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Objective

The main aim was to determine the incidence, risk factors, clinical phenotypes, and response to shunt surgery in chronic, shunt-dependent hydrocephalus (SDHC) after aneurysmal subarachnoid hemorrhage (aSAH).

Methods

In this observational, single-center study, 849 aSAH patients treated at Uppsala University Hospital between 2008–2018 were included. Variables on demography, injury severity, treatments, chronic hydrocephalus presentation, and outcome were evaluated.

Results

In total, 107 (13%) patients were treated with a shunt due to SDHC. In multivariate logistic regressions, risk factors for SDHC were worse neurologic (World Federation of Neurosurgical Societies) grade, larger ventricles (Evans index) at admission, the need to insert an external ventricular drain (EVD), decompressive craniectomy, and complications with meningitis. Six different SDHC phenotypes were identified: impeded neurological recovery (55%), Hakim-Adams syndrome (17%), high-pressure symptoms (13%), failed EVD removal (8%), external brain herniation after decompressive craniectomy (DC; 6%), and subdural hygroma (1%). The former 3 groups significantly improved in modified Rankin Scale (mRS) and 87%–100% exhibited subjective symptomatic relief. There was no significant change in mRS for the latter 3 groups, but 60%–100% experienced some subjective relief postoperatively.

Conclusions

Chronic SDHC was a common complication after aSAH, particularly in patients with severe primary brain injury, acute hydrocephalus, and treatment-related factors. The condition presents with distinct clinical phenotypes, which may influence treatment response. Recognizing these phenotypes could aid in optimizing patient selection and expectations for shunt surgery outcomes.

Background: 

Severe cerebral venous thrombosis (CVT) patients often require neurointensive care with multimodal monitoring. However, optimal treatment targets for intracranial pressure (ICP), cerebral perfusion pressure (CPP), and cerebral autoregulation remain unclear. This study investigated the relationships between ICP, CPP, and autoregulation indices (PRx, optimal CPP [CPPopt]) with clinical outcomes in severe CVT.

Methods: 

This observational study included 15 patients with severe CVT with ICP-monitoring, treated in the neurointensive care (NIC) unit, Uppsala. The percentage of eligible monitoring time (EMT) outside certain thresholds was calculated for ICP, PRx, CPP, and ΔCPPopt (CPP-CPPopt) and analysed in relation to outcome (Glasgow Outcome at Discharge Scale [GODS]). Outcome heatmaps were generated to visualize transitions from better to worse outcomes for single variables and 2 variables (ICP, CPP, or ΔCPPopt in combination with PRx).

Results: 

Median %EMT for ICP>20 mm Hg and CPP<60 mm Hg was <5%. Higher %EMT for ICP>20 mm Hg (r=−0.60, P=0.02) correlated with worse outcome (lower GODS). The median %EMT of impaired cerebral pressure autoregulation was 34%. Outcome heatmaps indicated transitions toward worse outcome when PRx exceeded zero and ΔCPPopt became negative, but these correlations were not significant. Higher PRx reduced the safe ICP and CPP range, in 2-variable heatmaps.

Conclusions: 

A higher %EMT of ICP>20 mm Hg was unfavorable in severe CVT. Impaired cerebral autoregulation with high PRx was frequent and may reduce the safe ICP/CPP range. Larger, multi-centre studies are needed to validate these findings in this rare condition.

Patient-tailored treatment, also known as precision-medicine, has been emphasized as a prioritized area in traumatic brain injury research. In fact, pre-injury patient genetic factors alone account for almost 26% of outcome prediction variance following traumatic brain injury. Among implicated genetic variants single-nucleotide polymorphism in apolipoprotein E has been linked to worse prognosis following traumatic brain injury, but the underlying mechanism is still unknown. We hypothesized that apolipoprotein E genotype would affect the levels of pathophysiology-driving structural, or inflammatory, proteins in cerebral microdialysate following severe traumatic brain injury. We conducted a prospective observational study of patients with severe traumatic brain injury treated with invasive neuromonitoring including cerebral microdialysis at Uppsala University Hospital. All patients were characterized regarding apolipoprotein E genotype. Utilizing fluid- and plate-based antibody arrays, we quantified 101 proteins (of which 89 were eligible for analysis) in cerebral microdialysate at 1 day and 3 days following trauma. Statistical analysis included clustering techniques, as well as uni- and multi-variate linear mixed modelling. In total, 26 patients were included, and all relevant genotypes of apolipoprotein E were represented in the data. Among all proteins tested, 41 proteins showed a time-dependent expression level. There was a weak clustering tendency in the data, and not primarily to genotype, either depicted through t-distributed stochastic neighbour embedding or hierarchical clustering. Using linear mixed models, two proteins [the inflammatory protein CD300 molecule like family member f (CLM-1) and the neurotrophic protein glial-derived neurotrophic factor family receptor α1] were found to have protein levels concomitantly dependent upon time and genotype, albeit this effect was not seen following multiple testing corrections. Apart from amyloid-β-40 (Aβ) and Microtubule-associated protein tau, neither Aβ peptide levels nor the Aβ42/40 ratio were seen related to time from trauma or apolipoprotein E genotype. This is the first study in clinical severe traumatic brain injury examining the influence of apolipoprotein E genotype on microdialysate protein expression. Protein levels in cerebral microdialysate following trauma are seen to be strongly dependent on time from trauma, corroborating previous work on protein expression longitudinally following traumatic brain injury. We also identified protein expression level alterations dependent on apolipoprotein E genotype, which might indicate that apolipoprotein E affects ongoing pathophysiology in the injured brain at the proteomic level.

Objective

Malignant middle cerebral artery infarction (MMI) is a severe neurological condition. Decompressive craniectomy (DC) is an established lifesaving surgical treatment. However, the role of neurocritical care with monitoring and management of the intracranial pressure (ICP), pressure reactivity index (PRx), cerebral perfusion pressure (CPP), and optimal perfusion pressure (CPPopt) remain unclear. This study aims to examine the dynamics of these variables post-DC in relation to clinical outcome.

Methods

This retrospective study included 70 MMI patients who underwent DC with ICP monitoring of at least 12 hours and available data of clinical outcome (modified Rankin Scale [mRS] at 6 months). The associations between mRS and cerebral physiology (ICP, PRx, CPP, and ∆CPPopt) was analysed and presented in different outcome heatmaps over the first 7 days following DC.

Results

ICP above 15 mmHg was associated with unfavourable outcome, particularly for longer durations. As PRx exceeded zero, outcome worsened progressively, and values above 0.5 correlated to poor outcome regardless of duration. As CPP dropped below 80 mmHg, there was a transition from favourable to unfavourable outcome. Negative ∆CPPopt, particularly below -20 mmHg, corresponded to unfavourable outcome. In two-variable heatmaps, elevated PRx combined with high ICP, low CPP or negative ∆CPPopt correlated with worse outcome.

Conclusion

Invasive ICP-monitoring may provide prognostic information for long-term recovery in MMI patients post-DC. The study highlighted disease-specific optimal physiological intervals for ICP, PRx, CPP, and ΔCPPopt. Of particular interest, the autoregulatory variable, PRx, influenced the safe and dangerous ICP, CPP, and ∆CPPopt intervals.

Background

The effect of positive end-expiratory pressure (PEEP) on intracranial pressure (ICP) dynamics in patients with acute brain injury (ABI) remains controversial. PEEP can benefit oxygenation by promoting alveolar recruitment, but its influence on ICP is complex. The primary aims of this study were to investigate 1) how lung recruitability influences oxygenation and 2) how lung recruitability and regional gas distribution, measured via recruitment-to-inflation (RI) ratio and electrical impedance tomography (EIT), affect ICP in response to PEEP changes in critically ill patients in their early phase of ABI.

Methods

Ten mechanically ventilated ABI patients were included. Pressure reactivity index (PRx) was estimated. Using RI manoeuvre and EIT, lung recruitability and gas distribution were assessed in response to a standardised PEEP change (from high to low levels, with a delta of 10 cmH₂O). Changes in ICP (ΔICP) were calculated between high and low PEEP. Lung inhomogeneity indices (global inhomogeneity index [GI] and local inhomogeneity index [LI]) were derived from EIT. Correlations between ventilatory variables and ICP were analysed.

Results

Blood oxygenation significantly decreased, going from high (14 [IQR: 12–15] cmH₂O) to low (4 [IQR: 2–5] cmH₂O) PEEP. Reducing PEEP significantly increased ICP (from 9 [IQR: 5–13] to 12 [IQR: 8–16] mmHg, p < 0.01), while cerebral perfusion pressure (CPP) improved (from 71 [IQR:67–83] to 75 [IQR: 70–84] mmHg, p = 0.03) and mean arterial pressure (MAP) increased (from 79 [IQR: 69–95] to 84 [IQR: 76–99] mmHg, p < 0.01). The RI ratio correlated significantly with ΔICP (rho = 0.87, p < 0.01), as did Vrec% (proportion of recruited volume, rho = 0.65) and GI (rho = 0.5). LI did not correlate with ΔICP. PRx was 0.30 [IQR: 0.12–0.42], indicating a deranged cerebral autoregulation.

Conclusions

Patients with a higher potential for lung recruitability had a more beneficial effect of PEEP on oxygenation. These effects should be interpreted cautiously, given that lung recruitability and global inhomogeneity of gas distribution significantly influenced the intracranial response to PEEP in ABI patients. As indicated by MAP and CPP, PEEP may impact systemic haemodynamics and cerebral perfusion when cerebral autoregulation is deranged. These findings underscore the importance of multimodal (i.e. respiratory, cerebral and haemodynamics) monitoring for optimising ventilation strategies in ABI patients and provide a framework for future research.

Trial registration Registration number: NCT05363085, Date of registration: May 2022

Background

Epidemiological studies show an increasing incidence of traumatic brain injury (TBI) among people aged 65 years and older. Advances in neurointensive care have improved survival after TBI. There is a need for knowledge about long-term outcome after TBI among older survivors of TBI.

Objective

To describe the overall outcome, long-term functioning, and disability of the participants in the Uppsala Long-term outcome in Older adults with Traumatic brain injury Study (U-LOTS), a cohort study assessing adults aged 60 years or older when admitted to a neurointensive care unit following a TBI, where 3 to 14 years had passed since the injury.

Design

Cross-sectional cohort study.

Setting

Home and community settings.

Interventions

Not applicable.

Participants

Data were collected from 79 survivors of TBI (65% men; mean age 76 years, mean time since TBI 7 years).

Main Outcome Measures

The Glasgow Outcome Scale Extended (GOSE), the Functional Independence Measure (FIM), the Mayo-Portland Adaptability-4 (MPAI-4), and the following sociodemographics and TBI characteristics: gender, age, marital status, vocational situation, rehabilitation, need of assistance, use of mobility devices, oropharyngeal dysphagia, impaired sense of smell and/or taste, prior brain disease, cause of accident, severity of TBI, comorbidities, dominant finding on first computed tomography scan, and assessment with GOSE 6 months after TBI.

Results

Falls (68%) and acute subdural hematoma (41%) were the most common cause and injury. For many participants (40%) the GOSE scores did not change between 6 months after TBI until the long-term follow-up, and a majority (57%) had a relatively good outcome as assessed with the MPAI-4. GOSE, FIM, and MPAI-4 Ability scores were significantly (p < .05) correlated with injury severity. Marital status remained unchanged for 70% of the participants.

Conclusions

Older adults surviving a TBI may have a relatively favorable outcome. A major factor that determined long-term outcome was injury severity.

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.

Background

Sweden covers a large land area, but is sparsely populated. The country is divided into six heterogenous healthcare regions, each with different geographic conditions and referral patterns when it comes to traumatic brain injury (TBI). This study aimed to explore the variation in demography, injury patterns, care pathways, management, and mortality (30 d) for TBI patients within the country.

Methods

A nationwide, observational study, using data from the Swedish Trauma Registry (SweTrau) between 2018–2022, was performed. A total of 5036 TBI patients were included. Data on demography, admission status (through Glasgow Coma Scale [GCS] value at arrival at first managing hospital), injury-related variables, and mortality (30 d) were evaluated.

Results

The median age was 65 years (interquartile range 46–78), and the majority of patients were male, had sustained fall-related injuries, and were conscious upon admission. Slight, but significant differences (p < 0.05) existed among the regions in these variables. In multivariate logistic regression models, the healthcare region (p < 0.05) was independently associated with patient referral to a university hospital (as compared to care at a local hospital alone), craniotomy rate, and receiving an intracranial pressure-monitoring device, after adjustment for demographic and injury variables. In similar regressions regarding mortality, specific healthcare regions (p < 0.05) were independently associated with said outcome.

Conclusions

The study highlights, from a systems-level perspective, that there was a significant variation in care pathways and management among the six healthcare regions in Sweden, which might have impacted on clinical outcome. These findings call for more granular studies to understand which aspects of patient management that were particularly beneficial or detrimental for patient survival and recovery.

OBJECTIVE: There is a paucity of studies on the optimal thresholds for neurointensive care (NIC) targets such as intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in spontaneous intracerebral hemorrhage (sICH). There is also a need to clarify the role of cerebral pressure autoregulatory disturbances (pressure reactivity index [PRx]) and to determine if the autoregulatory CPP target (optimal CPP [CPPopt]) is superior to traditional fixed CPP targets in sICH. In this study, the authors aimed to explore the role of ICP, PRx, CPP, and CPPopt insults in sICH patients treated in the NIC unit.

METHODS: In this observational study, 184 adults with sICH with intracerebral hemorrhage (ICH) volume above 10 ml who received > 12 hours of ICP monitoring during the first 7 days at the authors' NIC unit, Uppsala University Hospital, Sweden, between 2010 and 2019 (10 years) were included. Demographic characteristics, admission status, radiological examination, and clinical outcome were evaluated. Favorable outcome was defined as conscious at discharge, while unfavorable outcome as unconscious or deceased. ICP, CPP, PRx, and CPPopt during the first 7 days were analyzed in relation to outcome.

RESULTS: In total, 138 (75%) patients recovered favorably at discharge. Lower percentage of good monitoring time with ICP above 25 mm Hg was independently associated with favorable outcome. CPP above 80 mm Hg was frequent and independently associated with favorable outcome. Median PRx did not differ between the outcome groups, but there was a trend toward worse outcome when PRx exceeded +0.5. Furthermore, when PRx was analyzed together with the concurrent ICP and CPP values, higher values increased the ICP and CPP interval associated with unfavorable outcome. Lastly, there was no independent correlation between CPP deviation from CPPopt and outcome.

CONCLUSIONS: Avoiding ICP elevations above 20 to 25 mm Hg and maintaining CPP above 80 mm Hg may be beneficial in sICH patients with large bleeding volume who require NIC. PRx was not independently associated with outcome, but higher values appeared to narrow the safe zones of ICP and CPP.

Arterial carbon dioxide (pCO2) strongly affects cerebrovascular tone and cerebral physiology. While moderate hyperventilation is often used to reduce intracranial pressure (ICP) in acute brain injury, its broader physiological effects remain unclear. In this experimental study, 10 anesthetized pigs underwent multimodal neuromonitoring, including ICP, cerebral perfusion pressure, common autoregulatory indices (pressure reactivity index [PRx], cerebral blood flow index [CBFx], oxygen reactivity index), CBF, brain tissue oxygenation (pbtO2), and microdialysis. Animals were exposed to four ventilatory intervals (normoventilation, moderate and severe hyperventilation, and hypoventilation), first in a healthy state and then following induction of intracranial hypertension (ICP 30-40 mmHg) via epidural balloon inflation. In the healthy brain, moderate and severe hyperventilation numerically, but non-significantly, reduced CBF without affecting pbtO2 or cerebral energy metabolism, while hypoventilation increased CBF and pbtO2. Under intracranial hypertension, moderate hyperventilation improved PRx and preserved CBF, pbtO2, and metabolism, but severe hyperventilation reduced pbtO2. Hypoventilation produced variable responses: Animals with higher baseline blood pressure showed improved perfusion and oxygenation, whereas those with lower pressure experienced reduced CBF, impaired oxygenation, and metabolic distress. These findings underscore the complex and context-dependent effects of pCO2 on cerebral physiology, indicating that ventilatory strategies may both benefit and harm the injured brain depending on individual vulnerability and hemodynamic status.