Distinct manifestations and potential mechanisms of seizures due to cortical versus white matter injury in children.

PURPOSE: To study seizure manifestations and outcomes in children with cortical versus white matter injury, differences potentially explaining variability of epilepsy in children with cerebral palsy. METHODS: In this population-based retrospective cohort study, MRIs of children with cerebral palsy due to ischemia or haemorrhage were classified according to presence or absence of cortical injury. MRI findings were then correlated with history of neonatal seizures, seizures during childhood, epilepsy syndromes, and seizure outcomes. RESULTS: Of 256 children studied, neonatal seizures occurred in 57 and seizures during childhood occurred in 93. Children with neonatal seizures were more likely to develop seizures during childhood, mostly those with cortical injury. Cortical injury was more strongly associated with (1) developing seizures during childhood, (2) more severe epilepsy syndromes (infantile spasms syndrome, focal epilepsy, Lennox-Gastaut syndrome), and (3) less likelihood of reaching > 2 years without seizures at last follow-up, compared to children without cortical injury. Children without cortical injury, mainly those with white matter injury, were less likely to develop neonatal seizures and seizures during childhood, and when they did, epilepsy syndromes were more commonly febrile seizures and self-limited focal epilepsies of childhood, with most achieving > 2 years without seizures at last follow-up. The presence of cortical injury also influenced seizure occurrence, severity, and outcome within the different predominant injury patterns of the MRI Classification System in cerebral palsy, most notably white matter injury. CONCLUSIONS: Epileptogenesis is understood with cortical injury but not well with white matter injury, the latter potentially related to altered postnatal white matter development or myelination leading to apoptosis, abnormal synaptogenesis or altered thalamic connectivity of cortical neurons. These findings, and the potential mechanisms discussed, likely explain the variability of epilepsy in children with cerebral palsy and epilepsy following early-life brain injury in general.

Paroxysmal Nonepileptic Events in Children With Epilepsy and Cerebral Palsy.

Objective: To determine the frequency of paroxysmal nonepileptic events in children with cerebral palsy due to brain injury who have epilepsy and to describe the factors associated with paroxysmal nonepileptic events. Methods: Retrospective, population-based study of children from the Victorian CP Register born 1999-2006. Neuroimaging, medical records, electroencephalograms (EEG), and EEG requests were analyzed. Results: Of the included 256 children, 87 had epilepsy. EEGs (with video correlation) were available for 82 of 87. Eighteen (18/82, 22%) had epileptic events captured on EEG. Twenty-one (21/82, 26%) had paroxysmal nonepileptic events captured on EEG. The majority (13/18, 77%) of children with epileptic events also had paroxysmal nonepileptic events captured. Ten parents and carers continued to report events as epileptic despite there being no ictal EEG correlate for specific events on multiple EEGs. There were no clear associations to identify which children would have ongoing paroxysmal nonepileptic events reported. Conclusions: Paroxysmal nonepileptic events were captured on EEG in one-fourth of children from this cerebral palsy cohort with epilepsy and available EEG. Half the parents and carers reported previously identified paroxysmal nonepileptic events as epileptic on subsequent EEGs, highlighting the need for clearer counseling so that parents better understand seizure semiology in children with EEG-proven paroxysmal nonepileptic events.

Epilepsy syndromes in cerebral palsy: varied, evolving and mostly self-limited.

Seizures occur in approximately one-third of children with cerebral palsy. This study aimed to determine epilepsy syndromes in children with seizures and cerebral palsy due to vascular injury, anticipating that this would inform treatment and prognosis. We studied a population-based cohort of children with cerebral palsy due to prenatal or perinatal vascular injuries, born 1999-2006. Each child's MRI was reviewed to characterize patterns of grey and white matter injury. Children with syndromic or likely genetic causes of cerebral palsy were excluded, given their inherent association with epilepsy and our aim to study a homogeneous cohort of classical cerebral palsy. Chart review, parent interview and EEGs were used to determine epilepsy syndromes and seizure outcomes. Of 256 children, 93 (36%) had one or more febrile or afebrile seizures beyond the neonatal period and 87 (34%) had epilepsy. Children with seizures were more likely to have had neonatal seizures, have spastic quadriplegic cerebral palsy and function within Gross Motor Function Classification System level IV or V. Fifty-six (60%) children with seizures had electroclinical features of a self-limited focal epilepsy of childhood; we diagnosed these children with a self-limited focal epilepsy-variant given the current International League Against Epilepsy classification precludes a diagnosis of self-limited focal epilepsy in children with a brain lesion. Other epilepsy syndromes were focal epilepsy-not otherwise specified in 28, infantile spasms syndrome in 11, Lennox-Gastaut syndrome in three, genetic generalized epilepsies in two and febrile seizures in nine. No epilepsy syndrome could be assigned in seven children with no EEG. Twenty-one changed syndrome classification during childhood. Self-limited focal epilepsy-variant usually manifested with a mix of autonomic and brachio-facial motor features, and occipital and/or centro-temporal spikes on EEG. Of those with self-limited focal epilepsy-variant, 42/56 (75%) had not had a seizure for >2 years. Favourable seizure outcomes were also seen in some children with infantile spasms syndrome and focal epilepsy-not otherwise specified. Of the 93 children with seizures, at last follow-up (mean age 15 years), 61/91 (67%) had not had a seizure in >2 years. Children with cerebral palsy and seizures can be assigned specific epilepsy syndrome diagnoses typically reserved for normally developing children, those syndromes commonly being age-dependent and self-limited. Compared to typically developing children with epilepsy, self-limited focal epilepsy-variant occurs much more commonly in children with cerebral palsy and epilepsy. These findings have important implications for treatment and prognosis of epilepsy in cerebral palsy, and research into pathogenesis of self-limited focal epilepsy.

Histologic chorioamnionitis in preterm infants: correlation with brain magnetic resonance imaging at term equivalent age.

BACKGROUND: To explore the associations between histologic chorioamnionitis with brain injury, maturation and size on magnetic resonance imaging (MRI) of preterm infants at term equivalent age. METHODS: Preterm infants (23-36 weeks' gestational age) were recruited into two longitudinal cohort studies. Presence or absence of chorioamnionitis was obtained from placental histology and clinical data were recorded. MRI at term-equivalent age was assessed for brain injury (intraventricular haemorrhage, cysts, signal abnormalities), maturation (degree of myelination, gyral maturation) and size of cerebral structures (metrics and brain segmentation). Histologic chorioamnionitis was assessed as a predictor of MRI variables using linear and logistic regression, with adjustment for confounding perinatal variables. RESULTS: Two hundred and twelve infants were included in this study, 47 (22%) of whom had histologic chorioamnionitis. Histologic chorioamnionitis was associated with higher odds of intraventricular haemorrhage (odds ratio [OR] (95% confidence interval [CI]) = 7.4 (2.4, 23.1)), less mature gyral maturation (OR (95% CI) = 2.0 (1.0, 3.8)) and larger brain volume (mean difference in cubic centimeter (95% CI) of 14.1 (1.9, 26.2)); but all relationships disappeared following adjustment for perinatal variables. CONCLUSION: Histologic chorioamnionitis was not independently associated with IVH, less mature gyral maturation or brain volume at term-equivalent age in preterm infants.

Acute pancreatitis complicating choledochal cysts in children.

AIM: To analyse the characteristics of patients with choledochal cysts presenting with acute pancreatitis. METHODS: Multicenter retrospective review of all paediatric patients (<18 years) with choledochal cysts managed over a 14-year period (2001-2014) at two tertiary paediatric surgical centres. Patient data were analysed for demographics, presentation, radiological classification of cyst type (Todani), operative interventions, complications and long-term follow-up. RESULTS: A total of 49 patients with choledochal cysts were identified with 15 (31%) being Type I fusiform, 18 (37%) Type I cystic and 16 (32%) Type IV-A. Seventeen (35%) patients presented with acute pancreatitis, one having had an ante-natally diagnosed choledochal cyst. Patients presenting with pancreatitis were older when compared to the non-pancreatitis group (5.1 vs. 1.2 years, P = 0.005). Nine out of 16 (53%) patients with Type IV-A cysts presented with pancreatitis compared to five (33%) of Type I fusiform and three (17%) of Type I cystic. There was however no statistically significant association between Todani types and the development of pancreatitis (Type I fusiform, P = 1.0; Type I cystic, P = 0.063; Type IV-A, P = 0.053). The rate of complications was similar in both groups. CONCLUSION: Pancreatitis was a common presentation in children with a choledochal cyst, however, there was no clear statistically significant association with Todani types and pancreatitis.

Grey matter injury patterns in cerebral palsy: associations between structural involvement on MRI and clinical outcomes.

AIMS: In a population cohort of children with grey matter injury (GMI) and cerebral palsy (CP), we aimed to describe and classify magnetic resonance imaging characteristics specific to GMI, and to identify key structure-function associations that serve as a basis for rating GMI in clinically relevant ways. METHOD: Symmetry, extent of cerebral injury, and pathological pattern for 54 children (37 males, 17 females) with CP and a predominant GMI pattern on chronic-phase magnetic resonance imaging were related to gross motor function, motor type and topography, epilepsy, intellectual disability, blindness, and deafness. RESULTS: Relative to mild GMI where there was no pallidal abnormality, severe GMI, comprising pallidal abnormality alone or in conjunction with other deep nuclear and generalized cortical-subcortical involvement, was strongly associated with Gross Motor Function Classification System levels IV to V (OR 35.7 [95% CI 3.5, 368.8]). Involvement of the basal ganglia was associated with non-spastic/mixed motor types, but predominantly where cortical-subcortical grey and white matter involvement was not extensive. The prevalence of epilepsy was highest where there was diffuse cortical-subcortical involvement and white matter loss. INTERPRETATION: Better understanding of structure-function relationships in CP and GMI, and how to rate the severity of GMI, will be helpful in the clinical context and also as a basis for investigation of causal pathways in CP.

An Australian population study of factors associated with MRI patterns in cerebral palsy.

AIM: The aim of this study was to describe the distribution of magnetic resonance imaging (MRI) patterns in a large population sample of children with cerebral palsy (CP) and to examine associations between MRI patterns, and antenatal and perinatal variables. METHOD: Data were retrieved from the Victorian CP Register for 884 children (527 males, 357 females) born between 1999 and 2006. Postneonatal MRI was classified for 594 children. For 563 children (329 males, 234 females) for whom classification was to a single MRI pattern, the frequency of each variable was compared between patterns and with the population frequency. RESULTS: White matter injury was the most common MRI pattern (45%), followed by grey matter injury (14%), normal imaging (13%), malformations (10%), focal vascular insults (9%), and miscellaneous patterns (7%). Parity, birth gestation, level of neonatal care, Apgar score, and time to established respiration varied between MRI patterns (p<0.01). Nulliparity was most strongly associated with focal vascular insults, whereas multiparity was associated only with malformations. Grey matter injury was not associated with birth in a tertiary unit, but was strongly associated with severe perinatal compromise. The frequency of neonatal seizures and of nursery admissions was lowest among children with malformations. INTERPRETATION: As known risk factors for CP are differentially associated with specific MRI patterns, future exploration of causal pathways might be facilitated when performed in pathogenically defined groups.

Population-based studies of brain imaging patterns in cerebral palsy.

AIM: The aim of this study was to review the distribution of neuroimaging findings from a contemporary population cohort of individuals with cerebral palsy (CP) and to facilitate standardization of imaging classification. METHOD: Publications from 1995 to 2012 reporting imaging findings in population cohorts were selected through a literature search, and review of the titles, abstracts, and content of studies. Relevant data were extracted, including unpublished data from Victoria, Australia. The proportions for each imaging pattern were tabulated, and heterogeneity was assessed for all individuals with CP, and for subgroups based on gestational age, CP subtype, and Gross Motor Function Classification System level. RESULTS: Studies from three geographic regions met the inclusion criteria for individuals with CP, and two additional studies reported on specific CP subtypes. Brain abnormalities were observed in 86% of scans, but were observed least often in children with ataxia (24-57%). White matter injury was the most common imaging pattern (19-45%), although the proportions showed high heterogeneity. Additional patterns were grey matter injury (21%), focal vascular insults (10%), malformations (11%), and miscellaneous findings (4-22%). INTERPRETATION: This review suggests areas where further dialogue will facilitate progress towards standardization of neuroimaging classification. Standardization will enable future collaborations aimed at exploring the relationships among magnetic resonance imaging patterns, risk factors, and clinical outcomes, and, ultimately, lead to better understanding of causal pathways and opportunities for prevention.

ALG3-CDG (CDG-Id): clinical, biochemical and molecular findings in two siblings.

Congenital disorders of glycosylation (CDG) represent an expanding family of metabolic disorders with a wide range of biochemical, molecular and clinical phenotypes. ALG3-CDG (CDG-Id), due to a defect in endoplasmic reticulum (ER) mannosyltransferase VI, is one of the less common types of CDG-I. We describe two Vietnamese siblings with confirmed ALG3-CDG (CDG-Id) by molecular testing. As far as we are aware, they are the oldest reported patients in the literature at 15 and 21years. They share similar clinical features with previously reported patients including facial dysmorphism, severe psychomotor retardation, microcephaly, seizures, and gastrointestinal symptoms. Furthermore, our sibling pair highlights the intrafamilial variability, the natural clinical course of ALG3-CDG (CDG-Id) and the benefit of reassessing patients with undiagnosed and complex syndromes, particularly when they present with neurological deterioration.

Feasibility of 3-T MRI for the evaluation of Crohn disease in children.

BACKGROUND: Crohn disease (CD) is a chronic inflammatory bowel disease that can affect any part of the gastrointestinal tract from the oral cavity to the anal canal. It occurs in all ages and is a significant cause for morbidity in children. Interest in MRI evaluation of CD has increased because of the concern regarding cumulative radiation dose from contrast fluoroscopic studies and CT. Several reports have demonstrated MRI to be a useful technique for CD. Most of these studies were performed at 1.5-T field strength. Imaging at a higher field strength, with a greater signal-to-noise ratio, has the potential of reducing scan times and increasing the resolution. However, there is a concurrent increase in artefacts, and these can be pronounced with abdominal imaging at 3 T. OBJECTIVE: To determine the feasibility of 3-T MRI for CD in children and to assess the value of different sequences and the effect of artefacts that could potentially limit the role of bowel MR imaging at higher field strengths. MATERIALS AND METHODS: A retrospective study of 46 children with biopsy-proven CD (ages 8-19 years, 53% boys) was performed. Sixty-eight consecutive MRI studies were performed on a 3-T scanner between 2005 and 2007; 42 of the abdomen (62%) and 26 of the pelvis/perineum (38%). Sorbitol was administered for the abdominal studies; orally for 36/42 (86%) studies and via a naso-jejunal (NJ) tube for 6/42 (14%) studies. For the abdomen, T2-W half-fourier acquisition single-shot turbo spin-echo (T2-W HASTE), true steady-state free precession (true FISP), pre-contrast and contrast-enhanced (CE) T1-volume interpolated gradient-echo (T1-W VIBE) and CE T1-W fast low-angle shot (T1-W FLASH) sequences were performed. For the perianal and pelvic assessment, fat-saturated T2-W turbo spin-echo (TSE), pre-contrast and CE T1-W FLASH or VIBE sequences were performed. The sequences were scored for diagnostic quality by two paediatric radiologists for visualisation of the bowel wall, whether normal or pathological and the visualization of extra intestinal manifestations. The effects of distension, susceptibility artefact and motion were assessed. RESULTS: Six (14%) abdominal MRI studies were normal. Thirty-six (86%) were abnormal with good correlation with endoscopic findings. The pelvic and perianal MRI studies were all abnormal (26/26, 100%) with good correlation with proctoscopy and examination under anaesthesia. All the sequences had high average scores (greater than or close to 3), except true FISP with a score of 2.4. The score was greatest in those who had NJ administration of sorbitol; however, satisfactory distension was also possible with oral administration of contrast. True FISP was the sequence most affected by a combination of suboptimal distension and artefact from colonic contents. With adequate distension, true FISP image quality improved remarkably. The overall score of this sequence was satisfactory in the absence of susceptibility and movement artefact. CONCLUSION: With appropriate attention to technique, with optimal distension and control of movement, high-quality, 3-T assessment of the abdomen, pelvis and perineum is possible. All sequences used at 1.5 T can be used at 3 T, however true FISP was the most prone to artefact.