Objectives To determine neonatal global and regional brain volumes in infants with congenital heart disease (CHD) in comparison with healthy controls and to determine brain growth. Study design ...Prospective cohort study in infants undergoing open-heart surgery for complex CHD. Global and regional volumetric measurements on preoperative cerebral magnetic resonance imaging were manually segmented in children without overt brain lesions. Results Preoperative brain volumetry of 19 patients demonstrates reduction in total and regional brain volumes, without any specific regional predilection compared with 19 healthy control infants (total brain volume reduction: 21%, regional brain volume reduction 8%-28%, all P < .001). Conclusions Infants with CHD undergoing bypass surgery have smaller brain volumes prior to surgery without a specific regional predilection. This suggests a fetal origin of reduced brain growth.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Our purpose was to evaluate the within-subject reproducibility of
diffusion tensor imaging (DTI) metrics and the visibility of major white matter structures. Images for 30 fetuses (20-33. ...postmenstrual weeks, normal neurodevelopment: 6 cases, cerebral pathology: 24 cases) were acquired on 1.5 T or 3.0 T MRI. DTI with 15 diffusion-weighting directions was repeated three times for each case, TR/TE: 2200/63 ms, voxel size: 1 ∗ 1 mm, slice thickness: 3-5 mm, b-factor: 700 s/mm
. Reproducibility was evaluated from structure detectability, variability of DTI measures using the coefficient of variation (CV), image correlation and structural similarity across repeated scans for six selected structures. The effect of age, scanner type, presence of pathology was determined using Wilcoxon rank sum test. White matter structures were detectable in the following percentage of fetuses in at least two of the three repeated scans: corpus callosum genu 76%, splenium 64%, internal capsule, posterior limb 60%, brainstem fibers 40% and temporooccipital association pathways 60%. The mean CV of DTI metrics ranged between 3% and 14.6% and we measured higher reproducibility in fetuses with normal brain development. Head motion was negatively correlated with reproducibility, this effect was partially ameliorated by motion-correction algorithm using image registration. Structures on 3.0 T had higher variability both with- and without motion correction. Fetal DTI is reproducible for projection and commissural bundles during mid-gestation, however, in 16-30% of the cases, data were corrupted by artifacts, resulting in impaired detection of white matter structures. To achieve robust results for the quantitative analysis of diffusivity and anisotropy values, fetal-specific image processing is recommended and repeated DTI is needed to ensure the detectability of fiber pathways.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objectives To assess long-term neurodevelopmental outcome of adolescents with congenital heart disease after open-heart surgery and to evaluate whether deficits are associated with cerebral injury ...detectable on magnetic resonance imaging (MRI). Study design We conducted a cohort study with longitudinal follow-up of 53 adolescents (mean age, 13.7 years; range, 11.4 to 16.9 years) who had undergone open-heart surgery with full-flow cardiopulmonary bypass during childhood and compared them with 41 age-matched controls. Assessment included conventional MRI and neurodevelopmental testing. Results MRI abnormalities were detected in 11 of the 53 patients (21%), comprising predominately white matter abnormalities and volume loss. Neurodevelopmental outcome was impaired in several domains, including neuromotor, intellectual, and executive functions, as well as visuomotor perception and integration. Adolescents with cerebral abnormalities had greater impairment in most neurodevelopmental domains compared with those without cerebral abnormalities. Conclusions Cerebral abnormalities can be detected in a significant proportion of adolescents with corrected congenital heart disease. These abnormalities are found predominately in the white matter and are apparently of hypoxic-ischemic origin, most likely acquired during the neonatal period.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Glutamine synthetase (GS) is ubiquitously expressed in mammalian organisms and is a key enzyme in nitrogen metabolism. It is the only known enzyme capable of synthesising glutamine, an amino acid ...with many critical roles in the human organism. A defect in GLUL, encoding for GS, leads to congenital systemic glutamine deficiency and has been described in three patients with epileptic encephalopathy. There is no established treatment for this condition.Here, we describe a therapeutic trial consisting of enteral and parenteral glutamine supplementation in a four year old patient with GS deficiency. The patient received increasing doses of glutamine up to 1020 mg/kg/day. The effect of this glutamine supplementation was monitored clinically, biochemically, and by studies of the electroencephalogram (EEG) as well as by brain magnetic resonance imaging and spectroscopy.Treatment was well tolerated and clinical monitoring showed improved alertness. Concentrations of plasma glutamine normalized while levels in cerebrospinal fluid increased but remained below the lower reference range. The EEG showed clear improvement and spectroscopy revealed increasing concentrations of glutamine and glutamate in brain tissue. Concomitantly, there was no worsening of pre-existing chronic hyperammonemia.In conclusion, supplementation of glutamine is a safe therapeutic option for inherited GS deficiency since it corrects the peripheral biochemical phenotype and partially also improves the central biochemical phenotype. There was some clinical improvement but the patient had a long standing severe encephalopathy. Earlier supplementation with glutamine might have prevented some of the neuronal damage.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Oral-Facial-Digital Syndrome type VI (OFD VI) represents a rare phenotypic subtype of Joubert syndrome and related disorders (JSRD). In the original report polydactyly, oral findings, intellectual ...disability, and absence of the cerebellar vermis at post-mortem characterized the syndrome. Subsequently, the molar tooth sign (MTS) has been found in patients with OFD VI, prompting the inclusion of OFD VI in JSRD. We studied the clinical, neurodevelopmental, neuroimaging, and genetic findings in a cohort of 16 patients with OFD VI. We derived the following inclusion criteria from the literature: 1) MTS and one oral finding and polydactyly, or 2) MTS and more than one typical oral finding. The OFD VI neuroimaging pattern was found to be more severe than in other JSRD subgroups and includes severe hypoplasia of the cerebellar vermis, hypoplastic and dysplastic cerebellar hemispheres, marked enlargement of the posterior fossa, increased retrocerebellar collection of cerebrospinal fluid, abnormal brainstem, and frequently supratentorial abnormalities that occasionally include characteristic hypothalamic hamartomas. Additionally, two new JSRD neuroimaging findings (ascending superior cerebellar peduncles and fused thalami) have been identified. Tongue hamartomas, additional frenula, upper lip notch, and mesoaxial polydactyly are specific findings in OFD VI, while cleft lip/palate and other types of polydactyly of hands and feet are not specific. Involvement of other organs may include ocular findings, particularly colobomas. The majority of the patients have absent motor development and profound cognitive impairment. In OFD VI, normal cognitive functions are possible, but exceptional. Sequencing of known JSRD genes in most patients failed to detect pathogenetic mutations, therefore the genetic basis of OFD VI remains unknown. Compared with other JSRD subgroups, the neurological findings and impairment of motor development and cognitive functions in OFD VI are significantly worse, suggesting a correlation with the more severe neuroimaging findings. Based on the literature and this study we suggest as diagnostic criteria for OFD VI: MTS and one or more of the following: 1) tongue hamartoma(s) and/or additional frenula and/or upper lip notch; 2) mesoaxial polydactyly of one or more hands or feet; 3) hypothalamic hamartoma.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
The primary aim was to compare fractional anisotropy (FA) values derived with different diffusion tensor imaging (DTI) analysis approaches (atlas-based, streamline tractography, and ...combined). A secondary aim was to compare FA values and number of tracts (NT) with the clinical motor outcome quantified by the functional independence measure for children (WeeFIM).
Methods
Thirty-nine DTI datasets of children with acquired brain injury were analysed. Regions of interest for the ipsilesional corticospinal tract were defined and mean FA and NT were calculated. We evaluated FA values with Spearman correlation, the Friedman and Wilcoxon tests, and Bland-Altman analysis. DTI values were compared to WeeFIM values by non-parametric partial correlation and accuracy was assessed by receiver operating characteristics analysis.
Results
The FA values from all approaches correlated significantly with each other (
p
< 0.001). However, the FA values from streamline tractography were significantly higher (mean ± standard deviation (SD), 0.52 ± 0.08) than those from the atlas-based (0.42 ± 0.11) or the combined approach (0.41 ± 0.11) (
p
< 0.001 for both). FA and NT values correlated significantly with WeeFIM values (atlas-based FA, partial correlation coefficient (ρ) = 0.545,
p
= 0.001; streamline FA, ρ = 0.505,
p
= 0.002; NT, ρ = 0.434,
p
= 0.008; combined FA, ρ = 0.611,
p
< 0.001). FA of the atlas-based approach (sensitivity 90%, specificity 67%, area under the curve 0.82) and the combined approach (87%, 67%, 0.82), provided the highest predictive accuracy for outcome compared to FA (70%, 67%, 0.67) and NT (50%, 100%, 0.79, respectively) of the streamline approach.
Conclusion
FA values from streamline tractography were higher than those from the atlas-based and combined approach. The atlas-based and combined approach offer the best predictive accuracy for motor outcome, although both atlas-based and streamline tractography approaches provide significant predictors of clinical outcome.
Objectives
To describe characteristics of foetuses undergoing in utero repair of open neural tube defects (ONTD) and assess postoperative evolution of posterior fossa and brain morphology.
Methods
...Analysis of pre- and postoperative foetal as well as neonatal MRI of 27 foetuses who underwent in utero repair of ONTD. Type and level of ONTD, hindbrain configuration, posterior fossa and liquor space dimensions, and detection of associated findings were compared between MRI studies and to age-matched controls.
Results
Level of bony spinal defect was defined with exactness of ± one vertebral body. Of surgically confirmed 18 myelomeningoceles (MMC) and 9 myeloschisis (MS), 3 MMC were misdiagnosed as MS due to non-visualisation of a flat membrane on MRI. Hindbrain herniation was more severe in MS than MMC (
p
< 0.001). After repair, hindbrain herniation resolved in 25/27 cases at 4 weeks and liquor spaces increased. While posterior fossa remained small (
p
< 0.001), its configuration normalised. Lateral ventricle diameter indexed to cerebral width decreased in 48% and increased in 12% of cases, implying a low rate of progressive obstructive hydrocephalus. Neonatally evident subependymal heterotopias were detected in 33% at preoperative and 50% at postoperative foetal MRI.
Conclusion
MRI demonstrates change of Chiari malformation type II (CM-II) features.
Key Points
•
Hindbrain herniation is significantly more pronounced in myeloschisis than in myelomeningocele
•
Resolution of hindbrain herniation 4 weeks after in utero closure of ONTD
•
MRI is valuable for preoperative assessment and postoperative evaluation following in utero repair
Arhinia, or absence of the nose, is a rare malformation of unknown etiology that is often accompanied by ocular and reproductive defects. Sequencing of 40 people with arhinia revealed that 84% of ...probands harbor a missense mutation localized to a constrained region of SMCHD1 encompassing the ATPase domain. SMCHD1 mutations cause facioscapulohumeral muscular dystrophy type 2 (FSHD2) via a trans-acting loss-of-function epigenetic mechanism. We discovered shared mutations and comparable DNA hypomethylation patterning between these distinct disorders. CRISPR/Cas9-mediated alteration of smchd1 in zebrafish yielded arhinia-relevant phenotypes. Transcriptome and protein analyses in arhinia probands and controls showed no differences in SMCHD1 mRNA or protein abundance but revealed regulatory changes in genes and pathways associated with craniofacial patterning. Mutations in SMCHD1 thus contribute to distinct phenotypic spectra, from craniofacial malformation and reproductive disorders to muscular dystrophy, which we speculate to be consistent with oligogenic mechanisms resulting in pleiotropic outcomes.
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IJS, NUK, SBMB, UL, UM, UPUK
Summary
Introduction
Deep sedation using propofol has become a standard technique in children. This double‐blinded randomized clinical trial aims to compare the clinical effects of ...propofol‐mono‐sedation vs a combination of propofol and ketamine at induction and a reduced propofol infusion rate for maintenance in children undergoing diagnostic magnetic resonance imaging.
Methods
Children aged from 3 months to 10 years scheduled as outpatients for elective magnetic resonance imaging with deep sedation were included. They were randomized into 2 groups, receiving either 1 mg/kg ketamine at induction, then a propofol infusion rate of 5 mg/kg/h or a propofol infusion rate of 10 mg/kg/h without prior ketamine. Time to full recovery (modified Aldrete score = 10) was the primary outcome. Further outcomes were quality of induction, immobilization during image acquisition, recovery, postoperative nausea and vomiting, emergence delirium using the Pediatric Anesthesia Emergence Delirium scale, vital signs and adverse cardiorespiratory events. All patients and parents as well as anesthetists, imaging technicians, and postsedation personnel were blinded. Data are given as median (range).
Results
In total, 347 children aged 4.0 (0.25‐10.9) years, weighing 15.6 (5.3‐54) kg, ASA classification I, II, or III (141/188/18) were included. The ketamine‐propofol group showed significantly shorter recovery times (38 (22‐65) vs 54 (37‐77) minutes; median difference 14 (95% CI: 8, 20) minutes; P < .001), better quality of induction, and higher blood pressure, but higher incidence of movement requiring additional sedative drugs. There were no significant differences in respiratory side effects, cardiovascular compromise, emergence delirium, or postoperative nausea and vomiting.
Conclusion
Both sedation concepts proved to be reliable with a low incidence of side effects. Ketamine at induction with a reduced propofol infusion rate leads to faster postanesthetic recovery.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
BackgroundLittle is known about the relationship between brain volumes and neurodevelopmental outcome at 2 years of age in children with single-ventricle congenital heart disease (CHD). We ...hypothesized that reduced brain volumes may be associated with adverse neurodevelopmental outcome.MethodsVolumetric segmentation of cerebral magnetic resonance imaging (MRI) scans was carried out in 44 patients without genetic comorbidities and in 8 controls. Neurodevelopmental outcome was assessed with the Bayley-III scales.ResultsGray matter (GM), deep GM, white matter (WM), and cerebrospinal fluid (CSF) volumes were 611±59, 43±4.5, 277±30, and 16.4 ml, respectively (interquartile range (IQR) 13.1, 23.3 ml). Children undergoing neonatal cardiopulmonary bypass surgery showed smaller deep GM (P=0.005) and WM (P=0.021) volumes. Brain volumes were smaller in patients compared with controls (GM: P=0.017, deep GM: P=0.012, and WM: P=0.015), whereas CSF volumes were greater (P=0.014). Of all intracranial volumes, only CSF volume was associated with neurodevelopmental outcome, accounting for 21% (P=0.011) of variability in the cognitive composite score when combined with common risk factors in a multivariable analysis.ConclusionIncreased CSF volume represents a significant risk factor for neurodevelopmental impairment in children with single-ventricle CHD. Later assessments are warranted to determine the prognostic role of intracranial volumes for long-term outcome.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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