Sophelia Chan

Selective Dorsal Rhizotomy in Hong Kong: Multidimensional Outcome Measures

We prospectively case series study evaluated the short-term effectiveness of selective dorsal rhizotomy plus physiotherapy. Twenty children with spastic cerebral palsy, selected for selective dorsal rhizotomy (mean age, 8.57 years; range, 5.96-11.18 years), were assessed before, and 6 and 12 months after, selective dorsal rhizotomy. Main outcome measures included the Modified Ashworth Scale, passive range of joint movement, the Gross Motor Function Measure, the Pediatric Evaluation of Disability Inventory, the Canadian Occupational Performance Measure, and three-dimensional gait analysis. The results confirmed that selective dorsal rhizotomy plus physiotherapy provided a statistically significant reduction of spasticity, functional improvements in mobility and self-care performance, and increased participation in social situations in our study group (85% exhibited normal intelligence, and 90% belonged to Gross Motor Function Classification System levels I-III). The Gross Motor Function Measure proved to be sensitive in documenting motor functional changes, except for children at Gross Motor Function Classification System level I. Instrumental three-dimensional gait analysis with kinematics and kinetics data analysis confirmed gait improvements in children of higher motor function. The Canadian Occupational Performance Measure indicated improvements in social participation.

Anti-NMDA receptor encephalitis with atypical brain changes on MRI.

A young girl with antibodies to the N-methyl-D-aspartate receptor presented with a clinical syndrome suggestive of dyskinetic encephalitis lethargica with neuropsychiatric features at presentation, movement disorder, mutism, sleep disorder, and seizures. Persistent lesions in the white matter and pons were observed in magnetic resonance imaging of the brain, findings that have not been described previously in N-methyl-D-aspartate receptor antibody encephalitis.

NDUFA9 point mutations cause a variable mitochondrial complex I assembly defect

Mitochondrial respiratory chain complex I consists of 44 different subunits and contains 3 functional modules: the Q‐, the N‐ and the P‐module. NDUFA9 is a Q‐module subunit required for complex I assembly or stability. However, its role in complex I biogenesis has not been studied in patient fibroblasts. So far, a single patient carrying an NDUFA9 variant with a severe neonatally fatal phenotype has been reported. Via exome sequencing, we identified a novel homozygous NDUFA9 missense variant in another patient with a milder phenotype including childhood‐onset progressive generalized dystonia and axonal peripheral neuropathy. We performed complex I assembly analysis using primary skin fibroblasts of both patients. Reduced complex I abundance and an accumulation of Q‐module subassemblies were present in both patients but more pronounced in the severe clinical phenotype patient. The latter displayed additional accumulation of P‐module subassemblies, which was not present in the milder‐phenotype patient. Lentiviral complementation of both patient fibroblast cell lines with wild‐type NDUFA9 rescued complex I deficiency and the assembly defects. Our report further characterizes the phenotypic spectrum of NDUFA9 deficiency and demonstrates that the severity of the clinical phenotype correlates with the severity of the effects of the different NDUFA9 variants on complex I assembly.

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.

Parental restriction reduces the harmful effects of in-bedroom electronic devices

Objective To investigate whether school readiness could be affected by placing electronic devices (EDs) in children’s bedroom and whether the relationship was moderated by parental restriction and family socioeconomic status (SES). Design This is a cross-sectional study with bedroom ED placement and parental restriction reported by parents. Multiple linear regressions were used to test the relationship between school readiness and ED placement. Multiple regression with interaction terms were used to test whether the effect was consistent with and without parental restriction. Setting Kindergartens randomly selected from two districts of different socioeconomic backgrounds in Hong Kong, China. Patients 556 young children attending the third year of kindergarten. Main outcome measures Children’s school readiness was rated by teachers using the Chinese Early Development Instrument. Results 556 preschoolers (mean age 5.46; 51.8% girls) from 20 kindergartens participated in this study. About 30% of parents placed at least one ED in their children’s bedroom. After controlling for sex and SES, the placement of television in the bedroom was associated with lower overall school readiness (β −1.11, 95% CI −1.80 to −0.42) and the placement of game console was associated with lower social competence (β−0.94, 95% CI −1.74 to −0.15). Such harmful effect was more prominent among lower SES families and could be partially alleviated with parental restriction. Conclusion ED placement in children’s bedroom was associated with lower school readiness, particularly among lower SES families. Parental restriction might help to alleviate the harm.

A recurrent de novo DYNC1H1 tail domain mutation causes spinal muscular atrophy with lower extremity predominance, learning difficulties and mild brain abnormality

We describe four unrelated patients with the same de novo heterozygous missense mutation c.751C>T in the DYNC1H1 gene. We found a high phenotype-genotype correlation with all four patients having early childhood-onset predominant lower limb muscle weakness and wasting which was slowly progressing and later-onset mild upper extremities proximal weakness. All four patients presented minor cognitive dysfunction with learning difficulty and developmental behavioural comorbidities with mild abnormalities in the brain MRI. The leg muscle MRI findings are highly consistent in DYN1CH1-related spinal muscular atrophy with lower limb predominance (SMALED) with relative sparing of biceps femoris and semitendinosus, and hypertrophy of adductor longus in the thighs; and sparing the anterior and medial muscles in the calves. This report provides important clinical evidence indicating the de novo heterozygous missense mutation c.751C>T in the DYNC1H1 gene is pathogenic causing SMALED. Muscle MRI is more specific than muscle biopsy in the diagnosis of SMALED.

Cytoplasmic body pathology in severe ACTA1-related myopathy in the absence of typical nemaline rods

Mutations in ACTA1 cause a group of myopathies with expanding clinical and histopathological heterogeneity. We describe three patients with severe ACTA1-related myopathy who have muscle fiber cytoplasmic bodies but no classic nemaline rods. Patient 1 is a five-year-old boy who presented at birth with severe weakness and respiratory failure, requiring mechanical ventilation. Whole exome sequencing identified a heterozygous c.282C>A (p.Asn94Lys) ACTA1 mutation. Patients 2 and 3 were twin boys with hypotonia, severe weakness, and respiratory insufficiency at birth requiring mechanical ventilation. Both died at 6 months of age. The same heterozygous c.282C>A (p.Asn94Lys) ACTA1 mutation was identified by whole exome sequencing. We conclude that clinically severe ACTA1-related myopathy can present with muscle morphological findings suggestive of cytoplasmic body myopathy in the absence of definite nemaline rods. The Asn94Lys mutation in skeletal muscle sarcomeric α-actin may be linked to this histological appearance. These novel ACTA1 cases also illustrate the successful application of whole exome sequencing in directly arriving at a candidate genetic diagnosis in patients with unexpected phenotypic and histologic features for a known neuromuscular gene.

Spinal Primitive Neuroectodermal Tumor Mimicking as Chronic Inflammatory Demyelination Polyneuropathy A Case Report and Review of Literature

We report a young boy who presented with progressive weakness of lower extremities associated with areflexia and abnormal electrophysiological findings initially suggestive of chronic inflammatory demyelinating polyneuropathy. Initial lumbosacral spinal magnetic resonance imaging (MRI) showed thickened descending spinal nerve roots only. Immunomodulating therapy was given but with limited clinical response. Repeated spine magnetic resonance imaging showed cauda equina and also new spinal cord extramedullary contrast enhancement. The initial extensive investigations including open biopsy did not point to any specific diagnosis. Only through pursuing a repeated biopsy, the diagnosis of the spinal peripheral primitive neuroectodermal tumor was confirmed. This case highlights the diagnostic challenges of the spinal peripheral primitive neuroectodermal tumor that could have an initial chronic inflammatory demyelinating polyneuropathy-like presentation. The literature review confirms that this is a rare condition and cauda equina origin has only been reported in adults and teenagers, and this is the first reported case in a young child.

Prevalence and Characteristics of Chinese Patients With Duchenne and Becker Muscular Dystrophy A Territory Wide Collaborative Study in Hong Kong

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.