Mechanical Thrombectomy for Pediatric Arterial Ischemic Stroke from Acute M2 Occlusion.

Pediatric large-vessel occlusion has a poor natural history. Recent retrospective studies have demonstrated the potential benefits, feasibility, and safety profile of mechanical thrombectomy in children. However, the role of thrombectomy in pediatric M2 occlusions remains uncertain. In this clinical report, we present a multicenter series of 6 pediatric patients with acute M2 occlusion (female = 1, male = 5; age range, 0.9-16.0 years, mean = 9.2). All 6 patients having undergone thrombectomy had excellent clinical outcomes (pediatric mRS = 0-1) at 3 months and final available follow-up (median, 12 months; range, 3-72 months). Factors relevant to treatment decision-making in pediatric M2 occlusions are discussed, including the important role of multidisciplinary team discussions during acute management.

Newborn screening for Duchenne muscular dystrophy: the perspectives of stakeholders.

Background: The rapidly evolving clinical landscape of Duchenne muscular dystrophy (DMD) is driving innovative approaches for early diagnosis through genomic newborn bloodspot screening (NBS). However, the potential impact of these programs on families and healthcare systems remains unexplored. This study assessed the perceived benefits, harms, barriers, and enablers for DMD NBS amongst primary caregivers of children with DMD and healthcare professionals (HCPs). Methods: This Australian multi-centre cross-sectional study used a mixed-methods convergent methodology. Participants completed a codeveloped questionnaire and their perceptions on the utility, model of care, and processes of DMD NBS were thematically analysed. Findings: Participants included 50 caregivers and 26 HCPs (68.5% and 53.1% response rate respectively). Most caregivers (40/50, 80%) perceived net benefits of DMD NBS and highlighted an early diagnosis as actionable knowledge, even with the current paucity of disease modifying therapies. This knowledge was valued to enable access to multidisciplinary supportive care (29/50, 58%), clinical trials (27/50, 54%), psychological support (28/50, 56%), inform reproductive planning (27/50, 54%), and facilitate financial planning based on the future needs of their child (27/50, 54%). Whilst HCPs acknowledged these opportunities, only 16/26 (61.5%) believed there were definite net benefits, with notable concerns over the psychological harms of diagnostic knowledge without a recourse to disease modifying therapeutic intervention early in life. Interpretation: Caregivers and HCPs perceived a range of potential benefits of DMD NBS. Health system readiness will be founded on developing an integrated model of care that not only supports the psychosocial and information needs of families receiving a newborn diagnosis of DMD, but also provides care and clinical surveillance for individuals for whom a diagnosis may remain uncertain. Funding: Medical Research Futures fund (GNT2017165, MRF2015965).

Newborn Screening for the Diagnosis and Treatment of Duchenne Muscular Dystrophy.

A pilot newborn screening (NBS) program for Duchenne muscular dystrophy (DMD) study proposes to assess the feasibility of the screening procedure, temporal course of the various steps of screening, and the public acceptability of the program. This is particularly vital to ascertain as DMD is considered a 'non-treatable' disease and thus does not fit the traditional criteria for newborn screening. However, modern perspectives of NBS for DMD are changing and point to possible net benefits for children and their families undertaking NBS for DMD. The aim of this workshop was to establish pathways for the successful implementation and evaluation of a pilot NBS for DMD program in Australia. Consensus was reached as to the rationale for, potential benefits, risks, barriers and facilitators of screening, alongside the establishment of screening protocols and clinical referral pathways.

Rapid onset functional tic-like behaviours in children and adolescents during COVID-19: Clinical features, assessment and biopsychosocial treatment approach.

AIM: To report the prevalence and clinical characteristics of children with rapid onset functional tic-like behaviours during the COVID-19 pandemic. METHODS: Single centre, retrospective cohort study of children (<18 years) referred to the tic clinic from January 2018 to July 2021. We calculate the prevalence of newly diagnosed functional tics, and compare the clinical features to chronic tic disorder/Tourette syndrome (CTD/TS). RESULTS: A total of 185 new patients were referred to the tic clinic between 2018 and 2021. There was a significant increase in the percentage of functional tics in 2020 and 2021 (2% in 2018, 5.6% in 2019, 10.6% in 2020 and 36% in 2021). Differences between functional tics (n = 22) and CTD/TS (n = 163) include female predominance (100 vs. 28%, P < 0.0001), later age of onset (mean age 13.8 vs. 6.8 years, P < 0.0001) and higher rates of anxiety/depression (95 vs. 41%, P < 0.0001). The functional tic group were more likely to present with coprolalia-like behaviours (77 vs. 10%, P < 0.0001), complex phrases (45 vs. 0.6%, P < 0.0001), copropraxia (45 vs. 2%, P < 0.0001), self-injury (50 vs. 4%, P < 0.0001), hospitalisation/emergency visits (36 vs. 2%, P < 0.0001) and school absenteeism (56 vs. 7%, P < 0.0001). A total of 18.2% of patients with functional tics reported preceding exposure to social media content involving tics. CONCLUSIONS: There is an increase in adolescent females presenting with rapid onset functional tic-like behaviours during the COVID-19 pandemic. We highlight differences in clinical features between the functional tic group and CTD/TS to aid diagnosis and management in the community. Based on our findings, we propose a mixed model of neuropsychiatric vulnerability and social media contagion in this group of adolescents with functional tics.

Evaluation of an educational video providing key messages for doctors to counsel families following a first afebrile seizure.

AIM: The aim was to evaluate an educational video in educating doctors on the key messages and follow-up pathways following a first afebrile seizure presentation. A multidisciplinary expert team developed the video (http://www.pennsw.org.au/families/resources/first-seizure-pack-and-video) based on available evidence and best-practice. It contains a role-play between the parent/child and physician. It addresses: key messages to impart following a first seizure, seizure first aid, safety messages including necessary precautions post-discharge, contents of the First Seizure Pack for families, follow-up pathway and issues for discussion with the paediatrician at a later appointment. METHODS: Paediatric/Emergency department (ED) trainees across three Australian sites were recruited during terms 1 and 2, 2019. A repeated measures design was used. Multilevel modelling analyses were performed. The primary outcome was clinician knowledge. Secondary outcomes were confidence in answering questions and counselling families. Qualitative data on the utility, strengths and weaknesses of the video were evaluated. RESULTS: A total of 127 participants consented, one withdrew prior to commencing. A total of 126 baseline surveys, 115 follow-up surveys and 45 1-month follow-up surveys were returned. Viewing the video significantly improved knowledge of key messages at immediate follow-up (P < 0.001) and 1-month follow-up (P = 0.048). Likewise, confidence was significantly improved; 96.5% of responders found the video useful, 90.3% were likely to use the resource in the future and 82% would change their approach to counselling. Most liked aspects of the resource were clarity/conciseness of the information (n = 70) and comprehensiveness (n = 38). CONCLUSION: This education video significantly improved clinician knowledge and confidence in counselling families following first seizure.

Psychiatric comorbidity is common in dystonia and other movement disorders.

OBJECTIVE: To determine rates of psychiatric comorbidity in a clinical sample of childhood movement disorders (MDs). DESIGN: Cohort study. SETTING: Tertiary children's hospital MD clinics in Sydney, Australia and London, UK. PATIENTS: Cases were children with tic MDs (n=158) and non-tic MDs (n=102), including 66 children with dystonia. Comparison was made with emergency department controls (n=100), neurology controls with peripheral neuropathy or epilepsy (n=37), and community controls (n=10 438). INTERVENTIONS: On-line development and well-being assessment which was additionally clinically rated by experienced child psychiatrists. MAIN OUTCOME MEASURES: Diagnostic schedule and manual of mental disorders-5 criteria for psychiatric diagnoses. RESULTS: Psychiatric comorbidity in the non-tic MD cohort (39.2%) was comparable to the tic cohort (41.8%) (not significant). Psychiatric comorbidity in the non-tic MD cohort was greater than the emergency control group (18%, p<0.0001) and the community cohort (9.5%, p<0.00001), but not the neurology controls (29.7%, p=0.31). Almost half of the patients within the tic cohort with psychiatric comorbidity were receiving medical psychiatric treatment (45.5%) or psychology interventions (43.9%), compared with only 22.5% and 15.0%, respectively, of the non-tic MD cohort with psychiatric comorbidity. CONCLUSIONS: Psychiatric comorbidity is common in non-tic MDs such as dystonia. These psychiatric comorbidities appear to be under-recognised and undertreated.

Diagnostic yield of targeted massively parallel sequencing in children with epileptic encephalopathy.

PURPOSE: To report our institutional experience of targeted massively parallel sequencing (MPS) testing in children with epilepsy. METHOD: We retrospectively analysed the yield of targeted epileptic encephalopathy (EE) panel of 71 known EE genes in patients with epilepsy of unknown cause, who underwent clinical triage by a group of neurologists prior to the testing. We compared cost of the EE panel approach compared to traditional evaluation in patients with identified pathogenic variants. RESULTS: The yield of pathogenic variants was 28.5% (n = 30/105), highest in early onset EE <3 months including Ohtahara syndrome (52%, n = 10/19) and lowest in generalized epilepsy (0/17). Patients identified with pathogenic variants had earlier onset of seizures (median 3.6 m vs 1.1y, p < 0.001, OR 0.6/year, P < 0.02) compared to those without pathogenic variants. Pathogenic/likely pathogenic variants were found in ALDH7A1 (2), CACNA1A (1), CDKL5 (3), FOXG1 (2), GABRB3 (1), GRIN2A (1), KCNQ2 (4), KCNQ3 (1), PRRT2 (1), SCN1A (6), SCN2A (2), SCN8A (2), SYNGAP1 (1), UBE3A (2) and WWOX (1) genes. This study expands the inheritance pattern caused by KCNQ3 mutations to include an autosomal recessive severe phenotype with neonatal seizures and severe developmental delay. The average cost of etiological evaluation was less with early use of EE panel compared to the traditional investigation approach ($5990 Australian dollars (AUD) vs $13069 AUD ; p = 0.02) among the patients with identified pathogenic variants. CONCLUSION: Targeted MPS testing is a comprehensive and economical investigation that enables early genetic diagnosis in children with EE. Careful clinical triage and selection of patients with young onset EE may maximize the yield of EE panel testing.

Clinical Characteristics and Functional Motor Outcomes of Enterovirus 71 Neurological Disease in Children.

IMPORTANCE: Enterovirus 71 (EV71) causes a spectrum of neurological complications with significant morbidity and mortality. Further understanding of the characteristics of EV71-related neurological disease, factors related to outcome, and potential responsiveness to treatments is important in developing therapeutic guidelines. OBJECTIVE: To further characterize EV71-related neurological disease and neurological outcome in children. DESIGN, SETTING, AND PARTICIPANTS: Prospective 2-hospital (The Sydney Children's Hospitals Network) inpatient study of 61 children with enterovirus-related neurological disease during a 2013 outbreak of EV71 in Sydney, Australia. The dates of our analysis were January 1, to June 30, 2013. MAIN OUTCOMES AND MEASURES: Clinical, neuroimaging, laboratory, and pathological characteristics, together with treatment administered and functional motor outcomes, were assessed. RESULTS: Among 61 patients, there were 4 precipitous deaths (7%), despite resuscitation at presentation. Among 57 surviving patients, the age range was 0.3 to 5.2 years (median age, 1.5 years), and 36 (63%) were male. Fever (100% [57 of 57]), myoclonic jerks (86% [49 of 57]), ataxia (54% [29 of 54]), and vomiting (54% [29 of 54]) were common initial clinical manifestations. In 57 surviving patients, EV71 neurological disease included encephalomyelitis in 23 (40%), brainstem encephalitis in 20 (35%), encephalitis in 6 (11%), acute flaccid paralysis in 4 (7%), and autonomic dysregulation with pulmonary edema in 4 (7%). Enterovirus RNA was more commonly identified in feces (42 of 44 [95%]), rectal swabs (35 of 37 [95%]), and throat swabs (33 of 39 [85%]) rather than in cerebrospinal fluid (10 of 41 [24%]). Magnetic resonance imaging revealed characteristic increased T2-weighted signal in the dorsal pons and spinal cord. All 4 patients with pulmonary edema (severe disease) demonstrated dorsal brainstem restricted diffusion (odds ratio, 2; 95% CI, 1-4; P = .001). Brainstem or motor dysfunction had resolved in 44 of 57 (77%) at 2 months and in 51 of 57 (90%) at 12 months. Focal paresis was evident in 23 of 57 (40%) at presentation and was the most common persisting clinical and functional problem at 12 months (observed in 5 of 6 patients), with 1 patient also requiring invasive ventilation. Patients initially seen with acute flaccid paralysis or pulmonary edema had significantly greater frequencies of motor dysfunction at follow-up compared with patients initially seen with other syndromes (odds ratio, 15; 95% CI, 3-79; P < .001). CONCLUSIONS AND RELEVANCE: Enterovirus 71 may cause serious neurological disease in young patients. The distinct clinicoradiological syndromes, predominantly within the spinal cord and brainstem, enable rapid recognition within evolving outbreaks. Long-term functional neurological morbidity is associated with paresis linked to involvement of gray matter in the brainstem or spinal cord.