Correction: Modelling outcomes after paediatric brain injury with admission laboratory values: a machine-learning approach.

A correction to this paper has been published and can be accessed via a link at the top of the paper.

Modelling outcomes after paediatric brain injury with admission laboratory values: a machine-learning approach.

BACKGROUND: Severe traumatic brain injury (TBI) is a leading cause of mortality in children, but the accurate prediction of outcomes at the point of admission remains very challenging. Admission laboratory results are a promising potential source of prognostic data, but have not been widely explored in paediatric cohorts. Herein, we use machine-learning methods to analyse 14 different serum parameters together and develop a prognostic model to predict 6-month outcomes in children with severe TBI. METHODS: A retrospective review of patients admitted to Cambridge University Hospital's Paediatric Intensive Care Unit between 2009 and 2013 with a TBI. The data for 14 admission serum parameters were recorded. Logistic regression and a support vector machine (SVM) were trained with these data against dichotimised outcomes from the recorded 6-month Glasgow Outcome Scale. RESULTS: Ninety-four patients were identified. Admission levels of lactate, H+, and glucose were identified as being the most informative of 6-month outcomes. Four different models were produced. The SVM using just the three most informative parameters was the best able to predict favourable outcomes at 6 months (sensitivity = 80%, specificity = 99%). CONCLUSIONS: Our results demonstrate the potential for highly accurate outcome prediction after severe paediatric TBI using admission laboratory data.

Thresholds for identifying pathological intracranial pressure in paediatric traumatic brain injury.

Intracranial pressure (ICP) monitoring forms an integral part of the management of severe traumatic brain injury (TBI) in children. The prediction of elevated ICP from imaging is important when deciding on whether to implement invasive ICP monitoring for a patient. However, the radiological markers of pathologically elevated ICP have not been specifically validated in paediatric studies. Here in, we describe an objective, non-invasive, quantitative method of stratifying which patients are likely to require invasive monitoring. A retrospective review of patients admitted to Cambridge University Hospital's Paediatric Intensive Care Unit between January 2009 and December 2016 with a TBI requiring invasive neurosurgical monitoring was performed. Radiological biomarkers of TBI (basal cistern volume, ventricular volume, volume of extra-axial haematomas) from CT scans were measured and correlated with epochs of continuous high frequency variables of pressure monitoring around the time of imaging. 38 patients were identified. Basal cistern volume was found to correlate significantly with opening ICP (r = -0.53, p < 0.001). The optimal threshold of basal cistern volume for predicting high ICP ([Formula: see text]20 mmHg) was a relative volume of 0.0055 (sensitivity 79%, specificity 80%). Ventricular volume and extra-axial haematoma volume did not correlate significantly with opening ICP. Our results show that the features of pathologically elevated ICP in children may differ considerably from those validated in adults. The development of quantitative parameters can help to predict which patients would most benefit from invasive neurosurgical monitoring and we present a novel radiological threshold for this.

Radiological Correlates of Raised Intracranial Pressure in Children: A Review.

Radiological assessment of the head is a routine part of the management of traumatic brain injury. This assessment can help to determine the requirement for invasive intracranial pressure (ICP) monitoring. The radiological correlates of elevated ICP have been widely studied in adults but far fewer specific pediatric studies have been conducted. There is, however, growing evidence that there are important differences in the radiological presentations of elevated ICP between children and adults; a reflection of the anatomical and physiological differences, as well as a difference in the pathophysiology of brain injury in children. Here in, we review the radiological parameters that correspond with increased ICP in children that have been described in the literature. We then describe the future directions of this work and our recommendations in order to develop non-invasive and radiological markers of raised ICP in children.

Pre-hospital Predictors of Impaired ICP Trends in Continuous Monitoring of Paediatric Traumatic Brain Injury Patients.

OBJECTIVE: Although secondary insults such as raised intracranial pressure (ICP) or cardiovascular compromise strongly contribute to morbidity, a growing interest can be noticed in how the pre-hospital management can affect outcomes after traumatic brain injury (TBI). The objective of this study was to determine whether pre-hospital co-morbidity has influence on patterns of continuously measured waveforms of intracranial physiology after paediatric TBI. MATERIALS AND METHODS: Thirty-nine patients (mean age, 10 years; range, 0.5-15) admitted between 2002 and 2015 were used for the current analysis. Pre-hospital motor score, pupil reactivity, pre-hospital hypoxia (SpO2 < 90%) and hypotension (mean arterial pressure < 70 mmHg) were documented. ICP and arterial blood pressure (ABP) were monitored continuously with an intraparenchymal microtransducer and an indwelling arterial line. Pressure monitors were connected to bedside computers running ICM+ software. Pressure reactivity was determined as the moving correlation between 30 10-s averages of ABP and ICP (PRx). The mean ICP and PRx were calculated for the whole monitoring period for each patient. RESULTS: Those with pre-hospital hypotension were susceptible to higher ICP [20 (IQR 8) vs 13 (IQR 6) mmHg; p = 0.01] and more frequent ICP plateau waves [median = 0 (IQR 1), median = 4 (IQR 9); p = 0.001], despite having similar MAP, CPP and PRx during monitoring. Those with unreactive pupils tended to have higher ICP than those with reactive pupils (18 vs 14 mmHg, p = 0.08). Pre-hospital hypoxia, motor score and pupillary reactivity were not related to subsequent monitored intracranial or systemic physiology. CONCLUSION: In paediatric TBI, pre-hospital hypotension is associated with increased ICP in the intensive care unit.

Computed Tomography Indicators of Deranged Intracranial Physiology in Paediatric Traumatic Brain Injury.

OBJECTIVE: Computed tomography (CT) of the brain can allow rapid assessment of intracranial pathology after traumatic brain injury (TBI). Frequently in paediatric TBI, CT imaging can fail to display the classical features of severe brain injury with raised intracranial pressure. The objective of this study was to determine early CT brain features that influence intracranial or systemic physiological trends following paediatric TBI. MATERIALS AND METHODS: Thirty-three patients (mean age, 10 years; range, 0.5-16) admitted between 2002 and 2015 were used for the current analysis. Presence of petechial haemorrhages, basal cistern compression, subarachnoid blood, midline shift and extra-axial masses on the initial trauma CT head were assessed. ICP and arterial blood pressure (ABP) were then monitored continuously with an intraparenchymal microtransducer and an indwelling arterial line. Pressure monitors were connected to bedside computers running ICM+ software. Pressure reactivity was determined as the moving correlation between 30, 10-s averages of ABP and ICP (PRx). The mean ICP, ABP, cerebral perfusion pressure (CPP; ABP minus ICP) and PRx were calculated for the whole monitoring period for each patient. RESULTS: The presence of subarachnoid blood was related to higher ICP, higher ABP and a trend toward higher PRx. Smaller basal cisterns were related to increased ICP (R = -0.42, p = 0.02), impaired PRx (R = -0.5, p = 0.003). The presence of an extra-axial mass was associated with deranged PRx (-0.02 vs. 0.41, p = 0.003) and a trend toward higher ICP (14 vs. 40, p = 0.07). Interestingly the degree of midline shift was not related to ICP or PRx. CONCLUSIONS: The size of the basal cisterns, the presence of subarachnoid blood or an extra-axial mass are all related to disturbed ICP and pressure reactivity in this paediatric TBI cohort. Patients with these features are ideal candidates for invasive multimodal monitoring.

Continuous Multimodality Monitoring in Children after Traumatic Brain Injury-Preliminary Experience.

INTRODUCTION: Multimodality monitoring is regularly employed in adult traumatic brain injury (TBI) patients where it provides physiologic and therapeutic insight into this heterogeneous condition. Pediatric studies are less frequent. METHODS: An analysis of data collected prospectively from 12 pediatric TBI patients admitted to Addenbrooke's Hospital, Pediatric Intensive Care Unit (PICU) between August 2012 and December 2014 was performed. Patients' intracranial pressure (ICP), mean arterial pressure (MAP), and cerebral perfusion pressure (CPP) were monitored continuously using brain monitoring software ICM+®,) Pressure reactivity index (PRx) and 'Optimal CPP' (CPPopt) were calculated. Patient outcome was dichotomized into survivors and non-survivors. RESULTS: At 6 months 8/12 (66%) of the cohort survived the TBI. The median (±IQR) ICP was significantly lower in survivors 13.1±3.2 mm Hg compared to non-survivors 21.6±42.9 mm Hg (p = 0.003). The median time spent with ICP over 20 mm Hg was lower in survivors (9.7+9.8% vs 60.5+67.4% in non-survivors; p = 0.003). Although there was no evidence that CPP was different between survival groups, the time spent with a CPP close (within 10 mm Hg) to the optimal CPP was significantly longer in survivors (90.7±12.6%) compared with non-survivors (70.6±21.8%; p = 0.02). PRx provided significant outcome separation with median PRx in survivors being 0.02±0.19 compared to 0.39±0.62 in non-survivors (p = 0.02). CONCLUSION: Our observations provide evidence that multi-modality monitoring may be useful in pediatric TBI with ICP, deviation of CPP from CPPopt, and PRx correlating with patient outcome.

Diffuse cerebral vasospasm following resection of a hypoglossal schwannoma in a child.

Diffuse cerebral vasospasm is a rare complication following tumour resection. This phenomenon seems to be even rarer in the paediatric population and more so following resections of posterior fossa tumours. Here we report diffuse cerebral vasospasm in a child with hypoglossal nerve Schwannoma eight days following resection of the tumour.

Isolated hypoglossal schwannoma in a 9-year-old child.

The authors report a case of an isolated schwannoma of left hypoglossal nerve in a 9-year-old girl. To the authors' knowledge, this is the first case report of hypoglossal nerve schwannoma in the pediatric population in the absence of neurofibromatosis Type 2. The patient presented with a 2-month history of morning nausea and vomiting with occasional daytime headaches. Magnetic resonance imaging and subsequent CT scanning revealed a dumbbell tumor with a belly in the lower third of the posterior fossa and head underneath the left jugular foramen. Its neck protruded through an expanded hypoglossal canal. Although the lesion bore radiological characteristics of a hypoglossal schwannoma, the absence of hypoglossal palsy and the apparent lack of such tumors in the pediatric population the preoperative diagnosis was not certain. The tumor was approached via a midline suboccipital craniotomy, and gross-total resection was achieved. Pathological examination confirmed the diagnosis of schwannoma. Blood and tumor tests for mutations in the NF2 gene were negative. Postoperative mild hypoglossal palsy recovered by the 3-month follow-up, and an MRI study obtained at 1 year did not show recurrence.

Transient perioperative brainstem paralysis secondary to a local anesthetic.

Local anesthesia is widely used, in isolation or in conjunction with general anesthesia. The authors describe 2 adolescent patients presenting with absent brainstem reflexes and delayed awakening following elective foramen magnum decompression for Chiari Type I malformation. In both cases, neurological deficits were closely associated with the administration of a levobupivacaine field block following wound closure. In the absence of any structural or biochemical abnormalities, and with spontaneous recovery approximating the anesthetic half-life, the authors' observations are consistent with transient brainstem paralysis caused by perioperative local anesthetic infiltration.

Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial.

BACKGROUND: Spontaneous supratentorial intracerebral haemorrhage accounts for 20% of all stroke-related sudden neurological deficits, has the highest morbidity and mortality of all stroke, and the role of surgery remains controversial. We undertook a prospective randomised trial to compare early surgery with initial conservative treatment for patients with intracerebral haemorrhage. METHODS: A parallel-group trial design was used. Early surgery combined haematoma evacuation (within 24 h of randomisation) with medical treatment. Initial conservative treatment used medical treatment, although later evacuation was allowed if necessary. We used the eight-point Glasgow outcome scale obtained by postal questionnaires sent directly to patients at 6 months follow-up as the primary outcome measure. We divided the patients into good and poor prognosis groups on the basis of their clinical status at randomisation. For the good prognosis group, a favourable outcome was defined as good recovery or moderate disability on the Glasgow outcome scale. For the poor prognosis group, a favourable outcome also included the upper level of severe disability. Analysis was by intention to treat. FINDINGS: 1033 patients from 83 centres in 27 countries were randomised to early surgery (503) or initial conservative treatment (530). At 6 months, 51 patients were lost to follow-up, and 17 were alive with unknown status. Of 468 patients randomised to early surgery, 122 (26%) had a favourable outcome compared with 118 (24%) of 496 randomised to initial conservative treatment (odds ratio 0.89 [95% CI 0.66-1.19], p=0.414); absolute benefit 2.3% (-3.2 to 7.7), relative benefit 10% (-13 to 33). INTERPRETATION: Patients with spontaneous supratentorial intracerebral haemorrhage in neurosurgical units show no overall benefit from early surgery when compared with initial conservative treatment.

Reversible ischemia around intracerebral hemorrhage: a single-photon emission computerized tomography study.

OBJECT: A zone of perilesional ischemia has been demonstrated around intracerebral hemorrhage (ICH) in numerous experimental models and in human studies. There is potential for perfusion recovery in the zone of perilesional oligemia around ICH. The authors sought to demonstrate, quantify, and study the chronological evolution of perilesional ischemic change in ICH in humans by measuring cerebral blood flow. METHODS: Eleven patients with spontaneous supratentorial ICH underwent two technetium-99m hexamethylpropyleneamine oxime single-photon emission computerized tomography (SPECT) scanning, one in the acute stage (within days of ictus) and the other in the late stage (6-9 months postictus). All patients in this study were treated nonsurgically. Methods of SPECT data analysis based on count differences in regions of interest can be difficult to apply to images with large space-occupying lesions such as ICH, because of the distortion of intracranial anatomy, midline shift, and alterations in the three-dimensional (3D) characteristics of the lesion over time (that is, absorption of the hematoma on the later studies). The authors used the following method: the late and early images were registered and aligned to a common 3D orientation and were normalized to maximal counts. The late images were then compared voxel by voxel with the early ones. The region-growing algorithm was used to discern the difference between the two images, outlining voxels in the perihematoma region, with a signal improvement of at least 15% on the late image. Discrete brain regions around the hematoma with at least a 15% improvement in radiotracer uptake (and hence perfusion) in the late images were observed in all cases. The mean volume of brain with a greater than 15% improvement in perfusion between the two studies was 34.8 cm3 (range 7.2-71.3 cm3). These volumes represent regions of the brain that were poorly perfused in the initial studies. This may represent a zone of reversible perilesional oligemia (penumbra) in ICH in humans. CONCLUSIONS: This is the first study in which it is documented that some of the perilesional hypoperfused tissue around human ICH regains its perfusion in the long term, leading the authors to suggest that there may be a penumbra in human ICH. Medical or surgical therapeutic interventions could increase the volume of perilesional brain that recovers after the initial insult. The results of this study therefore support the concept that intervention in ICH has the potential to reduce the ultimate neurological deficit and improve outcome.

Comparative study of traumatic and spontaneous intracerebral hemorrhage.

OBJECT: Spontaneous intracerebral hemorrhage (SICH) and traumatic intracerebral hemorrhage (TICH) are common disorders. The authors planned to study how these two types of hemorrhage behave pathologically and clinically to gain further insight into their causes, pathogeneses, indications for surgical intervention, and prognoses. METHODS: Prospectively filled databases of demographic, clinical, radiological, and outcome details have been maintained for all patients admitted to the Regional Neurosciences Centre with head injury since 1987 and with SICH since 1993. Of the 5686 patients whose case information was included in the head-injury database, 90 were found to suffer from an isolated intracerebral hemorrhage (ICH) as the only major abnormality observed on computerized tomography scans (subdural and extradural hematomas were excluded). Case details on these 90 patients and the 440 patients from the SICH database were extracted and analyzed using a statistical software program. The median age of patients with TICH was lower than the median age of patients with SICH (51 years compared with 65 years, respectively), but it was much higher than the median age of the entire head-injury group (21 years). Among patients younger than 45 years of age, 0.8% of patients who experienced trauma suffered from an ICH compared with 4.3% of patients older than 45 years of age. Irrespective of intervention, much better outcomes were achieved by patients with TICH compared with those with SICH (67% favorable outcomes compared with 24% in patients with SICH). Following trauma, there was no significant relationship between the severity of injury and the development of ICH. At presentation the median Glasgow Coma Scale (GCS) score for both groups was 13. Younger age and higher GCS score at presentation were strongly related to a favorable outcome for both types of hemorrhage. There was no significant difference in patient age, presenting GCS score, or outcomes of patients who underwent surgery compared with those who did not for either type of hemorrhage. No conclusions can be drawn about the efficacy of surgery from such observational studies. CONCLUSIONS: On the basis of these data the authors suggest that TICH and SICH have different features: TICH affects a slightly younger age group and carries a much better prognosis compared with SICH. In addition, indications for surgical intervention are not well defined for either type of hemorrhage. Practice is subjective and inconsistent. The International Surgical Trial in Intracerebral Haemorrhage may resolve the dilemma for SICH. A similar trial in which surgery is compared with conservative management should be considered for cases of TICH.