Individualized Autoregulation-Derived Cerebral Perfusion Targets in Aneurysmal Subarachnoid Hemorrhage: A New Therapeutic Avenue?

Background: Cerebral perfusion pressure (CPP) is an important target in aneurysmal subarachnoid hemorrhage (aSAH), but it does not take into account autoregulatory disturbances. The pressure reactivity index (PRx) and the CPP with the optimal PRx (CPPopt) are new variables that may capture these pathomechanisms. In this study, we investigated the effect on the outcome of certain combinations of CPP or ΔCPPopt (actual CPP-CPPopt) with the concurrent autoregulatory status (PRx) after aSAH. Methods: This observational study included 432 aSAH patients, treated in the neurointensive care unit, at Uppsala University Hospital, Sweden. Functional outcome (GOS-E) was assessed 1-year postictus. Heatmaps of the percentage of good monitoring time (%GMT) of PRx/CPP and PRx/ΔCPPopt combinations in relation to GOS-E were created to visualize the association between these variables and outcome. Results: In the heatmap of the %GMT of PRx/CPP, the combination of lower CPP with higher PRx values was more strongly associated with lower GOS-E. The tolerance for lower CPP values increased with lower PRx values until a threshold of -0.50. However, for decreasing PRx below -0.50, there was a gradual reduction in the tolerance for lower CPP. In the heatmap of the %GMT of PRx/ΔCPPopt, the combination of negative ΔCPPopt with higher PRx values was strongly associated with lower GOS-E. In particular, negative ΔCPPopt together with PRx above +0.50 correlated with worse outcomes. In addition, there was a transition toward an unfavorable outcome when PRx went below -0.50, particularly if ΔCPPopt was negative. Conclusions: The PRx levels influenced the association between CPP/ΔCPPopt and outcome. Thus, this variable could be used to individualize a safe CPP-/ΔCPPopt-range.

Brain tissue oxygen plus intracranial pressure monitoring versus isolated intracranial pressure monitoring in patients with traumatic brain injury: an updated meta-analysis of randomized controlled trials.

BACKGROUND: Intracranial pressure (ICP) monitoring plays a key role in patients with traumatic brain injury (TBI), however, cerebral hypoxia can occur without intracranial hypertension. Aiming to improve neuroprotection in these patients, a possible alternative is the association of Brain Tissue Oxygen Pressure (PbtO2) monitoring, used to detect PbtO2 tension. METHOD: We systematically searched PubMed, Embase and Cochrane Central for RCTs comparing combined PbtO2 + ICP monitoring with ICP monitoring alone in patients with severe or moderate TBI. The outcomes analyzed were mortality at 6 months, favorable outcome (GOS ≥ 4 or GOSE ≥ 5) at 6 months, pulmonary events, cardiovascular events and sepsis rate. RESULTS: We included 4 RCTs in the analysis, totaling 505 patients. Combined PbtO2 + ICP monitoring was used in 241 (47.72%) patients. There was no significant difference between the groups in relation to favorable outcome at 6 months (RR 1.17; 95% CI 0.95-1.43; p = 0.134; I2 = 0%), mortality at 6 months (RR 0.82; 95% CI 0.57-1.18; p = 0.281; I2 = 34%), cardiovascular events (RR 1.75; 95% CI 0.86-3.52; p = 0.120; I2 = 0%) or sepsis (RR 0.75; 95% CI 0.25-2.22; p = 0.604; I2 = 0%). The risk of pulmonary events was significantly higher in the group with combined PbtO2 + ICP monitoring (RR 1.44; 95% CI 1.11-1.87; p = 0.006; I2 = 0%). CONCLUSIONS: Our findings suggest that combined PbtO2 + ICP monitoring does not change outcomes such as mortality, functional recovery, cardiovascular events or sepsis. Furthermore, we found a higher risk of pulmonary events in patients undergoing combined monitoring.

Cerebrovascular reactivity (PRx) and optimal cerebral perfusion pressure in elderly with traumatic brain injury.

PURPOSE: Cerebral perfusion pressure (CPP) guidance by cerebral pressure autoregulation (CPA) status according to PRx (correlation mean arterial blood pressure (MAP) and intracranial pressure (ICP)) and optimal CPP (CPPopt = CPP with lowest PRx) is promising but little is known regarding this approach in elderly. The aim was to analyze PRx and CPPopt in elderly TBI patients. METHODS: A total of 129 old (≥ 65 years) and 342 young (16-64 years) patients were studied using monitoring data for MAP and ICP. CPP, PRx, CPPopt, and ΔCPPopt (difference between actual CPP and CPPopt) were calculated. Logistic regression analyses with PRx and ΔCPPopt as explanatory variables for outcome. The combined effects of PRx/CPP and PRx/ΔCPPopt on outcome were visualized as heatmaps. RESULTS: The elderly had higher PRx (worse CPA), higher CPPopt, and different temporal patterns. High PRx influenced outcome negatively in the elderly but less so than in younger patients. CPP close to CPPopt correlated to favorable outcome in younger, in contrast to elderly patients. Heatmap interaction analysis of PRx/ΔCPPopt in the elderly showed that the region for favorable outcome was centered around PRx 0 and ranging between both functioning and impaired CPA (PRx range - 0.5-0.5), and the center of ΔCPPopt was - 10 (range - 20-0), while in younger the center of PRx was around - 0.5 and ΔCPPopt closer to zero. CONCLUSIONS: The elderly exhibit higher PRx and CPPopt. High PRx influences outcome negatively in the elderly but less than in younger patients. The elderly do not show better outcome when CPP is close to CPPopt in contrast to younger patients.

Early Intraventricular Antibiotic Therapy Improved In-Hospital-Mortality in Neurocritical Patients with Multidrug-Resistant Bacterial Nosocomial Meningitis and Ventriculitis.

BACKGROUND: Hospital-acquired multidrug-resistant (MDR) bacterial meningitis and/or ventriculitis (MEN) is a severe condition associated with high mortality. The risk factors related to in-hospital mortality of patients with MDR bacterial MEN are unknown. We aimed to examine factors related to in-hospital mortality and evaluate their prognostic value in patients with MDR bacterial MEN treated in the neurointensive care unit. METHODS: This was a single-center retrospective cohort study of critically ill neurosurgical patients with MDR bacterial MEN admitted to our hospital between January 2003 and March 2021. Data on demographics, admission variables, treatment, time to start of intraventricular (IVT) therapy, and in-hospital mortality were analyzed. Both univariate and multivariable analyses were performed to identify determinants of in-hospital mortality. RESULTS: All 142 included patients received systemic antibiotic therapy, and 102 of them received concomitant IVT treatment. The median time to start of IVT treatment was 2 days (interquartile range 1-5 days). The time to start of IVT treatment had an effect on in-hospital mortality (hazard ratio 1.17; 95% confidence interval 1.02-1.34; adjusted p = 0.030). The cutoff time to initiate IVT treatment was identified at 3 days: patients treated within 3 days had a higher cerebrospinal fluid (CSF) sterilization rate (81.5%) and a shorter median time to CSF sterilization (7 days) compared with patients who received delayed IVT treatment (> 3 days) (48.6% and 11.5 days, respectively) and those who received intravenous antibiotics alone (42.5% and 10 days, respectively). CONCLUSIONS: Early IVT antibiotics were associated with superior outcomes in terms of the in-hospital mortality rate, time to CSF sterilization, and CSF sterilization rate compared with delayed IVT antibiotics and intravenous antibiotics alone.

Preliminary Observations of the Loke Microdialysis in an Experimental Pig Model: Are We Ready for Continuous Monitoring of Brain Energy Metabolism?

BACKGROUND: Brain energy metabolism is often disturbed after acute brain injuries. Current neuromonitoring methods with cerebral microdialysis (CMD) are based on intermittent measurements (1-4 times/h), but such a low frequency could miss transient but important events. The solution may be the recently developed Loke microdialysis (MD), which provides high-frequency data of glucose and lactate. Before clinical implementation, the reliability and stability of Loke remain to be determined in vivo. The purpose of this study was to validate Loke MD in relation to the standard intermittent CMD method. METHODS: Four pigs aged 2-3 months were included. They received two adjacent CMD catheters, one for standard intermittent assessments and one for continuous (Loke MD) assessments of glucose and lactate. The standard CMD was measured every 15 min. Continuous Loke MD was sampled every 2-3 s and was averaged over corresponding 15-min intervals for the statistical comparisons with standard CMD. Intravenous glucose injections and intracranial hypertension by inflation of an intracranial epidural balloon were performed to induce variations in intracranial pressure, cerebral perfusion pressure, and systemic and cerebral glucose and lactate levels. RESULTS: In a linear mixed-effect model of standard CMD glucose (mM), there was a fixed effect value (± standard error [SE]) at 0.94 ± 0.07 (p < 0.001) for Loke MD glucose (mM), with an intercept at - 0.19 ± 0.15 (p = 0.20). The model showed a conditional R2 at 0.81 and a marginal R2 at 0.72. In a linear mixed-effect model of standard CMD lactate (mM), there was a fixed effect value (± SE) at 0.41 ± 0.16 (p = 0.01) for Loke MD lactate (mM), with an intercept at 0.33 ± 0.21 (p = 0.25). The model showed a conditional R2 at 0.47 and marginal R2 at 0.17. CONCLUSIONS: The established standard CMD glucose thresholds may be used as for Loke MD with some caution, but this should be avoided for lactate.

Fit for Service: Preparing Residents for Neurointensive Care with Entrustable Professional Activities: A Delphi Study.

BACKGROUND: Although the relevance of neurointensive medicine and high-quality training of corresponding physicians is increasingly recognized, there is high heterogeneity in the nature, duration, and quality of neurointensive care curricula around the world. Thus, we aimed to identify, define, and establish validity evidence for entrustable professional activities (EPAs) for postgraduate training in neurointensive care to determine trainees' readiness for being on-call. METHODS: After defining EPAs through an iterative process by an expert group, we used a modified Delphi approach with a single-center development process followed by a national consensus and a single-center validation step. EPAs were evaluated by using the EQual rubric (Queen's EPA Quality Rubric). Interrater reliability was measured with Krippendorff's α. RESULTS: The expert group defined seven preliminary EPAs for neurointensive care. In two consecutive Delphi rounds, EPAs were adapted, and consensus was reached for level of entrustment and time of expiration. Ultimately, EPAs reached a high EQual score of 4.5 of 5 and above. Interrater reliability for the EQual scoring was 0.8. CONCLUSIONS: Using a multistep Delphi process, we defined and established validity evidence for seven EPAs for neurointensive medicine with a high degree of consensus to objectively describe readiness for on-call duty in neurointensive care. This operationalization of pivotal clinical tasks may help to better train clinical residents in neurointensive care across sites and health care systems and has the potential to serve as a blueprint for training in general intensive care medicine. It also represents a starting point for further research and development of medical curricula.

Should Patients with Traumatic Brain Injury with Significant Contusions be Treated with Different Neurointensive Care Targets?

BACKGROUND: Patients with traumatic brain injury (TBI) with large contusions make up a specific TBI subtype. Because of the risk of brain edema worsening, elevated cerebral perfusion pressure (CPP) may be particularly dangerous. The pressure reactivity index (PRx) and optimal cerebral perfusion pressure (CPPopt) are new promising perfusion targets based on cerebral autoregulation, but they reflect the global brain state and may be less valid in patients with predominant focal lesions. In this study, we aimed to investigate if patients with TBI with significant contusions exhibited a different association between PRx, CPP, and CPPopt in relation to functional outcome compared to those with small/no contusions. METHODS: This observational study included 385 patients with moderate to severe TBI treated at a neurointensive care unit in Uppsala, Sweden. The patients were classified into two groups: (1) significant contusions (> 10 mL) and (2) small/no contusions (but with extra-axial or diffuse injuries). The percentage of good monitoring time (%GMT) with intracranial pressure > 20 mm Hg; PRx > 0.30; CPP < 60 mm Hg, within 60-70 mm Hg, or > 70 mm Hg; and ΔCPPopt less than - 5 mm Hg, ± 5 mm Hg, or > 5 mm Hg was calculated. Outcome (Glasgow Outcome Scale-Extended) was assessed after 6 months. RESULTS: Among the 120 (31%) patients with significant contusions, a lower %GMT with CPP between 60 and 70 mm Hg was independently associated with unfavorable outcome. The %GMTs with PRx and ΔCPPopt ± 5 mm Hg were not independently associated with outcome. Among the 265 (69%) patients with small/no contusions, a higher %GMT of PRx > 0.30 and a lower %GMT of ΔCPPopt ± 5 mm Hg were independently associated with unfavorable outcome. CONCLUSIONS: In patients with TBI with significant contusions, CPP within 60-70 mm Hg may improve outcome. PRx and CPPopt, which reflect global cerebral pressure autoregulation, may be useful in patients with TBI without significant focal brain lesions but seem less valid for those with large contusions. However, this was an observational, hypothesis-generating study; our findings need to be validated in prospective studies before translating them into clinical practice.

The Optimal pressure reactivity index range is disease-specific: A comparison between aneurysmal subarachnoid hemorrhage and traumatic brain injury.

PURPOSE: Impaired cerebral pressure autoregulation is common and detrimental after acute brain injuries. Based on the prevalence of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage (aSAH) patients compared to traumatic brain injury (TBI), we hypothesized that the type of autoregulatory disturbance and the optimal PRx range may differ between these two conditions. The aim of this study was to determine the optimal PRx ranges in relation to functional outcome following aSAH and TBI, respectively. METHODS: In this observational study, 487 aSAH patients and 413 TBI patients, treated in the neurointensive care, Uppsala, Sweden, between 2008 and 2018, were included. The percentage of good monitoring time (%GMT) of PRx was calculated within 8 intervals covering the range from -1.0 to + 1.0, and analyzed in relation to favorable outcome (GOS-E 5 to 8). RESULTS: In multiple logistic regressions, a higher %GMTs of PRx in the intervals -1.0 to -0.5 and + 0.75 to + 1.0 were independently associated with a lower rate of favorable outcome in the aSAH cohort. In a similar analysis in the TBI cohort, only positive PRx in the interval + 0.75 to + 1.0 was independently associated with a lower rate of favorable outcome. CONCLUSION: Extreme PRx values in both directions were unfavorable in aSAH, possibly as high PRx could indicate proximal vasospasm with exhausted distal vasodilatory reserve, while very negative PRx could reflect myogenic hyperreactivity with suppressed cerebral blood flow. Only elevated PRx was unfavorable in TBI, possibly as pressure passive vessels may be a more predominant pathomechanism in this disease.

Amantadine for NeuroenhaNcement in acutE patients Study - a protocol for a prospective pilot proof of concept phase IIb study in intensive and intermediate care unit patients (ANNES).

BACKGROUND: Persisting coma is a common complication in (neuro)intensive care in neurological disease such as acute ischemic stroke, intracerebral hemorrhage or subarachnoid hemorrhage. Amantadine acts as a nicotinic receptor antagonist, dopamine receptor agonist and non-competitive N-Methyl-D-aspartate receptor antagonist. Amantadine is a long-known drug, originally approved for treatment of influenza A and Parkinson`s Disease. It has been proven effective in improving vigilance after traumatic brain injury. The underlying mechanisms remain largely unknown, albeit anti-glutamatergic and dopaminergic effects might be most relevant. With limited evidence of amantadine efficacy in non-traumatic pathologies, the aim of our study is to assess the effects of amantadine for neuroenhancement in non-traumatic neurointensive patients with persisting coma. METHODS: An investigator-initiated, monocenter, phase IIb proof of concept open-label pilot study will be carried out. Based on the Simon design, 43 adult (neuro)intensive care patients who meet the clinical criteria of persisting coma not otherwise explained and < 8 points on the Glasgow Coma Scale (GCS) will be recruited. Amantadine will be administered intravenously for five days at a dosage of 100 mg bid. The primary endpoint is an improvement of at least 3 points on the GCS. If participants present as non-responders (increase < 3 points or decrease on the GCS) within the first 48 h, the dosage will be doubled from day three to five. Secondary objectives aim to demonstrate that amantadine improves vigilance via alternative scales. Furthermore, the incidence of adverse events will be investigated and electroencephalography (EEG) will be recorded at baseline and end of treatment. DISCUSSION: The results of our study will help to systematically assess the clinical utility of amantadine for treatment of persisting coma in non-traumatic brain injury. We expect that, in the face of only moderate treatment risk, a relevant number of patients will benefit from amantadine medication by improved vigilance (GCS increase of at least 3 points) finally leading to a better rehabilitation potential and improved functional neurological outcome. Further, the EEG data will allow evaluation of brain network states in relation to vigilance and potentially outcome prediction in this study cohort. TRIAL REGISTRATION: NCT05479032.

Neurocritical Care Recovery Clinics: An Idea Whose Time Has Come.

PURPOSE OF REVIEW: Purposes were to identify evidence for post-intensive care syndrome (PICS) and post-intensive care syndrome-family (PICS-F), defined as the psychological impact on families from exposure to critical care, in the neurologically injured population and to characterize existing models for neurorecovery clinics and the evidence to support their use. RECENT FINDINGS: There has been an explosion of post-ICU clinics among the general critical care population, with their use largely justified based on the management of PICS and PICS-F, terminology which excludes brain injured patients. In contrast, neurocritical care recovery clinics are not common and not well-described. There is however evidence in the neuro-ICU population supporting the provision of "dyadic" care, whereby the patient and caregiver are treated as one unit. Brain injured populations likely experience many of the same PICS phenomena as medically ill patients but are not represented in this body of literature. These patients deserve the same level of follow-up as other patients who have experienced critical illness. We propose a neuro-ICU transitional care clinic that addresses PICS-like symptoms and is modeled after transitional care provided to other brain injured populations. Future investigations should be targeted toward understanding the sequalae of a neuro-ICU admission, mechanisms for providing dyadic care, and the impact of neurorecovery clinics on long-term outcomes.

Selecting patients for early interdisciplinary rehabilitation during neurointensive care after moderate to severe traumatic brain injury.

BACKGROUND: Early interdisciplinary rehabilitation (EIR) in neurointensive care is a limited resource reserved for patients with moderate to severe traumatic brain injury (TBI) believed to profit from treatment. We evaluated how key parameters related to injury severity and patient characteristics were predictive of receiving EIR, and whether these parameters changed over time. METHODS: Among 1003 adult patients with moderate to severe TBI admitted over 72 h to neurointensive care unit during four time periods between 2005 and 2020, EIR was given to 578 and standard care to 425 patients. Ten selection criteria thought to best represent injury severity and patient benefit were evaluated (Glasgow Coma Scale, Head Abbreviated Injury Scale, New-Injury-Severity-Scale, intracranial pressure monitoring, neurosurgery, age, employment, Charlson Comorbidity Index, severe psychiatric disease, and chronic substance abuse). RESULTS: In multivariate regression analysis, patients who were employed (adjOR 1.99 [95% CI 1.41, 2.80]), had no/mild comorbidity (adjOR 3.15 [95% CI 1.72, 5.79]), needed neurosurgery, had increasing injury severity and were admitted by increasing time period were more likely to receive EIR, whereas receiving EIR was less likely with increasing age (adjOR 0.97 [95% CI 0.96, 0.98]) and chronic substance abuse. Overall predictive ability of the model was 71%. Median age and comorbidity increased while employment decreased from 2005 to 2020, indicating patient selection became less restrictive with time. CONCLUSION: Injury severity and need for neurosurgery remain important predictors for receiving EIR, but the importance of age, employment, and comorbidity have changed over time. Moderate prediction accuracy using current clinical criteria suggest unrecognized factors are important for patient selection.

Bilateral basal ganglia hemorrhage: a systematic review of etiologies, management strategies, and clinical outcomes.

Bilateral basal ganglia hemorrhages (BBGHs) represent rare accidents, with no clear standard of care currently defined. We reviewed the literature on BBGHs and analyzed the available conservative and surgical strategies. PubMed, Scopus, Web of Science, and Cochrane were searched following the PRISMA guidelines to include studies reporting patients with BBGHs. Clinical characteristics, management, and outcomes were analyzed. We included 64 studies comprising 75 patients, 25 (33%) traumatic and 50 (67%) non-traumatic. Traumatic cases affected younger patients (mean age 35 vs. 46 years, p=0.014) and males (84% vs. 71%, p=0.27) and were characterized by higher proportion of normal blood pressures at admission (66% vs. 13%, p=0.0016) compared to non-traumatic cases. Most patients were comatose at admission (56%), with a mean Glasgow Coma Scale (GCS) score of 7 and a higher proportion of comatose patients in the traumatic than in the non-traumatic group (64% vs. 52%, p=0.28). Among the traumatic group, motor vehicle accidents and falls accounted for 79% of cases. In the non-traumatic group, hemorrhage was most associated with hypertensive or ischemic (54%) and chemical (28%) etiologies. Management was predominantly conservative (83%). Outcomes were poor in 56% of patients with mean follow-up of 8 months. Good recovery was significantly higher in the traumatic than in the non-traumatic group (48% vs. 17%, p=0.019). BBGHs are rare occurrences with dismal prognoses. Standard management follows that of current intracerebral hemorrhage guidelines with supportive care and early blood pressure management. Minimally invasive surgery is promising, though substantial evidence is required to outweigh the potentially increased risks of bilateral hematoma evacuation.

Antithrombotic agent usage before ictus in aneurysmal subarachnoid hemorrhage: relation to hemorrhage severity, clinical course, and outcome.

BACKGROUND: The number of patients with aneurysmal subarachnoid hemorrhage (aSAH) who are on antithrombotic agents before ictus is rising. However, their effect on early brain injury and disease development remains unclear. The primary aim of this study was to determine if antithrombotic agents (antiplatelets and anticoagulants) were associated with a worse initial hemorrhage severity, rebleeding rate, clinical course, and functional recovery after aSAH. METHODS: In this observational study, those 888 patients with aSAH, treated at the neurosurgical department, Uppsala University Hospital, between 2008 and 2018 were included. Demographic, clinical, radiological (Fisher and Hijdra score), and outcome (Extended Glasgow Outcome Scale one year post-ictus) variables were assessed. RESULTS: Out of 888 aSAH patients, 14% were treated with antithrombotic agents before ictus. Seventy-five percent of these were on single therapy of antiplatelets, 23% on single therapy of anticoagulants, and 3% on a combination of antithrombotic agents. Those with antithrombotic agents pre-ictus were significantly older and exhibited more co-morbidities and a worse coagulation status according to lab tests. Antithrombotic agents, both as one group and as subtypes (antiplatelets and anticoagulants), were not associated with hemorrhage severity (Hijdra score/Fisher) nor rebleeding rate. The clinical course did not differ in terms of delayed ischemic neurological deficits or last-tier treatment with thiopental and decompressive craniectomy. These patients experienced a higher mortality and lower rate of favorable outcome in univariate analyses, but this did not hold true in multiple logistic regression analyses after adjustment for age and co-morbidities. CONCLUSIONS: After adjustment for age and co-morbidities, antithrombotic agents before aSAH ictus were not associated with worse hemorrhage severity, rebleeding rate, clinical course, or long-term functional recovery.

Lumbar puncture-verified subarachnoid hemorrhage: bleeding sources, need of radiological examination, and functional recovery.

BACKGROUND: The primary aim was to determine the diagnostic yield of vascular work-up, the clinical course during neurointensive care (NIC), and rate of functional recovery for patients with computed tomography (CT)-negative, lumbar puncture (LP)-verified SAH. METHODS: In this retrospective study, 1280 patients with spontaneous SAH, treated at our NIC unit, Uppsala University Hospital, Sweden, between 2008 and 2018, were included. Demography, admission status, radiological examinations (CT angiography (CTA) and digital subtraction angiography (DSA)), treatments, and functional outcome (GOS-E) at 12 months were evaluated. RESULTS: Eighty (6%) out of 1280 SAH patients were computed tomography (CT)-negative, LP-verified cases. Time between ictus and diagnosis was longer for the LP-verified SAH cohort in comparison to the CT-positive patients (median 3 vs 0 days, p < 0.001). One fifth of the LP-verified SAH patients exhibited an underlying vascular pathology (aneurysm/AVM), which was significantly less common than for the CT-verified SAH cohort (19% vs. 76%, p < 0.001). The CTA- and DSA-findings were consistent in all of the LP-verified cases. The LP-verified SAH patients exhibited a lower rate of delayed ischemic neurological deficits, but no difference in rebleeding rate, compared to the CT-verified cohort. At 1-year post-ictus, 89% of the LP-verified SAH patients had recovered favorably, but 45% of the cases did not reach good recovery. Having an underlying vascular pathology and an external ventricular drainage were associated with worse functional recovery (p = 0.02) in this cohort. CONCLUSIONS: LP-verified SAH constituted a small proportion of the entire SAH population. Having an underlying vascular pathology was less frequent in this cohort, but still occurred in one out of five patients. Despite the small initial bleeding in the LP-verified cohort, many of these patients did not reach good recovery at 1 year, this calls for more attentive follow-up and rehabilitation in this cohort.

Intracranial lesion features in moderate-to-severe traumatic brain injury: relation to neurointensive care variables and clinical outcome.

BACKGROUND: The primary aim was to determine the association of intracranial hemorrhage lesion type, size, mass effect, and evolution with the clinical course during neurointensive care and long-term outcome after traumatic brain injury (TBI). METHODS: In this observational, retrospective study, 385 TBI patients treated at the neurointensive care unit at Uppsala University Hospital, Sweden, were included. The lesion type, size, mass effect, and evolution (progression on the follow-up CT) were assessed and analyzed in relation to the percentage of secondary insults with intracranial pressure > 20 mmHg, cerebral perfusion pressure < 60 mmHg, and cerebral pressure autoregulatory status (PRx) and in relation to Glasgow Outcome Scale-Extended. RESULTS: A larger epidural hematoma (p < 0.05) and acute subdural hematoma (p < 0.001) volume, greater midline shift (p < 0.001), and compressed basal cisterns (p < 0.001) correlated with craniotomy surgery. In multiple regressions, presence of traumatic subarachnoid hemorrhage (p < 0.001) and intracranial hemorrhage progression on the follow-up CT (p < 0.01) were associated with more intracranial pressure-insults above 20 mmHg. In similar regressions, obliterated basal cisterns (p < 0.001) were independently associated with higher PRx. In a multiple regression, greater acute subdural hematoma (p < 0.05) and contusion (p < 0.05) volume, presence of traumatic subarachnoid hemorrhage (p < 0.01), and obliterated basal cisterns (p < 0.01) were independently associated with a lower rate of favorable outcome. CONCLUSIONS: The intracranial lesion type, size, mass effect, and evolution were associated with the clinical course, cerebral pathophysiology, and outcome following TBI. Future efforts should integrate such granular data into more sophisticated machine learning models to aid the clinician to better anticipate emerging secondary insults and to predict clinical outcome.

Should individual timeline and serial CT/MRI panels of all patients be presented in acute brain insult cohorts? A pilot study of 45 patients with decompressive craniectomy after aneurysmal subarachnoid hemorrhage.

PURPOSE: Our review of acute brain insult articles indicated that the patients' individual (i) timeline panels with the defined time points since the emergency call and (ii) serial brain CT/MRI slice panels through the neurointensive care until death or final brain tissue outcome at 12 months or later are not presented. METHODS: We retrospectively constructed such panels for the 45 aneurysmal subarachnoid hemorrhage (aSAH) patients with a secondary decompressive craniectomy (DC) after the acute admission to neurointensive care at Kuopio University Hospital (KUH) from a defined population from 2005 to 2018. The patients were indicated by numbers (1.-45.) in the pseudonymized panels, tables, results, and discussion. The timelines contained up to ten defined time points on a logarithmic time axis until death ([Formula: see text]; 56%) or 3 years ([Formula: see text]; 44%). The brain CT/MRI panels contained a representative slice from the following time points: SAH diagnosis, after aneurysm closure, after DC, at about 12 months (20 survivors). RESULTS: The timelines indicated re-bleeds and allowed to compare the times elapsed between any two time points, in terms of workflow swiftness. The serial CT/MRI slices illustrated the presence and course of intracerebral hemorrhage (ICH), perihematomal edema, intraventricular hemorrhage (IVH), hydrocephalus, delayed brain injury, and, in the 20 (44%) survivors, the brain tissue outcome. CONCLUSIONS: The pseudonymized timeline panels and serial brain imaging panels, indicating the patients by numbers, allowed the presentation and comparison of individual clinical courses. An obvious application would be the quality control in acute or elective medicine for timely and equal access to clinical care.

Treadmill Exercise Decreases Inflammation Via Modulating IL-6 Expression in the Rat Model of Middle Cerebral Artery Occlusion.

BACKGROUND: Long-term bed rest in neurointensive care (NIC) patients leads to skeletal muscle atrophy and cognitive dysfunction, which seriously affects the physical fitness and final prognosis of critically ill patients. Exercise therapy plays an increasingly important role in the treatment and rehabilitation of patients with sarcopenia. However, the therapeutic effect and mechanism of exercise therapy for patients with neurological impairment remain unclear. METHODS: Serum samples of NIC patients before and after exercise therapy and normal people were collected to detect interleukin-6 (IL-6) and interleukin-1ß levels by enzyme-linked immunosorbent assay (ELISA). Middle cerebral artery occlusion (MCAO) was used for the construction of a rat model. The Morris water maze test, exploration test, and open-field test were used to assess neurological function in rats. Western blot and quantitative real-time polymerase chain reaction were performed to evaluate the activation of IL-6/adenosine-monophosphate-activated protein kinase (AMPK) signaling. RESULTS: Exercise therapy attenuated IL-6 expression in NIC patients. Exercise therapy alleviated cognitive dysfunctions and decreased IL-6 expression in MCAO rats. Exercise therapy alleviated gastrocnemius muscle injury in rats after MCAO by modulating IL-6/AMPK signaling. CONCLUSIONS: Treadmill exercise decreases inflammation in MCAO rats via modulating IL-6/AMPK signaling.

Clinical Scoring and Ultrasound-Based Diaphragm Assessment in Predicting Extubation Failure in Neurointensive Care Unit: A Single-Center Observational Study.

BACKGROUND: Patients in the neurointensive care unit (NICU) fail extubation despite successful weaning from mechanical ventilation. Parameters currently used in the general intensive care unit do not accurately predict extubation success in the NICU. In this study, peak cough expiratory flow rate, ultrasound-based diaphragm function assessment, and comprehensive clinical scoring systems were measured to determine whether these new variables, in isolation or combination, could predict extubation failure successfully in the NICU. METHODS: All adult patients extubated after 48 h of mechanical ventilation in the NICU of a single tertiary care center were recruited into the prospective cohort. The patient's cough peak expiratory flow rate (C-PEFR), diaphragm function, and clinical scores were measured before extubation. C-PEFR was measured using a hand-held spirometer, diaphragm function (excursion, thickness fraction, and diaphragm contraction velocity on coughing) was assessed using ultrasound, and the clinical scores included the visual pursuit, swallowing, age, Glasgow Coma Scale for extubation (VISAGE) and respiratory insufficiency scale-intubated (RIS-i) scores. The patients requiring reintubation within 48 h were considered as extubation failure. Univariate and multivariate logistic regression analyses were done to identify predictors of extubation failure. RESULTS: Of the 193 patients screened, 43 were recruited, and 15 had extubation failure (20.9%). Patients with extubation failure had higher RIS-i scores (p < 0.001) and lower VISAGE scores (p = 0.043). The C-PEFR and diaphragm function (excursions and contraction velocity on coughing) were lower in patients with extubation failure but not statistically significant. The variables with p < 0.2 in univariate analysis (RIS-i, VISAGE, and diaphragm cough velocity) were subjected to multivariate regression analysis. RIS-I score remained an independent predictor (odds ratio 3.691, 95% confidence interval 1.5-8.67, p = 0.004). In a receiver operating characteristic analysis, the area under the curve for RIS-i was 0.963. An RIS-i score of 2 or more had 94% specificity and 89% sensitivity for predicting extubation failure. CONCLUSIONS: The RIS-i score predicts extubation failure in NICU patients. The addition of ultrasound-based diaphragm measurements to the RIS-i score to improve prediction accuracy needs further study. Clinical trial registration Clinical Trials Registry of India identifier CTRI/2021/03/031923.

One-Year Survival of Ischemic Stroke Patients Requiring Mechanical Ventilation.

BACKGROUND: The outcome of patients with acute ischemic stroke who require mechanical ventilation has been poor. Intubation due to a reversible condition could be associated with better 1-year survival. METHODS: All adult patients treated in Helsinki University Hospital in 2016-2020 who were admitted because of an ischemic stroke (either stroke or thrombosis seen on imaging) and needed mechanical ventilation were included in this retrospective cohort study. Data on demographics, medical history, index stroke, and indication for intubation were collected. The primary outcome was 1-year mortality. Secondary outcomes were modified Rankin Scale (mRS) score at 3 months and living arrangements at 1 year. RESULTS: The mean age of the cohort (N = 121) was 66 ± 11 (mean ± SD) years, and the mean admission National Institutes of Health Stroke Scale score was 17 ± 10. Forty-four (36%) patients were male. The most common indication for intubation was unconsciousness (51%), followed by respiratory failure or airway compromise (28%). One-year mortality was 55%. Three-month mRS scores were available for 114 (94%) patients, with the following distribution: 0-2, 18%; 3-5, 28%; and 6 (dead), 54%. Of the 1-year survivors, 72% were living at home. In the multivariate analysis, only age over 75 years and intubation due to unconsciousness, respiratory failure, or cardiac arrest remained significantly associated with mortality. CONCLUSIONS: The indication for intubation seems to significantly affect outcome. Functional outcome at 3 months is often poor, but a great majority of 1-year survivors are able to live at home.

Temperature Changes in Poor-Grade Aneurysmal Subarachnoid Hemorrhage: Relation to Injury Pattern, Intracranial Pressure Dynamics, Cerebral Energy Metabolism, and Clinical Outcome.

BACKGROUND: The aim was to study the course of body temperature in the acute phase of poor-grade aneurysmal subarachnoid hemorrhage (aSAH) in relation to the primary brain injury, cerebral physiology, and clinical outcome. METHODS: In this observational study, 166 patients with aSAH treated at the neurosurgery department at Uppsala University Hospital in Sweden between 2008 and2018 with temperature, intracranial pressure (ICP), and microdialysis (MD) monitoring were included. The first 10 days were divided into the early phase (days 1-3) and the vasospasm phase (days 4-10). RESULTS: Normothermia (temperature = 36-38 °C) was most prevalent in the early phase. A lower mean temperature at this stage was univariately associated with a worse primary brain injury, with higher Fisher grade and higher MD glycerol concentration, as well as a worse neurological recovery at 1 year. There was otherwise no association between temperature and cerebral physiological variables in the early phase. There was a transition toward an increased burden of hyperthermia (temperature > 38 °C) in the vasospasm phase. This was associated with concurrent infections but not with neurological or radiological injury severity at admission. Elevated temperature was associated with higher MD pyruvate concentration, lower rate of an MD pattern indicative of ischemia, and higher rate of poor neurological recovery at 1 year. There was otherwise no association between temperature and cerebral physiological variables in the vasospasm phase. The associations between temperature and clinical outcome did not hold true in multiple logistic regression analyses. CONCLUSIONS: Spontaneously low temperature in the early phase reflected a worse primary brain injury and indicated a worse outcome prognosis. Hyperthermia was common in the vasospasm phase and was more related to infections than primary injury severity but also with a more favorable energy metabolic pattern with better substrate supply, possibly related to hyperemia.