A diffusion tensor imaging analysis of white matter microstructures in non-operated craniosynostosis patients.

PURPOSE: In 7 to 15-year-old operated syndromic craniosynostosis patients, we have shown the presence of microstructural anomalies in brain white matter by using DTI. To learn more about the cause of these anomalies, the aim of the study is to determine diffusivity values in white matter tracts in non-operated syndromic craniosynostosis patients aged 0-2 years compared to healthy controls. METHODS: DTI datasets of 51 non-operated patients with syndromic craniosynostosis with a median [IQR] age of 0.40 [0.25] years were compared with 17 control subjects with a median of 1.20 [0.85] years. Major white matter tract pathways were reconstructed with ExploreDTI from MRI brain datasets acquired on a 1.5 T MRI system. Eigenvalues of these tract data were examined, with subsequent assessment of the affected tracts. Having syndromic craniosynostosis (versus control), gender, age, frontal occipital horn ratio (FOHR), and tract volume were treated as independent variables. RESULTS: ʎ2 and ʎ3 of the tracts genu of the corpus callosum and the hippocampal segment of the cingulum bundle show a ƞ2 > 0.14 in the comparison of patients vs controls, which indicates a large effect on radial diffusivity. Subsequent linear regressions on radial diffusivity of these tracts show that age and FOHR are significantly associated interacting factors on radial diffusivity (p < 0.025). CONCLUSION: Syndromic craniosynostosis shows not to be a significant factor influencing the major white matter tracts. Enlargement of the ventricles show to be a significant factor on radial diffusivity in the tracts corpus callosum genu and the hippocampal segment of the cingulate bundle. CLINICAL TRIAL REGISTRATION: MEC-2014-461.

Neurological deficits are present in syndromic craniosynostosis patients with and without tonsillar herniation.

BACKGROUND: Children with syndromic craniosynostosis (sCS) have a higher incidence of cerebellar tonsillar herniation (TH) than the general population. In the general population, TH ≥ 5 mm below the foramen magnum is associated with typical neurological deficits but, in sCS, we do not know whether this degree of TH is required before such deficits occur. OBJECTIVE: This prospective cohort study aimed to determine the association between findings on neurological assessment and cerebellar tonsillar position. METHODS: Magnetic resonance imaging (MRI) was used to determine TH ≥ 5 mm and the presence of syringomyelia. In regard to the outcome of neurological deficits, these were categorized according to: A, cerebellar function; B, cranial nerve abnormalities; and C, sensory or motor dysfunction. RESULTS: Twenty of 63 patients with sCS (32% [95% confidence interval 21-45%]) had TH ≥ 5 mm and/or syringomyelia. There was no significant difference in proportion between individual forms of sCS: 16/34 Crouzon, 2/11 Muenke, 2/12 Apert, and 0/7 Saethre-Chotzen patients. Neurological deficits were prevalent (73% [95% confidence interval 60-83%]), and as frequent in patients with TH ≥ 5 mm and/or syringomyelia as those without. Surgery occurred in 3 patients overall, and only in Crouzon patients. CONCLUSION: Determining the effect of TH ≥ 5 mm on neurologic functioning in sCS patients is used to better determine when surgical intervention is warranted. However, we have found that neurological deficits are prevalent in sCS patients, irrespective of cerebellar tonsillar position, suggesting that such findings are developmental and, in part, syndrome-specific central nervous system features.

Factors associated with treatment delays in pediatric refractory convulsive status epilepticus.

OBJECTIVE: To identify factors associated with treatment delays in pediatric patients with convulsive refractory status epilepticus (rSE). METHODS: This prospective, observational study was performed from June 2011 to March 2017 on pediatric patients (1 month to 21 years of age) with rSE. We evaluated potential factors associated with increased treatment delays in a Cox proportional hazards model. RESULTS: We studied 219 patients (53% males) with a median (25th-75th percentiles [p25-p75]) age of 3.9 (1.2-9.5) years in whom rSE started out of hospital (141 [64.4%]) or in hospital (78 [35.6%]). The median (p25-p75) time from seizure onset to treatment was 16 (5-45) minutes to first benzodiazepine (BZD), 63 (33-146) minutes to first non-BZD antiepileptic drug (AED), and 170 (107-539) minutes to first continuous infusion. Factors associated with more delays to administration of the first BZD were intermittent rSE (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.14-2.09; p = 0.0467) and out-of-hospital rSE onset (HR 1.5, 95% CI 1.11-2.04; p = 0.0467). Factors associated with more delays to administration of the first non-BZD AED were intermittent rSE (HR 1.78, 95% CI 1.32-2.4; p = 0.001) and out-of-hospital rSE onset (HR 2.25, 95% CI 1.67-3.02; p < 0.0001). None of the studied factors were associated with a delayed administration of continuous infusion. CONCLUSION: Intermittent rSE and out-of-hospital rSE onset are independently associated with longer delays to administration of the first BZD and the first non-BZD AED in pediatric rSE. These factors identify potential targets for intervention to reduce time to treatment.

Abnormal transcranial Doppler cerebral blood flow velocity and blood pressure profiles in children with syndromic craniosynostosis and papilledema.

OBJECTIVE: Children with syndromic craniosynostosis are at risk of intracranial hypertension. This study aims to examine patient profiles of transcranial Doppler (TCD) cerebral blood flow velocity (CBFv) and systemic blood pressure (BP) in subjects with and without papilledema at the time of surgery, and subsequent effect of cranial vault expansion. METHODS: Prospective study of patients treated at a national referral center. Patients underwent TCD of the middle cerebral artery 1 day before and 3 weeks after surgery. Measurements included mean CBFv, peak systolic velocity, and end diastolic velocity; age-corrected resistive index (RI) was calculated. Systemic BP was recorded. Papilledema was used to indicate intracranial hypertension. RESULTS: Twelve patients (mean age 3.1 years, range 0.4-9.5) underwent TCD; 6 subjects had papilledema. Pre-operatively, patients with papilledema, in comparison to those without, had higher TCD values, RI, and BP (all p = 0.04); post-operatively, the distinction regarding BP remained (p = 0.04). There is a significant effect of time following vault surgery with a decrease in RI (p < 0.01). CONCLUSION: Patients with syndromic craniosynostosis who have papilledema have a different TCD profile with raised BP. Vault surgery results in increased CBFv and decrease in RI, however the associated systemic BP response to intracranial hypertension remained at short-term follow-up.

Observational study of children admitted to United Kingdom and Republic of Ireland Paediatric Intensive Care Units after out-of-hospital cardiac arrest.

AIMS: To estimate the prevalence of children admitted after out-of-hospital cardiac arrest (OHCA) to UK and Republic of Ireland (RoI) Paediatric Intensive Care Units (PICUs) and factors associated with mortality to inform future clinical trial feasibility. METHOD: Observational study using a prospectively collected dataset of the Paediatric Intensive Care Audit Network (PICANet) of 33 UK and RoI PICUs (January 2003 to June 2010). Cases (0 to <16 years), with documented OHCA surviving to PICU admission and requiring mechanical ventilation were included. Main outcomes were prevalence for admission and death within PICU. Factors associated with mortality were examined with multiple logistic regression analysis. RESULTS: 827 of 111,170 admissions (0.73%; 95% CI [0.48 to 0.98%]) were identified as children admitted following OHCA. PICU mortality for OHCA was 50.5% (418/827). Recruitment into an adequately sized clinical trial would not be feasible with the current prevalence rate. Characteristics at PICU admission associated with increased risk of death included; bilateral unreactive pupils, genetically inherited condition, inter-hospital transfer to PICU, requirement for vasoactive drugs and greater base deficit. Factors associated with reduced risk of death were submersion or a respiratory aetiology and pre-existing respiratory or cardiac conditions. CONCLUSIONS: Less than 120 children a year are admitted to PICUs in the UK and RoI after OHCA, limiting options for conducting UK intervention trials. The risk factors associated with mortality identified in this study will allow risk stratification in future studies.

Intramuscular midazolam versus intravenous diazepam for treatment of seizures in the pediatric emergency department: a randomized clinical trial.

AIM: To compare the therapeutic efficacy of intramuscular midazolam (MDZ-IM) with that of intravenous diazepam (DZP-IV) for seizures in children. DESIGN: Randomized clinical trial. SETTING: Pediatric emergency department. PATIENTS: Children aged 2 months to 14 years admitted to the study facility with seizures. INTERVENTION: Patients were randomized to receive DZP-IV or MDZ-IM. MAIN MEASUREMENTS: Groups were compared with respect to time to treatment start (min), time from drug administration to seizure cessation (min), time to seizure cessation (min), and rate of treatment failure. Treatment was considered successful when seizure cessation was achieved within 5min of drug administration. RESULTS: Overall, 32 children (16 per group) completed the study. Intravenous access could not be obtained within 5min in four patients (25%) in the DZP-IV group. Time from admission to active treatment and time to seizure cessation was shorter in the MDZ-IM group (2.8 versus 7.4min; p<0.001 and 7.3 versus 10.6min; p=0.006, respectively). In two children per group (12.5%), seizures continued after 10min of treatment, and additional medications were required. There were no between-group differences in physiological parameters or adverse events (p=0.171); one child (6.3%) developed hypotension in the MDZ-IM group and five (31%) developed hyperactivity or vomiting in the DZP-IV group. CONCLUSION: Given its efficacy and ease and speed of administration, intramuscular midazolam is an excellent option for treatment of childhood seizures, enabling earlier treatment and shortening overall seizure duration. There were no differences in complications when applying MDZ-IM or DZP-IV.

Emergency management of children with severe sepsis in the United Kingdom: the results of the Paediatric Intensive Care Society sepsis audit.

OBJECTIVE: To audit current UK practice of the management of severe sepsis in children against the 2002 American College of Critical Care Medicine/Pediatric Advanced Life Support (ACCM-PALS) guideline. DESIGN: Prospective observational study. SETTING: 17 UK paediatric intensive care units (PICUs) and two UK PICU transport services. PARTICIPANTS: 200 children accepted for PICU admission within 12 h of arrival in hospital, whether or not successfully transported to a PICU, with a discharge diagnosis of sepsis or suspected sepsis. MAIN OUTCOME MEASURES: Medical interventions, physiological and laboratory data to determine the presence or absence of shock, inter-hospital transfer times, predicted mortality (using the Paediatric Index of Mortality, version 2 (PIM2) scoring system) and observed mortality. RESULTS: 34/200 (17%) children died following referral. Although children defined as being in shock received significantly more fluid (p<0.001) than those who were not in shock, overall fluid and inotrope management suggested by the 2002 ACCM-PALS guideline was not followed in 62% of shocked children. Binary logistic regression analysis demonstrated that the odds ratio for death, if shock was present at PICU admission, was 3.8 (95% CI 1.4 to 10.2, p = 0.008). CONCLUSIONS: The presence of shock at PICU admission is associated with an increased risk of death. Despite clear consensus guidelines for the emergency management of children with severe sepsis and septic shock, most children received inadequate fluid resuscitation and inotropic support in the crucial few hours following presentation.

Epidemiology of critically ill children in England and Wales: incidence, mortality, deprivation and ethnicity.

OBJECTIVE: The purpose of this work was to investigate the incidence rate for admission and mortality of children receiving paediatric intensive care in relation to socioeconomic status and ethnicity in England and Wales. DESIGN: National cohort of sequential hospital admissions. SETTING: Twenty nine paediatric intensive care units in England and Wales. PARTICIPANTS: All children aged under 16 years admitted to paediatric intensive care in the 4 years 2004-2007. MAIN OUTCOME MEASURES: Incidence rates for admission and odds ratios (OR) for risk-adjusted mortality by an area based measure of deprivation (Townsend score) and ethnic group (south Asian vs non-south Asian determined using two-name analysis algorithms). RESULTS: The incidence for south Asian children was higher than that of non-south Asian children (138 vs 95/100,000, incidence rate ratio 1.36, 95% CI 1.32 to 1.40). The age-sex standardised incidence for children admitted to paediatric intensive care ranged from 69/100,000 in the least deprived fifth of the population to 124/100,000 in the most deprived fifth. The risk-adjusted OR for mortality for south Asian children was 1.36 (95% CI 1.18 to 1.57) overall, rising to 2.40 (95% CI 1.40 to 4.10) in the least deprived fifth of the population when a statistical interaction term for deprivation was included. CONCLUSIONS: In England and Wales, the admission rate to paediatric intensive care is higher for children from more deprived areas and 36% higher for children from the south Asian population. Risk-adjusted mortality increases in south Asian children as deprivation decreases.

Severe head injury in children: emergency access to neurosurgery in the United Kingdom.

OBJECTIVE: To determine the scale of acute neurosurgery for severe traumatic brain injury (TBI) in childhood, and whether surgical evacuation for haematoma is achieved within four hours of presentation to an emergency department. METHODS: A 12 month audit of emergency access to all specialist neurosurgical and intensive care services in the UK. Severe TBI in a child was defined as that necessitating admission to intensive care. RESULTS: Of 448 children with severe head injuries, 91 (20.3%) underwent emergency neurosurgery, and 37% of these surgical patients had at least one non-reactive and dilated pupil. An acute subdural or epidural haematoma was present in 143/448 (31.9%) children, of whom 66 (46.2%) underwent surgery. Children needing surgical evacuation of haematoma were at a median distance of 29 km (interquartile range (IQR) 11.8-45.7) from their neurosurgical centre. One in four children took longer than one hour to reach hospital after injury. Once in an accident and emergency department, 41% took longer than fours hours to arrive at the regional centre. The median interval between time of accident and arrival at the surgical centre was 4.5 hours (IQR 2.23-7.73), and 79% of inter-hospital transfers were undertaken by the referring hospital rather than the regional centre. In cases where the regional centre undertook the transfer, none were completed within four hours of presentation-the median interval was 6.3 hours (IQR 5.1-8.12). CONCLUSIONS: The system of care for severely head injured children in the UK does not achieve surgical evacuation of a significant haematoma within four hours. The recommendation to use specialist regional paediatric transfer teams delays rather than expedites the emergency service.

Standards for head injury management in acute hospitals: evidence from the six million population of the Eastern region.

OBJECTIVES: To develop standards of care for head injury and thereby identify and prioritize areas of the service needing development; to report the findings from a survey of compliance with such standards in the Eastern region of UK. METHODS: The standards were collaboratively developed through an inclusive and iterative process of regional surveys, multidisciplinary conferences, and working groups, following a method similar to that used by the Society of British Neurological Surgeons. The standards cover seven topics relating to all aspects of service delivery, with standards within each objective. Each standard has been designated a priority level (A, B, or C). The standards were piloted using a self-assessment questionnaire, completed by all 20 hospitals of the Eastern region. RESULTS: Full compliance was 36% and a further 30% of standards were partially met across the region, with some areas of service delivery better than others. Seventy eight per cent of level A standards were either fully or partially met. Results were better in the north of the region compared with the south. CONCLUSION: A survey of compliance with the head injury standards indicate that, with their whole systems approach and subject to further refinement, they are a useful method for identifying deficiencies in service provision and monitoring for quality of care both within organisations and regionally.

Epidemiology of traumatic brain injury in children receiving intensive care in the UK.

AIMS: To describe the epidemiology of children with traumatic brain injury (TBI) admitted to paediatric intensive care units (PICUs) in the UK. METHODS: Prospective collection of clinical and demographic information from paediatric and adult intensive care units in the UK and Eire between February 2001 and August 2003. RESULTS: The UK prevalence rate for children (0-14 years) admitted to intensive care with TBI between February 2001 and August 2003 was 5.6 per 100,000 population per year (95% Poisson exact confidence intervals 5.17 to 6.05). Children admitted to PICUs with TBI were more deprived than the population as a whole (mean Townsend score for TBI admissions 1.19 v 0). The commonest mechanism of injury was a pedestrian accident (36%), most often occurring in children over 10. There was a significant summer peak in admissions in children under 10 years. Time of injury peaked in the late afternoon and early evening, a pattern that remained constant across the days of the week. Injuries involving motor vehicles have the highest mortality rates (23% of vehicle occupants, 12% of pedestrians) compared with cyclists (8%) and falls (3%). In two thirds of admissions (65%) TBI was an isolated injury. CONCLUSIONS: TBI in children requiring intensive care is more common in those from poorer backgrounds who have been involved in accidents as pedestrians. The summer peak in injury occurrence for 0-10 year olds and late afternoon timing give clear targets for community based injury prevention.

Which paediatric head injured patients might benefit from decompression? Thresholds of ICP and CPP in the first six hours.

Severe head injury in childhood continues to be associated with considerable mortality and morbidity. Early surgical decompression may be beneficial and the objective of this study was to examine the relationship between age-related thresholds of mean intracranial pressure (ICP) and cerebral perfusion pressure (CPP) over the first 6 hours and age outcome in paediatric head injury patients. A total of 209 head injured children admitted to five UK hospitals were studied. Patients aged 2 to 16 years were included if they had a minimum of six hours of invasive pressure monitoring. Mean values of ICP and CPP over this period were calculated and compared to those with independent (good recovery and moderate disability) and poor outcome (severe disability, and death) for different age groups. There were 148 children with independent outcome (92 good recovery, 56 moderately disabled), and 61 with poor outcome (30 severely disabled, 31 deaths). There was a significant difference between those with independent compared to poor outcome in relation to ICP (p < 0.001) and CPP (p < 0.001). Patients were divided into three groups according to age. The sensitivity of ICP and CPP in predicting outcome was similar for all groups but the specificity differed between groups. At a CPP of 50 mmHg the specificity varied between the age groups (2 to 6 years: 0.47, 7 to 10 years: 0.28 and 11 to 16 years: 0.10) and similarly for an ICP of 25 mmHg (2 to 6 years: 0.53, 7 to 10 years: 0.44 and 11 to 16 years: 0.38). Younger children may be able to tolerate lower perfusion pressures and still have an independent outcome. Our threshold values for young children are likely to be important in the identification of patients who might benefit from new treatments such as surgical decompression.

Age-related differences in intracranial pressure and cerebral perfusion pressure in the first 6 hours of monitoring after children's head injury: association with outcome.

OBJECTIVES: Severe head injury in childhood is associated with considerable mortality and morbidity. In this study we determined age-related differences in the relationship between outcome and intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in the first 6 h of monitoring in a large cohort of head-injured children. METHODS: Two hundred and thirty-five head-injured children (admitted to five UK hospitals over a 15-year period) in whom intracranial pressure monitoring was clinically indicated were studied. RESULTS: Patients were divided into three age groups (2-6, 7-10 and 11-16 years). The sensitivity of ICP and CPP were similar. Differences were found in the specificity of ICP and CPP for each group and these were more marked for CPP. For a specificity of 50% the pressures were 53, 63 and 66 mmHg for the three age groups. CONCLUSIONS: There are age-related differences in the specificity of intracranial pressure and cerebral perfusion pressure in relation to outcome. These differences may be important in the clinical management of head-injured children. Thus cerebral perfusion pressures of 53, 63 and 66 mmHg should be the minimum to strive for in these three age groups respectively.

Violence is not necessary to produce subdural and retinal haemorrhage: a reply to Punt et al.

In this article we reply to the recent critique by Punt et al. in Pediatric Rehabilitation. Our hypothesis about the pathogenesis of intracranial bleeding in infants has three important implications. First, in the case of an infant with a swollen brain, subdural and retinal haemorrhage but no objective evidence of trauma, the findings by themselves are not certain evidence of abuse; second, violence is not necessary to produce subdural and retinal haemorrhage; and lastly, non-traumatic events producing apnoea with a catastrophic rise in intracranial pressure could produce a clinical picture identical to that seen in trauma.

Severe head injury in children: geographical range of an emergency neurosurgical practice.

OBJECTIVE: To determine the timings of regional transfer for emergency neurosurgery and intensive care after severe head injury in children, and the effective operational range of a regional service. DESIGN: Prospective observational study of admissions to a regional paediatric intensive care unit (PICU). SETTING: East Anglia region in England, January 2000 to December 2001, where 18 referring hospitals are within two hours road transit time from the centre. PATIENTS: 69 severely head injured children (52 boys and 17 girls, aged 8.4 (3.6 to 12.5) years). MAIN OUTCOME MEASURES: Time interval between injury and arrival at first hospital (primary transfer); timing between arrival at first hospital and arrival in PICU or the operating theatre (secondary transfer). RESULTS: Arrival in one of the 19 accident and emergency departments occurred (median, IQR) within 48 (35 to 70) minutes of the accident. After arrival, the interval of secondary transfer was 4.4 (3.2 to 5.8) hours. Children rarely received their surgery within four hours of injury; for this to occur, the geographical range of this regional practice would need to be restricted to those hospitals within about 45 minute road transit time from the centre. CONCLUSIONS: Good evidence supporting the recommendation that acute neurosurgery for the evacuation of a haematoma within four hours of injury is still scarce. The timings of care after an accident suggest that this guideline is unworkable in regions covering areas with road distance travel times in excess of 45 minutes.

ESPE/LWPES consensus statement on diabetic ketoacidosis in children and adolescents.

Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes mellitus (TIDM). Mortality is predominantly related to the occurrence of cerebral oedema; only a minority of deaths in DKA are attributed to other causes. Cerebral oedema occurs in about 0.3-1% of all episodes of DKA, and its aetiology, pathophysiology, and ideal method of treatment are poorly understood. There is debate as to whether physicians treating DKA can prevent or predict the occurrence of cerebral oedema, and the appropriate site(s) for children with DKA to be managed. There is agreement that prevention of DKA and reduction of its incidence should be a goal in managing children with diabetes.