R.J. Vermeulen

Fetal origin of brain damage in 2 infants with a COL4A1 mutation: fetal and neonatal MRI.

Mutations in the gene COL4A1, encoding collagen IV A1, are associated with familial porencephaly. Previously, COL4A1 mutation-associated antenatal hemorrhages have been suggested by early post-natal imaging. We describe 2 children with fetal intracerebral hemorrhages and a COL4A1 mutation. There was also extensive hemispheric tissue loss in both infants and loss of cerebellar tissue in one infant. This paper show prenatal evidence of fetal hemorrhage in association with a COL4A1 mutation.

Quantitative MR Imaging and Spectroscopy in Congenital Cytomegalovirus Infection and Periventricular Leukomalacia Suggests a Comparable Neuropathological Substrate of the Cerebral White Matter Lesions

Congenital CYTOMEGALOVIRUS (CMV) infection and periventricular leukomalacia (PVL) both lead to static cerebral white matter lesions. In contrast to PVL, the neuropathologicAL substrate of these lesions in congenital CMV is not clear. By comparing changes in quantitative magnetic resonance (MR) parameters and MR spectroscopy metabolite concentrations we wanted to determine whether the nature of the white matter pathology in congenital CMV infection could be similar to the known pathology of PVL. Diffusion parameters, apparent diffusion coefficient (ADC) and fractional anisotropy (FA), magnetization transfer ratio (MTR) and MR spectroscopy concentrations were studied in white matter lesions in five patients with a congenital CMV infection and six patients with PVL. In both groups ADC values were increased, FA and MTR values were reduced, concentrations of total N-acetylaspartate and choline-containing compounds were reduced; and MYO-inositol concentrations were slightly increased. No differences were found between the two groups, suggesting that the pathology of the white matter lesions in congenital CMV infections is similar to that of PVL and also characterized by axonal losses, lack of myelin deposition due to oligodendrocytic losses, and astrogliosis. Congenital CMV infection and PVL affect the cerebral white matter in the same developmental period when immature oligodendrocytes are particularly vulnerable.

Effect of selective dorsal rhizotomy on gait in children with bilateral spastic paresis: kinematic and EMG-pattern changes.

INTRODUCTION Selective dorsal rhizotomy (SDR) is an effective treatment for reducing spasticity and improving gait in children with spastic cerebral palsy. Data concerning muscle activity changes after SDR treatment are limited. PATIENTS AND METHODS In 30 children who underwent SDR a gait analysis was performed before and 12-24 months postoperatively. Subjects walked on a 10-m walkway at comfortable walking speed. Biplanar video was registered and surface EMG was recorded. Sagittal knee angles were measured from video and observational gait assessments were performed using the Edinburgh gait assessment scale (EGAS). RESULTS The EGAS significantly improved after SDR (p<0.001). There were significant improvements of the knee angle kinematics (p<0.001). Only slight changes in EMG activity were observed. The activity of the m. gastrocnemius (GM) decreased and a late peak appeared in stance, the activity of the m. semitendinosus (ST) increased in stance. The activity of the m. rectus femoris (RF) decreased in swing. CONCLUSION SDR improved overall gait performance but EMG changes were only slight. Better timing of the GM in stance and reduced activity of RF in swing may have increased knee flexion in swing. Reduced hamstrings spasticity may have led to postural instability in the hip.

Satisfaction with intrathecal baclofen treatment in paediatric patients with progressive neurological disease

This retrospective report clearly has some limitations. We were dependent on seizure frequency being accurately recorded in notes and aware that some of the changes seen may reflect contemporaneous changes in therapy or circumstances. The trends over 61 switches do suggest a beneficial effect for most children, particularly for tonic seizures and drop attacks, without serious, persistent side effects. In this group of children with medically resistant epilepsies such an approach can be helpful during times of high seizure activity.

Effect of (minor or major) maternal trauma on fetal motility: A prospective study

BACKGROUND Fetal motility represents the spontaneous activity of the central nervous system and as such can be used to evaluate its functional integrity. Maternal mechanical trauma in pregnancy is a risk factor for hypoxic ischemic brain injury and can potentially affect the CNS and fetal motility. AIM To study motility in fetuses after maternal trauma. STUDY DESIGN Prospective study; 1-h sonographic observations at 2-8h (T1), 24-72h (T2) and >72h (T3) after trauma. SUBJECTS Fetuses exposed to trauma after 20weeks gestational age. OUTCOME MEASURES Motor aspects; differentiation into specific movement patterns, quality and quantity of general movements were compared to a normal population. Obstetrical outcome; neurological outcome at term and 1year of age. RESULTS Sixteen fetuses were examined between 2012 and 2014. Median gestational age at time of trauma was 25+6 (range 20-38) weeks. Most traumas were traffic accidents or falls, injuries were mainly minor. Motility assessment showed abnormal differentiation in 2/16; 2/14 and 0/16; abnormal quality in 2/16; 3/14 and 6/16; and abnormal quantity in 6/16, 9/14 and 9/16 at T1, T2 and T3 respectively. Preterm delivery occurred once. Neurological development was normal in 13/14 infants at term and 14/14 at one year. CONCLUSIONS This study shows that maternal trauma affected fetal motility in the majority of the fetuses. The changes in motility support the concern that even minor mechanical trauma may have influence on the functional integrity of the central nervous system, although no neurological sequelae were present at 1year.

Complicaties bij kinderen met intrathecale baclofentherapie en (gerelateerde) verzorgertevredenheid

SamenvattingDoel van dit onderzoek is een analyse van de complicaties bij kinderen met intrathecale baclofentherapie. Meer specifiek werd gekeken naar aard, frequentie, impact (d.m.v. verzorgertevredenheid) en mogelijke determinanten van het optreden van complicaties. Hiertoe werd retrospectief statusonderzoek uitgevoerd en een cross-sectionele tevredenheidsvragenlijst afgenomen. Alle kinderen (t/m 17 jaar) behandeld met intrathecale baclofentherapie in het VU medisch centrum zijn geanalyseerd. De minimale follow-up was zes maanden. Het betreft baclofenpompimplantaties tussen maart 2001 en mei 2007. Een complicatiefrequentie van 0,28 (0,19-0,42) complicaties per patiënt per jaar werd gevonden. In de literatuur bedraagt de complicatiefrequentie tussen de 0,09 en 0,58 complicaties per patiënt per jaar. Kathetergerelateerde complicaties kwamen het meest frequent voor. Drie gevonden determinanten voor het optreden van complicaties zijn: kathetertiphoogte, pulmonale comorbiditeit en corticosteroïdengebruik. Het tevredenheidsonderzoek wees uit dat ouders/verzorgers van kinderen met één of meer complicaties niet minder tevreden waren dan ouders van kinderen zonder complicaties. Van de ondervraagden zou 88% de keuze voor intrathecale baclofentherapie nog steeds maken. De resultaten van het tevredenheidsonderzoek bevestigen de hypothese dat ouders/verzorgers in hun oordeel de functionele waarde van de behandeling zwaarder laten wegen dan de eventuele complicaties.SummaryAim of this research is an analysis of the complications in children with intrathecal baclofen therapy. More specific by analysing nature, frequency, impact (by means of caregiver satisfaction) and possible determinants of complications. For that purpose retrospective data research was conducted and a cross-sectional satisfaction questionnaire was administered. All children treated with intrathecal baclofen therapy in the VU medical centre, Amsterdam, are included in the study. Minimum follow-up was six months. The baclofen pumps were implanted from March 2001 to May 2007.We found 0.28 (0.19-0.42) complications per patient per year. In other studies this value varies between 0.09 and 0.58 complications per patient per year. Catheter-related complications were the most common. Three determinants proved to be associated with the rate of complications: the level of the catheter tip, pulmonary co-morbidity and the use of corticosteroids. The results of the satisfaction questionnaire showed that there is no less satisfaction in parents/guardians of children with one or more complications as compared to parents of children without complications. Of parents questioned, 88% would again choose for intrathecal baclofen therapy. The results of the satisfaction questionnaire support the hypothesis that in their judgement parents/guardians focus more on functional gain of the treatment than on possible complications.

Cerebral ultrasound abnormalities in preterm infants caused by late-onset sepsis

Introduction This study describes cerebral ultrasound abnormalities caused by late-onset sepsis (LOS) in very preterm infants with a gestational age of < 32 weeks and/or birthweight < 1500 grams. Methods The prospective study (“INFANT study”) included 117 preterm infants with suspected LOS. Proven LOS was defined as a positive blood culture after 72 hours of life. In case of coagulase-negative staphylococci an elevated C-reactive protein was additionally required to establish proven LOS. Patients were identified as proven LOS and patients with only clinical symptoms of LOS. Cerebral ultrasound images were obtained in the first week after birth, during/after LOS and before discharge. Cerebral findings were divided in no/minor and major abnormalities. Results Eighty-six preterm infants had proven LOS and 31 preterm infants had only clinical signs of LOS. Four infants were excluded because pre-existing major brain abnormalities. No significant differences (p = 0.624) for incidence of major brain abnormalities on cerebral ultrasound were found. Conclusion No differences were revealed in prevalence of major brain abnormalities between the groups with proven LOS and with clinical signs of LOS. Both infants with a gram negative sepsis developed major brain abnormalities, whereas only two of 66 preterm infants coagulase-negative staphylococci sepsis developed major brain abnormalities.

Placental Histology After Minor Trauma in Pregnancy: A Pilot Study

Objective Trauma in pregnancy may cause placental abruption. Consequences of moderate placental injury on neurodevelopment are unknown. The aim was to evaluate placental histology after maternal trauma. Methods A prospective study was conducted at 2 tertiary medical centers in the Netherlands. Placentas from women exposed to maternal trauma ≥ 20 weeks’ gestational age were histologically examined. Neurological follow-up of the infants was performed at 1 year of age by means of Alberta Infant Motor Scale. Histological findings were compared to placentas from pregnancies without trauma. Principal Results Thirteen placentas were investigated in the trauma group. The control group consisted of 15 placentas. Placental pathology was seen more often in the trauma cases (11 of the 13) than in the controls (6 of the 15), P = .024. Neurological follow-up was normal. Conclusions In this small population, majority of the placentas showed pathology after minor trauma in pregnancy without consequences for neurodevelopment at 1 year.

Fetal MRI, lower acceptance by women in research vs. clinical setting

Abstract Aim: To determine acceptance of pregnant women to undergo fetal magnetic resonance imaging (MRI) examination in research and clinical setting. Methods: A prospective study included a research group [part of a study comparing brain ultrasound (US) to MRI in fetuses at risk for acquired brain damage] and a clinical group [fetuses with suspected (brain) anomalies after structural US examination] from 2011 to 2014. All women were advised to use sedatives. MRI declinations, use of sedation, MRI duration and imaging quality were compared between both groups. Results: Study participation was accepted in 57/104 (55%) research cases. Fetal MRI was performed in 34/104 (33%) research and 43/44 (98%) clinical cases. Reasons to decline study participation were MRI related in 41%, and participation was too burdensome in 46%. Acceptance was highest for indication infection and lowest in alloimmune thrombocytopenia and monochorionic twin pregnancy. Sedatives were used in 14/34 research and 43/43 clinical cases. Scan duration and quality were comparable (21 and 20 min in research and clinical cases, respectively, moderate/good quality in both groups). Conclusions: Pregnant women consider MRI more burdensome than professionals realize. Two-third of women at risk for fetal brain damage decline MRI examination. Future studies should evaluate which information about fetal MRI is supportive.

PP02.9 – 2853: Neurological follow-up of infants exposed to maternal trauma in pregnancy

Objective Limited knowledge is available about neurodevelopmental outcome after intrauterine mechanical trauma exposure, although 7–8% of pregnancies are complicated by trauma. Guidelines advise hospital admission after trauma in pregnancy, which enabled a prospective evaluation of perinatal and neurological outcome. Examination of fetal motility facilitates assessment of the integrity of the central nervous system. We hypothesize a transient influence on fetal motility after maternal trauma and normal neurological development at one year in case of minor trauma. Methods Pregnant women admitted for trauma after 20 weeks gestational age (GA) between 2011 and 2014 were eligible. Cause of trauma and severity of injuries were analyzed. Three one-hour ultrasonographic observations were performed within 8 hours (T1), 24–72 hours (T2) and > 72 hours (T3) after trauma. Assessment of motility concerned differentiation into specific movement patterns, quality and quantity of general movements (normal values: de Vries et al, Early Hum Dev 1982 and 1988). Neurological examinations were performed at term equivalent age according to Prechtl and at 1 year according to Touwen and Alberta Infant Motor Scale. Results Sixteen women participated at a median GA of 25+6 (range 20–38) weeks. Most traumas were traffic accidents or falls and injuries were mainly minor. Motility assessment showed abnormal differentiation in 2/16; 2/14 and 0/16; abnormal quality in 2/16; 3/14 and 6/16; and abnormal quantity in 6/16, 9/14 and 9/16 at T1, T2 and T3 respectively. Neurological development at 0 and 1 year was normal in 15/16 and 13/13 respectively. Conclusion This preliminary evaluation shows that fetal motility was affected after maternal trauma in majority of the fetuses, however, not transiently in all within four days. The neurological outcome at 0 and 1 year was normal. The changes in motility support the concern that even minor mechanical trauma may have influence on the functional integrity of the central nervous system.