Michael A. Sargent

Effect of chorioamnionitis on brain development and injury in premature newborns

The association of chorioamnionitis and noncystic white matter injury, a common brain injury in premature newborns, remains controversial. Our objectives were to determine the association of chorioamnionitis and postnatal risk factors with white matter injury, and the effects of chorioamnionitis on early brain development, using advanced magnetic resonance imaging.

Central nervous system involvement in neonatal lupus erythematosus.

Abstract: Computerized tomography (CT) of the brain was performed in 10 of 11 consecutive infants with neonatal lupus erythematosus (NLE) (five boys and six girls). Ten of the 11 infants had brain neurosonography. Nine of 10 infants had abnormal CT scans. There was diffuse, markedly reduced attenuation of the cerebral white matter in four infants studied in the first week of life, and also in an infant 5 weeks of age. Patchy reduced subcortical white matter attenuation was observed in another 5‐week‐old infant. Basal ganglia calcifications were present in two infants at 2 months of age, one of whom also had mild ventriculomegaly. A patient with macrocephaly studied at 4 months of age had enlarged ventricles and subarachnoid spaces consistent with benign macrocephaly of infancy. Cerebral ultrasound examination was abnormal in all five infants studied in the first week of life and in one infant at 2 months of age. Findings included subependymal cysts (4), echogenic white matter (3), and echogenic lenticulostriate vessels (3). Apart from one case of macrocephaly, there was no clinical evidence of neurologic disease and the subsequent development of these infants has been normal. Subclinical central nervous system (CNS) disease in NLE is likely to be a transient phenomenon that resolves as maternal antibodies are cleared from the infants circulation. It is important to be aware of these neuroimaging abnormalities to avoid misdiagnosis of congenital viral infection in a newborn with multisystem NLE. The potential for neurologic sequelae is uncertain.

White Matter Injury in Term Newborns With Neonatal Encephalopathy

White matter injury (WMI) is the characteristic pattern of brain injury detected on magnetic resonance imaging in the premature newborn. Focal noncystic WMI is increasingly recognized in populations of term newborns. The aim of this study was to describe the occurrence of focal noncystic WMI in a cohort of 48 term newborns with encephalopathy studied with magnetic resonance imaging at 72 ± 12 h of life, and to identify clinical risk factors for this pattern of injury. Eleven newborns (23%; 95% CI 11–35) were found to have WMI (four minimal, three moderate, and four severe). In 10 of the 11 newborns, the WMI was associated with restricted diffusion on apparent diffusion coefficient maps. An increasing severity of WMI was associated with lower gestational age at birth (p = 0.05), but not lower birth weight. Newborns with WMI had milder encephalopathy and fewer clinical seizures relative to other newborns in the cohort. Other brain injuries were seen in three of the 11 newborns: basal nuclei predominant pattern of injury in one and cortical strokes in two. These findings suggest that WMI in the term newborn is acquired near birth and that the state of brain maturation is an important determinant of this pattern of brain injury.

Predicting postresection hydrocephalus in pediatric patients with posterior fossa tumors

OBJECT Approximately 30% of children with posterior fossa tumors exhibit hydrocephalus after tumor resection. Recent literature has suggested that prophylactic endoscopic third ventriculostomy diminishes the risk of this event. Because the majority of patients will not have postoperative hydrocephalus, a preoperative clinical prediction rule that identifies patients at high or low risk for postresection hydrocephalus would be helpful to optimize the care of these children. METHODS The authors evaluated a derivation cohort of 343 consecutive children with posterior fossa tumors who underwent treatment between 1989 and 2003. Multivariate methods were used on these data to generate the Canadian Preoperative Prediction Rule for Hydrocephalus. The rules estimated risk of postresection hydrocephalus was compared with risk observed in 111 independent patients in the validation cohort. RESULTS Variables identified as significant in predicting postresection hydrocephalus were age < 2 years (score of 3), papilledema (score of 1), moderate to severe hydrocephalus (score of 2), cerebral metastases (score of 3), and specific estimated tumor pathologies (score of 1). Patients with scores > or = 5 were deemed as high risk. Predicted probabilities for the high- and low-risk groups were 0.73 and 0.25, respectively, from the derivation cohort, and 0.59 and 0.14 after prevalence adjustment compared with the observed values of 0.42 and 0.17 in the validation cohort. CONCLUSIONS A patients score on the Preoperative Prediction Rule for Hydrocephalus will allow improved patient counseling and surgical planning by identifying patients at high risk of developing postresection hydrocephalus. These patients might selectively be exposed to the risks of preresection CSF diversion to improve outcome.

Atelectasis on pediatric chest CT : comparison of sedation techniques

Background. A change in practice at our institution resulted in increased use of anesthesia for CT scan of the chest in children who required sedation. Objective. To determine whether there is a difference in the frequency or severity of pulmonary atelectasis on CT scan in children sedated by anesthesiologists compared with children sedated by radiologists using intravenous pentobarbital. Materials and methods. Retrospective blinded review of 60 CT scans of the chest performed in 41 children. Forty-one studies in children sedated by radiologists (median age 29 months) were compared with 19 studies in children sedated by anesthesiologists (median age 25 months). Results. Atelectasis sufficient to obscure pulmonary metastases was shown in 5 of 41 (12 %) radiology sedations and 13 of 19 (68 %) anesthesiology sedations (P < 0.01). Higher grades of atelectasis were recorded in children under anesthesia (P < 0.01). Conclusion. Atelectasis is more frequent and more severe in children undergoing general anesthesia compared with intravenous pentobarbital sedation. Consideration should be given to the use of forced inspiration in children anesthetized for CT scan of the chest.

Third ventricular shape: a predictor of endoscopic third ventriculostomy success in pediatric patients

OBJECT The criteria for identifying patients in whom endoscopic third ventriculostomy (ETV) provides control of hydrocephalus remain in evolution. In particular, it is not clear when ETV would be effective if intraventricular obstruction is not found preoperatively. The authors postulated that 1) displacement of the third ventricle floor inferiorly into the interpeduncular cistern and displacement of the lamina terminalis anteriorly into the lamina terminalis cistern could predict clinical success of ETV, and 2) improvement in these displacements would correlate with the success of ETV. METHODS Magnetic resonance imaging in 38 consecutive patients treated between 2004 and 2010 was reviewed to assess displacement of the lamina terminalis and third ventricular floor prior to and following ETV. Displacements of the floor and lamina terminalis were judged qualitatively and quantitatively, using a newly created index, the Third Ventricular Morphology Index (TVMI). The association between the aforementioned morphological features and clinical success of ETV was analyzed. RESULTS Ninety-six percent of patients in whom the authors preoperatively observed displacement of the lamina terminalis and the third ventricular floor were successfully treated with ETV. Displacements of the third ventricular floor and lamina terminalis, as judged qualitatively, correlated with the clinical success of ETV. The TVMI correlated with the qualitative assessments of displacement. Postoperative decrease in the TVMI occurred in the majority of successfully treated patients. Changes in third ventricular morphology preceded changes in other measures of third and lateral ventricular volume following ETV. CONCLUSIONS Assessment of third ventricular floor and lamina terminalis morphology is useful in predicting clinical success of ETV and in the follow-up in treated patients. The TVMI provided a quantitative assessment of the third ventricular morphology, which may be useful in equivocal cases and in research studies.

Brainstem Involvement in Neonatal Herpes Simplex Virus Type 2 Encephalitis

Herpes simplex virus encephalitis in the newborn typically involves the cerebral cortex in a widespread manner. Herpes simplex virus type 2 rarely involves the brainstem. Here we report a 16-day-old infant with predominant brainstem and cerebellar involvement secondary to herpes simplex virus type 2 infection. Diffusion-weighted MRI performed 3 days after the onset of symptoms revealed restricted diffusion mainly in brainstem and cerebellar structures. No abnormal findings were seen on conventional MRI. Subsequent MRI scans showed evolution of the brain injury with extension along the corticospinal tracts. However, there was no evidence of any other supratentorial gray or white matter injury. This is the first report of predominant brainstem involvement in neonatal herpes simplex virus type 2 encephalitis. In addition, the importance of performing diffusion-weighted sequences to detect early central nervous system involvement and serial MRI to follow the evolution of central nervous system lesions is emphasized.

Childhood craniopharyngioma: Vancouver experience

ObjectiveTo present our institution’s experience in the management of childhood craniopharyngioma since 1982.MethodsWe retrospectively reviewed the records of all children diagnosed with craniopharyngioma at our children’s hospital from its opening in 1982 through to 2003. One neuroradiologist systematically reviewed the neuroimaging. Kaplan–Meier curves were used to analyze the progression-free survival and the overall survival from the time of the first definitive intervention.ConclusionsMost children diagnosed with craniopharyngioma are long-term survivors. Survivors suffer from multiple deficits in the long term. A conservative surgical and radiotherapeutic approach and avoiding interventions that are known to cause severe morbidity may minimize these. The use of intracystic bleomycin is a strategy that allows the delay of more aggressive therapies in select patients.

Profound Neonatal Hypoglycemia and Lactic Acidosis Caused by Pyridoxine-Dependent Epilepsy

Pyridoxine-dependent epilepsy (PDE) was first described in 1954. The ALDH7A1 gene mutations resulting in α-aminoadipic semialdehyde dehydrogenase deficiency as a cause of PDE was identified only in 2005. Neonatal epileptic encephalopathy is the presenting feature in >50% of patients with classic PDE. We report the case of a 13-month-old girl with profound neonatal hypoglycemia (0.6 mmol/L; reference range >2.4), lactic acidosis (11 mmol/L; reference range <2), and bilateral symmetrical temporal lobe hemorrhages and thalamic changes on cranial MRI. She developed multifocal and myoclonic seizures refractory to multiple antiepileptic drugs that responded to pyridoxine. The diagnosis of α-aminoadipic semialdehyde dehydrogenase deficiency was confirmed based on the elevated urinary α-aminoadipic semialdehyde excretion, compound heterozygosity for a known splice mutation c.834G>A (p.Val278Val), and a novel putative pathogenic missense mutation c.1192G>C (p.Gly398Arg) in the ALDH7A1 gene. She has been seizure-free since 1.5 months of age on treatment with pyridoxine alone. She has motor delay and central hypotonia but normal language and social development at the age of 13 months. This case is the first description of a patient with PDE due to mutations in the ALDH7A1 gene who presented with profound neonatal hypoglycemia and lactic acidosis masquerading as a neonatal-onset gluconeogenesis defect. PDE should be included in the differential diagnosis of hypoglycemia and lactic acidosis in addition to medically refractory neonatal seizures.

Basal ganglia infarction associated with HHV-6 infection

A 6 year old boy presented with meningoencephalitis and was found to have serological evidence of acute human herpes virus-6 (HHV-6) infection. He did not develop symptomatic seizures or the rash of exanthum subitum (roseola). His course was marked by severe spastic quadriparesis associated with radiological evidence of basal ganglia infarction. HHV-6 infection should be considered in any child with acute meningoencephalitis.