Factors associated with outcomes of severe acute necrotizing encephalopathy: A multicentre experience in Malaysia.

This case series compared clinical variables and various combinations of immunotherapy received with outcomes of patients with severe acute necrotizing encephalopathy (ANE). We performed a retrospective review of clinical variables, immunotherapy received, and outcomes (based on the modified Rankin Scale) in Malaysia between February 2019 and January 2020. Twenty-seven children (12 male), aged 7 months to 14 years (mean 4 years) at diagnosis were included. Of these, 23 had an ANE severity score of 5 to 9 out of 9 (high risk). Eleven patients received tocilizumab (four in combination with methylprednisolone [MTP], seven with MTP + intravenous immunoglobulin [IVIG]) and 16 did not (two received MTP alone, 14 received MTP + IVIG). Nine died. Among the survivors, six had good outcomes (modified Rankin Score 0-2) at 6 months follow-up. All patients who received tocilizumab in combination with MTP + IVIG survived. Twenty children received first immunotherapy within 48 hours of admission. No significant association was found between the timing of first immunotherapy with outcomes. Those with brainstem dysfunction (p = 0.016) were observed to have poorer outcomes. This study showed a trend towards better survival when those with severe ANE were treated with tocilizumab in combination with MTP + IVIG. However, larger studies will be needed to determine the effect of this regime on the long-term outcomes.

Advance care plan discussion among parents of children with cerebral palsy.

AIM: To evaluate parental perception of advance care plan (ACP) discussions in families of Malaysian children with bilateral cerebral palsy (CP) classified in Gross Motor Function Classification System levels IV or V for (1) acceptance of the ACP discussion, (2) feedback on the usefulness of ACP discussion, and (3) exploration of possible factors related to parental acceptance of ACP. METHOD: This was a prospective pre- and post-ACP discussion questionnaire study for parents of children with bilateral CP. RESULTS: Sixty-nine patients were recruited to the study; 64 (93%) had at least one additional comorbidity. The median age was 8 years (interquartile range 5 years 1 month-11 years 6 months). Fifty-seven (82.6%) parents found the ACP discussion acceptable, and most reported positive feedback on various components of the discussion (88.4-97.1%). One-third of participants were not comfortable discussing end-of-life care plans. On multivariate analysis, parents who were comfortable discussing end-of-life care plans were more likely to find the ACP discussion acceptable (odds ratio 27.78, 95% confidence interval 2.9-265.1, p = 0.004). INTERPRETATION: Most parents of Malaysian children with bilateral CP reported the ACP discussion as both acceptable and beneficial. Parents need to be comfortable about discussing end-of-life care plans for their child to enable the ACP discussion to be an acceptable experience.

DISCUSIÓN SOBRE EL PLAN ANTICIPADO DE CUIDADOS CON PADRES DE NIÑOS CON PARÁLISIS CEREBRAL: OBJETIVO: Evaluar la percepción parental al discutir el Plan Anticipado de Cuidados (PAC) en familias de niños Malasios con parálisis cerebral bilateral (PC) niveles IV o V según el Sistema de Clasificación de la Función Motora Gruesa (GMFCS) para 1) Aceptación de la propuesta sobre el PAC, 2) opinión sobre la utilidad de discusión sobre el PAC y 3) exploración de posibles factores relacionados a la aceptación parental del PAC. MÉTODO: Se utilizó un estudio prospectivo con un cuestionario pre y post discusión sobre el PAC con padres de niños con PC bilateral. RESULTADOS: Se reclutaron sesenta y nueve pacientes para este estudio; 64 (93%) tenían como mínimo una comorbilidad adicional. La edad mediana fue 8 años (rango intercuartilo 5 años y 1 mes - 11 años y 6 meses). Cincuenta y siete (82,6%) padres hallaron aceptable la discusión sobre el PAC y la mayoría reportó una opinión positiva sobre varios componentes de la discusión (88,4 - 97,1%). Un tercio de los participantes no se sintieron bien discutiendo planes sobre cuidados del paciente terminal. Utilizando análisis multivariable, los padres que se sintieron cómodos discutiendo planes sobre cuidados del paciente terminal, con mayor probabilidad hallaron aceptable la discusión sobre el PAC (relación de probabilidades 27,78 (95%) Intervalo de confidencia 2,9-265,1, p=0,004). INTERPRETACIÓN: La mayoría de los padres de niños Malasios con PC bilateral reportaron la discusión sobre el PAC como aceptable y beneficioso. Los padres necesitan sentirse cómodos discutiendo planes sobre cuidados del paciente con múltiples comorbilidades, referidos a su hijo, a fin de permitir que la discusión sobre el PAC sea una experiencia aceptable.

Congenital myasthenic syndrome with novel pathogenic variants in the COLQ gene associated with the presence of antibodies to acetylcholine receptors.

Congenital myasthenic syndrome (CMS) is a heterogeneous group of inherited disorder which does not associate with anti-acetylcholine receptor (AChR) antibody. The presence of AChR autoantibody is pathogenic and highly sensitive and specific for autoimmune myasthenia gravis (MG). We describe 2 children from unrelated families who presented with hypotonia, ptosis and fatigability in early infancy with anti-AChR antibodies detected via ELISA on 2 separate occasions in the sera. Both were treated as refractory autoimmune MG due to poor clinical response to acetylcholinesterase inhibitor and immunotherapy. In view of the atypical clinical features, genetic studies of CMS were performed and both were confirmed to have novel pathogenic mutations in the COLQ gene. To the best of our knowledge, the presence of anti-AChR antibody in COLQ-related CMS has never been reported in the literature. The clinical presentation of early onset phenotype, and refractoriness to acetylcholinesterase inhibitor and immunotherapy should prompt CMS as a differential diagnosis.

Quality of life of children with tuberous sclerosis complex.

AIM: Evaluation of impaired quality of life (QOL) of Malaysian children with tuberous sclerosis complex (TSC) and its possible risk factors. METHOD: Cross-sectional study on 68 parents of Malaysian children aged 2-18 years with TSC. QOL was assessed using proxy-report Paediatric Quality of Life Inventory (PedsQL) V.4.0, and scores compared with those from a previous cohort of healthy children. Parents also completed questionnaires on child behaviour (child behaviour checklist (CBCL)) and parenting stress (parenting stress index-short form). Multiple regression analysis was used to determine sociodemographic, medical, parenting stress and behavioural factors that impacted on QOL. RESULTS: The mean proxy-report PedsQL V.4.0 total scale score, physical health summary score and psychosocial health summary score of the patients were 60.6 (SD 20.11), 65.9 (SD 28.05) and 57.8 (SD 19.48), respectively. Compared with healthy children, TSC patients had significantly lower mean PedsQL V.4.0 total scale, physical health and psychosocial health summary scores (mean difference (95% CI): 24 (18-29), 20 (12-27) and 26 (21-31) respectively). Lower total scale scores were associated with clinically significant CBCL internalising behaviour scores, age 8-18 years and Chinese ethnicity. Lower psychosocial health summary scale scores were associated with clinically significant CBCL internalising behaviour scores, Chinese ethnicity or >1 antiepileptic drug (AED). CONCLUSION: Parents of children with TSC reported lower PedsQL V.4.0 QOL scores in all domains, with psychosocial health most affected. Older children, those with internalising behaviour problems, of Chinese ethnicity or on >1 AED was at higher risk of lower QOL. Clinicians need to be vigilant of QOL needs among children with TSC particularly with these additional risk factors.

Neurologic manifestations and complications of pandemic influenza A H1N1 in Malaysian children: what have we learnt from the ordeal?

INTRODUCTION: In 2009, pandemic influenza A H1N1 emerged in Mexico and subsequently spread worldwide. In Malaysia, there were more than a thousand of confirmed cases among children. The general clinical characteristics of these children have been well-published. However, the description of neurologic complications is scarce. OBJECTIVE: This study aims to describe the characteristics of neurologic manifestations and complications in a national paediatric cohort with pandemic influenza A H1N1. METHODS: During the pandemic, children (12 years or less) admitted for novel influenza A H1N1 in 68 Malaysian public hospitals, were prospectively enrolled into national database. The clinical, laboratory and neuro-imaging data for children with neurologic manifestations, hospitalized from 15th June 2009 till 30th November 2009, was reviewed. RESULTS: Of 1244 children with influenza A H1N1 during the study period, 103 (8.3%) presented with influenza-related neurological manifestations. The mean age of our study cohort was 4.2 years (SD: 3.3 years). Sixty percent of them were males. Sixty-nine (66.9%) were diagnosed as febrile seizures, 16 (15.5%) as breakthrough seizures with underlying epilepsy, 14 (13.6%) as influenza-associated encephalopathy or encephalitis (IAE) and 4 (3.9%) as acute necrotizing encephalopathy of childhood (ANEC). All 4 available CSF specimens were negative for influenza viral PCR. Among 14 children with brain-imaging done, 9 were abnormal (2: cerebral oedema, 4: ANEC and 3: other findings). There were four deaths and three cases with permanent neurological sequelae. CONCLUSION: About one-tenth of children with pandemic influenza A H1N1 presented with neurologic complications. The most common diagnosis was febrile seizures. One-fifth of those children with neurologic presentation had IAE or ANEC, which carried higher mortality and morbidity. This large national study provides us useful data to better manage children with neurologic complications in the future pandemic influenza outbreaks.