Objective: The EEG (electroencephalogram) plays a crucial role in prognosticating outcomes for comatose patients after cardiac arrest (CA), but the precise probability of poor outcome (PPO) associated with specific EEG patterns and how it changes over time is not well understood. We aimed to quantify the PPO for individual EEG patterns, assess its precision, and evaluate time-dependent changes after CA. Methods: We retrospectively analyzed continuous EEGs from comatose adults treated at three Boston hospitals for CA (2010–2023). We evaluated the prognostic significance of 22 ACNS-standard patterns, and one additional pattern, “flat EEG (<2μV)”, using PPO (i.e., positive predictive value for poor outcome) with 95 % Wilson confidence intervals as the primary metric; sensitivity, and false-positive rate (FPR) were secondary. Temporal variabilities were assessed in four epochs (0–24, 24–48, 48–72, >72 h) using linear regression. Poor and favorable outcomes were defined as death and survival to discharge, respectively. Results: Among 1,000 patients, the mean age was 58 years for survivors and 60 years for non-survivors; 59% of patients were male. Flat EEG demonstrated PPO of 1.00 across epochs, but CIs ranged from 0.89–1.00 at 24 hours and widened to 0.54–1.00 beyond 72 hours. Status epilepticus (SE) showed PPO of 0.80 (0.44–0.97) at 24 hours, 1.00 (0.74–1.00) at 48 hours, and 0.67 (0.09–0.99) after 72 hours. Suppression (< 10 μV), the most common historically termed highly “malignant” pattern (prevalence 50–65%), had a PPO of 0.76–0.83 and sensitivity of up to 0.80, with 17–24% of patients experiencing a favorable outcome. Time-dependent analysis further demonstrated that PPO for suppression increased over time, while sensitivity declined for burst-suppression and flat EEG. Conclusion: The prognostic uncertainty of EEG patterns post-CA is highly variable, and evolves within the first 72 hours. Flat EEG, and SE are highly specific prognosticators of poor outcome, but, importantly, they are rare and not infallible. Suppression identifies the most patients with poor outcomes but has moderately high FPRs and variable prognostic certainty over time. Future large-scale prospective studies that incorporate long-term outcomes are needed to validate these findings.
Rajib Kanti Dey, A. Yaramış, Niels Turley et al.· Neurology open access· 0 citations
Recent studies suggest that cortical hyperexcitability in Alzheimer's disease (AD) may accelerate disease progression. However, the field lacks validated non-invasive methods to assay excitability in humans. In this study we used transcranial magnetic stimulation with electromyography to investigate mechanisms of motor cortical excitability in 63 biomarker-positive early-AD (ranging from mild cognitive impairment to mild dementia) participants and 72 cognitively unimpaired age-matched adults (CU). Single-pulse stimulation was applied to motor cortex to record resting motor thresholds (rMT) and motor-evoked potentials. An Input-Output curve was generated by delivering 10 pulses each at eight different intensities of maximum stimulator output (%MSO). Linear models or equivalent non-parametric tests 1) compared excitability metrics between groups, 2) tested correlations with cognition (mini-mental state exam, MMSE; Alzheimer's disease assessment scale-cognitive, ADAS-Cog), and 3) tested the impact of APOE4. Results show that early-AD participants have increased motor cortical excitability than CU, with lower rMT (p < 0.001), lower Input-Output curve Inflection Point (p = 0.007), and higher Dynamic Range (p = 0.035). An analysis of the Input-Output curve adjusting for rMT showed larger responses in AD specifically in the 135-150% rMT range (p = 0.023). In AD, higher excitability was related to worse cognition (rMT: MMSE p = 0.008, Inflection Point: MMSE p = 0.030 and ADAS-Cog p = 0.041). There was no relationship between APOE4 and excitability. In conclusion, AD participants have increased motor cortical excitability, related to cognition. This is evident both at lower and higher stimulation intensities. TMS may provide a useful measure of target engagement for therapies aimed at preserving cognition or slowing decline in early-AD.
Julia H. Cho, Brice Passera, Giacomo Bertazzoli et al.· Neurobiology of Aging· 0 citations
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