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.

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.

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.

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.

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.

[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.

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.

[Screening for intracranial aneurysms].

This review states the reasons for considering screening for intracranial aneurysms in Denmark: if patients have two first-degree relatives with intracranial aneurysms, are 30-70 years old, do not have competing disorders, which could significantly shorten life expectancy, and subsequently in patients with autosomal dominant kidney disease and a family history of subarachnoid haemorrhage. MR angiography should be the imaging study of choice, unless contraindicated. Generally, the ethical consequences ought to be considered before carrying out screening.

Consciousness in Neurocritical Care Cohort Study Using fMRI and EEG (CONNECT-ME): Protocol for a Longitudinal Prospective Study and a Tertiary Clinical Care Service.

Aims and Objectives: To facilitate individualized assessment of unresponsive patients in the intensive care unit for signs of preserved consciousness after acute brain injury. Background: Physicians and neuroscientists are increasingly recognizing a disturbing dilemma: Brain-injured patients who appear entirely unresponsive at the bedside may show signs of covert consciousness when examined by functional MRI (fMRI) or electroencephalography (EEG). According to a recent meta-analysis, roughly 15% of behaviorally unresponsive brain-injured patients can participate in mental tasks by modifying their brain activity during EEG- or fMRI-based paradigms, suggesting that they are conscious and misdiagnosed. This has major ethical and practical implications, including prognosis, treatment, resource allocation, and end-of-life decisions. However, EEG- or fMRI-based paradigms have so far typically been tested in chronic brain injury. Hence, as a novel approach, CONNECT-ME will import the full range of consciousness paradigms into neurocritical care. Methods: We will assess intensive care patients with acute brain injury for preserved consciousness by serial and multimodal evaluation using active, passive and resting state fMRI and EEG paradigms, as well as state-of-the-art clinical techniques including pupillometry and sophisticated clinical rating scales such as the Coma Recovery Scale-Revised. In addition, we are establishing a biobank (blood, cerebrospinal fluid and brain tissue, where available) to facilitate future genomic and microbiomic research to search for signatures of consciousness recovery. Discussion: We anticipate that this multimodal approach will add vital clinical information, including detection of preserved consciousness in patients previously thought of as unconscious, and improved (i.e., personalized) prognostication of individual patients. Our aim is two-fold: We wish to establish a cutting-edge tertiary care clinical service for unresponsive patients in the intensive care unit and lay the foundation for a fruitful multidisciplinary research environment for the study of consciousness in acute brain injury. Of note, CONNECT-ME will not only enhance our understanding of consciousness disorders in acute brain injury but it will also raise awareness for these patients who, for obvious reasons, have lacked a voice so far. Trial registration: The study is registered with clinicaltrials.org (ClinicalTrials.gov Identifier: NCT02644265).

Snaring of a Glued Microcatheter During Embolization of an Arteriovenous Malformation with N-Butyl Cyanoacrylate.

BACKGROUND: Microcatheter entrapment during embolization of brain arteriovenous malformations (AVMs) represents a potentially harmful technical complication. Although several techniques have been reported for endovascular catheter retrieval from an Onyx cast, such methods have never been demonstrated with acrylic glues. We report a case of removal of a glued microcatheter from an N-butyl cyanoacrylate (NBCA) cast using a microsnare. METHODS AND RESULTS: A 26-year-old woman presented with an intracranial hemorrhage resulting from a ruptured right choroidal AVM. A microcatheter used for transarterial embolization was unintentionally glued into the NBCA cast. Because attempts to remove the catheter by simple traction failed, a microsnare was used and allowed withdrawal of the entrapped microcatheter without causing damage to the cerebral vasculature. The patient woke up without clinical sequelae. CONCLUSIONS: Although it is not recommended as routine practice, snaring a glued microcatheter is feasible and can be used in selected cases as a last resort if thromboembolic complications are feared.

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.

Spreading depolarizations in patients with spontaneous intracerebral hemorrhage: Association with perihematomal edema progression.

Pathophysiologic mechanisms of secondary brain injury after intracerebral hemorrhage and in particular mechanisms of perihematomal-edema progression remain incompletely understood. Recently, the role of spreading depolarizations in secondary brain injury was established in ischemic stroke, subarachnoid hemorrhage and traumatic brain injury patients. Its role in intracerebral hemorrhage patients and in particular the association with perihematomal-edema is not known. A total of 27 comatose intracerebral hemorrhage patients in whom hematoma evacuation and subdural electrocorticography was performed were studied prospectively. Hematoma evacuation and subdural strip electrode placement was performed within the first 24 h in 18 patients (67%). Electrocorticography recordings started 3 h after surgery (IQR, 3-5 h) and lasted 157 h (median) per patient and 4876 h in all 27 patients. In 18 patients (67%), a total of 650 spreading depolarizations were observed. Spreading depolarizations were more common in the initial days with a peak incidence on day 2. Median electrocorticography depression time was longer than previously reported (14.7 min, IQR, 9-22 min). Postoperative perihematomal-edema progression (85% of patients) was significantly associated with occurrence of isolated and clustered spreading depolarizations. Monitoring of spreading depolarizations may help to better understand pathophysiologic mechanisms of secondary insults after intracerebral hemorrhage. Whether they may serve as target in the treatment of intracerebral hemorrhage deserves further research.

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.

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.

Transient global amnesia after cerebral angiography still occurs: Case report and literature review.

Transient global amnesia is considered a very rare complication of diagnostic cerebral angiography, and has been reported only in a limited number of case reports more than 15 years ago. We describe a patient experiencing transient global amnesia following cerebral digital subtraction angiography. While the condition by definition is self-limiting, its differential diagnoses may cause severe morbidity and/or mortality if left untreated. It is therefore important to build and maintain awareness of transient global amnesia as a possible complication of cerebral angiography.