inflammation is potentially an important but still undervalued factor. Here, we present a first-in-human prospective study using the 18-kDa translocator protein (TSPO) radioligand 18F-DPA714 for PET imaging to allow in vivo neuroimmune activation quantification in patients with coma (n = 17) following either anoxia or traumatic brain injuries in comparison with age- and sex-mat ...[more]

PMID: 38412555

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Project description:ObjectivesRecovery from coma might critically depend on the structural and functional integrity of frontoparietal networks. We aimed to measure this integrity in traumatic brain injury and anoxo-ischemic (cardiac arrest) coma patients by using an original multimodal MRI protocol.DesignProspective cohort study.SettingThree Intensive Critical Care Units affiliated to the University in Toulouse (France).PatientsWe longitudinally recruited 43 coma patients (Glasgow Coma Scale at the admission < 8; 29 cardiac arrest and 14 traumatic brain injury) and 34 age-matched healthy volunteers. Exclusion criteria were disorders of consciousness lasting more than 30 days and focal brain damage within the explored brain regions. Patient assessments were conducted at least 2 days (5 ± 2 d) after complete withdrawal of sedation. All patients were followed up (Coma Recovery Scale-Revised) 3 months after acute brain injury.InterventionsNone.Measurements and main resultsFunctional and structural MRI data were recorded, and the analysis was targeted on the posteromedial cortex, the medial prefrontal cortex, and the cingulum. Univariate analyses and machine learning techniques were used to assess diagnostic and predictive values. Coma patients displayed significantly lower medial prefrontal cortex-posteromedial cortex functional connectivity (area under the curve, 0.94; 95% CI, 0.93-0.95). Cardiac arrest patients showed specific structural disturbances within posteromedial cortex. Significant cingulum architectural disturbances were observed in traumatic brain injury patients. The machine learning medial prefrontal cortex-posteromedial cortex multimodal classifier had a significant predictive value (area under the curve, 0.96; 95% CI, 0.95-0.97), best combination of subregions that discriminates a binary outcome based on Coma Recovery Scale-Revised).ConclusionsThis exploratory study suggests that frontoparietal functional disconnections are specifically observed in coma and their structural counterpart provides information about brain injury mechanisms. Multimodal MRI biomarkers of frontoparietal disconnection predict 3-month outcome in our sample. These findings suggest that fronto-parietal disconnection might be particularly relevant for coma outcome prediction and could inspire innovative precision medicine approaches.

Project description:AimCurrent multimodal approaches leave approximately half of the comatose patients after cardiac arrest with an indeterminate prognosis. Here we investigated whether early MRI markers of brain network integrity can distinguish between comatose patients with a good versus poor neurological outcome six months later.MethodsWe performed a prospective cohort study in 48 patients after cardiac arrest submitted in a comatose state to the Intensive Care Unit of two Dutch hospitals. MRI was performed at three days after cardiac arrest, including resting state functional MRI and diffusion-tensor imaging (DTI). Resting state fMRI was used to quantify functional connectivity within ten resting-state networks, and DTI to assess mean diffusivity (MD) in these same networks. We contrasted two groups of patients, those with good (n = 29, cerebral performance category 1-2) versus poor (n = 19, cerebral performance category 3-5) outcome at six months. Mutual associations between functional connectivity, MD, and clinical outcome were studied.ResultsPatients with good outcome show higher within-network functional connectivity (fMRI) and higher MD (DTI) than patients with poor outcome across 8/10 networks, most prominent in the default mode network, salience network, and visual network. While the anatomical distribution of outcome-related changes was similar for functional connectivity and MD, the pattern of inter-individual differences was very different: functional connectivity showed larger inter-individual variability in good versus poor outcome, while the opposite was observed for MD. Exploratory analyses suggested that it is possible to define network-specific cut-off values that could help in outcome prediction: (1) high functional connectivity and high MD, associated with good outcome; (2) low functional connectivity and low MD, associated with poor outcome; (3) low functional connectivity and high MD, associated with uncertain outcome.DiscussionResting-state functional connectivity and mean diffusivity-three days after cardiac arrest are strongly associated with neurological recovery-six months later in a complementary fashion. The combination of fMRI and MD holds potential to improve prediction of outcome.

Project description:BackgroundPatients with isolated traumatic brain injury (TBI) are likely to benefit from effective prehospital care to prevent secondary brain injury. Only a few studies have focused on the impact of advanced interventions in TBI patients by prehospital physicians. The primary end-point of this study was to assess the possible effect of an on-scene anaesthetist on mortality of TBI patients. A secondary end-point was the neurological outcome of these patients.MethodsPatients with severe TBI (defined as a head injury resulting in a Glasgow Coma Score of ≤8) from 2005 to 2010 and 2012-2015 in two study locations were determined. Isolated TBI patients transported directly from the accident scene to the university hospital were included. A modified six-month Glasgow Outcome Score (GOS) was defined as death, unfavourable outcome (GOS 2-3) and favourable outcome (GOS 4-5) and used to assess the neurological outcomes. Binary logistic regression analysis was used to predict mortality and good neurological outcome. The following prognostic variables for TBI were available in the prehospital setting: age, on-scene GCS, hypoxia and hypotension. As per the hypothesis that treatment provided by an on-scene anaesthetist would be beneficial to TBI outcomes, physician was added as a potential predictive factor with regard to the prognosis.ResultsThe mortality data for 651 patients and neurological outcome data for 634 patients were available for primary and secondary analysis. In the primary analysis higher age (OR 1.06 CI 1.05-1.07), lower on-scene GCS (OR 0.85 CI 0.79-0.92) and the unavailability of an on-scene anaesthetist (OR 1.89 CI 1.20-2.94) were associated with higher mortality together with hypotension (OR 3.92 CI 1.08-14.23). In the secondary analysis lower age (OR 0.95 CI 0.94-0.96), a higher on-scene GCS (OR 1.21 CI 1.20-1.30) and the presence of an on-scene anaesthetist (OR 1.75 CI 1.09-2.80) were demonstrated to be associated with good patient outcomes while hypotension (OR 0.19 CI 0.04-0.82) was associated with poor outcome.ConclusionPrehospital on-scene anaesthetist treating severe TBI patients is associated with lower mortality and better neurological outcome.

Dataset Information

Neuroimmune activation is associated with neurological outcome in anoxic and traumatic coma.

Publications

Neuroimmune activation is associated with neurological outcome in anoxic and traumatic coma.

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