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This study aimed to improve the utilization of amplitude-integrated electroencephalography (aEEG) in a neonatal unit by improving aEEG documentation, aEEG knowledge, and pattern recognition ability of neonatal staff. A quality improvement (QI) program comprising the two Plan-Do-Study-Act (PDSA) cycles was conducted in a level-3 neonatal intensive care unit. The first cycle was focused on improving aEEG documentation with the primary outcome indicator being compliance with aEEG documentation. The second cycle was focused on aEEG interpretation in a health care professional education program with the outcome indicators being accuracy of seizure identification on aEEG and change in conventional EEGs (cEEG) performed. Other outcome indicators included accuracy in identification of background pattern, sleep-wake cycles and artifacts. Process indicators included improvement in aEEG-related knowledge. First PDSA cycle includes lectures on aEEG interpretation, a bedside key, and documentation form. Second PDSA cycle includes online aEEG education pack and detailed aEEG guideline. There was a significant improvement in aEEG documentation after the implementation of both PDSA cycles. Seven of the 46 patients (15.2%) had isolated electrographic seizures which would not have been identified in the pre-aEEG monitoring era. There was an increase in the number of patients with cEEGs done but a steady decrease in number of cEEGs per patient. With the successful application of standardized QI methods, improvements in outcome indicators, such as correct aEEG pattern recognition and improved coverage of at risk infants with cEEGs, were observed. Our QI measures were associated with improvement in aEEG pattern recognition.· Consistent and accurate use of aEEG is challenging.. · Standardized forms and guidelines improve aEEG interpretation consistency and documentation.. · Interactive self-paced online education packs can improve aEEG knowledge and pattern recognition..

Background: GNAO1 is an emerging disorder characterized with hypotonia, developmental delay, epilepsy, and movement disorder, which can be potentially life threatening during acute exacerbation. In the USA, deep brain stimulation (DBS) has been licensed for treating children with chronic, treatment-resistant primary dystonia, who are 7 years old or older. Case Description: A 4-year-old girl diagnosed to have GNAO1-related dyskinesia and severe global developmental delay. She had severe dyskinesia precipitated by intercurrent infection, requiring prolonged intensive care for heavy sedation and related complications. Her dyskinesia improved dramatically after DBS implantation. Technical difficulties and precautions of DBS in preschool children were discussed. Conclusion: DBS should be considered early in the treatment of drug-resistant movement disorders in young children with GNAO1, especially after dyskinetic crisis, as they tend to recur. Presurgical counseling to parents and close monitoring of complications is also important in the process.

Background Movement disorders are a group of heterogeneous neurological diseases including hyperkinetic disorders with unwanted excess movements and hypokinetic disorders with reduction in the degree of movements. The objective of our study is to investigate the genetic etiology of a cohort of paediatric patients with movement disorders by whole exome sequencing and to review the potential treatment implications after a genetic diagnosis. Results We studied a cohort of 31 patients who have paediatric-onset movement disorders with unrevealing etiologies. Whole exome sequencing was performed and rare variants were interrogated for pathogenicity. Genetic diagnoses have been confirmed in 10 patients with disease-causing variants in CTNNB1, SPAST, ATP1A3, PURA, SLC2A1, KMT2B, ACTB, GNAO1 and SPG11. 80% (8/10) of patients with genetic diagnosis have potential treatment implications and treatments have been offered to them. One patient with KMT2B dystonia showed clinical improvement with decrease in dystonia after receiving globus pallidus interna deep brain stimulation. Conclusions A diagnostic yield of 32% (10/31) was reported in our cohort and this allows a better prediction of prognosis and contributes to a more effective clinical management. The study highlights the potential of implementing precision medicine in the patients.

Background: Movement disorders are a group of heterogeneous neurological diseases including hyperkinetic disorders with unwanted excess movements and hypokinetic disorders with reduction in the degree of movements. The objective of our study is to investigate the genetic etiology of a cohort of paediatric patients with movement disorders by whole exome sequencing and to review the potential treatment implications after a genetic diagnosis. Results: We studied a cohort of 31 patients who have paediatric-onset movement disorders with unrevealing etiologies. Whole exome sequencing was performed and rare variants were interrogated for pathogenicity. Genetic diagnoses have been confirmed in 10 patients with disease-causing variants in CTNNB1, SPAST, ATP1A3, PURA, SLC2A1, KMT2B, ACTB, GNAO1 and SPG11. 80% (8/10) of patients with genetic diagnosis have potential targeted treatment implications and treatments have been offered to them. One patient with KMT2B dystonia showed clinical improvement with decrease in dystonia after receiving globus pallidus interna deep brain stimulation. Conclusion: A diagnostic yield of 32% (10/31) was reported in our cohort and this allows a better prediction of prognosis and contributes to a more effective clinical management using targeted therapies. The study highlights the potential of implementing precision medicine in the patients.

Aim The study aims to analyze the incidence, clinical features, investigation findings and treatment outcomes of anti-N-methyl- d -aspartate receptor encephalitis in children from Hong Kong. Method A retrospective study was carried out on paediatric patients diagnosed with anti-NMDAR encephalitis in Hong Kong from January 2009 to December 2015. Results Fifteen patients (67% female, 93% Chinese) were identified over seven years and the estimated incidence in Hong Kong was 2.2/million children per year (95% CI 1.2–3.6). The median age of presentation was 12 years (range 1–17 years). The most common symptom groups observed were abnormal psychiatric behavior or cognitive dysfunction (14/15, 93%) and seizures (14/15, 93%), followed by speech dysfunction (13/15, 87%), movement disorders (12/15, 80%), decreased level of consciousness (10/15, 67%) and autonomic dysfunction or central hypoventilation (5/15, 33%). The median number of symptom groups developed in each patient was 5 (range 3–6). All patients were treated with intravenous immunoglobulin and/or steroids. Three patients (20%) with more severe presentation required additional plasmapheresis and rituximab. Outcome was assessable in 14 patients. Among those eleven patients who had only received intravenous immunoglobulin and/or steroids, nine patients (82%) achieved full recovery. One patient (9%) had residual behavioral problem, while another one (9%) who developed anti-NMDAR encephalitis after herpes simplex virus encephalitis was complicated with dyskinetic cerebral palsy and epilepsy. Among those three patients who required plasmapheresis and rituximab, one (33%) had full recovery and two (66%) had substantial recovery. The median duration of follow up was 20.5 months (range 3–84 months). Conclusion Anti-NMDAR encephalitis is an acquired, severe, but potentially treatable disorder. Ethnicity may play a role in the incidence of anti-NMDAR encephalitis and we have provided a local incidence with the majority of patients being Chinese. The diagnosis of anti-NMDAR encephalitis should be considered in children presenting with a constellation of symptoms including psychiatric and neurological manifestations. Patients may respond to first line immunotherapy. For those who do not, second line therapy is indicated in order to achieve a better outcome.

Super-refractory status epilepticus (SRSE) is defined as status epilepticus (SE) that continues or recurs 24 hours or more after the onset of anesthetic therapy and constitutes up to 15% of all SE admissions. One underpowered randomized controlled study has compared barbiturate treatment and propofol treatment for SRSE. Limited additional information on potential treatments for SRSE comes from single case reports and small case series. A ketogenic diet (KD) has an antiepileptic effect and is suggested as a treatment option for refractory epilepsy in children and young adults. KD is generally well tolerated and side effects are relatively mild. However, the lack of robust data, together with limited clinical experience, has limited the use of KD in SRSE. In addition, SRSE is a heterogeneous group of conditions with variable etiology, course, and prognosis. It is recognized that conducting adequate trials to support the efficacy of KD in SRSE will be difficult. Shorvon and Ferlisi reviewed available therapies for SRSE and suggested that KD should probably be tried in all severe cases. Successful implementation of KD requires the collaboration and communication between neurologists, intensivists, dietitians, and nursing staff. Health care professionals using KD need to know the principles and

ObjectiveTo determine the clinical, radiologic, and molecular characteristics of RNA polymerase III-related leukodystrophy (POLR3-HLD) caused by biallelic POLR1C pathogenic variants.MethodsA cross-sectional observational study involving 25 centers worldwide was conducted. Clinical and molecular information was collected on 23 unreported and previously reported patients with POLR3-HLD and biallelic pathogenic variants in POLR1C. Brain MRI studies were reviewed.ResultsFourteen female and 9 male patients aged 7 days to 23 years were included in the study. Most participants presented early in life (birth to 6 years), and motor deterioration was seen during childhood. A notable proportion of patients required a wheelchair before adolescence, suggesting a more severe phenotype than previously described in POLR3-HLD. Dental, ocular, and endocrine features were not invariably present (70%, 50%, and 50%, respectively). Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including 1 individual with clear Treacher Collins syndrome (TCS) features. Brain MRI revealed hypomyelination in all cases, often with areas of pronounced T2 hyperintensity corresponding to T1 hypointensity of the white matter. Twenty-nine different pathogenic variants (including 12 new disease-causing variants) in POLR1C were identified.ConclusionsThis study provides a comprehensive description of POLR3-HLD caused by biallelic POLR1C pathogenic variants based on the largest cohort of patients to date. These results suggest distinct characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.

Glucose transporter type 1 deficiency syndrome (GLUT1DS) is increasingly recognized as a cause of various neurological disorders but a high index of suspicion is important to make the diagnosis. We report two Chinese patients with GLUT1DS, one of which had a novel mutation in the SLC2A1 gene.

AIM: To review the clinical response to levetiracetam (LEV) in neonatal seizure management in intensive care unit. METHODS: Medical records of neonates who received LEV from January 2009 to August 2014 were reviewed. Their demographic data, clinical characteristics, etiology, seizures, electroencephalograms, response to treatment and outcome were noted. Literature review of use of LEV in neonates were also performed via PubMed and EMBASE with keywords - “neonates”, “seizures”, “epilepsy” and “LEV” up to Sep 2014 and retrieved the publications. The response rate to LEV was compared. RESULTS: Twelve neonates were identified during the study period. All patients received phenobarbitone loading prior to consideration of LEV. Seven (58%) and nine (75%) achieved seizure freedom 24 h and 72 h after LEV was added, both clinically and electrographically. No serious adverse effects were associated with LEV use. From the literature, there are total 144 neonates reported to have used LEV. The overall results suggested that LEV could control up to 90% of neonatal seizures. CONCLUSION: LEV was found to be relatively safe and efficacious in treating neonatal seizures, but might not work well in the most severe hypoxic ischemic encephalopathy.

A small proportion of 4H (Hypomyelination, Hypodontia and Hypogonadotropic Hypogonadism) or RNA polymerase III (POLR3)-related leukodystrophy cases are negative for mutations in the previously identified causative genes POLR3A and POLR3B. Here we report eight of these cases carrying recessive mutations in POLR1C, a gene encoding a shared POLR1 and POLR3 subunit, also mutated in some Treacher Collins syndrome (TCS) cases. Using shotgun proteomics and ChIP sequencing, we demonstrate that leukodystrophy-causative mutations, but not TCS mutations, in POLR1C impair assembly and nuclear import of POLR3, but not POLR1, leading to decreased binding to POLR3 target genes. This study is the first to show that distinct mutations in a gene coding for a shared subunit of two RNA polymerases lead to selective modification of the enzymes' availability leading to two different clinical conditions and to shed some light on the pathophysiological mechanism of one of the most common hypomyelinating leukodystrophies, POLR3-related leukodystrophy., Some RNA polymerase (POLR) 3-related leukodystrophy cases do not have the causal mutations in POLR3A and POLR3B. Here, by exome sequencing, the authors identify recessive mutations in POLR1C, a gene encoding a shared POLR1 and POLR3 subunit, impairing assembly and nuclear import of POLR3, but not POLR1.

With the identification of anti-NMDAR (N-methyl-D-aspartate receptor) antibody, the spectrum of anti-NMDAR encephalitis has been expanding. The condition is also increasingly recognised in children, though younger patients are less likely to have tumours, while behavioural and speech problems, seizures, and abnormal movements are common early presenting features. Here we present yet another case with subtle, non-specific clinical symptoms that responded promptly to intravenous immunoglobulin. We believe this illustrates the importance of considering this uncommon differential diagnosis in the management of unexplained neurological conditions.

Previous studies have demonstrated that carnitine levels were lower in patients taking valproate, especially in those who are younger than 24 months of age, those with concomitant neurologic or metabolic disorders, and those on multiple antiepileptic drugs. We performed a cross-sectional surveillance study on pediatric patients taking valproate to evaluate the relationship between carnitine levels and demographic data including age, daily dosage of valproate, number of antiepileptic drugs, body mass index, and feeding problems. Among the 43 patients studied, only two patients were found to have carnitine levels below the normal limit. There were no statistically significant associations between carnitine levels and age, body mass index, additional antiepileptic drugs used, presence of mental retardation, cerebral palsy, or feeding problems, nonambulatory status, or dosage of valproate. We conclude that routine carnitine level checking is not justified in pediatric patients taking valproate.

Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease often associated with a highly specific autoantibody, aquaporin-4 antibody. Although the classic syndrome involves the optic nerves and spinal cord, aquaporin-4 antibody has been important in defining the true spectrum of NMO, which now includes brain lesions in areas of high aquaporin-4 expression. Brainstem involvement, specifically area postrema involvement in the medulla, has been associated with intractable vomiting in some patients with NMO. We describe a 14-year-old female with positive aquaporin-4 antibody whose clinical course was dominated by severe anorexia with associated weight loss (from 68-41kg; body mass index 25.2–15.6). Magnetic resonance imaging showed lesions in the medulla, pons, and thalami. Although she had asymptomatic radiological longitudinally extensive transverse myelitis, she never had symptoms or signs referable to the spinal cord or the optic nerves. We propose that anorexia and weight loss should be considered part of the NMO spectrum, probably related to area postrema involvement.

Objective To establish Down syndrome (DS)-specific growth charts for Hong Kong Chinese children. Design and setting Growth data were collected from (1) members of the Hong Kong Down Syndrome Association (cross-sectional); (2) DS children attending special schools or living in residential homes (cross-sectional); and (3) the paediatric departments of seven public hospitals (retrospective). Patients 425 DS children (57% males and 43% females) born in 1977–2000, yielding 4987 observations. Main outcome measures The LMS method was used to construct reference centile curves of weight, height, body mass index (BMI) from birth until 14 years and head circumference for the first 4 years. Results The median birth length was 49.8 cm and height at age 14 was 146.7 cm for DS boys. Corresponding figures for DS girls were 49.5 and 142.1 cm. The median birth weight was 3.0 kg for DS boys and 2.9 kg for DS girls. At age 14, 26% DS boys (BMI >22.6 kg/m 2 ) and 12% DS girls (BMI >23.3 kg/m 2 ) were overweight. The median head circumference at birth was 32.8 cm for boys and 32.0 cm for girls. Conclusions Chinese DS children had a shorter stature, lower weight and tendency to be overweight than local non-DS children. Their growth patterns differed from those of Chinese DS children in Taiwan, and DS children in the USA and Sweden. Growth retardation was most salient during the first year of life.

We examined the prevalence of medical problems in children and teenagers with Down syndrome in Hong Kong. Methods: Children with Down syndrome receiving care from seven regional hospitals were included and their hospital records were reviewed. A total of 407 patients, aged between 0.06 and 17.16 years were included. Cardiovascular problems were observed in 216 (53%), endocrine problems in 111 (27%), gastrointestinal problems in 46 (11%), haematological problems in 18 (4%), neurological problems in 27 (7%), sleep problems in 36 (9%), skeletal problems in 56 (14%), visual problems in 195 (48%) and auditory problems in 137 (34%). Conclusions: The prevalence of medical problems was high in children and teenagers with Down syndrome in Hong Kong and similar to previous findings elsewhere. Future studies on the local prevalence of medical problems in the adult population with Down syndrome would help to define their medical needs.

Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease often associated with a highly specific autoantibody, aquaporin-4 antibody. Although the classic syndrome involves the optic nerves and spinal cord, aquaporin-4 antibody has been important in defining the true spectrum of NMO, which now includes brain lesions in areas of high aquaporin-4 expression. Brainstem involvement, specifically area postrema involvement in the medulla, has been associated with intractable vomiting in some patients with NMO. We describe a 14-year-old female with positive aquaporin-4 antibody whose clinical course was dominated by severe anorexia with associated weight loss (from 68-41kg; body mass index 25.2-15.6). Magnetic resonance imaging showed lesions in the medulla, pons, and thalami. Although she had asymptomatic radiological longitudinally extensive transverse myelitis, she never had symptoms or signs referable to the spinal cord or the optic nerves. We propose that anorexia and weight loss should be considered part of the NMO spectrum, probably related to area postrema involvement.

The aim of this collaborative study on Duchenne muscular dystrophy and Becker muscular dystrophy is to determine the prevalence and to develop data on such patients as a prelude to the development of registry in Hong Kong. Information on clinical and molecular findings, and patient care, was systematically collected in 2011 and 2012 from all Pediatric Neurology Units in Hong Kong. Ninety patients with dystrophinopathy were identified, and 83% has Duchenne muscular dystrophy. The overall prevalence of dystrophinopathy in Hong Kong in 2010 is 1.03 per 10 000 males aged 0 to 24 years. Among the Duchenne group, we observed a higher percentage (40.6%) of point mutations with a lower percentage (45.3%) of exon deletions in our patients when compared with overseas studies. Although we observed similar percentage of Duchenne group received scoliosis surgery, ventilation support, and cardiac treatment when compared with other countries, the percentage (25%) of steroid use is lower.

Background: In the published reports of the developed society, subdural hematoma and/or retinal hemorrhages, in the absence of documented history of major trauma, should be considered diagnostic of child abuse. Many people used the above criteria for diagnosis, but subsequently found that retinal hemorrhages were more common in non-accidental injuries (NAI). To what extent is the proposed pathognomonic association between unexplained subdural hematoma/retinal hemorrhages and child abuse a self-fulfilling prophecy? Methods: Clinical details of nine children under 2 years with unexplained subdural hematoma admitted to Prince of Wales Hospital between 1995 and 1998 were reviewed. Results: Four had no other physical signs of injury, five had retinal hemorrhages and one had multiple bruises over the body. Following multidisciplinary case conferences for seven children, a diagnosis of NAI was concluded in four cases, but in no case could the abuser be definitely identified. Clinical outcome was poor with seven children showing either profound disability (n = 5) or evidence of developmental delay (n = 2). Conclusion: In this series, NAI were not established in three of the seven cases. Did we underdiagnose child abuse in these cases? Despite a magnitude of opinion to the contrary, the issue of whether ‘trivial’ head injury can cause subdural hemorrhages and/or retinal hemorrhages is yet unresolved. Clearly much more information on this very sensitive and serious issue is required and these data should be collected with an open mind.