Nonconvulsive seizures in subarachnoid hemorrhage link inflammation and outcome.

OBJECTIVE: Nonconvulsive seizures (NCSz) are frequent following acute brain injury and have been implicated as a cause of secondary brain injury, but mechanisms that cause NCSz are controversial. Proinflammatory states are common after many brain injuries, and inflammation-mediated changes in blood-brain barrier permeability have been experimentally linked to seizures. METHODS: In this prospective observational study of aneurysmal subarachnoid hemorrhage (SAH) patients, we explored the link between the inflammatory response following SAH and in-hospital NCSz studying clinical (systemic inflammatory response syndrome [SIRS]) and laboratory (tumor necrosis factor receptor 1 [TNF-R1], high-sensitivity C-reactive protein [hsCRP]) markers of inflammation. Logistic regression, Cox proportional hazards regression, and mediation analyses were performed to investigate temporal and causal relationships. RESULTS: Among 479 SAH patients, 53 (11%) had in-hospital NCSz. Patients with in-hospital NCSz had a more pronounced SIRS response (odds ratio [OR]=1.9 per point increase in SIRS, 95% confidence interval [CI]=1.3-2.9), inflammatory surges were more likely immediately preceding NCSz onset, and the negative impact of SIRS on functional outcome at 3 months was mediated in part through in-hospital NCSz. In a subset with inflammatory serum biomarkers, we confirmed these findings linking higher serum TNF-R1 and hsCRP to in-hospital NCSz (OR=1.2 per 20-point hsCRP increase, 95% CI=1.1-1.4; OR=2.5 per 100-point TNF-R1 increase, 95% CI=2.1-2.9). The association of inflammatory biomarkers with poor outcome was mediated in part through NCSz. INTERPRETATION: In-hospital NCSz were independently associated with a proinflammatory state following SAH as reflected in clinical symptoms and serum biomarkers of inflammation. Our findings suggest that inflammation following SAH is associated with poor outcome and that this effect is at least in part mediated through in-hospital NCSz.

Brain injury visible on early MRI after subarachnoid hemorrhage might predict neurological impairment and functional outcome.

BACKGROUND: In subarachnoid hemorrhage (SAH), brain injury visible within 48 h of onset may impact on admission neurological disability and 3-month functional outcome. With volumetric MRI, we measured the volume of brain injury visible after SAH, and assessed the association with admission clinical grade and 3-month functional outcome. METHODS: Retrospective cohort study conducted in the Neurocritical Care Division, Columbia University Medical Center, New York, USA. On brain MRI acquired within 48 h of SAH-onset and before aneurysm-securing (n = 27), two blinded readers measured DWI and FLAIR-lesion volumes using semi-automated, computer segmentation software. RESULTS: Compared to post-resuscitation Hunt-Hess grade 1-3 (70 %), high-grade patients (30 %) had higher lesion volumes on DWI (34 ml [IQR: 0-64] vs. 2 ml [IQR: 0.5-7], P = 0.02) and on FLAIR (81 ml [IQR: 24-127] vs. 3 ml [IQR: 0-27], P = 0.02). On DWI, each 10 ml increase in lesion volume was associated with a 101 %-increase in the odds of presenting with 1 grade more in the Hunt-Hess scale (aOR 2.01, 95 % CI 1.10-3.68, P = 0.02), but was not significantly associated with 3-month outcome. On FLAIR, each 10 ml increase in lesion volume was associated with 34 % higher odds of a 1-point increase on the Hunt-Hess scale (aOR 1.34, 95 % CI 1.06-1.68, P = 0.01) and 139 % higher odds of a 1-point increase on the 3-month mRS (aOR 2.39, 95 % CI 1.13-5.07, P = 0.02). CONCLUSION: The volume of brain injury visible on DWI and FLAIR within 48 h after SAH is proportional to neurological impairment on admission. Moreover, FLAIR-imaging implicates chronic brain injury-predating SAH-as potentially relevant cause of poor functional outcome.

Is pentobarbital safe and efficacious in the treatment of super-refractory status epilepticus: a cohort study.

INTRODUCTION: Seizures refractory to third-line therapy are also labeled super-refractory status epilepticus (SRSE). These seizures are extremely difficult to control and associated with poor outcome. We aimed to characterize efficacy and side-effects of continuous infusions of pentobarbital (cIV-PTB) treating SRSE. METHODS: We retrospectively reviewed continuous electroencephalography (cEEG) reports for all adults with RSE treated with cIV-PTB between May 1997 and April 2010 at our institution. Patients with post-anoxic SE and those receiving cIV-PTB for reasons other than RSE were excluded. We collected baseline information, cEEG findings, side-effects and functional outcome at discharge and one year. RESULTS: Thirty one SRSE patients treated with cIV-PTB for RSE were identified. Mean age was 48 years old (interquartile range (IQR) 28,63), 26% (N = 8) had a history of epilepsy. Median SE duration was 6.5 days (IQR 4,11) and the mean duration of cIV-PTB was 6 days (IQR 3,14). 74% (N = 23) presented with convulsive SE. Underlying etiology was acute symptomatic seizures in 52% (N = 16; 12/16 with encephalitis), remote 30% (N = 10), and unknown 16% (N = 5). cIV-PTB controlled seizures in 90% (N = 28) of patients but seizures recurred in 48% (N = 15) while weaning cIV-PTB, despite the fact that suppression-burst was attained in 90% (N = 28) of patients and persisted >72 hours in 56% (N = 17). Weaning was successful after adding phenobarbital in 80% (12/15 of the patients with withdrawal seizures). Complications during or after cIV-PTB included pneumonia (32%, N = 10), hypotension requiring pressors (29%, N = 9), urinary tract infection (13%, N = 4), and one patient each with propylene glycol toxicity and cardiac arrest. One-third (35%, N = 11) had no identified new complication after starting cIV-PTB. At one year after discharge, 74% (N = 23) were dead or in a state of unresponsive wakefulness, 16% (N = 5) severely disabled, and 10% (N = 3) had no or minimal disability. Death or unresponsive wakefulness was associated with catastrophic etiology (p = 0.03), but none of the other collected variables. CONCLUSIONS: cIV-PTB effectively aborts SRSE and complications are infrequent; outcome in this highly refractory cohort of patients with devastating underlying etiologies remains poor. Phenobarbital may be particularly helpful when weaning cIV-PTB.

Pancreatic stone protein as a biomarker for the early diagnosis of post-operative peritonitis, intra-abdominal infection and sepsis.

The diagnosis of intra-abdominal infection and post-operative peritonitis based on clinical examination, biomarkers and radiological signs, should be made as early as possible to improve outcomes and decrease mortality through early and optimal source control, adequate surgery and appropriate antibiotic therapy (Montravers et al. Therapeutic management of peritonitis: a comprehensive guide for intensivists. Intensive Care Med 2016;42:1234-47). However, the indication and the timing of the surgery is often not an easy decision. This case presents the use of a novel early biomarker of infection and sepsis, pancreatic stone protein (Fidalgo et al. Pancreatic stone protein: review of a new biomarker in sepsis. J Clin Med 2022;11:1085), as a tool to aid in the diagnosis of intra-abdominal infection and post-operative peritonitis and to help guide the decision for adequate surgeries in a patient with intra-abdominal infection and post radical prostatectomy peritonitis.

Case Report and Review of the Literature: Fatal Reversible Cerebral Vasoconstriction Syndrome.

Background: A fatal outcome occurs in 2% of patients with Reversible Cerebral Vasoconstriction Syndrome (RCVS). Due to its rarity, guidelines for the management of the most severe forms of RCVS are lacking. Case presentation: Here, we describe the case of a 55 year-old woman who died from complications of RCVS and reviewed patients with fatal outcome reported in the literature. In our patient, the first episode of neurological deterioration was preceded by an increase of cerebral blood flow velocities assessed with transcranial Doppler. A fatal evolution could not be prevented despite therapeutic escalation consisting of multiple non-invasive and invasive treatments including cervical sympathetic bloc and continuous arterial infusion of nimodipine at the site of severe vasoconstriction. Conclusion: This case and the review of literature illustrate the challenges in the management of patients with severe RCVS. We describe here how monitoring of cerebral blood flow might help anticipate clinical worsening at the beginning of the disease and propose novel invasive and non-invasive therapeutic strategies based on monitoring of neurophysiological parameters.

Corticosteroid Responsive Encephalopathy: Prolonged Coma in Patients Late in the Course of Dreadful Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

BACKGROUND: Responsible for the coronavirus disease 2019 pandemic that began in December 2019, severe acute respiratory syndrome coronavirus 2 mainly causes respiratory insult. Few cases were reported of extrapulmonary involvement, many of which were neurologic. CASE SUMMARY: In this case report, we present two cases of prolonged coma after weaning off sedation in severe acute respiratory syndrome coronavirus 2 patients with rapid neurologic improvement shortly after high-dose corticosteroid regimen. CONCLUSIONS: We thus hypothesize an inflammatory process being responsible for the prolonged coma. Inflammatory neurologic insult has been described with other coronaviruses. Further studies are needed to determinate the extent and underlying mechanism of neurologic involvement in severe acute respiratory syndrome coronavirus 2 infections.

Brain networks involved in generalized periodic discharges (GPD) in post-anoxic-ischemic encephalopathy.

AIM: Generalized periodic discharge (GPD) is an EEG pattern of poor neurological outcome, frequently observed in comatose patients after cardiac arrest. The aim of our study was to identify the neuronal network generating ≤2.5 Hz GPD using EEG source localization and connectivity analysis. METHODS: We analyzed 40 comatose adult patients with anoxic-ischemic encephalopathy, who had 19 channel-EEG recording. We computed electric source analysis based on distributed inverse solution (LAURA) and we estimated cortical activity in 82 atlas-based cortical brain regions. We applied directed connectivity analysis (Partial Directed Coherence) on these sources to estimate the main drivers. RESULTS: Source analysis suggested that the GPD are generated in the cortex of the limbic system in the majority of patients (87.5%). Connectivity analysis revealed main drivers located in thalamus and hippocampus for the large majority of patients (80%), together with important activation also in amygdala (70%). CONCLUSIONS: We hypothesize that the anoxic-ischemic dysfunction, leading to hyperactivity of the thalamo-cortical (limbic presumably) circuit, can result in an oscillatory thalamic activity capable of inducing periodic cortical (limbic, mostly medial-temporal and orbitofrontal) discharges, similarly to the case of generalized rhythmic spike-wave discharge in convulsive or non-convulsive status epilepticus.

COVID-19 is Associated with an Unusual Pattern of Brain Microbleeds in Critically Ill Patients.

BACKGROUND AND PURPOSE: Covid-19, initially described as a respiratory system's infection, is currently more and more recognized as a multiorganic disease, including neurological manifestations. There is growing evidence about a potential neuroinvasive role of SARS-CoV-2. The purpose of this study is to describe new findings, in the form of cerebral microbleeds affecting different brain structures, observed in MRIs of critically ill patients. METHODS: For this purpose, the MR images of 9 patients with a common pattern of abnormal findings (2 women/7 men; 55-79 years of age; mean age: 67.7 years) were depicted. All patients were tested positive for SARS-CoV-2 and presented with delayed recovery of consciousness or important agitation, requiring brain MRI. RESULTS: All patients had suffered from severe (5/9) or moderate (4/9) acute respiratory distress syndrome, requiring prolonged stay in the intensive care unit. Their common MRI finding was the presence of microbleeds in unusual distribution with a specific predilection for the corpus callosum. Other uncommon locations of microbleeds were the internal capsule (5/9), as well as middle cerebellar peduncles (5/9). Subcortical regions were also affected in the majority of patients. CONCLUSIONS: Brain MRI raised evidence that Covid-19 or its related treatment may involve the brain with an unusual pattern of microbleeds, predominantly affecting the corpus callosum. The mechanism of this finding is still unclear but the differential diagnosis should include thrombotic microangiopathy related to direct or indirect-through the cytokine cascade-damage by the SARS-CoV-2 on the endothelium of brain's vessels, as well as mechanisms similar to the hypoxemia brain-blood-barrier injury.

Preparedness and Reorganization of Care for Coronavirus Disease 2019 Patients in a Swiss ICU: Characteristics and Outcomes of 129 Patients.

OBJECTIVES: In many countries, large numbers of critically ill patients with coronavirus disease 2019 are admitted to the ICUs within a short period of time, overwhelming usual care capacities. Preparedness and reorganization ahead of the wave to increase ICU surge capacity may be associated with favorable outcome. The purpose of this study was to report our experience in terms of ICU organization and anticipation, as well as reporting patient characteristics, treatment, and outcomes. DESIGN: A prospective observational study. SETTING: The division of intensive care at the Geneva University Hospitals (Geneva, Switzerland). PATIENTS: All consecutive adult patients with acute respiratory failure due to coronavirus disease 2019 admitted in the ICU between March 9, 2020, and May 19, 2020, were enrolled. Patients' demographic data, comorbidities, laboratory values, treatments, and clinical outcomes were collected. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The ICU was reorganized into cells of six to eight patients under the care of three physicians and five nurses. Its capacity increased from 30 to 110 beds, fully equipped and staffed, transforming the surgical intermediate care unit, the postoperative care facility, and operating theaters into ICUs. Surge capacity has always exceeded the number of patients hospitalized. Among 129 critically ill patients with severe acute hypoxemic respiratory failure, 96% required invasive mechanical ventilation. A total of 105 patients (81%) were discharged alive and 24 died, corresponding to a mortality of 19%. Patients who died were significantly older, with higher severity scores at admission, had higher levels of d-dimers, plasma creatinine, high-sensitive troponin T, C-reactive protein, and procalcitonin, and required more frequent prone sessions. CONCLUSIONS: A rapid increase in ICU bed capacity, including adequate equipment and staffing, allowed for a large number of critically ill coronavirus disease 2019 patients to be taken care of within a short period of time. Anticipation and preparedness ahead of the wave may account for the low mortality observed in our center. These results highlight the importance of resources management strategy in the context of the ongoing coronavirus disease 2019 pandemic.

[Scuba diving and hyperbaric medicine]. / Plongée sous-marine et médecine hyperbare.

Scuba diving is widely practiced in Switzerland. Although rare, decompression sickness may be serious and require specialized treatment. Hyperbaric therapy has been used for a long time with beneficial effects on decompression sickness and gaseous embolism. Conversely, barotrauma does not require recompressive therapy.

[Carbon monoxide poisoning: an update for 2009]. / L'intoxication au monoxyde de carbone en 2009.

Carbon monoxide (CO) is the leading cause of death by poisoning in developed countries. In 2006, 23 deaths and more than 130 hospitalisations related to CO poisoning have been reported in Switzerland. Impairment in oxygen transport through competitive antagonist action on hemoglobin is well known. Other mechanisms, in particular CO induced mitochondrial dysfunction, participate in CO toxicity. CO intoxications carry a high risk of immediate mortality and long-term neuropsychiatric or cardiac sequelae which justify the need of early diagnosis and treatment. Administration of supplemental oxygen is the cornerstone of treatment of CO poisoning. Hyperbaric oxygen therapy must be considered for the treatment of severe intoxications.

A risk analysis method to evaluate the impact of a computerized provider order entry system on patient safety.

OBJECTIVES: Quantitative evaluation of safety after the implementation of a computerized provider order entry (CPOE) system, stratification of residual risks to drive future developments. DESIGN: Comparative risk analysis of the drug prescription process before and after the implementation of CPOE system, according to the Failure Modes, Effects and Criticality Analysis (FMECA) method. MEASUREMENTS: The failure modes were defined and their criticality indices calculated on the basis of the likelihood of occurrence, potential severity for patients, and detection probability. Criticality indices of handwritten and electronic prescriptions were compared, the acceptability of residual risks was discussed. Further developments were proposed and their potential impact on the safety was estimated. RESULTS: The sum of criticality indices of 27 identified failure modes was 3813 for the handwritten prescription, 2930 (-23%) for CPOE system, and 1658 (-57%) with 14 enhancements. The major safety improvements were observed for errors due to ambiguous, incomplete or illegible orders (-245 points), wrong dose determination (-217) and interactions (-196). Implementation of targeted pop-ups to remind treatment adaptation (-189), vital signs (-140), and automatic edition of documents needed for the dispensation (-126) were the most promising proposed improvements. CONCLUSION: The impact of a CPOE system on patient safety strongly depends on the implemented functions and their ergonomics. The use of risk analysis helps to quantitatively evaluate the relationship between a system and patient safety and to build a strategy for continuous quality improvement, by selecting the most appropriate improvements to the system.

Seizure burden in subarachnoid hemorrhage associated with functional and cognitive outcome.

OBJECTIVE: To assess the relationship between seizure burden on continuous EEG (cEEG) and functional as well as cognitive outcome 3 months after subarachnoid hemorrhage (SAH). METHODS: The study included all consecutive patients with a spontaneous SAH admitted to the Columbia University Medical Center Neurological Intensive Care Unit and monitored with cEEG between 1996 and 2013. Seizure burden was defined as the duration, in hours, of seizures on cEEG. Cognitive outcomes were measured with the Telephone Interview for Cognitive Status (TICS, ranging from 0 to 51, indicating poor to good global mental status). RESULTS: Overall, 402 patients with SAH were included with a median age of 58 years (interquartile range [IQR] 46-68 years). The median duration of cEEG monitoring was 96 hours (IQR 48-155 hours). Seizures were recorded in 50 patients (12%), in whom the median seizure burden was 6 hours (IQR 1-13 hours). At 3 months, in multivariate analysis, seizure burden was associated with unfavorable functional and cognitive outcome. Every hour of seizure on cEEG was associated with an odds ratio of 1.10 (95% confidence interval [CI] 1.01-1.21, p = 0.04) to 3-month disability and mortality, and the TICS-score decreased, on average, by 0.16 points (adjusted coefficient -0.19, 95% CI -0.33 to -0.05, p = 0.01). CONCLUSION: In this study, after adjusting for established predictors, seizure burden was associated with functional outcome and cognitive impairment 3 months after SAH.

[Management of status epilepticus in intensive care]. / Prise en charge des etats de mal epileptique aux soins intensifs.

Status epilepticus (SE) is an emergency situation for the neurologist as for the critical care physician, because it is caused by a focal or by a generalized severe brain suffering. Therefore, SE must be treated as soon as possible. The management, beyond a rapid and accurate diagnosis, must include the identification of the cause of SE, whereas seizures must be rapidly stopped.

Tonic-clonic activity at subarachnoid hemorrhage onset: impact on complications and outcome.

OBJECTIVE: Tonic-clonic activity (TCA) at onset complicates 3% to 21% of cases of subarachnoid hemorrhage (SAH). The impact of onset TCA on in-hospital complications, including seizures, remains unclear. One study associated onset TCA with poor clinical outcome at 6 weeks after SAH, but to our knowledge no other studies have confirmed this relationship. This study aims to assess the impact of onset TCA on in-hospital complications, poor functional outcome, mortality, and epilepsy at 3 months. METHODS: Analysis of a prospective study cohort of 1479 SAH patients admitted to Columbia University Medical Center between 1996 and 2012. TCA within 6 hours of hemorrhage onset was identified based on accounts of emergency care providers or family witnesses. RESULTS: TCA at onset was described in 170 patients (11%). Patients with onset TCA were younger (P = 0.002), presented more often with poor clinical grade (55% vs. 26%, P<0.001) and had larger amounts of cisternal, intraventricular, and intracerebral blood than those without onset TCA (all, P<0.001). After adjusting for known confounders, onset TCA was significantly associated with in-hospital seizures (OR 3.80, 95%-CI: 2.43-5.96, P<0.001), in-hospital pneumonia (OR 1.56, 95%-CI: 1.06-2.31, p = 0.02), and delayed cerebral ischemia (OR 1.77, 95%-CI: 1.21-2.58, P = 0.003). At 3 months, however, onset TCA was not associated with poor functional outcome, mortality, and epilepsy after adjusting for age, admission clinical grade, and cisternal blood volume. CONCLUSIONS: Onset TCA is not a rare event as it complicates 11% of cases of SAH. New and clinically relevant findings are the association of onset TCA with in-hospital seizures, pneumonia and delayed cerebral ischemia. Despite the increased risk of in-hospital complications, onset TCA is not associated with disability, mortality, and epilepsy at 3 months.