Long term functioning with poor neurologic outcome after cardiac arrest.

AIM: Around six percent of comatose patients after cardiac arrest have a Cerebral Performance Categories score of three (CPC3) at six months after the arrest, classified as severe neurological disability. There is limited knowledge regarding the likelihood of further recovery in the cognitive, emotional, and quality of life domains. We aimed to estimate the probability of recovery towards independency. METHODS: From a prospective Registry on comatose cardiac arrest patients admitted between 2013 and 2017 in two Dutch hospitals, we included patients with a CPC3 at six months after cardiac arrest. We followed patients up to November 2023. The primary outcome measure was the CPC score at time of follow up. Secondary outcomes were scores on questionnaires on cognition, mood, and quality of life according to the minimal dataset of acquired brain injury. RESULTS: In our cohort of 667 patients, 29 (4.3%) had a CPC3 score at six months (median age 68 years, 83% male). At a median time of eight years after cardiac arrest, sixteen patients had died. Twelve of thirteen alive patients still had a CPC3 score (92%) and one a CPC2 (8%). Seven patients agreed with further interviewing, one showed independency in activities of daily living (14%). Six patients (86%) reported limitations due to physical and one (14%) due to emotional problems. All had severe cognitive impairment. Six (86%) missed cognitive rehabilitation. CONCLUSION: Our study shows that while the probability of recovery towards independence for patients with severe neurological disability at six months after cardiac arrest is limited, most long-term survivors are satisfied with their quality of life.

Restoration of postictal cortical activity after electroconvulsive therapy relates to recovery of orientation in person, place, and time.

BACKGROUND: Most patients show temporary impairments in clinical orientation after electroconvulsive therapy (ECT)-induced seizures. It is unclear how postictal reorientation relates to electroencephalography (EEG) restoration. This relationship may provide additional measures to quantify postictal recovery and shed light on neurophysiological aspects of reorientation after ECT. METHODS: We analyzed prospectively collected clinical and continuous ictal and postictal EEG data from ECT patients. Postictal EEG restoration up to 1 h was estimated by the evolution of the normalized alpha-delta ratio (ADR). Times to reorientation in the cognitive domains of person, place, and time were assessed postictally. In each cognitive domain, a linear mixed model was fitted to investigate the relationships between time to reorientation and postictal EEG restoration. RESULTS: In total, 272 pairs of ictal-postictal EEG and reorientation times of 32 patients were included. In all domains, longer time to reorientation was associated with slower postictal EEG recovery. Longer seizure duration and postictal administration of midazolam were related to longer time to reorientation in all domains. At 1-hour post-seizure, most patients were clinically reoriented, while their EEG had only partly restored. CONCLUSIONS: We show a relationship between postictal EEG restoration and clinical reorientation after ECT-induced seizures. EEG was more sensitive than reorientation time in all domains to detect postictal recovery beyond 1-hour post-seizure. Our findings indicate that clinical reorientation probably depends on gradual cortical synaptic recovery, with longer seizure duration leading to longer postsynaptic suppression after ECT seizures.

Quantitative Characterization of Rhythmic and Periodic EEG Patterns in Patients in a Coma After Cardiac Arrest and Association With Outcome.

OBJECTIVES: Rhythmic and periodic patterns (RPPs) on EEG in patients in a coma after cardiac arrest are associated with a poor neurologic outcome. We characterize RPPs using qEEG in relation to outcomes. METHODS: Post hoc analysis was conducted on 172 patients in a coma after cardiac arrest from the TELSTAR trial, all with RPPs. Quantitative EEG included corrected background continuity index (BCI*), relative discharge power (RDP), discharge frequency, and shape similarity. Neurologic outcomes at 3 months after arrest were categorized as poor (CPC = 3-5) or good (CPC = 1-2). RESULTS: A total of 16 patients (9.3%) had a good outcome. Patients with good outcomes showed later RPP onset (28.5 vs 20.1 hours after arrest, p < 0.05) and higher background continuity at RPP onset (BCI* = 0.83 vs BCI* = 0.59, p < 0.05). BCI* <0.45 at RPP onset, maximum BCI* <0.76, RDP >0.47, or shape similarity >0.75 were consistently associated with poor outcomes, identifying 36%, 22%, 40%, or 24% of patients with poor outcomes, respectively. In patients meeting both BCI* >0.44 at RPP onset and BCI* >0.75 within 72 hours, the probability of good outcomes doubled to 18%. DISCUSSION: Sufficient EEG background continuity before and during RPPs is crucial for meaningful recovery. Background continuity, discharge power, and shape similarity can help select patients with relevant chances of recovery and may guide treatment. TRIAL REGISTRATION INFORMATION: February 4, 2014, ClinicalTrial.gov, NCT02056236.

Ghrelin for Neuroprotection in Post-Cardiac Arrest Coma: A Randomized Clinical Trial.

Importance: Out-of-hospital cardiac arrest survival rates have markedly risen in the last decades, but neurological outcome only improved marginally. Despite research on more than 20 neuroprotective strategies involving patients in comas after cardiac arrest, none have demonstrated unequivocal evidence of efficacy; however, treatment with acyl-ghrelin has shown improved functional and histological brain recovery in experimental models of cardiac arrest and was safe in a wide variety of human study populations. Objective: To determine safety and potential efficacy of intravenous acyl-ghrelin to improve neurological outcome in patients in a coma after cardiac arrest. Design, Setting, and Participants: A phase 2, double-blind, placebo-controlled, multicenter, randomized clinical trial, Ghrelin Treatment of Comatose Patients After Cardiac Arrest: A Clinical Trial to Promote Cerebral Recovery (GRECO), was conducted between January 18, 2019, and October 17, 2022. Adult patients 18 years or older who were in a comatose state after cardiac arrest were assessed for eligibility; patients were from 3 intensive care units in the Netherlands. Expected death within 48 hours or unfeasibility of treatment initiation within 12 hours were exclusion criteria. Interventions: Patients were randomized to receive intravenous acyl-ghrelin, 600 µg (intervention group), or placebo (control group) within 12 hours after cardiac arrest, continued for 7 days, twice daily, in addition to standard care. Main Outcomes and Measures: Primary outcome was the score on the Cerebral Performance Categories (CPC) scale at 6 months. Safety outcomes included any serious adverse events. Secondary outcomes were mortality and neuron-specific enolase (NSE) levels on days 1 and 3. Results: A total of 783 adult patients in a coma after cardiac arrest were assessed for eligibility, and 160 patients (median [IQR] age, 68 [57-75] years; 120 male [75%]) were enrolled. A total of 81 patients (51%) were assigned to the intervention group, and 79 (49%) were assigned to the control group. The common odds ratio (OR) for any CPC improvement in the intervention group was 1.78 (95% CI, 0.98-3.22; P = .06). This was consistent over all CPC categories. Mean (SD) NSE levels on day 1 after cardiac arrest were significantly lower in the intervention group (34 [6] µg/L vs 56 [13] µg/L; P = .04) and on day 3 (28 [6] µg/L vs 52 [14] µg/L; P = .08). Serious adverse events were comparable in incidence and type between the groups. Mortality was 37% (30 of 81) in the intervention group vs 51% (40 of 79) in the control group (absolute risk reduction, 14%; 95% CI, -2% to 29%; P = .08). Conclusions and Relevance: In patients in a coma after cardiac arrest, intravenous treatment with acyl-ghrelin was safe and potentially effective to improve neurological outcome. Phase 3 trials are needed for conclusive evidence. Trial Registration: Clinicaltrialsregister.eu: EUCTR2018-000005-23-NL.

Exploring postictal recovery with acetaminophen or nimodipine: A randomized-controlled crossover trial.

OBJECTIVE: The postictal state is underrecognized in epilepsy. Animal models show improvement of postictal symptoms and cerebral perfusion with acetaminophen or nimodipine. We studied the effects of acetaminophen or nimodipine on postictal electroencephalographic (EEG) recovery, clinical reorientation, and hypoperfusion in patients with ECT-induced seizures. METHODS: In this prospective clinical trial with three-condition randomized crossover design, study interventions were administered orally 2 h before ECT sessions (1000 mg acetaminophen, 60 mg nimodipine, or a placebo condition). Primary outcome measure was the speed of postictal EEG recovery. Secondary outcomes were the extent of postictal EEG recovery, clinical reorientation time, and postictal cerebral blood flow as assessed by perfusion-weighted MRI. Bayesian generalized mixed-effects models were applied for analyses. RESULTS: We included 300 seizures, postictal EEGs, and reorientation time values, and 76 MRI perfusion measures from 33 patients (median age 53 years, 19 female). Pretreatment with acetaminophen or nimodipine was not associated with change in speed of EEG recovery compared to placebo (1.13 [95%CI 0.92, 1.40] and 1.07 [95%CI 0.87, 1.31], respectively), nor with the secondary outcomes. No patient reached full EEG recovery at 1 h post-seizure, despite clinical recovery in 89%. Longer seizures were associated with slower EEG recovery and lower postictal perfusion. Nimodipine altered regional perfusion in the posterior cortex. INTERPRETATION: Pretreatment with acetaminophen or nimodipine did not alleviate symptoms and signs of the postictal state. Systematic study of the postictal state after ECT-induced seizures is feasible.

Sex differences in clot, vessel and tissue characteristics in patients with a large vessel occlusion treated with endovascular thrombectomy.

INTRODUCTION: To improve our understanding of the relatively poor outcome after endovascular treatment (EVT) in women we assessed possible sex differences in baseline neuroimaging characteristics of acute ischemic stroke patients with large anterior vessel occlusion (LVO). PATIENTS AND METHODS: We included all consecutive patients from the MR CLEAN Registry who underwent EVT between 2014 and 2017. On baseline non-contrast CT and CT angiography, we assessed clot location and clot burden score (CBS), vessel characteristics (presence of atherosclerosis, tortuosity, size, and collateral status), and tissue characteristics with the Alberta Stroke Program Early Computed Tomography Score (ASPECTS). Radiological outcome was assessed with the extended thrombolysis in cerebral infarction score (eTICI) and functional outcome with the modified Rankin Scale score (mRS) at 90 days. Sex-differences were assessed with multivariable regression analyses with adjustments for possible confounders. RESULTS: 3180 patients were included (median age 72 years, 48% women). Clots in women were less often located in the intracranial internal carotid artery (ICA) (25%vs 28%, odds ratio (OR) 0.85;95% confidence interval: 0.73-1.00). CBS was similar between sexes (median 6, IQR 4-8). Intracranial (aOR 0.73;95% CI:0.62-0.87) and extracranial (aOR 0.64;95% CI:0.43-0.95) atherosclerosis was less prevalent in women. Vessel tortuosity was more frequent in women in the cervical ICA (aOR 1.89;95% CI:1.39-2.57) and women more often had severe elongation of the aortic arch (aOR 1.38;95% CI:1.00-1.91). ICA radius was smaller in women (2.3vs 2.5 mm, mean difference 0.22;95% CI:0.09-0.35) while M1 radius was essentially equal (1.6vs 1.7 mm, mean difference 0.09;95% CI:-0.02-0.21). Women had better collateral status (⩾50% filling in 62%vs 53% in men, aOR 1.48;95% CI:1.29-1.70). Finally, ASPECT scores were equal between women and men (median 9 in both sexes, IQR 8-10vs 9-10). Reperfusion rates were similar between women and men (acOR 0.94;95% CI:0.83-1.07). However, women less often reached functional independence than men (34%vs 46%, aOR 0.68;95% CI:0.53-0.86). DISCUSSION AND CONCLUSION: On baseline imaging of this Dutch Registry, men and women with LVO mainly differ in vessel characteristics such as atherosclerotic burden, extracranial vessel tortuosity, and collateral status. These sex differences do not result in different reperfusion rates and are, therefore, not likely to explain the worse functional outcome in women after EVT.