Potentially Life-Threatening Interaction between Opioids and Intrathecal Baclofen in Individuals with a Childhood-Onset Neurological Disorder: A Case Series and Review of the Literature.

BACKGROUND: Spasticity and dystonia are movement impairments that can occur in childhood-onset neurological disorders. Severely affected individuals can be treated with intrathecal baclofen (ITB). Concomitant use of ITB and opioids has been associated with central nervous system (CNS) depression. This study aims to describe the clinical management of this interaction, based on a case series and review of literature. METHODS: Four individuals with childhood-onset CNS disorders (age 8-24) and CNS-depressant overdose symptoms after the concomitant use of ITB and opioids are described. The Drug Interaction Probability Scale (DIPS) was calculated to assess the cause-relationship (doubtful <2, possible 2-4, probable 5-8, and highly probable >8) of the potential drug-drug interaction. A literature review of similar previously reported cases and the possible pharmacological mechanisms of opioid-baclofen interaction is provided. RESULTS: After ITB and opioid co-administration, three out of four patients had decreased consciousness, and three developed respiratory depression. DIPS scores indicated a possible cause-relationship in one patient (DIPS: 4) and a probable cause-relationship in the others (DIPS: 6, 6, and 8). Discontinuation or adjusting ITB or opioid dosages resulted in clinical recovery. All patients recovered completely. In the literature, two articles describing nine unique cases were found. CONCLUSION: Although the opioid-ITB interaction is incompletely understood, concomitant use may enhance the risk of symptoms of CNS-depressant overdose, which are potentially life-threatening. If concomitant use is desirable, we strongly recommend to closely monitor these patients to detect interaction symptoms early. Awareness and monitoring of the potential opioid-ITB interaction is essential to reduce the risk of severe complications.

Surgical treatment options for spasticity in children and adolescents with hereditary spastic paraplegia.

PURPOSE: To provide an overview of outcome and complications of selective dorsal rhizotomy (SDR) and intrathecal baclofen pump implantation (ITB) for spasticity treatment in children with hereditary spastic paraplegia (HSP). METHODS: Retrospective study including children with HSP and SDR or ITB. Gross motor function measure (GMFM-66) scores and level of spasticity were assessed. RESULTS: Ten patients were included (most had mutations in ATL1 (n = 4) or SPAST (n = 3) genes). Four walked without and two with walking aids, four were non-walking children. Six patients underwent SDR, three patients ITB, and one both. Mean age at surgery was 8.9 ± 4.5 years with a mean follow-up of 3.4 ± 2.2 years. Five of the SDR patients were walking. Postoperatively spasticity in the legs was reduced in all patients. The change in GMFM-66 score was + 8.0 (0-19.7 min-max). The three ITB patients treated (SPAST (n = 2) and PNPLA6 (n = 1) gene mutation) were children with a progressive disease course. No complications of surgery occurred. CONCLUSIONS: SDR is a feasible treatment option in carefully selected children with HSP, especially in walking patients. The majority of patients benefit with respect to gross motor function, complication risk is low. ITB was used in children with severe and progressive disease.

Clinical and functional heterogeneity associated with the disruption of retinoic acid receptor beta.

PURPOSE: Dominant variants in the retinoic acid receptor beta (RARB) gene underlie a syndromic form of microphthalmia, known as MCOPS12, which is associated with other birth anomalies and global developmental delay with spasticity and/or dystonia. Here, we report 25 affected individuals with 17 novel pathogenic or likely pathogenic variants in RARB. This study aims to characterize the functional impact of these variants and describe the clinical spectrum of MCOPS12. METHODS: We used in vitro transcriptional assays and in silico structural analysis to assess the functional relevance of RARB variants in affecting the normal response to retinoids. RESULTS: We found that all RARB variants tested in our assays exhibited either a gain-of-function or a loss-of-function activity. Loss-of-function variants disrupted RARB function through a dominant-negative effect, possibly by disrupting ligand binding and/or coactivators' recruitment. By reviewing clinical data from 52 affected individuals, we found that disruption of RARB is associated with a more variable phenotype than initially suspected, with the absence in some individuals of cardinal features of MCOPS12, such as developmental eye anomaly or motor impairment. CONCLUSION: Our study indicates that pathogenic variants in RARB are functionally heterogeneous and associated with extensive clinical heterogeneity.

Brain structural and functional connectivity and network organization in cerebral palsy: A scoping review.

AIM: To explore altered structural and functional connectivity and network organization in cerebral palsy (CP), by clinical CP subtype (unilateral spastic, bilateral spastic, dyskinetic, and ataxic CP). METHOD: PubMed and Embase databases were systematically searched. Extracted data included clinical characteristics, analyses, outcome measures, and results. RESULTS: Sixty-five studies were included, of which 50 investigated structural connectivity, and 20 investigated functional connectivity using functional magnetic resonance imaging (14 studies) or electroencephalography (six studies). Five of the 50 studies of structural connectivity and one of 14 of functional connectivity investigated whole-brain network organization. Most studies included patients with unilateral spastic CP; none included ataxic CP. INTERPRETATION: Differences in structural and functional connectivity were observed between investigated clinical CP subtypes and typically developing individuals on a wide variety of measures, including efferent, afferent, interhemispheric, and intrahemispheric connections. Directions for future research include extending knowledge in underrepresented CP subtypes and methodologies, evaluating the prognostic potential of specific connectivity and network measures in neonates, and understanding therapeutic effects on brain connectivity.

Combining advanced MRI and EEG techniques better explains long-term motor outcome after very preterm birth.

BACKGROUND: Preterm born children are at high risk for adverse motor neurodevelopment. The aim of this study was to establish the relationship between motor outcome and advanced magnetic resonance imaging (MRI) and electroencephalography (EEG) measures. METHODS: In a prospective cohort study of 64 very preterm born children, the motor outcome was assessed at 9.83 (SD 0.70) years. Volumetric MRI, diffusion tensor imaging (DTI), and EEG were acquired at 10.85 (SD 0.49) years. We investigated associations between motor outcome and brain volumes (white matter, deep gray matter, cerebellum, and ventricles), white matter integrity (fractional anisotropy and mean, axial and radial diffusivity), and brain activity (upper alpha (A2) functional connectivity and relative A2 power). The independence of associations with motor outcome was investigated with a final model. For each technique, the measure with the strongest association was selected to avoid multicollinearity. RESULTS: Ventricular volume, radial diffusivity, mean diffusivity, relative A2 power, and A2 functional connectivity were significantly correlated to motor outcome. The final model showed that ventricular volume and relative A2 power were independently associated with motor outcome (B = -9.42 × 10-5, p = 0.027 and B = 28.9, p = 0.007, respectively). CONCLUSIONS: This study suggests that a lasting interplay exists between brain structure and function that might underlie motor outcome at school age. IMPACT: This is the first study that investigates the relationships between motor outcome and brain volumes, DTI, and brain function in preterm born children at school age. Ventricular volume and relative upper alpha power on EEG have an independent relation with motor outcome in preterm born children at school age. This suggests that there is a lasting interplay between structure and function that underlies adverse motor outcome.

Neonatal quantitative electroencephalography and long-term outcomes: a systematic review.

AIM: To evaluate quantitative electroencephalogram (EEG) measures as predictors of long-term neurodevelopmental outcome in infants with a postconceptional age below 46 weeks, including typically developing infants born at term, infants with heterogeneous underlying pathologies, and infants born preterm. METHOD: A comprehensive search was performed using PubMed, Embase, and Web of Science from study inception up to 8th January 2021. Studies that examined associations between neonatal quantitative EEG measures, based on conventional and amplitude-integrated EEG, and standardized neurodevelopmental outcomes at 2 years of age or older were reviewed. Significant associations between neonatal quantitative EEG and long-term outcome measures were grouped into one or more of the following categories: cognitive outcome; motor outcome; composite scores; and other standardized outcome assessments. RESULTS: Twenty-four out of 1740 studies were included. Multiple studies showed that conventional EEG-based absolute power in the delta, theta, alpha, and beta frequency bands and conventional and amplitude-integrated EEG-related amplitudes were positively associated with favourable long-term outcome across several domains, including cognition and motor performance. Furthermore, a lower presence of discontinuous background pattern was also associated with favourable outcomes. However, interpretation of the results is limited by heterogeneity in study design and populations. INTERPRETATION: Neonatal quantitative EEG measures may be used as prognostic biomarkers to identify those infants who will develop long-term difficulties and who might benefit from early interventions.

Neuromuscular Control before and after Independent Walking Onset in Children with Cerebral Palsy.

Early brain lesions which produce cerebral palsy (CP) may affect the development of walking. It is unclear whether or how neuromuscular control, as evaluated by muscle synergy analysis, differs in young children with CP compared to typically developing (TD) children with the same walking ability, before and after the onset of independent walking. Here we grouped twenty children with (high risk of) CP and twenty TD children (age 6.5-52.4 months) based on their walking ability, supported or independent walking. Muscle synergies were extracted from electromyography data of bilateral leg muscles using non-negative matrix factorization. Number, synergies' structure and variability accounted for when extracting one (VAF1) or two (VAF2) synergies were compared between CP and TD. Children in the CP group recruited fewer synergies with higher VAF1 and VAF2 compared to TD children in the supported and independent walking group. The most affected side in children with asymmetric CP walking independently recruited fewer synergies with higher VAF1 compared to the least affected side. Our findings suggest that early brain lesions result in early alterations of neuromuscular control, specific for the most affected side in asymmetric CP.

Care Pathway for Foetal Joint Contractures, Foetal Akinesia Deformation Sequence, and Arthrogryposis Multiplex Congenita.

INTRODUCTION: The majority of arthrogryposis multiplex congenita (AMC) and lethal forms of AMC such as foetal akinesia deformation sequence (FADS) cases are missed prenatally. We have demonstrated the additional value of foetal motor assessment and evaluation in a multidisciplinary team for the period 2007-2016. An applied care pathway was developed for foetuses presenting with joint contracture(s) in one anatomic region (e.g., talipes equinovarus [TEV]), more than one body part with non-progressive contractures and motility (AMC) and with deterioration over time (FADS). METHODS: The multidisciplinary team of Amsterdam University Medical Centre Expertise Centre FADS and AMC developed the care pathway. Additional tools are provided including a motor assessment by ultrasound examination and a post-mortem assessment form. RESULTS: An eight-step care pathway is presented with a proposed timing for prenatal sonographic examination, genetic examinations, multidisciplinary meetings, prenatal and postnatal counselling of the parents by a specialist also treating after birth, and the follow-up of prenatal and postnatal findings with counselling for future pregnancies. DISCUSSION/CONCLUSION: The scheduled serial structural and motor sonograpahic assessment together with follow-up examinations and genetic analysis should be tailored per prenatal centre per available resources. The multidisciplinary care pathway may pave the way to increase the detection rate and diagnosis of isolated contracture(s), TEV with underlying genetic causes, and the rare phenotypes AMC/FADS and prompt treatment after birth within expertise teams.

Spectroscopic detection of brain propylene glycol in neonates: Effects of different pharmaceutical formulations of phenobarbital.

BACKGROUND: The first choice for treatment of neonatal convulsions is intravenous phenobarbital, which contains propylene glycol (PG) as a solvent. Although PG is generally considered safe, the dosage can exceed safety thresholds in neonates. High PG levels can cause lactic acidosis. PURPOSE/HYPOTHESIS: To investigate a relationship between brain PG concentration and medication administered to neonates, and to study if a correlation between spectroscopically detected PG and lactate was present. STUDY TYPE: Retrospective. POPULATION: Forty-one neonates who underwent MRI/MRS. FIELD STRENGTH/SEQUENCE: Short echo time single voxel MRS at 1.5T. ASSESSMENT: Spectra were quantified. Concentrations of PG were correlated with medication administered, because intravenously administered phenobarbital solutions contained 10, 25, or 50 mg phenobarbital per ml, all containing 350 mg PG per ml. The interval between medication and MRI/MRS was determined. STATISTICAL TESTS: Chi-square test, Student's t-test, Mann-Whitney U-test and Spearman correlation. RESULTS: Eighteen neonates had brain PG >1 mM (median 3.4 mM, maximum 9.5 mM). All 18 neonates with high brain PG and 14 neonates with low brain PG (<1 mM) received phenobarbital as the only source of PG. Nine neonates did not receive any phenobarbital/PG-containing medication. Neonates with high brain PG more often received 10 mg/ml phenobarbital, resulting in higher PG dose (high vs. low brain PG (median [interquartile range]: 1400 [595] vs. 350 [595] mg/kg, respectively, P < 0.01). In addition, the interval between the last phenobarbital dose and MRI was shorter in the high brain PG group (high vs. low brain PG: 16 [21] vs. 95 [83] hours, respectively, P < 0.001). Within neonates that received phenobarbital, there was no conclusive correlation between spectroscopically detected PG and lactate (Spearman's rho = 0.23, P = 0.10). DATA CONCLUSION: These MRS findings may increase awareness of potentially toxic PG concentrations in the neonatal brain due to intravenous phenobarbital administration and its dependence on the phenobarbital formulation used. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019;49:1062-1068.

Intrathecal baclofen in metachromatic leukodystrophy.

Metachromatic leukodystrophy (MLD) is a rare progressive neurological disorder, often accompanied by motor impairments that are challenging to treat. In this case series, we report the course of treatment with intrathecal baclofen (ITB), aimed at improving daily care and comfort in children and young adults with MLD. All patients with MLD in our centre on ITB treatment for a minimum of 6 months were included (n=10; 4 males, 6 females; mean age 10y 8mo [range 6-24y]). Eight patients had MLD with a predominant spastic movement disorder (sMLD) and two were mainly dyskinetic. Patients with sMLD were compared with matched patients with spastic cerebral palsy (CP). Complication rates related to ITB treatment were similar in both groups. ITB treatment course in the first 6 months after pump implantation appears to show more dose increase in most patients MLD, compared to patients with spastic CP. This may be due to the progressive disease in MLD. ITB is a feasible therapy to improve daily care and comfort in patients with MLD and should therefore be considered early. WHAT THIS PAPER ADDS: Intrathecal baclofen (ITB) is a feasible therapy to improve comfort and daily care in children and young people with metachromatic leukodystrophy (MLD). In the first 6 months of ITB treatment, MLD seems to show more dose increase compared to spastic cerebral palsy.

Fetal akinesia deformation sequence, arthrogryposis multiplex congenita, and bilateral clubfeet: Is motor assessment of additional value for in utero diagnosis? A 10-year cohort study.

OBJECTIVE: The diagnosis of fetal akinesia deformation sequence (FADS) is a challenge. Motor assessment is of additional value to advanced ultrasound examinations (AUE) for in utero FADS diagnosis before 24 weeks of gestation. METHODS: All consecutive fetuses with greater than or equal to two contractures on the 20 week structural anomaly scan (2007-2016) were included. Findings at AUE, including motor assessment were analysed and related to outcome. RESULTS: Sixty-six fetuses fulfilled the inclusion criteria. On the basis of the first AUE, FADS was suspected in 13 of 66, arthrogryposis multiplex congenita (AMC) in 12 of 66, bilateral pes equinovares (BPEV) in 40 of 66, and Holt-Oram syndrome in one of 66. On the basis of the first motor assessment, the suspected diagnosis changed in 19 of 66, in 13 of 66 worsening to FADS, six of 66 amelioration from FADS, and confirmed FADS in seven of 13. The result was 20 FADS, seven AMC, and 38 BPEV. Second AUE in 44 fetuses showed additional contractures in two of eight FADS, and one intrauterine fetal death (IUFD). The second motor assessment changed the diagnosis in three of 43, one worsening from BPEV into FADS, two ameliorations from FADS, and confirmed FADS in seven by deterioration of motility. The result was nine FADS, six AMC, and 29 BPEV. CONCLUSION: The results suggest that motor assessment has additional value to distinguish between FADS, AMC, and BPEV.

Factors Associated With Long-Term Improvement of Gait After Selective Dorsal Rhizotomy.

OBJECTIVE: To identify factors associated with long-term improvement in gait in children after selective dorsal rhizotomy (SDR). DESIGN: Retrospective cohort study. SETTING: University medical center. PARTICIPANTS: Children (N=36) (age 4-13y) with spastic diplegia of Gross Motor Function Classification System (GMFCS) level I (n=14), II (n=15), and III (n=7) were included retrospectively from the database of our hospital. Children underwent SDR between January 1999 and May 2011. Patients were included if they received clinical gait analysis before and 5 years post-SDR, age >4 years at time of SDR and if brain magnetic resonance imaging (MRI) scan was available. INTERVENTION: Selective dorsal rhizotomy. MAIN OUTCOME MEASURES: Overall gait quality was assessed with Edinburgh visual gait score (EVGS), before and 5 years after SDR. In addition, knee and ankle angles at initial contact and midstance were evaluated. To identify predictors for gait improvement, several factors were evaluated including functional mobility level GMFCS, presence of white matter abnormalities on brain MRI, and selective motor control during gait (synergy analysis). RESULTS: Overall gait quality improved after SDR, with a large variation between patients. Multiple linear regression analysis revealed that worse score on EVGS and better GMFCS were independently related to gait improvement. Gait improved more in children with GMFCS I and II compared to III. No differences were observed between children with or without white matter abnormalities on brain MRI. Selective motor control during gait was predictive for improvement of knee angle at initial contact and midstance, but not for EVGS. CONCLUSION: Functional mobility level and baseline gait quality are both important factors to predict gait outcomes after SDR. If candidates are well selected, SDR can be a successful intervention to improve gait both in children with brain MRI abnormalities as well as other causes of spastic diplegia.

Risk Factors for Dystonia after Selective Dorsal Rhizotomy in Nonwalking Children and Adolescents with Bilateral Spasticity.

We recently showed a beneficial effect of selective dorsal rhizotomy (SDR) on daily care and comfort in nonwalking children with severe bilateral spasticity. However, despite careful selection, some patients showed dystonia after the intervention, in which cases caregivers tended to be less satisfied with the result.The aim of this study is to identify risk factors for dystonia after SDR in children and adolescents with severe bilateral spasticity (GMFCS levels IV/V).Clinical and MRI risk factors for dystonia after SDR were studied in our cohort of 24 patients. Patients with clinical evidence of dystonia and brain MRI showing basal ganglia abnormalities were excluded for SDR.Nine of 24 patients (38%) showed some degree of dystonia after SDR. There was a significant association between the cause of spasticity and dystonia after SDR; in six (67%) patients with a congenital disorder, dystonia was present versus three (20%) with an acquired disorder (Chi-squared test: C(1) = 5.23, p = 0.02).This study allows more optimal selection of patients that may benefit from SDR. Patients with an acquired cause of spasticity, when selected carefully on clinical examination and MRI, rarely show dystonia after SDR. However, patients with an underlying congenital disorder have a considerable risk of dystonia after SDR.

Pediatric neurocysticercosis: three cases presented in the Netherlands with divergent clinical presentations.

BACKGROUND: Neurocysticercosis is a helminthic disease that affects the central nervous system by the larvae of the Taenia solium, the pork tapeworm. Because of the growing number of immigrants from endemic areas, its incidence is increasing in Western Europe. CASES: We describe three children, aged between 2 and 13 years, two of whom have a definite and one a probable diagnosis of neurocysticercosis based on the "Del Brutto criteria." They presented with different symptoms and signs: symptomatic epilepsy, asymmetric cerebral palsy, and headache. Serological evaluation was negative in two of the three cases. All cases showed comparable abnormalities on magnetic resonance imaging of the brain: solitary or multiple, cystic lesions, with surrounding edema. In one of them, the "scolex" (part of the larvae) could be visualized. One case was treated with albendazole, the other two cases did not receive medication. CONCLUSION: A prompt diagnosis of neurocysticercosis by recognition of its typical brain lesions is important to prevent unnecessary diagnostic tests and treatment.

Early-Onset Severe Encephalopathy with Epilepsy: The BRAT1 Gene Should Be Added to the List of Causes.

A variety of pathologies can underlie early-onset severe encephalopathy with epilepsy. To aid the diagnostic process in such patients we present an overview of causes, including the rapidly expanding list of genes involved. When no explanation is found, whole-exome sequencing (WES) can be used in an attempt to identify gene defects in patients suspected to suffer from a genetic form. We describe three siblings, born to consanguineous parents, with a lethal severe epileptic encephalopathy with early-infantile onset, including their magnetic resonance imaging, electroencephalography and, in one case, neuropathological findings. Using WES a homozygous frameshift mutation in the BRAT1 gene, c.638dup p.(Val214Glyfs*189), was identified. We present our cases in the context of all published cases with mutations in the BRAT1 gene and conclude that BRAT1 should be added to the growing list of genes related to early-onset severe encephalopathy with epilepsy.

Predictive value of brain MRI for neurodevelopmental outcome in infants with severe unconjugated hyperbilirubinemia: A systematic review.

CONTEXT: Debate exists regarding predictive value of brain MRI for long-term neurodevelopmental outcome (NDO) in infants with severe unconjugated hyperbilirubinemia (above exchange transfusion levels). OBJECTIVE: To investigate whether MRI findings among (pre-)term infants with severe unconjugated hyperbilirubinemia can predict NDO at ≥ 12 months and determine optimal timing for MRI. DATA SOURCES: PubMed and Embase. Last update: June 14, 2024. STUDY SELECTION: Studies in which (pre-)term infants with severe unconjugated hyperbilirubinemia who underwent an MRI before 24 months and had a reported NDO at ≥ 12 months were included. DATA EXTRACTION: Patient characteristics, MRI and NDO details were extracted. RESULTS: The search yielded 732 studies, of which 22 were included. Individual patient information was obtained for 120 infants (MRI-timing: early (≤6 weeks) n = 75, late (>6 weeks) n = 19, unknown n = 26). Positive predictive value (PPV) of abnormal MRI in the total group for impaired NDO was high (77.5 %). The PPV of late compared to early MRI was much higher, 92.3 % versus 71.7 %. Negative predictive value of normal MRI for normal NDO in the total group was low (29.0 %) and again higher in late compared to early MRI, 50.0 % versus 27.3 %. LIMITATIONS: Quantitative synthesis of results was impossible due to large heterogeneity in study designs. Furthermore, selection bias towards patients with impaired outcome might have influenced our results. CONCLUSIONS: Brain MRI can serve as prognostic tool for NDO in infants with severe unconjugated hyperbilirubinemia, both in early and late stages, but each timing has inherent constraints. Further prospective studies are necessary.

Dyskinetic crisis in GNAO1-related disorders: clinical perspectives and management strategies.

Background: GNAO1-related disorders (GNAO1-RD) encompass a diverse spectrum of neurodevelopmental and movement disorders arising from variants in the GNAO1 gene. Dyskinetic crises, marked by sudden and intense exacerbations of abnormal involuntary movements, present a significant challenge in GNAO1-RD. Objectives: This study aimed to establish a standardized framework for understanding dyskinetic crises, addressing crucial aspects such as definition, triggers, diagnostic criteria, complications, and management strategies. Methods: A Delphi consensus process was conducted involving international experts in GNAO1-RD. The panel of thirteen experts participated in three voting rounds, discussing 90 statements generated through a literature review and clinical expertise. Results: Consensus was achieved on 31 statements, defining dyskinetic crises as abrupt, paroxysmal episodes involving distinct abnormal movements in multiple body regions, triggered by emotional stress or infections. Dyskinetic crises may lead to functional impairment and complications, emphasizing the need for prompt recognition. While individualized pharmacological recommendations were not provided, benzodiazepines and clonidine were suggested for acute crisis management. Chronic treatment options included tetrabenazine, benzodiazepines, gabapentin, and clonidine. Deep brain stimulation should be considered early in the treatment of refractory or prolonged dyskinetic crisis. Conclusion: This consensus provides a foundation for understanding and managing dyskinetic crises in GNAO1-RD for clinicians, caregivers, and researchers. The study emphasizes the importance of targeted parental and caregiver education, which enables early recognition and intervention, thereby potentially minimizing both short- and long-term complications. Future research should concentrate on differentiating dyskinetic crises from other neurological events and investigating potential risk factors that influence their occurrence and nature. The proposed standardized framework improves clinical management, stakeholder communication, and future GNAO1-RD research.

Brain MRI Injury Patterns across Gestational Age among Preterm Infants with Perinatal Asphyxia.

INTRODUCTION: Brain injury patterns of preterm infants with perinatal asphyxia (PA) are underreported. We aimed to explore brain magnetic resonance imaging (MRI) findings and associated neurodevelopmental outcomes in these newborns. METHODS: Retrospective multicenter study included infants with gestational age (GA) 24.0-36.0 weeks and PA, defined as ≥2 of the following: (1) umbilical cord pH ≤7.0, (2) 5-min Apgar score ≤5, and (3) fetal distress or systemic effects of PA. Findings were compared between GA <28.0 (group 1), 28.0-31.9 (group 2), and 32.0-36.0 weeks (group 3). Early MRI (<36 weeks postmenstrual age or <10 postnatal days) was categorized according to predominant injury pattern, and MRI around term-equivalent age (TEA, 36.0-44.0 weeks and ≥10 postnatal days) using the Kidokoro score. Adverse outcomes included death, cerebral palsy, epilepsy, severe hearing/visual impairment, or neurodevelopment <-1 SD at 18-24 months corrected age. RESULTS: One hundred nineteen infants with early MRI (n = 94) and/or MRI around TEA (n = 66) were included. Early MRI showed predominantly hemorrhagic injury in groups 1 (56%) and 2 (45%), and white matter (WM)/watershed injury in group 3 (43%). Around TEA, WM scores were highest in groups 2 and 3. Deep gray matter (DGM) (aOR 15.0, 95% CI: 3.8-58.9) and hemorrhagic injury on early MRI (aOR 2.5, 95% CI: 1.3-4.6) and Kidokoro WM (aOR 1.3, 95% CI: 1.0-1.6) and DGM sub-scores (aOR 4.8, 95% CI: 1.1-21.7) around TEA were associated with adverse neurodevelopmental outcomes. CONCLUSION: The brain injury patterns following PA in preterm infants differ across GA. Particularly DGM abnormalities are associated with adverse neurodevelopmental outcomes.

Improving paediatric movement disorders care: Insights on rating scales utilization and clinical practice.

AIM: This exploratory study evaluates rating scale usage by experts from the European Reference Network for Rare Neurological Diseases (ERN-RND) for paediatric MD, considering factors like diagnosis, intellectual disability, age, and transition to adult care. The aim is to propose a preliminary framework for consistent application. METHODS: A multicentre survey among 25 ERN-RND experts from 10 European countries examined rating scale usage in paediatric MD, categorizing MD into acute, non-progressive, and neurodegenerative types. Factors influencing scale choice and the transition to adult care practices were analysed. A comprehensive literature search was conducted to identify the earliest age of application of these scales in paediatric patients. RESULTS: The study identifies various rating scales and establishes their usage frequencies for different MDs. Experts highlighted the need for standardized scales and proposed preliminary evaluation strategies based on clinical contexts. Challenges in applying scales to young, non-cooperative patients were acknowledged. INTERPRETATION: The study recommends developing standardized rating scales for paediatric MDs to improve evaluations and data collection. It suggests potential scales for specific clinical scenarios to better evaluate disease progression. Comprehensive, patient-centred care remains crucial during the transition to adult care, despite the identified challenges. This exploratory approach aims to enhance patient outcomes and care.