Multimodal prediction of residual consciousness in the intensive care unit: the CONNECT-ME study.

Functional MRI (fMRI) and EEG may reveal residual consciousness in patients with disorders of consciousness (DoC), as reflected by a rapidly expanding literature on chronic DoC. However, acute DoC is rarely investigated, although identifying residual consciousness is key to clinical decision-making in the intensive care unit (ICU). Therefore, the objective of the prospective, observational, tertiary centre cohort, diagnostic phase IIb study 'Consciousness in neurocritical care cohort study using EEG and fMRI' (CONNECT-ME, NCT02644265) was to assess the accuracy of fMRI and EEG to identify residual consciousness in acute DoC in the ICU. Between April 2016 and November 2020, 87 acute DoC patients with traumatic or non-traumatic brain injury were examined with repeated clinical assessments, fMRI and EEG. Resting-state EEG and EEG with external stimulations were evaluated by visual analysis, spectral band analysis and a Support Vector Machine (SVM) consciousness classifier. In addition, within- and between-network resting-state connectivity for canonical resting-state fMRI networks was assessed. Next, we used EEG and fMRI data at study enrolment in two different machine-learning algorithms (Random Forest and SVM with a linear kernel) to distinguish patients in a minimally conscious state or better (≥MCS) from those in coma or unresponsive wakefulness state (≤UWS) at time of study enrolment and at ICU discharge (or before death). Prediction performances were assessed with area under the curve (AUC). Of 87 DoC patients (mean age, 50.0 ± 18 years, 43% female), 51 (59%) were ≤UWS and 36 (41%) were ≥ MCS at study enrolment. Thirty-one (36%) patients died in the ICU, including 28 who had life-sustaining therapy withdrawn. EEG and fMRI predicted consciousness levels at study enrolment and ICU discharge, with maximum AUCs of 0.79 (95% CI 0.77-0.80) and 0.71 (95% CI 0.77-0.80), respectively. Models based on combined EEG and fMRI features predicted consciousness levels at study enrolment and ICU discharge with maximum AUCs of 0.78 (95% CI 0.71-0.86) and 0.83 (95% CI 0.75-0.89), respectively, with improved positive predictive value and sensitivity. Overall, both machine-learning algorithms (SVM and Random Forest) performed equally well. In conclusion, we suggest that acute DoC prediction models in the ICU be based on a combination of fMRI and EEG features, regardless of the machine-learning algorithm used.

Ventriculostomy-associated infection (VAI) in patients with acute brain injury-a retrospective study.

BACKGROUND: Ventriculostomy-associated infection (VAI) is common after external ventricular drains (EVD) insertion but is difficult to diagnose in patients with acute brain injury. Previously, we proposed a set of criteria for ruling out VAI in traumatic brain injury. This study aimed to validate these criteria. For exploratory purposes, we sought to develop and validate a score for VAI risk assessment in patients with different types of severe acute brain injury. METHODS: This retrospective cohort study included adults with acute brain injury who received an EVD and in whom CSF samples were taken over a period of 57 months. As standard non-coated bolt-connected EVDs were used. The predictive performance of biomarkers was analyzed as defined previously. A multivariable regression model was performed with five variables. RESULTS: A total of 683 patients with acute brain injury underwent EVD placement and had 1272 CSF samples; 92 (13.5%) patients were categorized as culture-positive VAI, 130 (19%) as culture-negative VAI, and 461 (67.5%) as no VAI. A low CSF WBC/RBC ratio (< 0.037), high CSF/plasma glucose ratio (> 0.6), and low CSF protein (< 0.5g/L) showed a positive predictive value of 0.09 (95%CI, 0.05-0.13). In the multivariable logistic regression model, days to sample (OR 1.09; 95%CI, 1.03-1.16) and CSF WBC/RBC ratio (OR 34.86; 95%CI, 3.94-683.15) were found to predict VAI. CONCLUSION: In patients with acute brain injury and an EVD, our proposed combined cut-off for ruling out VAI performed satisfactorily. Days to sample and CSF WBC/RBC ratio were found independent predictors for VAI in the multivariable logistic regression model.

Arterial Spin Labeling Magnetic Resonance Imaging for Acute Disorders of Consciousness in the Intensive Care Unit.

BACKGROUND: To investigate patients with disorders of consciousness (DoC) for residual awareness, guidelines recommend quantifying glucose brain metabolism using positron emission tomography. However, this is not feasible in the intensive care unit (ICU). Cerebral blood flow (CBF) assessed by arterial spin labeling magnetic resonance imaging (ASL-MRI) could serve as a proxy for brain metabolism and reflect consciousness levels in acute DoC. We hypothesized that ASL-MRI would show compromised CBF in coma and unresponsive wakefulness states (UWS) but relatively preserved CBF in minimally conscious states (MCS) or better. METHODS: We consecutively enrolled ICU patients with acute DoC and categorized them as being clinically unresponsive (i.e., coma or UWS [≤ UWS]) or low responsive (i.e., MCS or better [≥ MCS]). ASL-MRI was then acquired on 1.5 T or 3 T. Healthy controls were investigated with both 1.5 T and 3 T ASL-MRI. RESULTS: We obtained 84 ASL-MRI scans from 59 participants, comprising 36 scans from 35 patients (11 women [31.4%]; median age 56 years, range 18-82 years; 24 ≤ UWS patients, 12 ≥ MCS patients; 32 nontraumatic brain injuries) and 48 scans from 24 healthy controls (12 women [50%]; median age 50 years, range 21-77 years). In linear mixed-effects models of whole-brain cortical CBF, patients had 16.2 mL/100 g/min lower CBF than healthy controls (p = 0.0041). However, ASL-MRI was unable to discriminate between ≤ UWS and ≥ MCS patients (whole-brain cortical CBF: p = 0.33; best hemisphere cortical CBF: p = 0.41). Numerical differences of regional CBF in the thalamus, amygdala, and brainstem in the two patient groups were statistically nonsignificant. CONCLUSIONS: CBF measurement in ICU patients using ASL-MRI is feasible but cannot distinguish between the lower and the upper ends of the acute DoC spectrum. We suggest that pilot testing of diagnostic interventions at the extremes of this spectrum is a time-efficient approach in the continued quest to develop DoC neuroimaging markers in the ICU.

Multimodal Prediction of 3- and 12-Month Outcomes in ICU Patients with Acute Disorders of Consciousness.

BACKGROUND: In intensive care unit (ICU) patients with coma and other disorders of consciousness (DoC), outcome prediction is key to decision-making regarding prognostication, neurorehabilitation, and management of family expectations. Current prediction algorithms are largely based on chronic DoC, whereas multimodal data from acute DoC are scarce. Therefore, the Consciousness in Neurocritical Care Cohort Study Using Electroencephalography and Functional Magnetic Resonance Imaging (i.e. CONNECT-ME; ClinicalTrials.gov identifier: NCT02644265) investigates ICU patients with acute DoC due to traumatic and nontraumatic brain injuries, using electroencephalography (EEG) (resting-state and passive paradigms), functional magnetic resonance imaging (fMRI) (resting-state) and systematic clinical examinations. METHODS: We previously presented results for a subset of patients (n = 87) concerning prediction of consciousness levels in the ICU. Now we report 3- and 12-month outcomes in an extended cohort (n = 123). Favorable outcome was defined as a modified Rankin Scale score ≤ 3, a cerebral performance category score ≤ 2, and a Glasgow Outcome Scale Extended score ≥ 4. EEG features included visual grading, automated spectral categorization, and support vector machine consciousness classifier. fMRI features included functional connectivity measures from six resting-state networks. Random forest and support vector machine were applied to EEG and fMRI features to predict outcomes. Here, random forest results are presented as areas under the curve (AUC) of receiver operating characteristic curves or accuracy. Cox proportional regression with in-hospital death as a competing risk was used to assess independent clinical predictors of time to favorable outcome. RESULTS: Between April 2016 and July 2021, we enrolled 123 patients (mean age 51 years, 42% women). Of 82 (66%) ICU survivors, 3- and 12-month outcomes were available for 79 (96%) and 77 (94%), respectively. EEG features predicted both 3-month (AUC 0.79 [95% confidence interval (CI) 0.77-0.82]) and 12-month (AUC 0.74 [95% CI 0.71-0.77]) outcomes. fMRI features appeared to predict 3-month outcome (accuracy 0.69-0.78) both alone and when combined with some EEG features (accuracies 0.73-0.84) but not 12-month outcome (larger sample sizes needed). Independent clinical predictors of time to favorable outcome were younger age (hazard ratio [HR] 1.04 [95% CI 1.02-1.06]), traumatic brain injury (HR 1.94 [95% CI 1.04-3.61]), command-following abilities at admission (HR 2.70 [95% CI 1.40-5.23]), initial brain imaging without severe pathological findings (HR 2.42 [95% CI 1.12-5.22]), improving consciousness in the ICU (HR 5.76 [95% CI 2.41-15.51]), and favorable visual-graded EEG (HR 2.47 [95% CI 1.46-4.19]). CONCLUSIONS: Our results indicate that EEG and fMRI features and readily available clinical data predict short-term outcome of patients with acute DoC and that EEG also predicts 12-month outcome after ICU discharge.

Cerebellar mutism syndrome of non-tumour surgical aetiology-a case report and literature review.

Cerebellar mutism syndrome (CMS) is a well-known complication of posterior fossa (PF) tumour surgery. CMS has previously been reported in cases of non-tumour surgical aetiology in a limited number of publications. We report a case of a 10-year-old girl who suffered a cerebellar haemorrhage and subsequent CMS following surgical treatment of a ruptured arteriovenous malformation (AVM) in the cerebellar vermis. The AVM was removed acutely through a transvermian access, and hydrocephalus was treated with temporary external drainage. In the postoperative period, she suffered diffuse vasospasms of the anterior cerebral circulation and had a permanent shunt placed for hydrocephalus. Her mutism resolved after 45 days but severe ataxia persisted. To our knowledge, this is the first reported case of CMS related to a vermian haemorrhagic stroke with postoperative diffuse vasospasms. Based on this case, we present a literature review on CMS of non-tumour surgical origin in children.

Diagnostic criteria of CNS infection in patients with external ventricular drainage after traumatic brain injury: a pilot study.

BACKGROUND: Ventriculostomy-related infection (VRI) is a common complication in patients with traumatic brain injury (TBI) treated with an external ventricular drain (EVD). The aim of this study was to investigate incidence and characteristics of patients with VRI, and to explore diagnostic criteria to confidently rule out VRI in patients with TBI. METHODS: This retrospective cohort pilot study included adults with severe TBI who were admitted to the ICU and received an EVD, during a 26-month period. Patients were categorized as having Culture-positive VRI, Culture-negative VRI, or No VRI. Variables that were potentially associated with Culture-positive VRI was analyzed, and predictive values were calculated. RESULTS: 75 of 215 patients with severe TBI (35%) underwent EVD placement; nine of these (12%) were classified as Culture-negative VRI and eight (11%) as Culture-positive VRI. The CSF cell counts that led to VRI treatment were compared with 46 CSF cell counts from No VRI patients. A CSF/plasma glucose ratio below 0.6 had a negative predictive value (NPV) for culture-verified VRI of 0.97 (95% CI: 0.85-1), whereas a combination of three CSF-derived biomarkers within the reference limits (white/red blood cell ratio, CSF/plasma glucose ratio, and protein content) ruled out Culture-positive VRI in this cohort (PPV 0, 95% CI: 0-0.14). C-reactive protein did not reliably predict VRI. CONCLUSIONS: In this pilot study of patients after severe, a combination of biomarkers within reference limits ruled out VRI (PPV 0, CI: 0-0.14). Hypoglycorrhachia was a sensitive marker of VRI (NPV 0.97, CI: 0.85-1). Systemic signs and markers of infection did not predict VRI.

Hemorrhage due to a pseudoaneurysm on a dural-pial anastomosis after decompression for Chiari malformation type I: case report.

While intracranial aneurysms rarely develop after neurosurgical procedures, delayed pseudoaneurysm formation after foramen magnum decompression (FMD) has never been reported. A 52-year-old woman presented with an atypical subarachnoid hemorrhage in the posterior fossa 12 years after a FMD for symptomatic Chiari malformation type I was performed. A pseudoaneurysm on a dural-pial anastomosis was identified as the bleeding source and successfully occluded by endovascular means with full clinical recovery of the patient. Injury to the distal posterior inferior cerebellar artery related to surgery and postoperative infection likely caused formation of a dural-pial anastomosis. Additionally, hemodynamic stress or dissection may have contributed to delayed pseudoaneurysm formation and rupture.

Mortality among patients treated for aneurysmal subarachnoid hemorrhage in Eastern Denmark 2017-2019.

OBJECTIVE: The aim of the study was to investigate (1) the 30-day, 3-month, and 12-month cumulative mortalities for patients who underwent aneurysm occlusion, and (2) the causes of death, and (3) the potential risk factors for death. METHODS: All patients who underwent surgical clipping or endovascular treatment of a ruptured aneurysm at Copenhagen University Hospital, during the period of January 1, 2017-December 31, 2019, were included and followed up for 12 months. Data regarding vital status, causes of death, comorbidities, treatment, and clinical presentations on admission was collected. The absolute mortality risk was estimated as a function of time with a 95% confidence interval. The associations between potential risk factors and death were estimated as odds ratios with 95% confidence intervals using logistic regression models. RESULTS: A total of 317 patients were included. The overall cumulative mortalities after 30 days, 3 months, and 12 months were 10.7%, 12.9%, and 16.1%, respectively. The most common cause of death was severe primary hemorrhage (52.9%), followed by infections (15.7%) and rebleeding (11.8%). WFNS score > 3 and Fisher score > 3 on admission, preprocedural hydrocephalus, and preprocedural rebleeding were found significantly associated with higher risk of death. CONCLUSIONS: Considerable mortality was seen. Possible preventable causes accounted for approximately 22% of the deaths. The occurrence of both pre- and postprocedural rebleeding's indicates an opportunity of further improvement of the mortality by (1) further reduction of time from aSAH to aneurysm occlusion and (2) continuous efforts in improving methods of aneurysm occlusion.

Prognosis regarding shunt revision and mortality among hydrocephalus patients below the age of 2 years and the association to patient-related risk factors.

BACKGROUND: Little is known about the prognosis regarding shunt revision and mortality among hydrocephalus patients below 2 years of age. The aims of this study were to investigate (1) the cumulative risks of shunt revision (SR) and mortality and (2) the potential associations between prematurity, low weight for gestational age (LWGA), underlying aetiology, sex, age of the child at shunt placement, and the risk of SR. METHOD: This was a purely register-based cohort study including all shunted hydrocephalic infants in Denmark 1996-2015. The cumulative risks of SR and mortality were estimated using the Aalen-Johansen and Kaplan-Meier estimators, respectively. A multivariable Cox-regression model was used to estimate hazard ratios (HRs) for SR according to the listed patient-related risk factors. RESULTS: Among 374 shunted infantile hydrocephalus patients accounting for 1047 SRs, the 3-month and 1-year cumulative risks of SR were 36% and 50%, respectively. The overall 10-year cumulative mortality was 12%, and for non-tumour subgroups 7-16% (isolated hydrocephalus 7%). The 10-year cumulative mortality for children born with LWGA was 21%. Except for aetiology, we observed no strong overall associations between the investigated risk factors and the risk of SR but interaction analyses for aetiology showed that patients with Dandy-Walker malformation born with LWGA had a higher risk of SR compared to patients of similar aetiology with normal WGA (HR 2.47, 95% CI: 1.39-4.40). CONCLUSIONS: We found very high cumulative risks of SR and mortality among this youngest group of hydrocephalus patients, disregarding aetiology, but none of them were strongly related to the investigated risk factors.

Functional MRI for Assessment of the Default Mode Network in Acute Brain Injury.

BACKGROUND: Assessment of the default mode network (DMN) using resting-state functional magnetic resonance imaging (fMRI) may improve assessment of the level of consciousness in chronic brain injury, and therefore, fMRI may also have prognostic value in acute brain injury. However, fMRI is much more challenging in critically ill patients because of cardiovascular vulnerability, intravenous sedation, and artificial ventilation. METHODS: Using resting-state fMRI, we investigated the DMN in a convenience sample of patients with acute brain injury admitted to the intensive care unit. The DMN was classified dichotomously into "normal" and "grossly abnormal." Clinical outcome was assessed at 3 months. RESULTS: Seven patients with acute brain injury (4 females; median age 37 years [range 14-71 years]; 1 traumatic brain injury [TBI]; 6 non-TBI) were investigated by fMRI a median of 15 days after injury (range 5-25 days). Neurological presentation included 2 coma, 1 vegetative state/unresponsive wakefulness syndrome (VS/UWS), 3 minimal conscious state (MCS) minus, and 1 MCS plus. Clinical outcomes at 3 months included 1 death, 1 VS/UWS, 1 MCS plus, and 4 conscious states (CS; 1 modified Rankin Scale 0; 2 mRS 4; 1 mRS 5). Normal DMNs were seen in 4 out of 7 patients (1 MCS plus, 3 CS at follow-up). CONCLUSIONS: It is feasible to assess the DMN by resting-state fMRI in patients with acute brain injury already in the very early period of intensive care unit admission. Although preliminary data, all patients with a preserved DMN regained consciousness levels at follow-up compatible with MCS+ or better.

A multicentre randomized controlled trial of moderate hypothermia to prevent intracranial hypertension in acute liver failure.

BACKGROUND & AIMS: Animal models and human case series of acute liver failure (ALF) suggest moderate hypothermia (MH) to have protective effects against cerebral oedema (CO) development and intracranial hypertension (ICH). However, the optimum temperature for patient management is unknown. In a prospective randomized controlled trial we investigated if maintenance of MH prevented development of ICH in ALF patients at high risk of the complication. METHODS: Patients with ALF, high-grade encephalopathy and intracranial pressure (ICP) monitoring in specialist intensive care units were randomized by sealed envelope to targeted temperature management (TTM) groups of 34°C (MH) or 36°C (control) for a period of 72h. Investigators were not blinded to group assignment. The primary outcome was a sustained elevation in ICP >25mmHg, with secondary outcomes the occurrence of predefined serious adverse effects, magnitude of ICP elevations and cerebral and all-cause hospital mortality (with or without transplantation). RESULTS: Forty-six patients were randomized, of whom forty-three were studied. There was no significant difference between the TTM groups in the primary outcome during the study period (35% vs. 27%, p=0.56), for the MH (n=17) or control (n=26) groups respectively, relative risk 1.31 (95% CI 0.53-3.2). Groups had similar incidence of adverse events and overall mortality (41% vs. 46%, p=0.75). CONCLUSIONS: In patients with ALF at high risk of ICH, MH at 33-34°C did not confer a benefit above management at 36°C in prevention of ICH or in overall survival. This study did not confirm advantage of its prophylactic use. (ISRCTN registration number 74268282; no funding.) LAY SUMMARY: Studies in animals with acute liver failure (ALF) have suggested that cooling (hypothermia) could prevent or limit the development of brain swelling, a dangerous complication of the condition. There is limited data on its effects in humans. In a randomized controlled trial in severely ill patients with ALF we compared the effects of different temperatures and found no benefit on improving survival or preventing brain swelling by controlling temperature at 33-34°C against 36°C.

Post procedure headache in patients treated for neurovascular arteriovenous malformations and aneurysms using endovascular therapy.

BACKGROUND: Though endovascular therapy (EVT) is increasingly applied in the treatment of intracranial vascular lesions, little is known about the effect of EVT on post-procedure headache. We aimed to investigate the prevalence of headache in patients who have undergone EVT for cerebral arteriovenous malformations (AVMs) and aneurysms. METHODS: A total of 324 patients underwent EVT treatment for aneurysms and AVMs at the Danish National Hospital from January 2012 to December 2014. We applied strict exclusion criteria in order to minimize the effect of other factors on headache occurrence, e.g., craniotomy. Eligible subjects were phone-interviewed using a purpose-developed semi-structured questionnaire. Headaches were classified according to ICHD-III beta criteria. RESULTS: The 59 patients underwent treatment of aneurysms (n = 43), cranial dural fistulas (n = 11), and AVMs (n = 5). There was a significant increase in overall headache (p = 0.017) and tension-type headache (TTH) (p = 0.012) within the first 3 months after EVT compared to 1 month before EVT. However, at interview time (median 2.5 years post-EVT), the increase in overall headache, migraine, and tension-type headache was not statistically significant. A minority of patients experienced headaches for the first time within 3 months of their EVT (migraine 4, TTH 10). At interview time, 50 % of these new headaches still persisted. CONCLUSION: Our results suggest a temporary increase in headache in the first 3 months after EVT, which normalizes over time. Clinicians may use this knowledge to better inform their patients of functional outcomes after their EVT procedure.

Subarachnoid haemorrhage and intracranial aneurysms in Greenland in the period 2018-2021: incidence, outcome and familial disposition.

Subarachnoid haemorrhages (SAH) caused by rupture of intracranial aneurysms (IA) are a severe condition. Earlier studies found a higher incidence of SAH in Greenlandic patients compared to Danish patients, with familial aggregation also higher in Greenland. However, updated data is lacking. To investigate the contemporary incidence, outcome, and familial disposition of SAH/IA in Greenlandic patients in 2018-2021. Greenlandic patients diagnosed with ruptured or unruptured IA (UIA) during 2018-2021 were included. Data was obtained from patient files, x-ray department, and discharge registry. Incidence rates were estimated as cases/100,000/year. Direct age-standardised incidence rates were calculated using WHO 2000-2025 as standards. Of 30 SAH patients, 20 (66.7%) were females, 10 (33.3%) males. Of 36 UIA patients, 27 (75.0%) were females, 9 (25.0%) males. For SAH, crude incidence was 13.4/100,000/year, age-standardised incidence was 10.8/100,000/year. Familial history was observed in 30.0% of SAH patients. 5 patients (16.7%) died before treatment, 28-day case-fatality rate (CFR) for all patients was 23.3%. Overall and age-standardised incidence rates were similar to previous studies but higher among females and compared to neighbouring countries. A high occurrence of familial history was reported. SAH remains a serious condition in Greenland, as evidenced by five fatalities before treatment was administered.

The effect of fractionated plasma separation and adsorption on cerebral amino acid metabolism and oxidative metabolism during acute liver failure.

BACKGROUND & AIMS: Patients with acute liver failure have a disturbed amino acid metabolism and a compromised oxidative metabolism in the brain. A limited number of clinically neuroprotective interventions are available. This study aimed at assessing the effect of fractionated plasma separation and adsorption (FPSA), an extracorporeal liver support system, on cerebral amino acids and lactate to pyruvate ratio. METHODS: Seven patients with acute liver failure and high risk of intracranial hypertension were included for cerebral microdialysis and intracranial pressure monitoring. Microdialysate, arterial blood, and venous blood from the jugular bulb were sampled, before and after an FPSA session, and the content of nineteen amino acids, lactate, and pyruvate was determined. RESULTS: The total amino acid concentration in arterial plasma was not significantly reduced by FPSA (11.2 mM (3.0-26.0 mM) vs. 9.7 mM (2.7-13.6 mM); median with range). The total amino acid content in the microdialysate was 5.6 mM both before and after FPSA and no change in glutamine content was observed in plasma or microdialysate. The content of aromatic amino acids in arterial plasma, but not in microdialysate, was marginally reduced (p<0.05). Arterial lactate concentration and lactate to pyruvate ratio in the microdialysate did not change following FPSA. CONCLUSIONS: One single treatment session with FPSA had a marginal effect on plasma amino acid composition. We found minimal changes in the amino acids content in the microdialysate, and the lactate to pyruvate ratio was unaffected.

Treatment of intracranial aneurysms. Reconstruction of the parent artery with flow-diverting (Silk) stent.

INTRODUCTION: Since the flow diverters (FDs) have been introduced it is possible to treat aneurysms that are considered difficult or impossible to treat with usual endovascular or surgical methods. It is still uncertain which aneurysms are suitable for this new treatment. We present the periprocedural complications, immediate result, late complications, imaging follow-up at 6 and 12 months and clinical follow-up at 2-23 months. METHODS: Twenty-two patients with 26 wide-necked or blister-like aneurysms had 23 treatments with implantation of a Silk stent. Eleven patients had re-canalizations, and 11 patients were either untreated or had been treated for another aneurysm. RESULTS: Periprocedural complications were seen in four treatments (17%). However, none of these had clinical consequences. Mortality and morbidity rates were 1 of 22 (5%) and 1 of 22 (5%), respectively. Clinical outcome was unchanged in 16 patients (72%), 3 patients improved (14%) and 3 patients worsened (14%). The end-of-procedure angiography did not show complete occlusion of any of the aneurysms, but at 6 months follow-up angiography, 17 of 25 aneurysms (68%) were completely occluded, and at 12 months, 18 of 21 aneurysms (86%) were occluded. CONCLUSION: The effect of the Silk FD in terms of occlusion of the aneurysms seems to occur mainly during the first 6 months after placement but continues during the following time. Most delayed complications occur immediately after discontinuing the anticoagulation medication. Considering the complexity of the aneurysms treated, the rate of complications is acceptable.

Multimodality treatment approach in children with cerebral arteriovenous malformation--a survey in the Danish population.

INTRODUCTION: Arteriovenous malformations are not a common disease in childhood. A national survey was conducted to reveal the Danish incidence of the disease, presentation, choice of treatment, and outcome. MATERIALS AND METHODS: Forty patients were admitted to any of the five neurosurgical centers during the years 2000-2008. A retrospective survey was conducted using hospital records. RESULTS: Twenty-three males and 17 females presented with AVM with a mean age of 11.3 (1 month-18 years). The incidence was found to be 0.4/100,000. Early fatal outcome was seen in three patients. Treatment was surgery (12), endovascular (5), radiosurgery (6), or a combination of the above (10). Four patients were treated conservatively. Complications of the treatment were seen in 27%. Occlusion rate was 74%. Good or excellent outcome was seen in 65%. CONCLUSION: A national survey may give a lower rate of success than in the specialized centers accepting patients more eligible for treatment. Still, the low number of children could call for centralization and collaboration in this population.

[Challenges and advances in paediatric arterial ischaemic stroke].

Neurological sequelae occur in more than 50% of children with arterial ischemic stroke. Early recognition and treatment are essential in improving outcome. However, diagnostic delay in paediatric stroke often extends beyond 24 hours, and children rarely access hyperacute recanalisation therapies. This review describes clinical presentations, risk factors and treatment of paediatric ischaemic stroke. Additionally, we share our experience from a systematic paediatric stroke pathway implemented in Eastern Denmark since 2017.

Brain hypoxanthine concentration correlates to lactate/pyruvate ratio but not intracranial pressure in patients with acute liver failure.

BACKGROUND & AIMS: The pathogenesis of cerebral edema in acute liver failure is suggested, in in vitro and animal studies, to involve a compromised oxidative metabolism with a decrease in cerebral ATP levels and an increase in purine concentrations. In this study we hypothesize that the cerebral concentrations of hypoxanthine, inosine, and lactate/pyruvate (LP) ratio are increased and correlated in patients with acute liver failure. Furthermore, we expect the purines and L/P ratio to correlate with intracranial pressure (ICP) (positively), and cerebral perfusion pressure (CPP) (negatively). METHODS: In 17 patients (aged 18-60 years) with acute liver failure and severe hyperammonemia (182 ± 36 µM (mean ± SD)), cerebral microdialysis was performed, and ICP and CPP were monitored. Microdialysate concentrations of hypoxanthine, inosine, lactate, and pyruvate were measured. RESULTS: The hypoxanthine concentration was 23.0 ± 12 µM in early samples and 11.7 ± 6.8 µM in late samples (normal level ~2.0 µM). The inosine concentration was 7.2 ± 7.1 µM and 2.8 ± 1.6 µM, and the LP ratio was 55.8 ± 21.6 and 45.6 ± 20.8, respectively (normal level ~18). Hypoxanthine correlated significantly to LP ratio (r(2)=0.40, p<0.01) while inosine did not. The purine levels and L/P ratio did not correlate to ICP or CPP, nor did they differ between patients with high ICP (>20 mmHg, n=9) and patients without (n=8). CONCLUSIONS: This study shows that the high cerebral LP ratio correlates to the hypoxanthine level in patients with acute liver failure. However, these metabolic alterations were not related to the development of intracranial hypertension.

Considerable delay in diagnosis and acute management of subarachnoid haemorrhage.

INTRODUCTION: Rebleeding from subarachnoid haemorrhage (SAH) usually occurs within the first six hours after the initial bleeding. Rebleeding can be prevented effectively with tranexamic acid (TXA). Although a broad consensus has evolved that SAH should be treated as an emergency, it is likely that delays do exist in the diagnosis and treatment of SAH patients. The aim of this study was to prospectively assess the interval between symptom onset, emergency room (ER) admission, initial diagnosis and treatment, and final closure of the aneurysm. MATERIAL AND METHODS: We prospectively studied the time course from the initial bleeding to ER admission, computed tomography (CT), TXA treatment, referral to the neurosurgical department, and to the final closure of the aneurysm. RESULTS: A total of 133 patients with SAH due to ruptured intracranial aneurysms were admitted to two neurosurgical units in Copenhagen, Denmark, during a one-year period. The median time to admission was 60 min. The median delay from admission to CT scan was 55 min. Long pre-hospital delay (p = 0.03) and high Glasgow Coma Scale score on arrival (p = 0.0006) were associated with a longer time to CT scan. The median time from CT scan to initiation of TXA treatment was 50 min. The median time from initial insult to final closure of the aneurysm was 30 hours. CONCLUSION: The present study demonstrates that considerable diagnostic delays exist in connection with CT and TXA treatment after patients' arrival to the ER.

Outcome after emergency surgery without angiography in patients with intracerebral haemorrhage after aneurysm rupture.

BACKGROUND: Patients with large intracerebral haematomas (ICH) from aneurysm rupture often present in a poor clinical condition and have a poor prognosis. Time delay for preoperative angiography might in some cases be unappealing. We evaluated the outcome after immediate haematoma removal and aneurysm occlusion without preoperative angiography. METHODS: We retrospectively identified 13 consecutive patients. We recorded clinical data and evaluated mortality and morbidity with the Glasgow Outcome Score (GOS) and Telephone Interview of Cognitive Status (TICS). FINDINGS: At follow up seven of thirteen patients had favourable outcome assessed by GOS. Three patients had severe disability and three patients died. None of the survived patients interviewed had impaired cognition. CONCLUSIONS: In patients presented in a critical state with aneurysmal ICH, emergency haematoma removal and aneurysm clipping without the delay for diagnostic angiography may be life saving and a satisfactory outcome can be accomplished.