Early Lance-Adams syndrome after cardiac arrest: Prevalence, time to return to awareness, and outcome in a large cohort.

Early myoclonus after cardiac arrest (CA) is traditionally viewed as a poor prognostic sign (status myoclonus). However, some patients may present early Lance-Adams syndrome (LAS): under appropriate treatment, they can reach a satisfactory functional outcome. Our aim was to describe their profile, focusing on pharmacologic management in the ICU, time to return of awareness, and long-term prognosis. Adults with early LAS (defined as generalized myoclonus within 96h, with epileptiform EEG within 48h after CA) were retrospectively identified in our CA registry between 2006 and 2016. Functional outcome was assessed through cerebral performance categories (CPC) at 3 months, CPC 1-2 defined good outcome. Among 458 consecutive patients, 7 (1.5%) developed early LAS (4 women, median age 59 years). Within 72h after CA, in normothemia and off sedation, all showed preserved brainstem reflexes and localized pain. All patients were initially treated with valproate, levetiracetam and clonazepam; additional agents, including propofol and midazolam, were prescribed in the majority. First signs of awareness occurred after 3-23 days (median 11.8); 3/7 reached a good outcome at 3 months. Early after CA, myoclonus together with a reactive, epileptiform EEG, preserved evoked potentials and brainstem reflexes suggests LAS. This condition was managed with a combination of highly dosed, large spectrum antiepileptic agents including propofol and midazolam. Even if awakening was at times delayed, good outcome occurred in a substantial proportion of patients

Prediction of awakening from hypothermic post anoxic coma based on auditory discrimination.

OBJECTIVE: Most of the available clinical tests for prognosis of post-anoxic coma are informative of poor outcome. Previous work has shown that an improvement in auditory discrimination over the first days of coma is predictive of awakening. Here, we aimed at evaluating this test on a large cohort of patients undergoing therapeutic hypothermia and at investigating its added value on existing clinical measures. METHODS: We recorded electroencephalography responses to auditory stimuli in 94 comatose patients, under hypothermia and after re-warming to normal temperature. Auditory discrimination was semi-automatically quantified by decoding electroencephalography responses to frequently repeated vs. rare sounds. Outcome prediction was based on the change of decoding performance from hypothermia to normothermia. RESULTS: An increase in auditory discrimination from hypothermia to normothermia was observed for 33 out of 94 patients. Among them, 27 awoke from coma, resulting in a positive predictive value of awakening of 82% (95% confidence interval: 0.65-0.93). Most non-survivors showing an improvement in auditory discrimination had incident status epilepticus. By excluding them, 27 out of 29 patients with improvement in auditory discrimination survived, resulting in a considerable improvement of the predictive value for awakening (93%, with 95% confidence interval: 0.77-0.99). Importantly, this test predicted the awakening of 13 out of 51 patients for which the outcome was uncertain based on current tests. INTERPRETATION: The progression of auditory discrimination from hypothermia to normothermia has a high predictive value for awakening. This quantitative measure provides an added value to existing clinical tests and encourages the maintenance of life support. This article is protected by copyright. All rights reserved

Evidence of trace conditioning in comatose patients revealed by the reactivation of EEG responses to alerting sounds.

Trace conditioning refers to a learning process occurring after repeated presentation of a neutral conditioned stimulus (CS+) and a salient unconditioned stimulus (UCS) separated by a temporal gap. Recent studies have reported that trace conditioning can occur in humans in reduced levels of consciousness by showing a transfer of the unconditioned autonomic response to the CS+ in healthy sleeping individuals and in vegetative state patients. However, no previous studies have investigated the neural underpinning of trace conditioning in the absence of consciousness in humans. In the present study, we recorded the EEG activity of 29 post-anoxic comatose patients while presenting a trace conditioning paradigm using neutral tones as CS+ and alerting sounds as UCS. Most patients received therapeutic hypothermia and all were deeply unconscious according to standardized clinical scales. After repeated presentation of the CS+ and UCS couple, learning was assessed by measuring the EEG activity during the period where the UCS is omitted after CS+ presentation. Specifically we assessed the 'reactivation' of the neural response to UCS omission by applying a decoding algorithm derived from the statistical model of the EEG activity in response to the UCS presentation. The same procedure was used in a group of 12 awake healthy controls. We found a reactivation of the UCS response in absence of stimulation in eight patients (five under therapeutic hypothermia) and four healthy controls. Additionally, the reactivation effect was temporally specific within trials since it manifested primarily at the specific latency of UCS presentation and significantly less before or after this period. Our results show for the first time that trace conditioning may manifest as a reactivation of the EEG activity related to the UCS and even in the absence of consciousness

Non-Ischemic Cerebral Energy Dysfunction at the Early Brain Injury Phase following Aneurysmal Subarachnoid Hemorrhage.

The pathophysiology of early brain injury following aneurysmal subarachnoid hemorrhage (SAH) is still not completely understood. Using brain perfusion CT (PCT) and cerebral microdialysis (CMD), we examined whether non-ischemic cerebral energy dysfunction may be a pathogenic determinant of EBI. A total of 21 PCTs were performed (a median of 41 h from ictus onset) among a cohort of 18 comatose mechanically ventilated SAH patients (mean age 58 years, median admission WFNS score 4) who underwent CMD and brain tissue PO2 (PbtO2) monitoring. Cerebral energy dysfunction was defined as CMD episodes with lactate/pyruvate ratio (LPR) >40 and/or lactate >4 mmol/L. PCT-derived global CBF was categorized as oligemic (CBF < 28 mL/100 g/min), normal (CBF 28-65 mL/100 g/min), or hyperemic (CBF 69-85 mL/100 g/min), and was matched to CMD/PbtO2 data. Global CBF (57 ± 14 mL/100 g/min) and PbtO2 (25 ± 9 mm Hg) were within normal ranges. Episodes with cerebral energy dysfunction (n = 103 h of CMD samples, average duration 7.4 h) were frequent (66% of CMD samples) and were associated with normal or hyperemic CBF. CMD abnormalities were more pronounced in conditions of hyperemic vs. normal CBF (LPR 54 ± 12 vs. 42 ± 7, glycerol 157 ± 76 vs. 95 ± 41 µmol/L; both p < 0.01). Elevated brain LPR correlated with higher CBF (r = 0.47, p < 0.0001). Cerebral energy dysfunction is frequent at the early phase following poor-grade SAH and is associated with normal or hyperemic brain perfusion. Our data support the notion that mechanisms alternative to ischemia/hypoxia are implicated in the pathogenesis of early brain injury after SAH

Mediterranean Sea response to climate change in an ensemble of twenty first century scenarios

The Mediterranean climate is expected to become warmer and drier during the twenty-first century. Mediterranean Sea response to climate change could be modulated by the choice of the socio-economic scenario as well as the choice of the boundary conditions mainly the Atlantic hydrography, the river runoff and the atmospheric fluxes. To assess and quantify the sensitivity of the Mediterranean Sea to the twenty-first century climate change, a set of numerical experiments was carried out with the regional ocean model NEMOMED8 set up for the Mediterranean Sea. The model is forced by air–sea fluxes derived from the regional climate model ARPEGE-Climate at a 50-km horizontal resolution. Historical simulations representing the climate of the period 1961–2000 were run to obtain a reference state. From this baseline, various sensitivity experiments were performed for the period 2001–2099, following different socio-economic scenarios based on the Special Report on Emissions Scenarios. For the A2 scenario, the main three boundary forcings (river runoff, near-Atlantic water hydrography and air–sea fluxes) were changed one by one to better identify the role of each forcing in the way the ocean responds to climate change. In two additional simulations (A1B, B1), the scenario is changed, allowing to quantify the socio-economic uncertainty. Our 6-member scenario simulations display a warming and saltening of the Mediterranean. For the 2070–2099 period compared to 1961–1990, the sea surface temperature anomalies range from +1.73 to +2.97 °C and the SSS anomalies spread from +0.48 to +0.89. In most of the cases, we found that the future Mediterranean thermohaline circulation (MTHC) tends to reach a situation similar to the eastern Mediterranean Transient. However, this response is varying depending on the chosen boundary conditions and socio-economic scenarios. Our numerical experiments suggest that the choice of the near-Atlantic surface water evolution, which is very uncertain in General Circulation Models, has the largest impact on the evolution of the Mediterranean water masses, followed by the choice of the socio-economic scenario. The choice of river runoff and atmospheric forcing both have a smaller impact. The state of the MTHC during the historical period is found to have a large influence on the transfer of surface anomalies toward depth. Besides, subsurface currents are substantially modified in the Ionian Sea and the Balearic region. Finally, the response of thermosteric sea level ranges from +34 to +49 cm (2070–2099 vs. 1961–1990), mainly depending on the Atlantic forcing

Grey and white matter correlates of recent and remote autobiographical memory retrieval:Insights from the dementias

The capacity to remember self-referential past events relies on the integrity of a distributed neural network. Controversy exists, however, regarding the involvement of specific brain structures for the retrieval of recently experienced versus more distant events. Here, we explored how characteristic patterns of atrophy in neurodegenerative disorders differentially disrupt remote versus recent autobiographical memory. Eleven behavioural-variant frontotemporal dementia, 10 semantic dementia, 15 Alzheimer's disease patients and 14 healthy older Controls completed the Autobiographical Interview. All patient groups displayed significant remote memory impairments relative to Controls. Similarly, recent period retrieval was significantly compromised in behavioural-variant frontotemporal dementia and Alzheimer's disease, yet semantic dementia patients scored in line with Controls. Voxel-based morphometry and diffusion tensor imaging analyses, for all participants combined, were conducted to investigate grey and white matter correlates of remote and recent autobiographical memory retrieval. Neural correlates common to both recent and remote time periods were identified, including the hippocampus, medial prefrontal, and frontopolar cortices, and the forceps minor and left hippocampal portion of the cingulum bundle. Regions exclusively implicated in each time period were also identified. The integrity of the anterior temporal cortices was related to the retrieval of remote memories, whereas the posterior cingulate cortex emerged as a structure significantly associated with recent autobiographical memory retrieval. This study represents the first investigation of the grey and white matter correlates of remote and recent autobiographical memory retrieval in neurodegenerative disorders. Our findings demonstrate the importance of core brain structures, including the medial prefrontal cortex and hippocampus, irrespective of time period, and point towards the contribution of discrete regions in mediating successful retrieval of distant versus recently experienced events