Brainstem depolarization-induced lethal apnea associated with gain-of-function SCN1AL263V is prevented by sodium channel blockade.

Apneic events are frightening but largely benign events that often occur in infants. Here, we report apparent life-threatening apneic events in an infant with the homozygous SCN1AL263V missense mutation, which causes familial hemiplegic migraine type 3 in heterozygous family members, in the absence of epilepsy. Observations consistent with the events in the infant were made in an Scn1aL263V knock-in mouse model, in which apnea was preceded by a large brainstem DC-shift, indicative of profound brainstem depolarization. The L263V mutation caused gain of NaV1.1 function effects in transfected HEK293 cells. Sodium channel blockade mitigated the gain-of-function characteristics, rescued lethal apnea in Scn1aL263V mice, and decreased the frequency of severe apneic events in the patient. Hence, this study shows that SCN1AL263V can cause life-threatening apneic events, which in a mouse model were caused by profound brainstem depolarization. In addition to being potentially relevant to sudden infant death syndrome pathophysiology, these data indicate that sodium channel blockers may be considered therapeutic for apneic events in patients with these and other gain-of-function SCN1A mutations.

Multiple motor disorders in cerebral palsy.

AIM: To characterize motor disorders in children and young people with cerebral palsy (CP). METHOD: This was a cross-sectional study of 582 children and young people with CP (mean age 9 years 7 months; range 11 months-19 years 9 months; standard deviation 4 years 11 months; 340 males) attending a rehabilitation clinic at a specialized children's hospital (May 2018-March 2020). Data on motor disorders, topography, functional classifications, and non-motor features, such as epilepsy, intellectual disability, and sensory impairments, were collected using the Australian Cerebral Palsy Register CP Description Form. RESULTS: Fifty-five per cent (n = 321) of children and young people with CP presented with multiple motor disorders, often affecting the same limb(s). The most common motor disorders were spasticity and dystonia (50%), spasticity only (36%), and dystonia only (6%), but 18 different combinations were identified, including choreoathetosis, ataxia, and generalized hypotonia with increased reflexes. Children with spasticity only had less severe functional deficits (p < 0.001) and lower rates of associated intellectual disability (p < 0.01) and epilepsy (p < 0.001) than those with both spasticity and dystonia. INTERPRETATION: Multiple motor disorders in children and young people with CP are common and associated with more severe functional impairment. Accurate assessment of motor disorders is essential to guide prognosis and ensure personalized evidence-based interventions. WHAT THIS PAPER ADDS: More than half of children and young people with cerebral palsy presented with multiple motor disorders. Dystonia was identified in 60% of study participants. Dystonia was associated with more severe functional impairments and rates of non-motor features.

Informing knowledge translation for selective dorsal rhizotomy: A survey of Australian clinicians and people with lived experience of cerebral palsy.

AIM: Selective dorsal rhizotomy (SDR) is a neurosurgical intervention used to reduce spasticity in children with cerebral palsy (CP). There is minimal relevant, evidence-based information available for Australian families and clinicians. This study aims to investigate the knowledge of people with lived experience and clinicians regarding SDR, including how they currently access information and what information they seek. METHODS: Adults with CP, carers of children with CP and clinicians treating children with CP were invited to complete an online survey. Data regarding participant demographics, current knowledge and confidence in knowledge about CP and SDR, information source/s used and participants level of trust in these sources are presented as counts and percentages. Comparisons in knowledge between groups were analysed. RESULTS: A total of 114 surveys were completed: 63 clinicians, 48 carers, and 3 adults with CP. Eighty percent of clinicians were allied health professionals. People with lived experience were less confident in their knowledge about SDR compared to knowledge of CP (P < 0.001). Clinicians rated scientific research literature and the hospital team as the most useful and trustworthy information source. People with lived experience used a wider range of information sources including the internet, rating their community therapy team and other people with lived experience as the most useful. CONCLUSION: This study identified a lack of confidence in knowledge of SDR for people with lived experience, likely due to a gap in accessible and readable evidence-based information. While both groups differed in how they access information, there was agreement that greater information about SDR is needed.

Early childhood epilepsies: epidemiology, classification, aetiology, and socio-economic determinants.

Epilepsies of early childhood are frequently resistant to therapy and often associated with cognitive and behavioural comorbidity. Aetiology focused precision medicine, notably gene-based therapies, may prevent seizures and comorbidities. Epidemiological data utilizing modern diagnostic techniques including whole genome sequencing and neuroimaging can inform diagnostic strategies and therapeutic trials. We present a 3-year, multicentre prospective cohort study, involving all children under 3 years of age in Scotland presenting with epilepsies. We used two independent sources for case identification: clinical reporting and EEG record review. Capture-recapture methodology was then used to improve the accuracy of incidence estimates. Socio-demographic and clinical details were obtained at presentation, and 24 months later. Children were extensively investigated for aetiology. Whole genome sequencing was offered for all patients with drug-resistant epilepsy for whom no aetiology could yet be identified. Multivariate logistic regression modelling was used to determine associations between clinical features, aetiology, and outcome. Three hundred and ninety children were recruited over 3 years. The adjusted incidence of epilepsies presenting in the first 3 years of life was 239 per 100 000 live births [95% confidence interval (CI) 216-263]. There was a socio-economic gradient to incidence, with a significantly higher incidence in the most deprived quintile (301 per 100 000 live births, 95% CI 251-357) compared with the least deprived quintile (182 per 100 000 live births, 95% CI 139-233), χ2 odds ratio = 1.7 (95% CI 1.3-2.2). The relationship between deprivation and incidence was only observed in the group without identified aetiology, suggesting that populations living in higher deprivation areas have greater multifactorial risk for epilepsy. Aetiology was determined in 54% of children, and epilepsy syndrome was classified in 54%. Thirty-one per cent had an identified genetic cause for their epilepsy. We present novel data on the aetiological spectrum of the most commonly presenting epilepsies of early childhood. Twenty-four months after presentation, 36% of children had drug-resistant epilepsy (DRE), and 49% had global developmental delay (GDD). Identification of an aetiology was the strongest determinant of both DRE and GDD. Aetiology was determined in 82% of those with DRE, and 75% of those with GDD. In young children with epilepsy, genetic testing should be prioritized as it has the highest yield of any investigation and is most likely to inform precision therapy and prognosis. Epilepsies in early childhood are 30% more common than previously reported. Epilepsies of undetermined aetiology present more frequently in deprived communities. This likely reflects increased multifactorial risk within these populations.

Electrocardiographic Changes in Children with Multisystem Inflammation Associated with COVID-19: Associated with Coronavirus Disease 2019.

OBJECTIVE: To analyze findings and trends on serial electrocardiograms (ECGs) in multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease taken during the course of illness and at follow-up. STUDY DESIGN: We included all children presenting with MIS-C at a single center with 3 or more ECGs taken during the course of their illness. We measured ECG intervals (PR, QRSd, and QTc) and amplitudes (R-, S-, and T-waves) on each ECG and documented any arrhythmias and ST-segment changes. RESULTS: A majority of children (n = 42, 67%) showed ECG changes. The most common findings were low QRS amplitudes and transient T-wave inversion. ST changes were uncommon and included ST-segment elevation consistent with pericarditis in 1 child and acute coronary ischemia in 1 child. Arrhythmias were seen in 13 children (21%) but were benign with the exception of 1 child who was compromised by an atrial tachycardia requiring support with extracorporeal membrane oxygenation. No children were found to have high-grade atrioventricular block. CONCLUSIONS: MIS-C is associated with electrocardiographic changes over the course of the illness, with low amplitude ECGs on presentation, followed by transient T-wave inversion, particularly in the precordial leads. There was a low prevalence of ST-segment changes and tachyarrhythmias.

The Dyskinetic Cerebral Palsy Functional Impact Scale: development and validation of a new tool.

AIM: To outline the development and examine the content and construct validity of a new tool, the Dyskinetic Cerebral Palsy Functional Impact Scale (D-FIS), which measures the impact of dyskinesia on everyday activities in children with cerebral palsy (CP). METHOD: D-FIS content was informed by a systematic review of dyskinesia outcome measures, in collaboration with children with dyskinetic CP, parents, caregivers, and expert clinicians. The D-FIS uses parent proxy to rate impact of dyskinesia on everyday activities. Construct validity was determined by examining internal consistency; known groups validity with the Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), Communication Function Classification System (CFCS), and Eating and Drinking Ability Classification System (EDACS); and convergent validity with the Barry-Albright Dystonia Scale (BADS). RESULTS: Fifty-seven parents of children (29 males, 28 females, mean [SD] age 11y 8mo [4y 4mo], range 2y 6mo-18y) completed the D-FIS. Correlation between D-FIS and GMFCS was r=0.86 (95% confidence interval [CI]: 0.77-0.91, p<0.001); MACS r=0.84 (95% CI: 0.73-0.90, p<0.001); CFCS r=0.80 (95% CI: 0.67-0.88, p<0.001); and EDACS r=0.78 (95% CI: 0.66-0.87). Correlation between D-FIS and BADS was r=0.77 (95% CI: 0.64-0.86, p<0.001). Cronbach's alpha was 0.96. INTERPRETATION: The D-FIS demonstrates good construct validity and high internal consistency. The D-FIS will be useful for identifying priorities for intervention. It adds to the measurement tool kit for children with dyskinetic CP by addressing functional impact of dyskinetic movements and postures. What this paper adds The Dyskinetic Cerebral Palsy Functional Impact Scale (D-FIS) assesses the perceived impact of dyskinesia on daily activities in children with cerebral palsy (CP). The D-FIS demonstrates good construct validity and high internal consistency. The D-FIS is a clinically feasible, family-centred tool that fills a current gap in the dyskinetic CP assessment toolkit.

A pilot feasibility study of gabapentin for managing pain in children with dystonic cerebral palsy.

BACKGROUND: Gabapentin is often used to manage pain in children with dystonic cerebral palsy, however the evidence for its effectiveness in this population is limited. The primary objective of this feasibility pilot study was to assess the factors which might impact on a future randomised controlled trial including the ability to recruit and retain participants, assess adherence/compliance to the prescribed intervention, and ability to complete all outcome assessments. The secondary objective was to gather preliminary evidence for the effectiveness of gabapentin at reducing pain, improving comfort and reducing dystonia in children with dystonic cerebral palsy. METHODS: This open label pilot study recruited children aged 5-18 years with dystonic cerebral palsy and accompanying pain affecting daily activities from four centres around Australia. Children were prescribed gabapentin for 12 weeks and were assessed at baseline, 6 weeks and 12 weeks. The primary outcome was feasibility of the protocol. Secondary outcomes were pain behaviour, pain intensity, care and comfort, individualised goal setting and dystonia severity. RESULTS: Thirteen children (mean age 10.4 years (SD 2.4yrs), 9 females) were recruited from 71 screened over 15 months. Two children withdrew while eight children experienced side effects. There were issues with adherence to medication dosage regimens and data collection. Improvements were seen in pain behaviour, comfort and pain related goals at 12 weeks. Dystonia was not significantly changed. CONCLUSIONS: Whilst gabapentin has potential to improve pain and comfort in children with dystonic CP, the feasibility of implementing a definitive randomised controlled trial is low. Alternative trials designs are required to further examine the effectiveness of gabapentin in this heterogeneous population. TRIAL REGISTRATION: The trial was registered with the Australian Clinical Trial Registry ( ACTRN12616000366459 ) on 22/03/2016 and the Therapeutic Goods Administration (CT-2016-CTN-00500-1) on 22/06/2016.

Current Australian clinical practice in use of botulinum toxin-A to manage paediatric hypertonicity.

AIM: To describe current rehabilitation paediatricians' use of intramuscular botulinum toxin-A (BoNT-A) to manage hypertonicity. METHODS: Cross-sectional survey. RESULTS: In late 2019, 32 of the 35 identified Australian rehabilitation paediatricians who use BoNT-A to manage paediatric hypertonicity completed the survey. Annually, they administer just over 3750 courses of BoNT-A to manage hypertonicity with a mean of 11 years of clinical experience. Sedation was used by all but 1 clinician who used a number of other strategies during the procedure. Mean (and median) maximum dose of OnabotulinumtoxinA (Botox) was 400 Units (range 300-450 Units). Only three clinicians indicated that they used AbobotulinumtoxinA (Dysport) - the other BoNT-A preparation approved for children available in Australia; analysis of its use was not performed. Dose modifications were made by clinicians according to a patient's response to a previous course of BoNT-A (88% of respondents); patient experience of a previous adverse event (78%); history of aspiration or dysphagia (65 and 63%, respectively); and the presence of dystonia; and where the patient was GMFCS level V (53% each). Intervals between courses ranged from 3 to 24 months with the variation due to clinical circumstances. CONCLUSION: Clinical practice in BoNT-A management of paediatric hypertonicity was largely consistent in regard to maximum doses of OnabotulinumtoxinA (Botox) used. Dose modification and time between injection courses varied according to individual clinical presentation. Procedural sedation was used extensively.

SCN1A variants from bench to bedside-improved clinical prediction from functional characterization.

Variants in the SCN1A gene are associated with a wide range of disorders including genetic epilepsy with febrile seizures plus (GEFS+), familial hemiplegic migraine (FHM), and the severe childhood epilepsy Dravet syndrome (DS). Predicting disease outcomes based on variant type remains challenging. Despite thousands of SCN1A variants being reported, only a minority has been functionally assessed. We review the functional SCN1A work performed to date, critically appraise electrophysiological measurements, compare this to in silico predictions, and relate our findings to the clinical phenotype. Our results show, regardless of the underlying phenotype, that conventional in silico software correctly predicted benign from pathogenic variants in nearly 90%, however was unable to differentiate within the disease spectrum (DS vs. GEFS+ vs. FHM). In contrast, patch-clamp data from mammalian expression systems revealed functional differences among missense variants allowing discrimination between disease severities. Those presenting with milder phenotypes retained a degree of channel function measured as residual whole-cell current, whereas those without any whole-cell current were often associated with DS (p = .024). These findings demonstrate that electrophysiological data from mammalian expression systems can serve as useful disease biomarker when evaluating SCN1A variants, particularly in view of new and emerging treatment options in DS.

Incidence and phenotypes of childhood-onset genetic epilepsies: a prospective population-based national cohort.

Epilepsy is common in early childhood. In this age group it is associated with high rates of therapy-resistance, and with cognitive, motor, and behavioural comorbidity. A large number of genes, with wide ranging functions, are implicated in its aetiology, especially in those with therapy-resistant seizures. Identifying the more common single-gene epilepsies will aid in targeting resources, the prioritization of diagnostic testing and development of precision therapy. Previous studies of genetic testing in epilepsy have not been prospective and population-based. Therefore, the population-incidence of common genetic epilepsies remains unknown. The objective of this study was to describe the incidence and phenotypic spectrum of the most common single-gene epilepsies in young children, and to calculate what proportion are amenable to precision therapy. This was a prospective national epidemiological cohort study. All children presenting with epilepsy before 36 months of age were eligible. Children presenting with recurrent prolonged (>10 min) febrile seizures; febrile or afebrile status epilepticus (>30 min); or with clusters of two or more febrile or afebrile seizures within a 24-h period were also eligible. Participants were recruited from all 20 regional paediatric departments and four tertiary children's hospitals in Scotland over a 3-year period. DNA samples were tested on a custom-designed 104-gene epilepsy panel. Detailed clinical information was systematically gathered at initial presentation and during follow-up. Clinical and genetic data were reviewed by a multidisciplinary team of clinicians and genetic scientists. The pathogenic significance of the genetic variants was assessed in accordance with the guidelines of UK Association of Clinical Genetic Science (ACGS). Of the 343 patients who met inclusion criteria, 333 completed genetic testing, and 80/333 (24%) had a diagnostic genetic finding. The overall estimated annual incidence of single-gene epilepsies in this well-defined population was 1 per 2120 live births (47.2/100 000; 95% confidence interval 36.9-57.5). PRRT2 was the most common single-gene epilepsy with an incidence of 1 per 9970 live births (10.0/100 000; 95% confidence interval 5.26-14.8) followed by SCN1A: 1 per 12 200 (8.26/100 000; 95% confidence interval 3.93-12.6); KCNQ2: 1 per 17 000 (5.89/100 000; 95% confidence interval 2.24-9.56) and SLC2A1: 1 per 24 300 (4.13/100 000; 95% confidence interval 1.07-7.19). Presentation before the age of 6 months, and presentation with afebrile focal seizures were significantly associated with genetic diagnosis. Single-gene disorders accounted for a quarter of the seizure disorders in this cohort. Genetic testing is recommended to identify children who may benefit from precision treatment and should be mainstream practice in early childhood onset epilepsy.

Implementing accurate identification and measurement of dyskinesia in cerebral palsy into clinical practice: A knowledge translation study.

AIM: The application of current, best evidence into clinical practice is problematic. This article describes a knowledge translation (KT) project aimed at improving clinician identification, classification and measurement of dyskinesia in children with cerebral palsy (CP). METHOD: A 2-year KT fellowship investigated clinicians' understanding of dyskinetic CP, identified knowledge gaps, determined educational needs and implemented a multifaceted KT strategy and dissemination framework to address those needs. RESULTS: Australian and New Zealand medical and allied health clinicians identified significant gaps in their clinical knowledge regarding dyskinetic CP, particularly confidence in identifying and measuring dyskinesia and poor knowledge of available identification and measurement tools. Following a targeted implementation strategy, there was a definite shift towards increased awareness of dyskinetic CP, a significant improvement in identification and measurement confidence (mean change from 47 to 66% confidence, P < 0.0001), and the embedding of the knowledge and skills into everyday clinical practice. CONCLUSIONS: This targeted and well-resourced KT project in dyskinetic CP improved clinician knowledge and led to meaningful change in clinical practice. The strategy utilised would be appropriate across a range of health-care settings.

Intrathecal baclofen therapy in children: an analysis of individualized goals.

AIM: To determine whether intrathecal baclofen (ITB) therapy improves performance and performance satisfaction in goal areas identified by patients' parents. METHOD: This study formed part of an ongoing multicentre national audit involving six paediatric ITB pump implant centres across Australia. The Canadian Occupational Performance Measure was the primary outcome measure utilized at baseline, 6 months, and 12 months after pump implants in paediatric patients receiving ITB therapy for the first time between 31st December 2009 and 31st December 2014. RESULTS: Twenty-five children had goals identified (mean age 11y 1mo), 19 had a diagnosis of cerebral palsy and 22 were at Gross Motor Function Classification System level IV, V, or equivalent. Strong evidence for an improvement in goal performance (2.33, 95% CI 1.70, 2.96, p<0.001) and performance satisfaction scores (3.08, 95% CI 2.28, 3.88, p<0.001) were demonstrated at 6 months, compared to baseline. The differences were clinically significant and were sustained to 12 months. INTERPRETATION: ITB therapy in paediatric patients with hypertonia results in clinically significant improvements in average performance and performance satisfaction scores. WHAT THIS PAPER ADDS: The most commonly identified goals of parents of children treated with intrathecal (ITB) therapy were: improving ease of dressing, positioning, and transfers. ITB therapy is effective in improving performance and performance satisfaction in children with hypertonia. Score improvements are mainly evident within the first 6 months of therapy.

Identification, classification and assessment of dyskinesia in children with cerebral palsy: A survey of clinicians.

AIM: The aims of this study were to investigate clinicians' knowledge, and barriers they perceive exist, relating to the identification and measurement of dyskinesia (dystonia/choreoathetosis) in children with cerebral palsy (CP) and to explore educational needs regarding improving identification and assessment of dyskinesia. METHODS: This was a cross-sectional online survey of clinicians working with children with CP. Data analysis was descriptive, with qualitative analysis of unstructured questions. RESULTS: In total, 163 completed surveys from Australian clinicians were analysed. Respondents were allied health (n = 140) followed by medical doctors (n = 18) working mainly in tertiary hospitals and not-for-profit organisations. Hypertonia subtypes and movement disorders seen in children with CP appear to be identified by clinicians, although limited knowledge about dyskinesia and access to training were reported as significant barriers to accurate identification. Despite knowledge of available measurement scales, only a small percentage were used clinically and reported to be only somewhat useful or not useful at all. Barriers identified for use of scales included limited training opportunities and knowledge of scales and lack of confidence in their use. CONCLUSION: A lack of confidence in identifying and measuring movement disorders in children with CP was reported by Australian clinicians. It was identified that a greater understanding of dyskinetic CP and the tools available to identify and measure it would be valuable in clinical practice. The results of this survey will inform the development of a 'Toolbox' to help identify, classify and measure dyskinetic CP and its impact on activity and participation using the framework of the International Classification of Functioning, Disability and Health.

A systematic review of scales to measure dystonia and choreoathetosis in children with dyskinetic cerebral palsy.

AIM: To identify and systematically review the psychometric properties and clinical utility of dystonia and choreoathetosis scales reported for children with cerebral palsy (CP). METHOD: Six electronic databases were searched for dystonia and choreoathetosis scales with original psychometric data for children with CP aged 0 to 18 years. RESULTS: Thirty-four papers met the inclusion criteria, which contained six scales purported to measure dystonia and/or choreoathetosis in children with CP: the Burke-Fahn-Marsden Dystonia Rating Scale; Barry-Albright Dystonia Scale; Unified Dystonia Rating Scale; Movement Disorder-Childhood Rating Scale; Movement Disorder-Childhood Rating Scale 0-3 Years; and the Dyskinesia Impairment Scale. INTERPRETATION: Each scale provides useful information about dyskinesia, with most focusing on dystonia. The Barry-Albright Dystonia Scale, which was designed for CP, is the most commonly reported scale and least complex to use clinically. The Dyskinesia Impairment Scale is the only tool to consider both dystonia and choreoathetosis in CP. All tools are designed to classify movement disorders at the level of body functions and structures, rather than activity limitations or participation restrictions, although many provide some insight into the impact of dystonia on activities. Further studies are required to fully examine the validity, reliability, responsiveness, and clinical utility of each scale specifically for children with CP.

Content and readability of patient educational materials about neuromodulation for childhood movement disorders.

PURPOSE: To assess content and readability of online patient educational materials (PEMs) for paediatric deep brain stimulation (DBS) and intrathecal baclofen (ITB). METHODS: A content analysis of PEMs identified from top children's hospitals, institutions affiliated with published neuromodulation research, and DBS and ITB device manufacturers was conducted. PEM content was analysed using a predetermined framework. Readability was assessed using the Simple Measure of Gobbledygook (SMOG). RESULTS: Of 109 PEMs (72 DBS; 37 ITB) identified, most (77 (71%)) originated in the United States. More ITB PEMs (27 (73%)) contained specific paediatric information than DBS PEMs (16 (22%)). PEMS more frequently described benefits (DBS: 92%; ITB: 89%) than risks (DBS: 49%; ITB: 78%). Frequent content included pre- and post-operative care, procedural details, and device information. Less common content included long-term lifestyle considerations, alternatives, patient experiences, and financial details. Median readability of PEMs was 13.2 (interquartile range [IQR]: 11.4-14.45) for DBS and 11.8 (IQR: 11-12.9) for ITB. CONCLUSIONS: Available ITB and DBS PEMs often miss important broader details of the treatments, and have additional shortcomings such as poor readability scores. Our findings highlight need for more holistic content within neuromodulation PEMs, improved accessibility, and more balanced representation of risks and benefits.

Neuromodulation patient education materials (PEMs) require more comprehensive information to address needs of families of children with movement disorders.There is a paucity of online PEMs for paediatric deep brain stimulation (DBS), and limited English-language neuromodulation information originating outside the USA.Neuromodulation PEMs do not meet readability standards and underutilise testimonials and audiovisual communication.Benefits of neuromodulation are described more frequently than risk information in PEMs.

Caregiver perspectives of scoliosis surgery for children with cerebral palsy: a qualitative study.

PURPOSE: To explore the perspectives of primary caregivers of children with cerebral palsy (CP) who had spinal surgery for scoliosis. MATERIALS AND METHODS: A qualitative study was conducted using semi-structured interviews and guided by qualitative description methodology. Participants were caregivers of children with CP aged 5-18, who had undergone spinal surgery for scoliosis in Australia. The research team included a parent with lived experience. RESULTS: Fourteen participants (8 biological mothers), aged 40-49 years, completed online semi-structured interviews. Four themes were identified emerged. Life with a child with CP underpinned all experiences which were founded on familiarity with their child, medical procedures, and hospitalisation. Three subthemes were parents are the experts in knowing their child, children are vulnerable, and impact on caregivers. Theme 2 involved the significance of decision making to proceed with surgery. Theme 3 underscored a need to be prepared for the surgical journey and, in Theme 4, participants spoke of needing to expect the unexpected. CONCLUSION: The findings highlight the importance of understanding caregiver experiences and can help inform health professionals and other families in the decision-making process, preparing for and navigating spinal surgery.

Spinal surgery for scoliosis in children with cerebral palsy is a major surgery and poses substantial challenges for the family.Understanding the magnitude of the decision for families to proceed with surgery will equip health professionals to adequately support and partner with families.Detailed information and extensive preparation are necessary for families to proceed with and navigate surgery, the hospital stay and to return home and to the community.

Autosomal dominant ADAR c.3019G>A (p.(G1007R)) variant is an important mimic of hereditary spastic paraplegia and cerebral palsy.

BACKGROUND: The type 1 interferonopathy, Aicardi-Goutières syndrome 6 (AGS6), is classically caused by biallelic ADAR mutations whereas dominant ADAR mutations are associated with dyschromatosis symmetrica hereditaria (DSH). The unique dominant ADAR c.3019G>A variant is associated with neurological manifestations which mimic spastic paraplegia and cerebral palsy (CP). CASE SUMMARIES: We report three cases of spastic paraplegia or CP diagnosed with AGS6 caused by the ADAR c.3019G>A variant. Two children inherited the variant from an asymptomatic parent, and each child had a different clinical course. The youngest case demonstrated relentless progressive symptoms but responded to immunomodulation using steroids and ruxolitinib. CONCLUSION: The ADAR c.3019G>A variant has incomplete penetrance and is a likely underrecognized imitator of spastic paraplegia and dystonic CP. A high level of clinical suspicion is required to diagnose this form of AGS, and disease progression may be ameliorated by immunomodulatory treatment with selective Janus kinase inhibitors.