Mutations of complement factor I and potential mechanisms of neuroinflammation in acute hemorrhagic leukoencephalitis.

PURPOSE: Acute Hemorrhagic Leukoencephalitis (AHLE) is a rare demyelinating disorder of acute onset, rapid deterioration and significant morbidity and mortality. Most often described as a post-infectious complication of an upper respiratory illness, its precise pathophysiology remains unclear. We describe two pediatric patients with AHLE with partial complement factor I (FI) deficiency whose successful treatment included the interleukin-1 (IL-1) receptor antagonist, anakinra, implicating a role for FI and IL-1 in this disorder. METHODS: Extensive clinical workup of two patients presenting with AHLE revealed complement abnormalities, specifically related to the alternative pathway and its regulator, FI. Aggressive management with steroids, immunoglobulin, and anakinra ultimately led to improvement of clinical status and near return to neurologic baseline in both patients. Genetic sequencing of the FI coding regions of the patients and their families was performed. In vitro protein expression studies and immunohistochemistry of fixed brain tissue was used to investigate pathogenic mechanisms. RESULTS: Two novel mutations in FI were identified in our patients, which result in failure to secrete FI. Immunohistochemical evaluation of brain tissue demonstrated positive staining for C3, membrane attack complex (MAC) and IL-1. CONCLUSIONS: We propose AHLE is an unreported, rare phenotype for partial FI deficiency. The upregulation of C3, MAC and IL-1 with subsequent demyelination support a pathologic role for complement activation in AHLE, and suggest anakinra as an important adjunctive therapy in this disease.

Complications associated with prolonged hypertonic saline therapy in children with elevated intracranial pressure.

OBJECTIVES: Safe upper limits for therapeutic hypernatremia in the treatment of intracranial hypertension have not been well established. We investigated complications associated with hypernatremia in children who were treated with prolonged infusions of hypertonic saline. DESIGN: Retrospective chart analysis. SETTING: PICU in university-affiliated children's hospital. PATIENTS: All children from 2004 to 2009 requiring intracranial pressure monitoring (external ventricular drain or fiberoptic intraparenchymal monitor) for at least 4 days who were treated with hypertonic saline infusion for elevated intracranial pressure and did not meet exclusion criteria. INTERVENTION: Continuous hypertonic saline infusion on a sliding scale was used to achieve target sodium levels that would keep intracranial pressure less than 20 mm Hg once the conventional therapies failed. MEASUREMENTS AND MAIN RESULTS: Eighty-eight children met inclusion criteria. Etiologies of elevated intracranial pressure included trauma (n = 48), ischemic or hemorrhagic stroke (n = 20), infection (n = 8), acute disseminated encephalomyelitis (n = 5), neoplasm (n = 2), and others (n = 5). The mean peak serum sodium was 171.3 mEq/L (range, 150-202). The mean Glasgow Outcome Score was 2.8 (± 1.1) at time of discharge from the hospital. Overall mortality was 15.9%. Children with sustained (> 72 hr) serum sodium levels above 170 mEq/L had a significantly higher occurrence of thrombocytopenia (p < 0.001), renal failure (p < 0.001), neutropenia (p = 0.006), and acute respiratory distress syndrome (p = 0.029) after controlling for variables of age, gender, Pediatric Risk of Mortality score, duration of barbiturate-induced coma, duration of intracranial pressure monitoring, vasopressor requirements, and underlying pathology. Children with sustained serum sodium levels greater than 165 mEq/L had a significantly higher prevalence of anemia (p < 0.001). CONCLUSIONS: Children treated by continuous hypertonic saline infusion for intracranial hypertension whose serum sodium levels exceeded certain thresholds experienced significantly more events of acute renal failure, thrombocytopenia, neutropenia, anemia, and acute respiratory distress syndrome than those whose sodium level was maintained below these thresholds.

Recurrent coagulopathy with delayed significant bleeding after crotaline envenomation.

OBJECTIVES: Report of delayed significant coagulopathy, thrombocytopenia, and bleeding after Crotaline envenomation. METHODS: Recurrent coagulopathy and thrombocytopenia have been described after treatment of Crotaline envenomation with Crotalidae polyvalent immune Fab (CroFab). Until now, there have been no reports of significant spontaneous bleeding despite these abnormalities. RESULTS: Crotalidae polyvalent immune Fab has a relatively short half-life compared with previous antivenoms used to treat snake bite. This shorter half-life allows for recurrence of venom effects. Therefore, patients with Crotaline envenomation should undergo close monitoring for recurrence of coagulopathy or thrombocytopenia after treatment with CroFab. CONCLUSIONS: If coagulopathy or thrombocytopenia recurs, retreatment with CroFab should be considered to prevent significant bleeding.

Conventional and Unconventional Lifesaving Therapies in an Adolescent With Amlodipine Ingestion.

Amlodipine, a dihydropyridine calcium channel blocker, is commonly prescribed for the treatment of hypertension. Ingestion of an overdose leads to severe hypotension; if the hypotension is not treated, death may be imminent. Conventional and unconventional interventions were used to treat an adolescent who ingested a life-threatening dose of amlodipine. Severe hypotension resistant to conventional treatment with intralipids and hyperinsulinemia-euglycemia therapy led to the use of plasmapheresis and a pneumatic antishock garment as lifesaving measures. Plasmapheresis has been described in only one other case of severe amlodipine overdose, and the use of a pneumatic antishock garment has never been described in the management of a calcium channel blocker overdose. Because short-term use of a pneumatic antishock garment has associated risks, the critical care nurse's anticipation of side effects and promotion of safe use of the garment were instrumental in the patient's care and outcome. (Critical Care Nurse 2016; 36[4]:64-69).

Detection of traumatic brain injury with magnetic resonance imaging and S-100B protein in children, despite normal computed tomography of the brain.

OBJECTIVE: The objective of this study was to obtain data to further define the extent of traumatic brain injury by using S-100B protein and standard noncontrast magnetic resonance imaging with added fluid-attenuated inversion recovery (FLAIR) and gradient echo sequence in children with normal head computed tomography. DESIGN: Pilot, single cohort, prospective, clinical diagnostic study. SETTING: Pediatric intensive care and intermediate care unit in a tertiary care children's hospital. PATIENTS: Children ages 5-18 yrs who sustained traumatic brain injury, had a negative computed tomography of the brain, and were admitted to hospital were eligible for enrollment. INTERVENTIONS: Two blood samples were drawn for S-100B protein analysis: the first (t-1) as soon as possible or close to 6 hrs of injury and the second (t-2) close to 12 hrs from the time of injury. A magnetic resonance image of the brain was obtained within 96 hrs of injury. MEASUREMENTS AND MAIN RESULTS: Seven of 17 patients (41%) had positive magnetic resonance image. Of the seven patients with positive magnetic resonance image, 100% (seven of seven) had a positive magnetic resonance image with FLAIR sequence, 85% (six of seven) with axial T2 sequence and 50% (three of six) with gradient echo sequence. There was no statistically significant difference in S-100B protein concentrations in patients with a positive magnetic resonance image (n = 7) and those with a negative magnetic resonance image (n = 10; p =.40 at t-1 and p =.13 at t-2). The concentration of S-100B protein was statistically significantly higher in patients with head and other bodily injury (n = 9) compared with isolated head injury (n = 6; p =.018 at t-1 and p =.025 at t-2). Patients with a positive magnetic resonance image had a lower Glasgow Coma Scale score and longer duration of hospital stay. CONCLUSIONS: Magnetic resonance imaging seems to be a useful modality to better define the spectrum of brain injury in children with mild head trauma. The addition of S-100B protein measurement does not seem to be useful in this setting.

B-type natriuretic peptide: perioperative patterns in congenital heart disease.

OBJECTIVE: B-type natriuretic peptide (BNP) has diagnostic, prognostic, and therapeutic roles in adults with heart failure. BNP levels in children undergoing surgical repair of congenital heart disease (CHD) were characterized broadly, and distinguishable subgroup patterns delineated. DESIGN: Prospective, blinded, observational case series. SETTING: Academic, tertiary care, free-standing pediatric hospital. PATIENTS: Children with CHD; controls without cardiopulmonary disease. Interventions. None. MEASUREMENTS: Preoperative cardiac medications/doses, CHD lesion types, perioperative BNP levels, intraoperative variables (lengths of surgery, bypass, cross-clamp), postoperative outcomes (lengths of ventilation, hospitalization, open chest; averages of inotropic support, central venous pressure, perfusion, urine output; death, low cardiac output syndrome (LCOS), cardiac arrest; readmission; and discharge medications). RESULTS: Median BNP levels for 102 neonatal and non-neonatal controls were 27 and 7 pg/mL, respectively. Serial BNP measures from 105 patients undergoing CHD repair demonstrated a median postoperative peak at 12 hours. The median and interquartile postoperative 24-hour average BNP levels for neonates were 1506 (782-3784) pg/mL vs. 286 (169-578) pg/mL for non-neonates (P < 0.001). Postoperative BNP correlated with inotropic requirement, durations of open chest, ventilation, intensive care unit stay, and hospitalization (r = 0.33-0.65, all P < 0.001). Compared with biventricular CHD, Fontan palliations demonstrated lower postoperative BNP (median 150 vs. 306 pg/mL, P < 0.001), a 3-fold higher incidence of LCOS (P < 0.01), and longer length of hospitalization (median 6.0 vs. 4.5 days, P= 0.01). CONCLUSIONS: Perioperative BNP correlates to severity of illness and lengths of therapy in the CHD population, overall. Substantial variation in BNP across time as well as within and between CHD lesions limits its practical utility as an isolated point-of-care measure. BNP commonly peaks 6-12 hours postoperatively, but the timing and magnitude of BNP elevation demonstrates notable age-dependency, peaking earlier and rising an order of magnitude higher in neonates. In spite of higher clinical acuity, non-neonatal univentricular CHD paradoxically demonstrates lower BNP levels compared with biventricular physiologies.

Vasospasm in children with traumatic brain injury.

OBJECTIVE: To determine the incidence of vasospasm in children who have suffered moderate to severe traumatic brain injury. METHODS: A prospective observational pilot study in a 24-bed pediatric intensive care unit was performed. Twenty-two children aged 7 months to 14 years with moderate to severe traumatic brain injury as indicated by Glasgow Coma Score 120 cm/s were considered to have vasospasm by criterion A. If flow velocity in the MCA was >120 cm/s and the Lindegaard ratio was >3, vasospasm was considered to be present by criterion B. Patients with basilar artery (BA) flow velocity >90 cm/s met criteria for vasospasm in the posterior circulation (criterion C). RESULTS: In the MCA, 45.5% of patients developed vasospasm based on criterion A and 36.3% developed vasospasm based on criterion B. A total of 18.2% of patients developed vasospasm in the BA by criterion C. Typical day of onset of vasospasm was hospital day 2-3. Duration of vasospasm in the anterior circulation was 4 +/- 2 days based on criteria A and 3 +/- 1 days based on criteria B. Vasospasm in the posterior circulation persisted for 2 +/- 1 days. CONCLUSIONS: Using the adult criteria outlined above to diagnose vasospasm, a significant proportion of pediatric patients who have suffered moderate to severe traumatic brain injury develop vasospasm during the course of their treatment.