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Targeting single monitoring modalities such as intracranial pressure (ICP) or cerebral perfusion pressure alone has shown to be insufficient in improving outcome after traumatic brain injury (TBI). Multimodality monitoring (MMM) allows for a more complete description of brain function and for individualized management. Transcranial Doppler (TCD) represents the gold standard for continuous cerebral blood flow velocity assessment, but requires high levels skill and time. In TBI, the practical aspects of conducting extended TCD monitoring sessions have yet to be evaluated. Patients with acute moderate-to-severe TBI admitted to the neurocritical care unit between March 2022 and December 2023 receiving invasive ICP measurements were evaluated for inclusion. Exclusion criteria included trauma incompatible with TCD monitoring and if MMM was unwarranted. Daily MMM sessions (in addition to regular monitoring) were performed using TCD (Delica EMS 9D System or the DWL Doppler Box) for ≤5 d. Quantitative and qualitative feasibility, safety, and quality metrics were assessed. Of 74 patients, 36 (75% male; mean age, 44 ± 17 y) were included. Common reasons for exclusion were skull fractures (n = 12) and decompressive craniectomy (n = 9). We acquired 88 recordings (mean, 275 ± 88 min). Overall monitoring times increased, and set-up times decreased. Physiologic variables (including ICP/brain temperature) did not change with TCD application. A single adverse event (dislodging of a microdialysis catheter) occurred. Implementing extended TCD monitoring in MMM protocols is feasible and safe. Considering these results, inclusion of long-term TCD as part of the MMM is strongly encouraged to allow for in-depth description and direct evaluation of hemodynamic changes after TBI. [ABSTRACT FROM AUTHOR]

Cerebrovascular autoregulation is defined as the capacity of cerebral blood vessels to maintain stable cerebral blood flow despite changing blood pressure. It is assessed using the pressure reactivity index (the correlation coefficient between mean arterial blood pressure and intracranial pressure). The objective of this scoping review is to describe the existing evidence concerning the association of EEG and cerebrovascular autoregulation in order to identify key concepts and detect gaps in the current knowledge. Embase, MEDLINE, SCOPUS, and Web of Science were searched considering articles between their inception up to September 2023. Inclusion criteria were human (paediatric and adult) and animal studies describing correlations between continuous EEG and cerebrovascular autoregulation assessments. Ten studies describing 481 human subjects (67% adult, 59% critically ill) were identified. Seven studies assessed qualitative (e.g. seizures, epileptiform potentials) and five evaluated quantitative (e.g. bispectral index, alpha-delta ratio) EEG metrics. Cerebrovascular autoregulation was evaluated based on intracranial pressure, transcranial Doppler, or near infrared spectroscopy. Specific combinations of cerebrovascular autoregulation and EEG metrics were evaluated by a maximum of two studies. Seizures, highly malignant patterns or burst suppression, alpha peak frequency, and bispectral index were associated with cerebrovascular autoregulation. The other metrics showed either no or inconsistent associations. There is a paucity of studies evaluating the link between EEG and cerebrovascular autoregulation. The studies identified included a variety of EEG and cerebrovascular autoregulation acquisition methods, age groups, and diseases allowing for few overarching conclusions. However, the preliminary evidence for the presence of an association between EEG metrics and cerebrovascular autoregulation prompts further in-depth investigations. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) remains a significant global problem with an increasing socioeconomic impact. Increasing knowledge of the pathophysiology of TBI has led to a systematic multidisciplinary approach towards management aiming to protect the brain from secondary injury. Early management starting from the scene of injury, to intensive care and surgical settings is paramount to achieve this purpose. TBI includes a large spectrum of diseases, therefore identifying the correct pathology on imaging is fundamental to define the appropriate next steps of management. Computed tomography (CT) imaging to date remains the gold standard for initial radiological assessment. Intracranial and cerebral perfusion pressure targeted therapies are still the minimum requirement in most of modern intensive care units worldwide. Decompressive craniectomy is a fundamental technique to control medically refractory intracranial hypertension and reduce mortality; however, its burden in terms of outcomes remains a controversial topic requiring further debate. There is emerging evidence that TBI is a chronic illness, with increased incidence of cognitive and behavioural deficits, neurodegenerative disease such as seizures and epilepsy, and an increased mortality that extends well beyond the initial TBI stage. Ongoing research into novel biomarkers, the application of artificial intelligence (AI) and an increasing global effort may yield future therapeutic strategies to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

• On days with delirium, stroke patients had more generalized EEG abnormalities, even when excluding those with anesthetic use. • Delirious stroke patients had fewer focal EEG abnormalities, though these differences were not significant. • These findings may reinforce the diffuse nature of delirium, even in patients with structural brain lesions. Delirium is an acute cognitive disorder associated with multiple electroencephalographic (EEG) abnormalities in non-neurological patients, though specific EEG characteristics in patients with stroke remain unclear. We aimed to compare the prevalence of EEG abnormalities in stroke patients during delirium episodes with periods that did not correspond to delirium. We retrospectively analyzed clinical EEG reports for stroke patients who received daily delirium assessments as part of a prospective study. We compared the prevalence of EEG features corresponding to patient-days with vs. without delirium, including focal and generalized slowing, and focal and generalized epileptiform abnormalities (EAs). Among 58 patients who received EEGs, there were 192 days of both EEG and delirium monitoring (88% [n = 169] corresponding to delirium). Generalized slowing was significantly more prevalent on days with vs. without delirium (96% vs. 57%, p = 0.03), as were bilateral or generalized EAs (38% vs. 13%, p = 0.03). In contrast, focal slowing (53% vs. 74%, p = 0.11) and focal EAs were less prevalent on days with delirium (38% vs. 48%, p = 0.37), though these differences were not statistically significant. We found a higher prevalence of generalized but not focal EEG abnormalities in stroke patients with delirium. These findings may reinforce the diffuse nature of delirium-associated encephalopathy, even in patients with discrete structural lesions. [ABSTRACT FROM AUTHOR]

We aimed to identify clinical characteristics, risk factors for diagnosis, and describe outcomes among children with AHT. We performed an observational cohort study in tertiary care hospitals from 14 countries across Asia and Ibero-America. We included patients <5 years old who were admitted to participating pediatric intensive care units (PICUs) with moderate to severe traumatic brain injury (TBI). We performed descriptive analysis and multivariable logistic regression for risk factors of AHT. 47 (12%) out of 392 patients were diagnosed with AHT. Compared to those with accidental injuries, children with AHT were more frequently < 2 years old (42, 89.4% vs 133, 38.6%, p < 0.001), more likely to arrive by private transportation (25, 53.2%, vs 88, 25.7%, p < 0.001), but less likely to have multiple injuries (14, 29.8% vs 158, 45.8%, p = 0.038). The AHT group was more likely to suffer subdural hemorrhage (SDH) (39, 83.0% vs 89, 25.8%, p < 0.001), require antiepileptic medications (41, 87.2% vs 209, 60.6%, p < 0.001), and neurosurgical interventions (27, 57.40% vs 143, 41.40%, p = 0.038). Mortality, PICU length of stay, and functional outcomes at 3 months were similar in both groups. In the multivariable logistic regression, age <2 years old (aOR 8.44, 95%CI 3.07-23.2), presence of seizures (aOR 3.43, 95%CI 1.60-7.36), and presence of SDH (aOR 9.58, 95%CI 4.10-22.39) were independently associated with AHT. AHT diagnosis represented 12% of our TBI cohort. Overall, children with AHT required more neurosurgical interventions and the use of anti-epileptic medications. Children younger than 2 years and with SDH were independently associated with a diagnosis of AHT. Observational cohort study. III. [ABSTRACT FROM AUTHOR]

In recent years, a lot of controversies have emerged regarding conservative versus liberal oxygen therapy in critically ill patients. While neurologically injured patients might have higher oxygen demand due to high cerebral metabolism, recent studies have clearly shown that hyperoxia may not be beneficial in improving the neurological outcome in traumatic brain injury, subarachnoid hemorrhage, and acute ischemic stroke. Rather, hyperoxia might worsen neurological outcome in such conditions by various mechanisms like direct cerebral vasoconstriction or by increased excitotoxicity, which in turn leads to lipid peroxidation and generation of harmful reactive oxygen species. This article brings into insight the current evidence on the effect of hyperoxia on these three acute neurological insults. [ABSTRACT FROM AUTHOR]

Gunshot wounds to the head (GSWH) are a cause of severe penetrating traumatic brain injury (TBI). Although multimodal neuromonitoring has been increasingly used in blunt pediatric TBI, its role in the pediatric population with GSWH is not known. We report on 3 patients who received multimodal neuromonitoring as part of clinical management at our institution and review the existing literature on pediatric GSWH. We identified 3 patients ≤18 years of age who were admitted to a quaternary children's hospital from 2005 to 2021 with GSWH and received invasive intracranial pressure (ICP) and Pbto 2 (brain tissue oxygenation) monitoring with or without noninvasive near-infrared spectroscopy (NIRS). We analyzed clinical and demographic characteristics, imaging findings, and ICP, Pbto 2 , cerebral perfusion pressure, and rSo 2 (regional cerebral oxygen saturation) NIRS trends. All patients were male with an average admission Glasgow Coma Scale score of 4. One patient received additional NIRS monitoring. Episodes of intracranial hypertension (ICP ≥20 mm Hg) and brain tissue hypoxia (Pbto 2 <15 mm Hg) or hyperemia (Pbto 2 >35 mm Hg) frequently occurred independently of each other, requiring unique targeted treatments. rSo 2 did not consistently mirror Pbto 2. All children survived, with favorable Glasgow Outcome Scale–Extended score at 6 months after injury. Use of ICP and Pbto 2 multimodality neuromonitoring enabled specific management for intracranial hypertension or brain tissue hypoxia episodes that occurred independently of one another. Multimodality neuromonitoring has not been studied extensively in pediatric GSWH; however, its use may provide a more complete picture of patient injury and prognosis without significant added procedural risk. [ABSTRACT FROM AUTHOR]

Traumatic brain injury is a common type of acquired brain injury of varying severity carrying potentially deleterious consequences for the afflicted individuals, families, and society. Following the initial, traumatically induced insult, cellular injury processes ensue. These are believed to be amenable to treatment. Among such injuries, neuroinflammation has gained interest and has become a specific focus for both experimental and clinical researchers. Neuroinflammation is elicited almost immediately following trauma, and extend for a long time, possibly for years, after the primary injury. In the acute phase, the inflammatory response is characterized by innate mechanisms such as the activation of microglia which among else mediates cytokine production. Among the earliest cytokines to emerge are the interleukin- (IL-) 1 family members, comprising, for example, the agonist IL-1β and its competitive antagonist, IL-1 receptor antagonist (IL-1ra). Because of its early emergence following trauma and its increased concentrations also after human TBI, IL-1 has been hypothesized to be a tractable treatment target following TBI. Ample experimental data supports this, and demonstrates restored neurological behavior, diminished lesion zones, and an attenuated inflammatory response following IL-1 modulation either through IL-1 knock-out experiments, IL-1β inhibition, or IL-1ra treatment. Of these, IL-1ra treatment is likely the most physiological. In addition, recombinant human IL-1ra (anakinra) is already approved for utilization across a few rheumatologic disorders. As of today, one randomized clinical controlled trial has utilized IL-1ra inhibition as an intervention and demonstrated its safety. Further clinical trials powered for patient outcome are needed in order to demonstrate efficacy. In this review, we summarize IL-1 biology in relation to acute neuroinflammatory processes following TBI with a particular focus on current evidence for IL-1ra treatment both in the experimental and clinical context. [ABSTRACT FROM AUTHOR]

There is a lack of consistent, evidence-based guidelines for the management of patients with fever after brain injury. The aim was to update previously published consensus recommendations on targeted temperature management after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in patients who require admission to critical care. A modified Delphi consensus, the Neuroprotective Therapy Consensus Review (NTCR), included 19 international neuro-intensive care experts with a subspecialty interest in the acute management of intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke. An online, anonymised survey was completed ahead of the meeting before the group came together to consolidate consensus and finalise recommendations on targeted temperature management. A threshold of ≥80% for consensus was set for all statements. Recommendations were formulated based on existing evidence, literature review, and consensus. After intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in patients who require critical care admission, core temperature should ideally be monitored continuously and maintained between 36.0°C and 37.5°C using automated feedback-controlled devices, where possible. Targeted temperature management should be commenced within 1 h of first fever identification with appropriate diagnosis and treatment of infection, maintained for as long as the brain remains at risk of secondary injury, and rewarming should be controlled. Shivering should be monitored and managed to limit risk of secondary injury. Following a single protocol for targeted temperature management across intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke is desirable. Based on a modified Delphi expert consensus process, these guidelines aim to improve the quality of targeted temperature management for patients after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in critical care, highlighting the need for further research to improve clinical guidelines in this setting. [ABSTRACT FROM AUTHOR]

Volatile sedation after aneurysmal subarachnoid hemorrhage (aSAH) promises several advantages, but there are still concerns regarding intracranial hypertension due to vasodilatory effects. We prospectively analyzed cerebral parameters during the switch from intravenous to volatile sedation with isoflurane in patients with poor-grade (World Federation of Neurosurgical Societies grade 4–5) aSAH. Eleven patients were included in this prospective observational study. Between day 3 and 5 after admission, intravenous sedation was switched to isoflurane using the Sedaconda Anesthetic Conserving Device (Sedana Medical, Danderyd, Sweden). Intracranial pressure (ICP), cerebral perfusion pressure (CPP), brain tissue oxygenation (PBrO 2), cerebral mean flow velocities (MFVs; transcranial Doppler ultrasound) and regional cerebral oxygen saturation (rSO 2 , near-infrared spectroscopy monitoring), as well as cardiopulmonary parameters were assessed before and after the sedation switch (–12 to +12 hours). Additionally, perfusion computed tomography data during intravenous and volatile sedation were analyzed retrospectively for changes in cerebral blood flow. There were no significant changes in mean ICP, CPP, and PBrO 2 after the sedation switch to isoflurane. Mean rSO 2 showed a non-significant trend towards higher values, and mean MFV in the middle cerebral arteries increased significantly after the initiation of volatile sedation. Isoflurane sedation resulted in a significantly increased norepinephrine administration. Despite an increase in mean inspiratory pressure, we observed a significant increase in mean partial arterial pressure of carbon dioxide. Isoflurane sedation does not compromise ICP or cerebral oxygenation in poor-grade aSAH patients, but the significant depression of CPP could limit the use of volatiles in case of hemodynamic instability or high vasopressor demand. [ABSTRACT FROM AUTHOR]

• Pharmacologic paralysis improves detection of EEG epileptiform activity regardless of type of movement-related artifact present. • Artifact reduction improves detection of EEG epileptiform activity as much as pharmacologic paralysis when primary source of artifact is EMG. • In the appropriate setting, both artifact reduction and paralysis facilitate identification of epileptiform activity in critically ill patients. Epileptiform activity is common in critically ill patients, but movement-related artifacts—including electromyography (EMG) and myoclonus—can obscure EEG, limiting detection of epileptiform activity. We sought to determine the ability of pharmacologic paralysis and quantitative artifact reduction (AR) to improve epileptiform discharge detection. Retrospective analysis of patients who underwent continuous EEG monitoring with pharmacologic paralysis. Four reviewers read each patient's EEG pre- and post- both paralysis and AR, and indicated the presence of epileptiform discharges. We compared the interrater reliability (IRR) of identifying discharges at baseline, post-AR, and post-paralysis, and compared the performance of AR and paralysis according to artifact type. IRR of identifying epileptiform discharges at baseline was slight (N = 30; κ = 0.10) with a trend toward increase post-AR (κ = 0.26, p = 0.053) and a significant increase post-paralysis (κ = 0.51, p = 0.001). AR was as effective as paralysis at improving IRR of identifying discharges in those with high EMG artifact (N = 15; post-AR κ = 0.63, p = 0.009; post-paralysis κ = 0.62, p = 0.006) but not with primarily myoclonus artifact (N = 15). Paralysis improves detection of epileptiform activity in critically ill patients when movement-related artifact obscures EEG features. AR improves detection as much as paralysis when EMG artifact is high, but is ineffective when the primary source of artifact is myoclonus. In the appropriate setting, both AR and paralysis facilitate identification of epileptiform activity in critically ill patients. [ABSTRACT FROM AUTHOR]

Background: Limited data exist regarding seizure burden, electroencephalogram (EEG) background, and associated outcomes in neonates with acute intracranial infections.Methods: This secondary analysis was from a prospective, multicenter study of neonates enrolled in the Neonatal Seizure Registry with seizures due to intracranial infection. Sites used continuous EEG monitoring per American Clinical Neurophysiology Society guidelines. High seizure burden was defined a priori as seven or more EEG-confirmed seizures. EEG background was categorized using standardized terminology. Primary outcome was neurodevelopment at 24-months corrected age using Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS). Secondary outcomes were postneonatal epilepsy and motor disability.Results: Twenty-seven of 303 neonates (8.9%) had seizures due to intracranial infection, including 16 (59.3%) bacterial, 5 (18.5%) viral, and 6 (22.2%) unknown. Twenty-three neonates (85%) had at least one subclinical seizure. Among 23 children with 24-month follow-up, the WIDEA-FS score was, on average, 23 points lower in children with high compared with low seizure burden (95% confidence interval, [-48.4, 2.1]; P = 0.07). After adjusting for gestational age, infection etiology, and presence of an additional potential acute seizure etiology, the effect size remained unchanged (β = -23.8, P = 0.09). EEG background was not significantly associated with WIDEA-FS score. All children with postneonatal epilepsy (n = 4) and motor disability (n = 5) had high seizure burden, although associations were not significant.Conclusion: High seizure burden may be associated with worse neurodevelopment in neonates with intracranial infection and seizures. EEG monitoring can provide useful management and prognostic information in this population. [ABSTRACT FROM AUTHOR]

Objective: To summarize and evaluate clinical experiences with refractory status epilepticus in which cannabidiol (CBD) was utilized for cessation of seizure activity.Methods: A comprehensive literature review was performed on PubMED, MEDLINE, Scopus, and CINAHL between May - June 2022 with the assistance of a medical reference librarian using the following search terms: "Cannabidiol" [MAJR], "Status Epilepticus" [MAJR], "New-Onset Refractory Status Epilepticus", and "cannabidiol." Reports that provided dosing regimens and patient outcomes were included.Results: Thirty-two articles were screened. Five articles were selected for inclusion in this review and detailed the clinical courses of 11 patients. Five of the 11 patients received CBD during the chronic epilepsy stage, while the remaining 6 received it during a period of acute status epilepticus. Patients were trialed on an average of 9 anti-epileptic drugs prior to CBD administration, after which 9 of the 11 patients experienced a reduction of seizure activity. Dosing of CBD ranged between 5-25 mg/kg/day and was titrated based on patient response to therapy. Adverse effects were relatively benign and were generally limited to gastrointestinal discomfort, reported after seizure cessation.Conclusions: CBD may provide a potentially efficacious and safe management strategy in refractory status epilepticus, including patients with new-onset refractory status epilepticus and febrile infection-related epilepsy syndrome. A potential for drug-drug interactions between CBD and anti-epileptic drugs warrants judicious monitoring. Additional research is necessary to determine a definitive dosing strategy for this agent. [ABSTRACT FROM AUTHOR]

Neurocritical management of aneurysmal subarachnoid hemorrhage focuses on delayed cerebral ischemia (DCI) after aneurysm repair. This study conceptualizes the pathophysiology of cerebral ischemia and its management using a brain oxygen–directed protocol (intracranial pressure [ICP] control, eubaric hyperoxia, hemodynamic therapy, arterial vasodilation, and neuroprotection) in patients with subarachnoid hemorrhage, undergoing aneurysm clipping (n = 40). The brain oxygen–directed protocol reduced Lb o 2 (Pbt o 2 [partial pressure of brain tissue oxygen] <20 mm Hg) from 67% to 15% during acute brain attack (<24 hours of ictus), by increasing Pbt o 2 from 11.31 ± 9.34 to 27.85 ± 6.76 (P < 0.0001) and then to 29.09 ± 17.88 within 72 hours. Day-after-bleed, Fi o 2 change, ICP, hemoglobin, and oxygen saturation were predictors for Pbt o 2 during early brain injury. Transcranial Doppler ultrasonography velocities (>20 cm/second) increased at day 2. During DCI caused by territorial sonographic vasospasm (TSV), middle cerebral artery mean velocity (V m) increased from 45.00 ± 15.12 to 80.37 ± 38.33/second by day 4 with concomitant Pbt o 2 reduction from 29.09 ± 17.88 to 22.66 ± 8.19. Peak TSV (days 7–12) coincided with decline in Pbt o 2. Nicardipine mitigated Lb o 2 during peak TSV, in contrast to nimodipine, with survival benefit (P < 0.01). Intravenous and cisternal nicardipine combination had survival benefit (Cramer Φ = 0.43 and 0.327; G 2 = 28.32; P < 0.001). This study identifies 4 zones of Lb o 2 during survival benefit (Cramer Φ = 0.43 and 0.3) TSV, uncompensated; global cerebral ischemia, compensated, and normal Pbt o 2. Admission Glasgow Coma Scale score (not increased ICP) was predictive of low Pbt o 2 (β = 0.812, R 2 = 0.661, F 1,30 = 58.41; P < 0.0001) during early brain injury. Coma was the only credible predictor for mortality (odds ratio, 7.33/>4.8∗; χ2 = 7.556; confidence interval, 1.70–31.54; P < 0.01) followed by basilar aneurysm, poor grade, high ICP and Lb o 2 during TSV. Global cerebral ischemia occurs immediately after the ictus, persisting in 30% of patients despite the high therapeutic intensity level, superimposed by DCI during TSV. We propose implications for clinical practice and patient management to minimize cerebral ischemia. [ABSTRACT FROM AUTHOR]

We aim to evaluate the role of frailty and inflammatory markers in predicting the short-term outcomes after catheter-associated urinary tract infections (CAUTI) and central line–associated bloodstream infections (CLABSI). Data regarding the patients' characteristics, isolates on CAUTI and CLABSI, antibiotic susceptibility, frailty (11-point Modified Frailty Index), and inflammatory markers were retrospectively collected. Their impact on the short-term outcomes was assessed using regression modeling response. One hundred and one patients with CAUTI (n = 71) and CLABSI (n = 30) between January 2018 and December 2019 were included in this study. The pooled incidence rates for CAUTI were 5.50 and for CLABSI 3.58 episodes/1000 catheter-days. We observed 74.7% drug resistance in our CAUTI isolates and 93.3% in CLABSI. In the multivariate analysis, frailty (P = 0.006), neutrophil/lymphocyte ratio (NLR) (P = 0.007) and the presence of sepsis (P = 0.029) were found to be significant predictors of in-hospital mortality in CAUTI. In patients with CLABSI, frailty (P = 0.029) and NLR (P = 0.029) were found significant and along with sepsis (P = 0.069) resulted in a regression model with good accuracy in predicting mortality. The receiver operating characteristic curve showed that 11-point Modified Frailty Index and NLR as well as the regression model significantly predicted mortality with an area under the curve of 86.1%, 81.4%, and 95.4%, respectively, in CAUTI, and 70.9%, 77.8%, and 95.2%, respectively, in CLABSI. [ABSTRACT FROM AUTHOR]

Background: Congenital cerebral arteriovenous fistulas (AVFs), including vein of Galen malformations, presenting in infancy carry variable mortality and morbidity. This study aimed to describe the outcome of neonates with cerebral AVFs who present with refractory cardiac failure.Methods: Retrospective chart review of neonates with refractory cardiac failure due to cerebral AVFs presenting before 28 days of age in a single-center neuro-intensive care nursery over a 12-year period (2008-2020) was conducted.Results: Seventeen neonates were included. Twelve had a vein of Galen malformation, four a non-galenic pial AVF, and one a dural AVF. Seven neonates (41%) died without receiving an embolization procedure. The remaining ten were critically ill. Seven (70%) were mechanically ventilated and on nitric oxide, 5 (50%) were on pressors, and 6 (60%) had renal and/or hepatic dysfunction. Seven (70%) had pre-existing brain injury on imaging. The first embolization procedure occurred at a median age of 4 days (range: 0-8 d). Complications included intracranial hemorrhage in 8 of 10 (80%) and seizures in 5 of 8 (62%). Five (50%) neonates who underwent embolization died. Among the 5 neonates who survived, all have motor impairment. Four (80%) developed hydrocephalus requiring a ventriculoperitoneal shunt, and 2 (40%) developed epilepsy and are nonverbal.Conclusion: In this cohort of critically ill neonates with cerebral AVF, all seven who did not receive embolization and half of ten who were treated died. The five survivors all have neurodevelopmental impairment. This information may be helpful to parents and providers who make decisions regarding life-sustaining treatments for neonates with cerebral AVFs and refractory cardiac failure. [ABSTRACT FROM AUTHOR]

• The pupillary light reflex provides essential information about cranial nerve functional. • The NPi-200 has high inter-device reliability when compared with the NPi-300 device. • NPi-200 data can be directly translated to results using the NPi-300. The pupillary evaluation is an essential part of the neurological examination. Research suggests that the traditional examination of the pupil with a handheld flashlight has limited interrater reliability. Automated pupillometers were developed to provide an objective scoring of various pupillary parameters. The NPi-200 pupillometer is used for quantitative pupillary examinations, the NPi-300 was launched in July 2021 with enhanced features. The purpose of this study is to compare results from the NPi-200 to the NPi-300 to ensure that data are translatable across both platforms. This study examines the inter-device reliability of the NPi-200 compared to the NPi-300 in two cohorts: 20 patients at risk for cerebral edema and 50 healthy controls. Paired assessments of the devices were made from all participants. Each assessment included bilateral PLR readings within a 5-minute interval. Data showed high agreement between the two devices for the Neurological Pupil Index (NPi) reading (k = 0.94; CI: 0.91–0.99) and for pupil diameter assessment (k = 0.91; CI: 0.87–0.96). There is a very high level of agreement between the NPi-200 and NPi-300 among healthy controls and critically ill patients. Clinicians and researchers can interpret the results from either device equally. [ABSTRACT FROM AUTHOR]

• There are strong associations between mitochondrial dysfunction and microglial activation in older individuals. Therefore, mitochondria-targeted treatment could be promising for the advancement of microglia-targeted therapeutics. Mitochondrial protection strategies focusing on energy metabolism and mitophagy have shown neuroprotective effects in preclinical animal models of neurodegenerative disorders and neurocritical care diseases, which suggest that mitochondrial protection is an attractive target for the treatment. The incidence of aging-related neurodegenerative disorders and neurocritical care diseases is increasing worldwide. Microglia, the main inflammatory cells in the brain, could be potential viable therapeutic targets for treating neurological diseases. Interestingly, mitochondrial functions, including energy metabolism, mitophagy and transfer, fission and fusion, and mitochondrial DNA expression, also change in activated microglia. Notably, mitochondria play an active and important role in the pathophysiology of neurodegenerative disorders and neurocritical care diseases. This review briefly summarizes the current knowledge on mitochondrial dysfunction in microglia in neurodegenerative disorders and neurocritical care diseases and comprehensively discusses the prospects of the application of neurological injury prevention and treatment targets by mitochondria. [ABSTRACT FROM AUTHOR]

Following acute brain injury, frequent neurological examinations ("neurochecks") are commonly prescribed and form the cornerstone of many care protocols and guidelines (e.g., for intracranial hemorrhage). While these assessments are intended to identify and mitigate secondary injury, they may unintentionally contribute to additional injury related to neurocheck-associated sleep disruption. Data are lacking to define patterns of neurological decline following acute brain injury, as are data to define the short- and long-term consequences (e.g., neuropsychological sequelae) of frequent and prolonged neurochecks. A critical need exists for rigorous evaluation of neurocheck practices, perceptions, benefits and risks, along with interventions to optimize neurocheck frequency and duration. [ABSTRACT FROM AUTHOR]

This scoping review addresses the challenges of neuroanesthesiologic research: the population, the methods/treatment/exposure, and the outcome/results. These challenges are put into the context of a future research agenda for peri-/intraoperative anesthetic management, neurocritical care, and applied neurosciences. Finally, the opportunities of adaptive trial design in neuroanesthesiologic research are discussed. [ABSTRACT FROM AUTHOR]

Manual pupillary assessments are an integral part of the neurologic evaluation in critically ill patients. Automated pupillometry provides reliable, consistent, and accurate measurement of the light response. We established a computer interface that allows for direct download of pupillometer information to our hospital electronic medical record (EMR). Here, we report our single-center experience. An interface allowing direct download of pupillometer data to our EMR was developed. We then performed a prospective study using an electronic survey distributed to nurses that used pupillometers in 2015, 2018, and 2020 using a 5-point Likert-style format to evaluate the acceptance of this implementation. In 2015, 22 nurses were surveyed, with 50% of the respondents citing lack of pupillometers and 41% citing the labor intensity associated with data entry as the reason for the reluctance to use the pupillometer. The number of nurse responses in 2018 increased to 123, with 78% of nurses finding that the direct download to hospital EMR improved the efficiency of their neurologic exams. In 2020, 108 nurses responded with similar responses to those in 2018. We added 3 additional questions regarding utility of the pupillometer during the COVID-19 pandemic. Fifty-eight percent of nurses were reassured of the neurologic exam when using the pupillometer in lieu of a full exam to limit infectious exposure. This is the first report of the implementation of a direct interface to download pupillometer data to the EMR. The positive effect on nursing workflow and documentation of pupillary findings is discussed. [ABSTRACT FROM AUTHOR]

Children with acute neurologic illness are at high risk of mortality and long-term neurologic disability. Severe traumatic brain injury, cardiac arrest, stroke, and central nervous system infection are often complicated by cerebral hypoxia, hypoperfusion, and edema, leading to secondary neurologic injury and worse outcome. Owing to the paucity of targeted neuroprotective therapies for these conditions, management emphasizes close physiologic monitoring and supportive care. In this review, we will discuss advanced neurologic monitoring strategies in pediatric acute neurologic illness, emphasizing the physiologic concepts underlying each tool. We will also highlight recent innovations including novel monitoring modalities, and the application of neurologic monitoring in critically ill patients at risk of developing neurologic sequelae. [ABSTRACT FROM AUTHOR]

• Both VA-and NVA-HARTI are prevalent in neurosurgical critical care patients. • While the VA-HARTI incidence reduced over time, NVA-HARTI incidence did not change. • NVA-HARTI was associated with higher hospital and ICU LOS. • VA-HARTI was an independent predictor of mortality while NVA-HARTI was not. • Extrapolating VA-HARTI research findings to NVA-HARTI should be avoided. The incidence of healthcare-associated respiratory tract infections in non-ventilated patients (NVA-HARTI) in neurosurgical intensive care units (ICUs) is unknown. The impact of NVA-HARTI on patient outcomes and differences between NVA-HARTI and ventilator-associated healthcare-associated respiratory tract infections (VA-HARTI) are poorly understood. Our objectives were to report the incidence, hospital length of stay (LOS), ICU LOS, and mortality in NVA-HARTI patients and compare these characteristics to VA-HARTI in neurocritical care patients. This cohort study was conducted in a neurosurgical ICU in Moscow. From 2011 to 2020, all patients with an ICU LOS > 48 h were included. A competing risk model was used for survival and risk analysis. A total of 3,937 ICU admissions were analyzed. NVA-HARTI vs VA-HARTI results were as follows: cumulative incidence 7.2 (95%CI: 6.4–8.0) vs 15.4 (95%CI: 14.2–16.5) per 100 ICU admissions; incidence rate 4.2 ± 2.0 vs 9.5 ± 3.0 per 1000 patient-days in the ICU; median LOS 32 [Q1Q3: 21, 48.5] vs 46 [Q1Q3: 28, 76.5] days; median ICU LOS 15 [Q1Q3: 10, 28.75] vs 26 [Q1Q3: 17, 43] days; mortality 12.3% (95%CI: 7.9–16.8) vs 16.7% (95%CI: 13.6–19.7). The incidence of VA-HARTI decreased over ten years while NVA-HARTI incidence did not change. VA-HARTI was an independent risk factor of death, OR 1.54 (1.11–2.14), while NVA-HARTI was not. Our findings suggest that NVA-HARTI in neurocritical care patients represents a significant healthcare burden with relatively high incidence and associated poor outcomes. Unlike VA-HARTI, the incidence of NVA-HARTI remained constant despite preventive measures. This suggests that extrapolating VA-HARTI research findings to NVA-HARTI should be avoided. [ABSTRACT FROM AUTHOR]

Background: Although seizures in neonates are common and often due to acute brain injury, 10-15% are unprovoked from congenital brain malformations. A better understanding of the risk of neonatal-onset epilepsy by the type of brain malformation is essential for counseling and monitoring.Methods: In this retrospective cohort study, we evaluated 132 neonates with congenital brain malformations and their risk of neonatal-onset epilepsy. Malformations were classified into one of five categories based on imaging patterns on prenatal or postnatal imaging. Infants were monitored with continuous video EEG (cEEG) for encephalopathy and paroxysmal events in addition to abnormal neuroimaging.Results: Seventy-four of 132 (56%) neonates underwent EEG monitoring, and 18 of 132 (14%) were diagnosed with neonatal-onset epilepsy. The highest prevalence of epilepsy was in neonates with disorders of neuronal migration/organization (9/34, 26%; 95% confidence interval [CI] = 13-44%), followed by disorders of early prosencephalic development (6/38, 16%; 95% CI = 6-31%), complex total brain malformations (2/16, 13%; 95% CI = 2-38%), and disorders of midbrain/hindbrain malformations (1/30, 3%; 95% CI = 0-17%). Of neonates with epilepsy, 5 of 18 (28%) had only electrographic seizures, 13 of 18 (72%) required treatment with two or more antiseizure medicines (ASMs), and 7 of 18 (39%) died within the neonatal period.Conclusion: Our results demonstrate that disorders of neuronal migration/organization represent the highest-risk group for early-onset epilepsy. Seizures are frequently electrographic only, require treatment with multiple ASMs, and portend a high mortality rate. These results support American Clinical Neurophysiology Society recommendations for EEG monitoring during the neonatal period for infants with congenital brain malformations. [ABSTRACT FROM AUTHOR]

• EVD systems can get blocked by blood clots, air bubbles and debris. • Repeated use of invasive measures can lead to increased rates of ventriculitis. • A non-invasive novel technique utilises pressure differentials to rectify blockages. • A sequential approach to EVD blockages will prevent unnecessary invasive procedures. External ventricular drainage (EVD) is carried out in many neurosurgical conditions for the diversion of cerebrospinal fluid. These EVD systems can, however, malfunction with potentially lethal consequences. Air bubbles within the EVD can result in air locking of the system with subsequent blockage of drainage, with blood clots and debris being the other causes. There are both non-invasive and invasive methods of rectifying such blockages, with invasive procedures having its associated risks. This is especially so for EVD revisions, with each surgery increasing the risk of ventriculitis. We describe a case of bilateral air locked EVD managed successfully with a novel non-invasive 'pressure differential efflux technique'. This method exploits the pressure gradient established by adjusting each EVD to a different height to evacuate the pneumoventricle. In addition, we present a sequential approach to the management of EVD malfunction, based on the current literature and our institutional protocol. [ABSTRACT FROM AUTHOR]

• A novel burst suppression detection algorithm that doesn't require annotated data. • The algorithm adapts to each patient, is fast and provides confidence scores. • We report competitive performance compared to supervised deep neural networks. The burst suppression pattern in clinical electroencephalographic (EEG) recordings is an important diagnostic tool because of its association with comas of various etiologies, as with hypoxia, drug related intoxication or deep anesthesia. The detection of bursts and the calculation of burst/suppression ratio are often used to monitor the level of anesthesia during treatment of status epilepticus. However, manual counting of bursts is a laborious process open to inter-rater variation and motivates a need for automatic detection. METHODS: We describe a novel unsupervised learning algorithm that detects bursts in EEG and generates burst-per-minute estimates for the purpose of monitoring sedation level in an intensive care unit (ICU). We validated the algorithm on 29 hours of burst annotated EEG data from 29 patients suffering from status epilepticus and hemorrhage. RESULTS: We report competitive results in comparison to neural networks learned via supervised learning. The mean absolute error (SD) in bursts per minute was 0.93 (1.38). CONCLUSION: We present a novel burst suppression detection algorithm that adapts to each patient individually, reports bursts-per-minute quickly, and does not require manual fine-tuning unlike previous approaches to burst-suppression pattern detection. SIGNIFICANCE: Our algorithm for automatic burst suppression quantification can greatly reduce manual oversight in depth of sedation monitoring. [ABSTRACT FROM AUTHOR]

• Errors in communication are a major source of medical errors and adverse events. • The IPASS format is a validated format to improve multidisciplinary handoffs. • Standardizing postoperative handoffs for neurosurgical patients improves communication. • Standardizing postoperative handoffs improves staff satisfaction. • Standardization of postoperative neurosurgical handoffs is sustainable long-term. Errors in communication are a major source of preventable medical errors. Neurosurgical patients frequently present to the neuro-intensive care unit (NICU) postoperatively, where handoffs occur to coordinate care within a large multidisciplinary team. A multidisciplinary working group at our institution started an initiative to improve postoperative neurosurgical handoffs using validated quality improvement methodology. Baseline handoff practices were evaluated through staff surveys and serial observations. A formalized handoff protocol was implemented using the evidence based IPASS format (I llness severity, P atient summary, A ction list, S ituational awareness and contingency planning, S ynthesis by receiver). Cycles of objective observations and surveys were employed to track practice improvements and guide iterative process changes over one year. Surveys demonstrated improved perceptions of handoffs as organized (17.1% vs 69.7%, p < 0.001), efficient (27.0% vs. 72.7%, p < 0.001), comprehensive (17.1% vs. 66.7%, p < 0.001), and safe (18.0% vs. 66.7%, p < 0.001), noting improved teamwork (31.5% vs. 69.7%, p < 0.001). Direct observations demonstrated improved communication of airway concerns (47.1% observed vs. 92.3% observed, p < 0.001), hemodynamic concerns (70.6% vs. 97.1%, p = 0.001), intraoperative events (52.9% vs. 100%, p < 0.001), neurological examination (76.5% vs. 100%, p < 0.001), vital sign goals (70.6% vs. 100%, p < 0.001), and required postoperative studies (76.5% vs. 100%, p < 0.001). Receiving teams demonstrating improved rates of summarization (47.1% vs. 94.2%, p = 0.005) and asking questions (76.5% vs 98.1%, p = 0.004). The mean handoff time during long-term follow-up was 4.4 min (95% confidence interval = 3.9–5.0 min). Standardization of handoff practices yields improvements in communication practices for postoperative neurosurgical patients. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a huge global problem with an increasing socioeconomic impact. Current understanding of the pathophysiology of TBI has led to a systematic approach towards management in the pre-hospital, operating theatre and critical care settings, with early management directed towards protecting the brain from secondary injury. TBI is a spectrum of diseases, and rapid radiological identification of the underlying pathology is paramount to determine appropriate surgical intervention. Most modern neurocritical care centres augment intracranial pathophysiology with intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targeted therapies at a minimum. Decompressive craniectomy (DC) can be a useful mechanism to control medically refractory intracranial hypertension and reduce mortality; however, it also results in a spectrum of outcome categories and remains a controversial topic. There is emerging evidence that TBI is a chronic illness, with increased incidence of cognitive and behavioural deficits, neurodegenerative disease, and an increased mortality that extends well beyond the initial TBI stage. Ongoing research into novel biomarkers may yield future therapeutic targets to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Cerebral complications are common in perioperative settings even in non-neurosurgical procedures. These include postoperative cognitive dysfunction or delirium as well as cerebrovascular accidents. During surgery, it is essential to ensure an adequate degree of sedation and analgesia, and at the same time, to provide hemodynamic and respiratory stability in order to minimize neurological complications. In this context, the role of neuromonitoring in the operating room is gaining interest, even in the non-neurolosurgical population. The use of multimodal neuromonitoring can potentially reduce the occurrence of adverse effects during and after surgery, and optimize the administration of anesthetic drugs. In addition to the traditional focus on monitoring hemodynamic and respiratory systems during general anesthesia, the ability to constantly monitor the activity and maintenance of brain homeostasis, creating evidence-based protocols, should also become part of the standard of care: in this challenge, neuromonitoring comes to our aid. In this review, we aim to describe the role of the main types of noninvasive neuromonitoring such as those based on electroencephalography (EEG) waves (EEG, Entropy module, Bispectral Index, Narcotrend Monitor), near-infrared spectroscopy (NIRS) based on noninvasive measurement of cerebral regional oxygenation, and Transcranial Doppler used in the perioperative settings in non-neurosurgical intervention. We also describe the advantages, disadvantage, and limitation of each monitoring technique. [ABSTRACT FROM AUTHOR]

Neuropatients often require invasive mechanical ventilation (MV). Ideal ventilator settings and respiratory targets in neuro patients are unclear. Current knowledge suggests maintaining protective tidal volumes of 6-8 ml/kg of predicted body weight in neuropatients. This approach may reduce the rate of pulmonary complications, although it cannot be easily applied in a neuro setting due to the need for special care to minimize the risk of secondary brain damage. Additionally, the weaning process from MV is particularly challenging in these patients who cannot control the brain respiratory patterns and protect airways from aspiration. Indeed, extubation failure in neuropatients is very high, while tracheostomy is needed in one-third of the patients. The aim of this manuscript is to review and describe the current management of invasive MV, weaning, and tracheostomy for the main four subpopulations of neuro patients: traumatic brain injury, acute ischemic stroke, subarachnoid hemorrhage, and intracerebral hemorrhage. [ABSTRACT FROM AUTHOR]

• Improved threshold compliance may improve outcomes from neurotrauma. • ICP threshold compliance was markedly improved with a threshold compliance tool. • A trial assessing our tool was negative, likely as a result of a delay in initiation.. Better physiologic threshold compliance holds promise for improving outcomes in neurocritical care patients. Our group developed a threshold compliance tool. This software computes and displays the proportion of values out of range in real time. We captured intracranial pressure (ICP) measures in our patients before and after implementation of this technology. Ten months after the threshold compliance tool was introduced we initiated a randomized controlled trial involving acute traumatic brain injury (TBI) patients to assess whether the tool was effective at reducing out-of-range ICP values. A total of 54 patients with ICP monitors were included in our analysis, 42 of whom sustained a TBI. Implementation of the threshold compliance tool was associated with an 85.3% reduction in ICP values exceeding 22 mmHg in neurocritical care patients (p = 0.004) and a 76.8% reduction in patients with TBI (p = 0.043). Out-of-range values in an area-under-the-curve analysis were reduced by 78.8% in all patients (p = 0.009) and in TBI patients by 77.9% (p = 0.051). Out-of-range values were not further reduced during our randomized controlled trial examining the threshold compliance tool, and a difference between treatment groups was not suggested. Implementation of a threshold compliance tool was associated with a marked and significant reduction in out-of-range ICP values. Benefit was, however, not evident in a randomized controlled trial. Our analysis provides a unique perspective on our failure to detect an apparent true difference and may provide insights into other neurotrauma trial failures. [ABSTRACT FROM AUTHOR]

Children admitted to neurocritical care units often experience new neurodevelopmental disabilities due to both their acquired neurologic injuries and deconditioning from prolonged hospitalizations. Rehabilitation for critically ill children is multifactorial and begins in the intensive care unit itself. The goals of rehabilitation include prevention of complications associated with immobilization and evolving tone, comprehensive evaluation and treatment of functional deficits, and implementation of adaptive strategies with the goal of maximizing recovery. As a child progresses along the medical continuum from the neurocritical care unit to acute care to post-hospitalization settings, their rehabilitative needs and interventions should also evolve. A child in the neurocritical care unit is likely to have sustained an acquired brain injury. Whether resulting from traumatic or non-traumatic causes, all etiologies of pediatric acquired brain injury can result in significant challenges for the child and their family. Post-intensive care syndrome-pediatrics is a clinical construct that that systematically organizes the range of physical, cognitive, psychological, and social symptoms that emerge in both a child and their family members following a critical illness. Ideally, outpatient care for this population evaluates and supports all areas of post-intensive care syndrome-pediatrics through an interdisciplinary clinical care model. Proactive and comprehensive rehabilitation across the continuum provides the opportunity to support the child and their family in all areas affected, thereby minimizing distress, maximizing function, and optimizing outcomes. [ABSTRACT FROM AUTHOR]

Clinical pharmacists are a part of the integrated health care team and provide valuable input on medication management for patients with acute and chronic disease states. Using epilepsy as a model, pharmacist involvement in patient care has been associated with significant reductions in monthly seizure frequency. Given differences in etiology, pediatric patients with epilepsy are likely to have higher number of treatments, with additional pharmacodynamic and pharmacokinetic differences, adding to the importance of utilizing a pediatric clinical pharmacist practitioner with neuropharmacology expertise. There is an increasing exposure to critically ill patients with epilepsy and other neurological disorders in the pediatric intensive care unit (PICU). These patients are more medically complex, increasing the risk for medication errors and increased health care costs. Emphasis on neurocritical care education is a vital component to improving patient outcomes. Inclusion of a clinical pharmacist practitioner in these settings yields a positive impact on major health outcomes. In 2018, the Neurocritical Care Society developed consensus recommendations on the standards for the development of adult neurocritical care units. A pharmacist-delivered pediatric critical care neuropharmacology rotation represents a novel approach to expanding physician education to improve patient outcomes. While there are sparse publications highlighting the importance of adult critical care and NCC pharmacists, no such literature exists describing the benefits of pediatric neurocritical care (PNCC) pharmacists. To the best of our knowledge, this is the first manuscript describing the role of clinical pharmacist practitioners in the development of PNCC program and the benefits they provide to patient care and education. [ABSTRACT FROM AUTHOR]

Background: Cerebral palsy (CP) is the most common motor disability of childhood. Its early identification is an important priority for parents and is critical for access to early intervention resources, which may optimize function.Methods: A prospective cohort of term neonates at high risk for CP was assessed by neonatal magnetic resonance imaging (MRI) to determine myelination of the posterior limb of the internal capsule, General Movements Assessment to assess typical fidgety movements at age three months, and followed to at least age two years to determine diagnosis of CP based on neurological examination.Results: Seven of 58 children developed CP (12%), two with moderate/severe CP. Sensitivity and specificity for abnormal myelination of the posterior limb of the internal capsule were (PLIC) was 29% and 94%, and for absent fidgety movements, 29% and 98%, respectively. Negative predictive value of both absent myelination of the PLIC and absent fidgety movements was 90% (79% to 96%) for any CP and 98% (90% to 100%) for moderate/severe CP cerebral palsy. None of the children with both normal PLIC and normal fidgety movements had moderate/severe CP.Conclusion: Normal neonatal MRI and General Movements Assessment at age three months are reassuring that a high-risk term-born child is at low risk for moderate/severe CP. These results are important for counseling parents and individualizing therapy resources in the community. [ABSTRACT FROM AUTHOR]

• Atraumatic antiplatelet-associated intracerebral hemorrhage is a devastating disease. • DDAVP may have beneficial properties on platelet function. • Meta-analysis of controlled studies shows no benefit of DDAVP on hematoma expansion. • Until completion of randomized trials individualized assessment is recommended. The purpose of this study was to perform a systematic review and meta-analysis on the effect of desmopressin on hematoma expansion (HE) in antiplatelet-associated intracerebral hemorrhage (AA-ICH). Secondary outcomes examined were the rate of thrombotic complications and neurologic outcome. Three databases were searched (Pubmed, Scopus, and Cochrane) for randomized clinical trials and controlled studies comparing desmopressin versus controls in adult patients with AA-ICH. The Mantel-Haenszel method was applied to calculate an overall effect estimate for each outcome by combining stratum-specific risk ratio (RR). Risk of bias was computed using the Newcastle-Ottawa Scale. The protocol was registered in PROSPERO (42020190234). Three retrospective controlled studies involving 263 patients were included in the meta-analysis. Compared to controls, desmopressin was associated with a non-significant reduction in HE (19.1% vs. 30%; RR:0.61; 95%CI, 0.27–1.39; P = 0.24), a similar rate of thrombotic events (5.5% vs. 9.9%; RR:0.47; 95%CI, 0.17–1.31; P = 0.15), and significantly worse neurologic outcome (mRS ≥ 4) (66.3% vs. 50%; RR:1.36; 95%CI, 1.08–1.7; P = 0.008). Qualitative analysis of included studies for each outcome revealed low to moderate risk of bias. The available literature does not support the routine use of desmopressin in the setting of AA-ICH. Until larger prospective trials are performed, the administration of desmopressin should be judiciously considered on a case-by-case basis. [ABSTRACT FROM AUTHOR]

Background: Neonatal seizures are associated with death and neurological morbidity; however, little is known about how neonates with seizures die.Methods: This was a prospective, observational cohort study of neonates with seizures treated at seven sites of the Neonatal Seizure Registry. We characterized the mode of death, evaluated the association between infant characteristics and mode of death, and evaluated predictors of death or transfer to hospice.Results: We enrolled 611 consecutive neonates with seizures, and 90 neonates (15%) died before hospital discharge at a median age of 11 days (range: 1 to 163 days); 32 (36%) died in the first postnatal week. An additional 19 neonates (3%) were transferred to hospice. The most common mode of in-hospital death was death after extubation amidst concerns for poor neurological prognosis, in the absence of life-threatening physiologic instability (n = 43, 48%). Only one infant died while actively receiving cardiopulmonary resuscitation. In an adjusted analysis, premature birth (odds ratio: 3.06, 95% confidence interval 1.59 to 5.90) and high seizure burden (odds ratio: 4.33, 95% confidence interval 1.88 to 9.95) were associated with increased odds of death or transfer to hospice.Conclusion: In a cohort of neonates with seizures, death occurred predominantly after decisions to withdraw or withhold life-sustaining intervention(s). Future work should characterize how these decisions occur and develop optimized approaches to support families and clinicians caring for newborns with seizures. [ABSTRACT FROM AUTHOR]

To determine the effect of offering a subset of the Emergency Neurological Life Support (ENLS) course modules on provider knowledge and self-reported confidence in acute management of neurocritically ill patients in a low-middle income country (LMIC). Eight ENLS modules were provided by in-person lecture using English to Khmer translated slides and a medical translator to physicians and nurses of 2 hospitals in Phnom Penh, Cambodia in May 2019. Providers included emergency, neurology, neurologic surgery, and general intensive care. Demographics, pre- and postcourse knowledge of ENLS content areas, and pre- and postcourse confidence in managing neurocritically ill patients were assessed. Data were pooled across both hospitals for analysis. A total of 57 health care providers were approached for participation: 52 (25 physicians, 27 nurses) participated; 45 completed all study instruments. Pre- and postcourse knowledge scores showed no significant differences between providers. Postcourse, 37/45 (82.2%) participants reported that the content had prepared them for acute management of neurocritically ill patients. Satisfaction with module content ranged from 77.8%–80.0% per module. For the 8 modules, a majority of participants agreed that course material had provided them with knowledge and skills to provide acute care for patients' neurologic emergencies (68.4%–88.6%). Provision of ENLS course module content increased LMIC provider self-reported knowledge and confidence in acute management of neurocritically ill patients immediately postcourse. Tailoring ENLS course presentation to a particular LMIC setting warrants additional investigation, as does the effect of ENLS course training on neurocritically ill patient outcomes in the LMIC setting. [ABSTRACT FROM AUTHOR]

Pediatric cerebral malaria (CM) is a severe complication of Plasmodium falciparum that often leaves survivors with severe neurologic impairment. Increased intracranial pressure (ICP) as a result of cerebral edema has been identified as a major predictor of morbidity and mortality in CM. Past studies have demonstrated that survivors are more likely to have resolution of elevated ICP and that efficient management of ICP crises may lead to better outcomes. However, data on invasive brain tissue oxygen monitoring are unknown. We report a case of a pediatric patient with cerebral malaria who developed encephalopathy and cerebral edema and describe the pathophysiology of this disease process with invasive ICP and brain tissue oxygen multimodality neuromonitoring. The utilization of both ICP and brain tissue oxygen monitoring allowed prompt diagnosis and successful treatment of severe intracranial hypertension and low brain tissue oxygenation crisis. The patient was discharged to home in good neurologic condition. Multimodality neuromonitoring may be considered in pediatric patients who have cerebral edema and encephalopathy from CM. [ABSTRACT FROM AUTHOR]

Background: Single-center studies suggest that up to 30% of children undergoing extracorporeal membrane oxygenation have electrographic seizures. The aim of this study was to characterize seizure prevalence, seizure risk factors, and brain injury prevalence in the pediatric extracorporeal membrane oxygenation population at a tertiary care children's hospital.Methods: We performed a retrospective systematic review of medical records for 86 consecutive children (neonates to age 21 years) who received Neurology consults and continuous video electroencephalography while undergoing extracorporeal membrane oxygenation from November 2015 to September 2018.Results: Continuous video electroencephalography was initiated in 86 of 170 children who required extracorporeal membrane oxygenation (51%); median duration of continuous vodeo electroencephalography was four days. Nineteen of 86 had electroencephalography-confirmed seizures (22%). Sixteen of 19 had seizures within the first 48 hours on continuous video electroencephalography. Interictal epileptiform discharges were a significant risk factor for seizures; 89% of those with seizures versus 46% of those without had interictal epileptiform discharges (P < 0.001, Fisher's exact test). Children with seizures also had higher pericannulation lactate (median 6.7, interquartile range of 4.3 to 19.0 for those with, and median 4.0, interquartile range of 2.0 to 7.3 for those without; P = 0.02, Mann-Whitney U test). Seizures were associated with hemorrhage on neuroimaging (68% of children with seizures had intracranial hemorrhage versus 34% of those without, P = 0.01, chi-square test).Conclusion: Approximately half the children undergoing extracorporeal membrane oxygenation received continuous video electroencephalography during the study period, and 22% had seizures. Interictal epileptiform discharges and elevated pre-extracorporeal membrane oxygenation lactate levels were risk factors for seizures; seizures were associated with intracranial hemorrhage. [ABSTRACT FROM AUTHOR]

Intracranial pressure (ICP) monitoring has become an important tool in neurocritical care. Despite being used in intensive care units all over the world, many are unfamiliar with its origins and the people and events that shaped the development of this technique. Herein, we provide a comprehensive historical review of the evolution of ICP monitoring, beginning with the earliest descriptions of cerebrospinal fluid (CSF). We conducted a database search in PubMed, Google Scholar, and Google Books for relevant articles using the key words "cerebrospinal fluid," "intracranial pressure," and "monitoring." Papers were further snowballed using reference lists of relevant papers. Although the earliest descriptions of CSF date back several hundred years bce , the history of ICP monitoring itself is not a long one. Alexander Monro and his student George Kellie laid the foundation of CSF physiology in the early 1800s through the Monro-Kellie doctrine. Their principles were later consolidated by John Abercrombie and Harvey Cushing. However, 10 years earlier than Cushing's work on CSF physiology, Hans Queckenstedt's utilization of a lumbar needle to measure the pressure in CSF marked the beginning of the era of ICP monitoring. Thenceforward, ICP monitoring technology underwent progressive improvements through the contributions of French scientists Jean Guillaume and Pierre Janny, Swedish neurosurgeon Nils Lundberg, among others. Nowadays, ICP monitoring can be performed via direct and indirect methods using a potpourri of devices such as, but not limited to, subarachnoid bolts, microtransducer catheters, and telemetric monitors. Nevertheless, despite advancements in ICP monitoring technology, the criterion standard remains an extraventricular drain catheter connected to an external pressure transducer. [ABSTRACT FROM AUTHOR]

Impaired cerebrovascular reactivity in adult moderate and severe traumatic brain injury (TBI) is known to be associated with worse global outcome at 6-12 months. As technology has improved over the past decades, monitoring of cerebrovascular reactivity has shifted from intermittent measures, to experimentally validated continuously updating indices at the bedside. Such advances have led to the exploration of individualised physiologic targets in adult TBI management, such as optimal cerebral perfusion pressure (CPP) values, or CPP limits in which vascular reactivity is relatively intact. These targets have been shown to have a stronger association with outcome compared with existing consensus-based guideline thresholds in severe TBI care. This has sparked ongoing prospective trials of such personalised medicine approaches in adult TBI. In this narrative review paper, we focus on the concept of cerebral autoregulation, proposed mechanisms of control and methods of continuous monitoring used in TBI. We highlight multimodal cranial monitoring approaches for continuous cerebrovascular reactivity assessment, physiologic and neuroimaging correlates, and associations with outcome. Finally, we explore the recent 'state-of-the-art' advances in personalised physiologic targets based on continuous cerebrovascular reactivity monitoring, their benefits, and implications for future avenues of research in TBI. [ABSTRACT FROM AUTHOR]

Disease-specific therapeutic options for critically ill neurological patients are limited. The identification of new preventive, therapeutic, and rehabilitation strategies is of the utmost importance in the field of neurocritical care research. Population genetics offers powerful tools to identify and prioritize biological pathways to be targeted by novel interventions. New treatments with supportive genetic evidence have twice the chances of obtaining final FDA approval compared to those without this support. Large collaborations, public access to data, reproducible science, and innovative analytical methods have exponentially increased the pace of discoveries related to neurocritical care genetics. [ABSTRACT FROM AUTHOR]

The critical care environment drives huge volumes of data, and clinicians are tasked with quickly processing this data and responding to it urgently. The neurocritical care environment increasingly involves EEG, multimodal intracranial monitoring, and complex imaging which preclude comprehensive human synthesis, and requires new concepts to integrate data into clinical care. By definition, Big Data is data that cannot be handled using traditional infrastructures and is characterized by the volume, variety, velocity, and variability of the data being produced. Big Data in the neurocritical care unit requires rethinking of data storage infrastructures and the development of tools and analytics to drive advancements in the field. Preprocessing, feature extraction, statistical inference, and analytic tools are required in order to achieve the primary goals of Big Data for clinical use: description, prediction, and prescription. Barriers to its use at bedside include a lack of infrastructure development within the healthcare industry, lack of standardization of data inputs, and ultimately existential and scientific concerns about the outputs that result from the use of tools such as artificial intelligence. However, as implied by the fundamental theorem of biomedical informatics, physicians remain central to the development and utility of Big Data to improve patient care. [ABSTRACT FROM AUTHOR]

Modern neurocritical care relies on ancillary diagnostic testing in the form of multimodal monitoring to address acute changes in the neurological homeostasis. Much of our armamentarium rests upon physiological and biochemical surrogates of organ or regional level metabolic activity, of which a great deal is invested at the metabolic-hemodynamic-hydrodynamic interface to rectify the traditional intermediaries of glucose consumption. Despite best efforts to detect cellular neuroenergetics, current modalities cannot appreciate the intricate coupling between astrocytes and neurons. Invasive monitoring is not without surgical complication, and noninvasive strategies do not provide an adequate spatial or temporal resolution. Without knowledge of the brain's versatile behavior in specific metabolic states (glycolytic vs oxidative), clinical practice would lag behind laboratory empiricism. Noninvasive metabolic imaging represents a new hope in delineating cellular, nigh molecular level energy exchange to guide targeted management in a diverse array of neuropathology. [ABSTRACT FROM AUTHOR]

Translational genomics represents a broad field of study that combines genome and transcriptome-wide studies in humans and model systems to refine our understanding of human biology and ultimately identify new ways to treat and prevent disease. The approaches to translational genomics can be broadly grouped into two methodologies, forward and reverse genomic translation. Traditional (forward) genomic translation begins with model systems and aims at using unbiased genetic associations in these models to derive insight into biological mechanisms that may also be relevant in human disease. Reverse genomic translation begins with observations made through human genomic studies and refines these observations through follow-up studies using model systems. The ultimate goal of these approaches is to clarify intervenable processes as targets for therapeutic development. In this review, we describe some of the approaches being taken to apply translational genomics to the study of diseases commonly encountered in the neurocritical care setting, including hemorrhagic and ischemic stroke, traumatic brain injury, subarachnoid hemorrhage, and status epilepticus, utilizing both forward and reverse genomic translational techniques. Further, we highlight approaches in the field that could be applied in neurocritical care to improve our ability to identify new treatment modalities as well as to provide important information to patients about risk and prognosis. [ABSTRACT FROM AUTHOR]

Intracranial pressure monitoring remains the foundation for prevention of secondary injury after traumatic brain injury and is most commonly performed using an external ventricular drain or intraparenchymal pressure monitor. The Integra Flex ventricular catheter combines an external ventricular catheter with a pressure transducer embedded in the tip of the catheter to allow continuous pressure readings while simultaneously draining cerebrospinal fluid. Discrepancies between measurements from the continuously reported internal pressure transducer and intermittently assessed and externally transduced ventricular drain prompted an analysis and characterization of pressures transduced from the same ventricular source. More than 500 hours of high-resolution (125 Hz) continuous recordings were manually reviewed to identify 73 hours of simultaneous measurements (clamped external ventricular drain) from internal and external transducers in patients with traumatic brain injury. A significant positive bias was found in pressure readings obtained from external relative to internal measurements. The 2 methods of measurement generally correlated poorly with each other and variably. Although proportional bias was found with Bland-Altman analysis, coherence revealed rare shifts in the external transducer as a major source of discrepancy. Infrequent changes in the 0-level of the external transducer were found to be the primary source of discrepancy. Relative to the observed differences, no significant trend was observed over time between the 2 modalities. This study suggests that the internal pressure transducer may be a more reliable estimate of intracranial pressure relative to bedside external transducers due to the inherent behavioral requirement of leveling. [ABSTRACT FROM AUTHOR]

• Our mathematical models attempt the optimization of cerebral blood volume estimation. • Cerebral blood volume changes underscore clinical phenomena (i.e. high ICP). • These models can be applied to individualized treatment plans for TBI patients. Mathematical modeling of cerebral hemodynamics by descriptive equations can estimate the underlying pulsatile component of cerebral arterial blood volume (CaBV). This way, clinical monitoring of changes in cerebral compartmental compliances becomes possible. Our aim is to validate the most adequate method of CaBV estimation in neurocritical care. We retrospectively reviewed patients with severe traumatic brain injury (TBI) [admitted from 1992–2012] and continuous transcranial Doppler (TCD) monitoring of cerebral blood flow velocity (FV) displaying either plateau waves of intracranial pressure (ICP), episodes of controlled, mild hypocapnia, or vasopressor-induced increases in arterial blood pressure (ABP). Each cohort was analyzed with continuous flow forward (CFF, pulsatile blood inflow and steady blood outflow) or pulsatile flow forward (PFF, both blood inflow and outflow are pulsatile) modeling approaches for estimating the pulse component of CaBV. Spectral pulsatility index (sPI, the first harmonic of the FV pulse/mean FV) can be estimated using the compliance of the vascular bed (Ca) and the cerebrovascular resistance (CVR – here, Ra). We compared three possible methods of assessing Ca (C1: the CFF model, C2 and C3: the PFF models based on ABP or cerebral perfusion pressure (CPP) pulsations, respectively) and combined them with three possible methods of assessing Ra (Ra1= ABP/FV, Ra2= the resistance area product, and Ra3= CPP/FV). Linear regression techniques were applied to describe the strength of each CaBV estimator (a combination of Ca and Ra) against sPI. The combination of C1 and Ra3 (PI_C1Ra3) was the superior descriptor of CaBV as approximated by sPI for both the plateau waves and the hypocapnia cohorts (r = 0.915 and r = 0.955, respectively). The combination of C1 and Ra1 (PI_C1Ra1) was nearly as robust in the vasopressors cohort (r = 0.938 and r = 0.931, respectively). TCD-based estimation of CaBV pulsations seems to be feasible when employing the CFF modeling approach. [ABSTRACT FROM AUTHOR]

Intracranial pressure (ICP)–guided therapy has been the mainstay of treatment of patients with severe traumatic brain injury (TBI), but recent data have questioned its efficacy. The aim of this study was to demonstrate trends in compliance to TBI guidelines and use of ICP-guided care in a mature trauma system. A retrospective analysis was conducted of 36,915 patients with severe TBI collected by the Pennsylvania Trauma Systems Foundation. The registry includes all patients >18 years old with a diagnosis of TBI with a Glasgow Coma Scale score ≤8 who were admitted from January 2000 to December 2017. Of 36,915 patients, 73.6% were men with a median age of 43.0 ± 21.3 years. An ICP monitor was placed in 16.3% of all patients. The rate of ICP monitoring ranged from 17.8% of patients in 2000–2004 to 16.7% in 2005–2009, 16.4% in 2010–2014, and 12.8% in 2015–2017 (P < 0.001). The most statistically significant decrease was noted from 2014 (16.4%) to 2015 (14.1%, P = 0.042). The percent decrease in ICP monitoring from 2000–2014 to 2015–2017 was equivalent for patients with Glasgow Coma Scale scores of 3–5 (−4.0%) and 6–8 (−4.5%). As studies emerged that demonstrated unclear benefit of ICP monitoring in improving care in patients with severe TBI, there was a significant statewide decline in the use of ICP monitoring after 2014 among all TBI subpopulations despite noteworthy limitations in the aforementioned studies and clear recommendations from the Brain Trauma Foundation guidelines. [ABSTRACT FROM AUTHOR]

Neurocritical care combines the management of extremely complex disease states with the inherent limitations of clinically assessing patients with brain injury. As the management of neurocritical care patients can be immensely complicated, the automation of data-collection and basic management by artificial intelligence systems have garnered interest. In this opinion article, we highlight the potential artificial intelligence has in monitoring and managing several aspects of neurocritical care, specifically intracranial pressure, seizure monitoring, blood pressure, and ventilation. The two major AI methods of analytical technique currently exist for analyzing critical care data: the model-based method and data driven method. Both of these methods have demonstrated an ability to analyze vast quantities of patient data, and we highlight the ways in which these modalities of artificial intelligence might one day play a role in neurocritical care. While none of these artificial intelligence systems are meant to replace the clinician's judgment, these systems have the potential to reduce healthcare costs and errors or delays in medical management. [ABSTRACT FROM AUTHOR]

Highlights • The most common page tag was "for your information" • The most common paging domains were cardiovascular, pain agitation distress, and sodium. • Critical illness severity and critical care workflow resulted in highest paging frequency. Abstract Indicator of response urgency (page tag), paging domains, distribution of pages by time of the day, and factors associated with neurocritical care paging remain elusive and were examined in this study. We examined the association between patient, neurocritical care workflow characteristics, and paging domains on frequency of paging using Student's t -test, Chi-square test, and analysis of covariance. A total of 1852 patients generated 36,472 pages. The most common page tagging was "for your information" (n = 15067, 41.3%), while 2.8% (n = 1006) pages were tagged urgent. Paging was most frequent for cardiovascular (12.2%), pain, agitation, distress (6.9%) and sodium (5.3%) concerns. Paging frequency was highest for mechanically ventilated patients (p < 0.001), those with indwelling intracranial pressure monitor (p < 0.04), arterial catheter (p < 0.001), central venous access catheter (p < 0.001), and in those with lower Glasgow Coma Score (p < 0.001). Patients admitted between 18:00–06:00 (aOR 1.47, 95% CI 1.16–1.86) and 14:30–18:00 (aOR 1.46, 95% CI 1.14–1.86), and sodium (aOR 1.52, 95% CI 1.39–1.66), and cardiovascular concerns (aOR 1.24, 95% CI 1.15–1.32) were associated with higher night time paging frequency. Incorporating paging domains in daily workflow and their impact on outcome of paging on escalation of clinical care and patient outcomes warrants further examination. [ABSTRACT FROM AUTHOR]