Lee Coleman

Clinical and neuroradiologic features of acute disseminated encephalomyelitis in children

Objective: To identify the clinical and neuroradiologic features of acute disseminated encephalomyelitis (ADEM) in childhood. Methods: A retrospective review was conducted of the medical records and MRI of children who presented to the Royal Children’s Hospital in Melbourne with ADEM between January 1993 and December 1998. Results: Of the 31 patients included in this study, 22 (71%) experienced a prodromal illness. Two patients (6%) had received hepatitis B vaccine 3 to 6 weeks before developing their illness. Symptoms and signs typically evolved over several days. Ataxia was the most common presenting feature, occurring in 20 patients (65%). MRI findings were variable, but lesions were most commonly seen bilaterally and asymmetrically in the frontal and parietal lobes. The authors found a high incidence of the corpus callosal and periventricular changes more typically associated with MS, but they also found a high rate of deep gray matter involvement (61% of patients). The use of high-dose IV methylprednisolone was usually associated with rapid recovery. Eighty-one percent of patients recovered completely, with only mild sequelae recorded in the remaining children. Conclusion: In the absence of a biological marker, the distinction between ADEM and MS cannot be made with certainty at the time of first presentation, but the authors suggest that a viral prodrome, early-onset ataxia, high lesion load on MRI, involvement of the deep gray matter, and absence of oligoclonal bands are more indicative of ADEM.

Childhood brain insult: can age at insult help us predict outcome?

Until recently, the impact of early brain insult (EBI) has been considered to be less significant than for later brain injuries, consistent with the notion that the young brain is more flexible and able to reorganize in the context of brain insult. This study aimed to evaluate this notion by comparing cognitive and behavioural outcomes for children sustaining EBI at different times from gestation to late childhood. Children with focal brain insults were categorized according to timing of brain insult, represented by six developmental periods: (i) Congenital (n = 38): EBI: first-second trimester; (ii) Perinatal (n = 33); EBI: third trimester to 1 month post-natal; (iii) Infancy (n = 23): EBI: 2 months-2 years post-birth; (iv) Preschool (n = 19): EBI: 3-6 years; (v) Middle Childhood (n = 31): EBI: 7-9 years; and (vi) Late Childhood (n = 19): EBI: after age 10. Groups were similar with respect to injury and demographic factors. Children were assessed for intelligence, academic ability, everyday executive function and behaviour. Results showed that children with EBI were at increased risk for impairment in all domains assessed. Furthermore, children sustaining EBI before age 2 years recorded global and significant cognitive deficits, while children with later EBI performed closer to normal expectations, suggesting a linear association between age at insult and outcome. In contrast, for behaviour, children with EBI from 7 to 9 years performed worse than those with EBI from 3 to 6 years, and more like those with younger insults, suggesting that not all functions share the same pattern of vulnerability with respect to age at insult.

Clinical and imaging features of cortical malformations in childhood

Objective: To determine the types, relative frequencies, clinical features, and MRI characteristics of malformations of cortical development (MCD) occurring in a cohort of children referred to a tertiary pediatric center. Methods: Original MR images were reviewed by two investigators, who were blinded to clinical details, to determine the elemental imaging features of each malformation and to label these malformations according to an existing system of classification. Clinical information was collected by a review of hospital records. Results: A total of 109 children with MCD were identified. There were 58 boys and 51 girls, age 8 days to 18 years at initial imaging (mean age, 5 years). Seizures were present in 75%, developmental delay or intellectual disability in 68%, abnormal neurologic findings in 48%, and congenital anomalies apart from the CNS malformation in 18%. The main malformations identified were heterotopic gray matter (19%), cortical tubers (17%), focal cortical dysplasia (16%), polymicrogyria (16%), agyria/pachygyria (15%), schizencephaly/cleft (5%), transmantle dysplasia (5%), and hemimegalencephaly (4%). Eight patients had features of more than one malformation. Most lesions were multilobar (47%), with the frontal lobe being the most common lobe involved (78%). A total of 68% of patients had other cerebral malformations including ventricular dilatation or dysmorphism (46%) and abnormalities of the corpus callosum (29%). Conclusions: This study illustrates the spectrum of MCD in a pediatric cohort and highlights some of the differences between pediatric and adult patients. Patients with MCD presenting in childhood have a wider spectrum of malformations and more varied, often more severe, clinical manifestations. The lesions are frequently multifocal or generalized and many are associated with noncortical developmental brain anomalies.

New White Matter Brain Injury After Infant Heart Surgery Is Associated With Diagnostic Group and the Use of Circulatory Arrest

Background— Abnormalities on magnetic resonance imaging scans are common both before and after surgery for congenital heart disease in early infancy. The aim of this study was to prospectively investigate the nature, timing, and consequences of brain injury on magnetic resonance imaging in a cohort of young infants undergoing surgery for congenital heart disease both with and without cardiopulmonary bypass. Methods and Results— A total of 153 infants undergoing surgery for congenital heart disease at <8 weeks of age underwent serial magnetic resonance imaging scans before and after surgery and at 3 months of age, as well as neurodevelopmental assessment at 2 years of age. White matter injury (WMI) was the commonest type of injury both before and after surgery. It occurred in 20% of infants before surgery and was associated with a less mature brain. New WMI after surgery was present in 44% of infants and at similar rates after surgery with or without cardiopulmonary bypass. The most important association was diagnostic group (P<0.001). In infants having arch reconstruction, the use and duration of circulatory arrest were significantly associated with new WMI. New WMI was also associated with the duration of cardiopulmonary bypass, postoperative lactate level, brain maturity, and WMI before surgery. Brain immaturity but not brain injury was associated with impaired neurodevelopment at 2 years of age. Conclusions— New WMI is common after surgery for congenital heart disease and occurs at the same rate in infants undergoing surgery with and without cardiopulmonary bypass. New WMI is associated with diagnostic group and, in infants undergoing arch surgery, the use of circulatory arrest.

Apparent Diffusion Coefficient in the Posterior Limb of the Internal Capsule Predicts Outcome After Perinatal Asphyxia

Objective. Predicting long-term outcome in infants with hypoxic-ischemic encephalopathy (HIE) is a difficult task. Magnetic resonance imaging, particularly diffusion imaging, holds promise in this regard as it is more sensitive to brain injury than any other available imaging modality. Previous studies have suggested that abnormal signal intensity in the posterior limb of the internal capsule (PLIC), detectable on inversion-recovery T1-weighted imaging, is a strong predictor of outcome. The aim of this study was to assess the relationship between apparent diffusion coefficient (ADC) values from the PLIC, measured by diffusion imaging, and neuromotor outcome in term infants with HIE. Methods. Twenty-eight term infants with a clinical diagnosis of HIE underwent magnetic resonance imaging as soon as practicable after birth (mean age: 5.6 days), including diffusion-weighted imaging, from which ADC values in the PLIC were measured. Motor outcome was assessed in 12 of 16 survivors. Results. The ADC value in the PLIC was significantly associated with survival in term infants with HIE. For survivors, the mean ADC value in the PLIC was 0.89 ± 0.17 μm2/ms, whereas the mean ADC value for nonsurvivors was 0.75 ± 0.17 μm2/ms (t = 2.25). Among survivors, the ADC value in the PLIC was also associated with neuromotor outcome (F = 5.60). Conclusion. The ADC value in the PLIC is an indicator of ischemic injury and may be of use as an objective prognostic marker for infants with HIE.

Are neuropsychological impairments in children with early-treated phenylketonuria (PKU) related to white matter abnormalities or elevated phenylalanine levels?

This study aimed to enhance our understanding of neuropsychological functioning in children with early-treated phenylketonuria (PKU) and assess the relative impact of white matter abnormalities (WMA) and neurotransmitter deficiencies on cognitive functions in this population. The study consisted of 33 children with early-treated PKU and 34 healthy control children aged between 7 to 18 years. All children had a neuropsychological evaluation that included measures of general intelligence, attention, processing speed, memory and learning, executive function, and academic achievement. Children in the PKU group also had a magnetic resonance (MR) brain scan. When compared with the control group, the PKU group exhibited global cognitive impairment including lower IQ, attention problems, slow information processing, reduced learning capacity, mild executive impairments, and educational difficulties. Children in the PKU group with extensive WMA (n = 14) displayed significant impairments across all cognitive domains. Metabolic control correlated weakly to moderately with attention, executive, and memory/learning factors. Within the PKU group, regressions revealed that executive function and attention factors were independently related to severity of WM pathology and age, while the memory and learning factor was independently related to metabolic control and age. It is concluded that children with early-treated PKU exhibit a global pattern of impairment, with a particular deficit in processing speed. WM pathology extending into frontal and subcortical regions correlates with the greatest deficits and a profile of impairment consistent with diffuse WM damage. Our findings also offer some support for dopamine depletion in the prefrontal cortex, however adverse consequences as a result of norepinephrine and serotonin deficiencies should not be discounted.

Pre-operative brain injury in newborn infants with transposition of the great arteries occurs at rates similar to other complex congenital heart disease and is not related to balloon atrial septostomy.

OBJECTIVES The goal of this study was to determine the prevalence and pattern of pre-operative brain injury in infants with transposition of the great arteries (TGA) compared with other complex congenital heart disease (CHD) and to define the risk of balloon atrial septostomy (BAS) for the development of brain injury. BACKGROUND It has recently been suggested that infants with TGA are at increased risk of pre-operative brain injury, in particular, stroke, and that this is strongly associated with having a BAS. METHODS Sixty-four newborn infants with TGA (n = 44), hypoplastic left heart syndrome (n = 13), or pulmonary atresia (n = 7) had magnetic resonance imaging (MRI) scans performed before surgery. RESULTS Thirty-three (75%) of the infants with TGA had a BAS. Brain injury occurred in 19 (30%) infants: white matter injury (WMI) in 17 (27%), and stroke in 3 (5%). There was no difference in the prevalence or pattern of brain injury between diagnostic groups. There was no association between BAS and brain injury in infants with TGA. There was a trend toward increased brain injury in TGA with an intact interventricular septum compared with TGA with a ventricular septal defect (38% vs. 8%, p = 0.075). There was no association between brain injury and any clinical variables. CONCLUSIONS Pre-operative brain injury on MRI scan was present in 30% of infants with CHD. The predominant pattern was WMI. The rates and patterns of pre-operative brain injury are similar in infants with TGA compared with other complex CHD, and BAS does not increase the risk of pre-operative brain injury.

Prognostic Utility of Magnetic Resonance Imaging in Neonatal Hypoxic-Ischemic Encephalopathy: Substudy of a Randomized Trial

OBJECTIVE To investigate the effects of hypothermia treatment on magnetic resonance imaging (MRI) patterns of brain injury in newborns with hypoxic-ischemic encephalopathy compared with normothermia, including the prognostic utility of MRI for death and/or disability at a postnatal age of 2 years. DESIGN Substudy of a randomized controlled trial. SETTING Participating centers in the Infant Cooling Evaluation trial. PARTICIPANTS Trial participants (gestational age ≥35 weeks with moderate to severe hypoxic-ischemic encephalopathy, randomized to whole-body hypothermia or normothermia) with available MRIs. MAIN EXPOSURE We performed qualitative evaluation of T1- and T2-weighted and diffusion MRIs. The posterior limb of the internal capsule was classified as normal or abnormal, whereas the basal ganglia and thalami, white matter, and cortical gray matter were classified as normal or mildly abnormal or moderately/severely abnormal. MAIN OUTCOME MEASURES Death or major disability at 2 years. RESULTS We evaluated 127 MRIs (66 patients treated with hypothermia and 61 with normothermia; mean age at scan, 6 postnatal days). The odds of having moderate/severe white matter or cortical gray matter abnormalities on T1- and T2-weighted MRI were reduced by hypothermia (white matter odds ratio, 0.28 [95% CI, 0.09-0.82]; gray matter odds ratio, 0.41 [0.17-1.00]). Abnormal MRI findings predicted adverse outcomes, with T1- and T2-weighted and diffusion MRI abnormalities in the posterior limb of the internal capsule and basal ganglia and thalami demonstrating the greatest predictive value. There was little evidence that prognostic value of the MRI was modified by therapeutic hypothermia (all interactions, P > .05). CONCLUSIONS Brain injury on T1- and T2-weighted MRI is reduced in hypothermia-treated newborns. Abnormal MRI findings are prognostic of long-term outcome in moderate to severe hypoxic-ischemic encephalopathy regardless of treatment with hypothermia.

Value and Limitations of Diffusion-Weighted Imaging in Grading and Diagnosis of Pediatric Posterior Fossa Tumors

SUMMARY: DWI reportedly accurately differentiates pediatric posterior fossa tumors, but anecdotal experience suggests limitations. In 3 years, medulloblastoma and JPA were differentiated by DWI alone in 23/26 cases (88%). Ependymoma (n = 5) could not be reliably differentiated from medulloblastoma or JPA. A trend toward increased diffusion restriction in higher grade tumors (1/14 grade I, 7%; 9/12 grade IV, 75%) had too much overlap to predict the grade of individual cases. The overlap in ADC between tumor types appeared partly due to technical factors (in small, heterogeneous, calcific, or hemorrhagic tumors) but also likely reflected true histologic variability, given that our 3 overlap cases included a desmoplastic medulloblastoma, an anaplastic ependymoma, and a JPA with restricted diffusion in its nodule. Simple structural features (macrocystic tumor, location off midline) aided in distinguishing JPA from the other tumors in these cases.

Does Early Age at Brain Insult Predict Worse Outcome? Neuropsychological Implications

OBJECTIVE Traditionally early brain insult (EBI) has been argued to have better outcome than later injury, consistent with the notion that the young brain is flexible and able to reorganize. This view was investigated by comparing neurobehavioral outcomes of children sustaining EBI at different developmental stages (gestation to late childhood). METHODS One hundred and sixty four children who had sustained focal brain insult (confirmed by MRI) formed six groups, based on age at EBI, (a) Congenital; (b) Peri-natal; (c) Infancy; (d) Preschool; (e) Middle Childhood; (f) Late Childhood, and were compared on a range of standardized neurobehavioral measures. Groups were matched for lesion characteristics and demographics. RESULTS Children sustaining EBI before age 2 recorded global deficits, while children with later EBI performed closer to average. CONCLUSION These results question the advantages of early brain plasticity, demonstrating poorer outcome from very early insults, and increasingly better function with lesions later in childhood.