Focal cerebral arteriopathy-inflammatory type in a child - MR diagnosis using vessel wall imaging technique with review of classification and diagnostic evaluation criteria.

Acute ischemic stroke (AIS) in childhood is defined by a stroke occurring after 28 days of life to 18 years of age. This presents a distinct clinical challenge in terms of both diagnosis and treatment. The overlapping clinical presentations of acute ischemic stroke and its mimics such as migraine with aura, seizure with Todd paresis and encephalitis renders early accurate diagnosis of this time-sensitive condition difficult, with a change in the final diagnosis in up to 40% of patients. Identification of the etiology after establishing the diagnosis of ischemic stroke is paramount for prognostication and treatment decisions. These include cardioembolic, arteriopathy, thrombophilia and inflammatory causes. Magnetic resonance imaging (MRI) plays an indispensable role towards tackling the initial diagnostic dilemma and subsequent evaluation of the underlying etiology, particularly in patients with arteriopathy. Here we present the MRI findings including vessel wall imaging with longitudinal follow-up, which support the diagnosis of focal cerebral arteriopathy-inflammatory type (FCAi) in a pediatric patient.

Deep brain stimulation in a young child with GNAO1 mutation - Feasible and helpful.

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.

Exome sequencing in paediatric patients with movement disorders.

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.

Anti-N-methyl-d-aspartate receptor encephalitis in children: Incidence and experience in Hong Kong.

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.

Response of levetiracetam in neonatal seizures.

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.

Growth charts for Chinese Down syndrome children from birth to 14 years.

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.

Aquaporin-4 autoantibody: a neurogenic cause of anorexia and weight loss.

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.

First report of GLUT1 deficiency syndrome in Chinese patients with novel and hot spot mutations in SLC2A1 gene.

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.

Medical issues among children and teenagers with Down syndrome in Hong Kong.

UNLABELLED: 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.

Unexplained subdural hematoma in young children: is it always child abuse?

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.