Matthew R. Garnett

Stereotactic biopsy of diffuse pontine lesions in children

OBJECT Empirical radiotherapy is the current treatment for children with diffuse pontine lesions that have imaging characteristics of an infiltrative malignant astrocytoma. The use of chemotherapeutic agents is, however, currently under investigation in the treatment of these tumors. To be included into a trial, patients need a definitive histological diagnosis. The authors present their prospective study of the stereotactic biopsy of these lesions during a 4-year period. METHODS A suboccipital, transcerebellar approach was used to obtain biopsy samples in 24 children. RESULTS Two patients suffered deficits. Both had a transient (< 2 months) new cranial nerve palsy; one of these patients also experienced an exacerbation of a preoperative hemiparesis. No patient died during the perioperative period. A histological diagnosis was made in all 24 patients as follows: 22 had a malignant infiltrative astrocytoma, one had a low-grade astrocytoma, and one had a pilocytic astrocytoma. The diagnosis of the latter two patients affected the initial treatment after the biopsy. CONCLUSIONS The findings of this study imply that stereotactic biopsy sampling of a diffuse pontine tumor is a safe procedure, is associated with minimal morbidity, and has a high diagnostic yield. A nonmalignant tumor was identified in two of the 24 patients in whom the imaging findings were characteristic of a malignant infiltrative astrocytoma. With the advent of new treatment protocols, stereotactic biopsy sampling, which would allow specific tumor characterization of diffuse pontine lesions, may become standard.

Changes in elemental concentrations are associated with early stages of apoptosis in human monocyte-macrophages exposed to oxidized low-density lipoprotein: an X-ray microanalytical study.

This study examines ion homeostasis in monocyte–macrophages committed to death by apoptosis. X‐ray microanalysis has been used to demonstrate that intracellular concentrations of potassium decreased whilst those of sodium increased following 3 h of exposure to 100 µg/ml of oxidized low‐density lipoprotein (LDL) in vitro. In contrast, the maximal incidence of cell death, as determined by the inability to exclude trypan blue, was not seen until 24 h of exposure. At 12 h, less than 1 per cent of cells were stained using terminal transferase‐mediated DNA nick‐end labelling, which is generally accepted as a marker of late stages in the apoptotic pathway. This is the first demonstration of early perturbations of ion homeostasis in monocyte–macrophages exposed to concentrations of oxidized LDL known to cause apoptosis. Copyright

Cerebral localization of Rosai–Dorfman disease in a child

Rosai-Dorfman disease (RDD) is a rare idiopathic histiocytic disorder that only occasionally involves the central nervous system (CNS). Previous cases of RDD involving the CNS were generally seen in adults. Pediatric cases of RDD are rare, and the disease in these cases typically has an indolent clinical course. In this report, the authors describe a pediatric case of intracranial RDD with rapid clinical and radiological progression. A previously healthy 13-year-old girl presented with a 15-day history of progressive left-sided headaches, vomiting, and fever. On examination she was pyrexial but otherwise normal. Neuroimaging results demonstrated an extraaxial left frontal lesion with peripheral enhancement. A bur hole was drilled over the lesion to obtain a tissue sample and de-bulk the lesion. The initial histological results showed a nonspecific inflammatory lesion. Postoperatively, the patient was asymptomatic, and neuroimaging results confirmed a significant reduction in the size of the lesion. Repeated neuroimaging 3 months later, however, revealed a large recurrence of the lesion, which was removed macroscopically by a craniotomy. Histological analysis of the tissue confirmed the RDD diagnosis. At the latest follow-up (12 months) the patient had remained asymptomatic with no evidence of recurrence on neuroimaging. This is the first reported case of intracranial RDD with an aggressive clinical course.

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.

Cerebral critical closing pressure in hydrocephalus patients undertaking infusion tests

Abstract Objectives: Links between cerebrospinal fluid (CSF) compensation and cerebral blood flow (CBF) have been studied in many clinical scenarios. In hydrocephalus, disturbed CSF circulation seems to be a primary problem, having been linked to CBF disturbances, particularly in white matter close to surface of dilated ventricles. We studied possible correlations between cerebral haemodynamic indices using transcranial Doppler (TCD) ultrasonography and CSF compensatory dynamics assessed during infusion tests. Methods: We analysed clinical data from infusion tests performed in 34 patients suspected to suffer from normal pressure hydrocephalus, with signals including intracranial pressure (ICP), arterial blood pressure (ABP) and TCD blood flow velocity (FV). Cerebrospinal fluid compensatory parameters (including elasticity) were calculated according to a hydrodynamic model of the CSF circulation. Critical closing pressure (CrCP) was calculated with the cerebrovascular impedance methodology, while wall tension (WT) was estimated as CrCP-ICP. Closing margin (CM) was expressed as the difference between ABP and CrCP. Results: Intracranial pressure increased during infusion from 6.7 ± 4.6 to 25.0 ± 10.5 mmHg (mean ± SD; P < 0.001), resulting in CrCP rising by 22.9% (P < 0.001) and WT decreasing by 11.3% (P = 0.005). Closing margin showed a tendency to decrease, albeit not significantly (P = 0.070) due to rising ABP (9.1%; P = 0.005). Closing margin at baseline ICP was inversely correlated to brain elasticity (R = (0.358; P = 0.038), while being significantly different from zero for the whole duration of the tests (52.8 ± 22.8 mmHg; P < 0.001). Neither CrCP nor WT was correlated with CSF compensatory parameters. Discussion: Critical closing pressure increases and WT decreases during infusion tests. Closing margin at baseline pressure may act as an indicator of the cerebrospinal compensatory reserve.

Giant intracranial hemangioma in a neonate

In this report we detail the case of an infant presenting with a giant intracranial congenital hemangioma and describe the clinical features and surgical management. Congenital hemangiomas are benign vascular tumors that typically present as skin lesions in neonates and infants. On rare occasions they present as intracranial tumors. The possibility that these tumors may undergo spontaneous regression poses a treatment dilemma.

The management of birth-related posterior fossa hematomas in neonates.

BACKGROUND Symptomatic posterior fossa hematoma in the term newborn is rare. OBJECTIVE To report on the management and outcome of posterior fossa subdural hematoma (PFSDH) in neonates. METHODS A retrospective analysis of the department database and clinical notes of neonates admitted since 1985 with a PFSDH was performed together with a literature review of similar case series. RESULTS Sixteen patients were included. The median gestational age was 40 weeks with a high proportion of primiparous mothers (n = 9) and forceps delivery (n = 9). Nine neonates had symptoms of brainstem dysfunction within the first 24 hours of life, whereas the other 7 had a delayed presentation (median 4 days) with signs of raised intracranial pressure due to hydrocephalus. Each patient had a cranial ultrasound followed by computed tomography scan that showed the PFSDH. Eleven neonates required surgical evacuation of the PFSDH, whereas hydrocephalus was managed by transient external ventricular drainage in 2 further patients. Eventually, 2 neonates required a permanent ventriculoperitoneal shunt. Five neonates had no operative intervention. With a mean follow-up of 7.8 years, 2 patients had mild developmental delay and 1 had severe developmental delay. The 13 other patients had a normal development. CONCLUSION In neonates with a PFSDH, surgery can be safely performed in those who have clinical and radiological signs of brainstem compression or hydrocephalus. A small number of neonates require a ventriculoperitoneal shunt in the long term. Initial aggressive resuscitation should be performed even in cases of initial severe brainstem dysfunction because of the good long-term neurological outcome.

The application of adult traumatic brain injury models in a pediatric cohort.

OBJECTIVE There is increasing interest in the use of predictive models of outcome in adult head injury. Two international models have been identified to be reliable modalities for predicting outcome: the Corticosteroid Randomisation After Significant Head Injury (CRASH) model, and the International Mission on Prognosis and Analysis of randomized Controlled Trials in TBI (IMPACT) model. However, these models are designed only to identify outcomes in adult populations. METHODS A retrospective analysis was performed on pediatric patients with severe traumatic brain injury (TBI) admitted to the pediatric intensive care unit (PICU) of Addenbrookes Hospital between January 2009 and December 2013. The individual risk of 14-day mortality was calculated using the CRASH-Basic and -CT models, and the risk of 6-month mortality calculated using the IMPACT-Core and -Extended (including CT findings) models. Model accuracy was determined by standardized mortality ratio (SMtR; observed/expected deaths), discrimination was evaluated as the area under the receiver operating curve (AUROC), and calibration assessed using the Hosmer-Lemeshow χ2 test. RESULTS Ninety-four patients with an average age of 7.3 years were admitted to the PICU with a TBI. The mortality rate was 12.7% at 14 days and at 6 months. For the CRASH-Basic model, the SMtR was 1.42 and both calibration (χ2 = 6.1, p = 0.64) and discrimination (AUROC = 0.92) were good. For the IMPACT-Core model, the SMtR was 1.03 and the model was also well calibrated (χ2 = 8.99, p = 0.34) and had good discrimination (AUROC = 0.85). Poor outcome was observed in 17% of the cohort and identified with the CRASH-Basic and IMPACT-Core models to varying degrees: standardized morbidity ratio = 0.89 vs 0.67, respectively; calibration = 6.5 (χ2) and 0.59 (p value) versus 8.52 (χ2) and 0.38 (p value), respectively; and discrimination (AUROC) = 0.92 versus 0.83, respectively. CONCLUSIONS Adult head injury models may be applied with sufficient accuracy to identify predictors of morbidity and mortality in pediatric TBI.

Phase-shift between arterial flow and ICP pulse during infusion test.

BackgroundThe dynamic relationship between pulse waveform of intracranial pressure (ICP) and transcranial Doppler (TCD) cerebral blood flow velocity (CBFV) may contain information about cerebrospinal compliance. This study investigated the possibility by focusing on the phase shift between fundamental harmonics of CBFV and ICP.MethodsThirty-seven normal pressure hydrocephalus patients (20 men, mean age 58) underwent the cerebrospinal fluid (CSF) infusion tests. The infusion was performed via pre-implanted Ommaya reservoir. The TCD FV was recorded in the middle cerebral artery. Resulting continuous ICP and pressure-volume (PV) signals were analyzed by ICM+ software.ResultsIn initial stage of the CSF infusion, the phase shift was negative (median value = −11°, range = +60 to −117). There was significant inverse association of phase shift with brain elasticity (R = −0.51; p = 0.0009). In all tests, phase shift consistently decreased during gradual elevation of ICP (p = 0.00001). Magnitude of decrease in phase shift was inversely related to the peak-to-peak amplitude of ICP pulse waveform at a baseline (R = −0.51; p = 0.001).ConclusionsPhase shift between fundamental harmonics of ICP and TCD waveforms decreases during elevation of ICP. This is caused by an increase of time delay between systolic peak of flow velocity wave and ICP pulse.

Neuro-critical care: A valuable placement during foundation and early neurosurgical training

Abstract Introduction. Neurosciences critical care units (NCCUs) present a unique opportunity to junior trainees in neurosurgery as well as foundation trainees looking to gain experience in the management of critically ill patients with neurological conditions. Placements in NCCUs are undertaken in the early years of neurosurgical training or during neurosciences themed foundation programmes. We sought to quantify the educational benefits of such placements from the trainee perspective. Methods. Thirty-two trainees who had undertaken placements at Foundation Year 2 (FY2) to Specialty Trainee Year 3 (ST3) level between August 2009 and April 2013 were invited to take part in an online questionnaire survey. Competence in individual skills was self-rated on a ranked scale from one (never observed) to five (performed unsupervised) both before and after the placement. Trainees were also asked a series of questions pertaining to their ability to manage common neurosurgical conditions, as well as the perceived educational rigour of their placement. Results. Twenty-three responses were received. Eighteen responses were from FY2s and seven were from ST1–3 level trainees. Following their placements, 100% of respondents felt better equipped to deal with neurosurgical and neurological emergencies and cranial trauma. Most felt better equipped to manage hydrocephalus (95.7%), polytrauma patients (95.7%), spontaneous intracranial haemorrhage (91.3%) and spinal trauma (82.6%). Significant increases were seen in experience in all practical skills assessed. These included central venous catheterisation (p < 0.001), intracranial pressure (ICP) bolt insertion (p < 0.001), ICP bolt removal (p < 0.001), external ventricular drain (EVD) insertion (p = 0.001) and tapping of EVD for cerebrospinal fluid sample (p < 0.001). Conclusion. Our results clearly demonstrate the educational benefits of NCCU placements in the early stages of a neurosurgical training programme as well as in the Foundation Programme. This supports the incorporation of a four- to six-month NCCU rotation in early years training as educationally valuable.