Eva Lai-wah Fung

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?

Carnitine level in Chinese epileptic patients taking sodium valproate

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.

Ketogenic Diet as a Therapeutic Option in Super-refractory Status Epilepticus

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

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.

Inherited metabolic diseases in the Southern Chinese population: spectrum of diseases and estimated incidence from recurrent mutations

Inherited metabolic diseases (IMDs) are a large group of rare genetic diseases. The spectrum and incidences of IMDs differ among populations, which has been well characterised in Caucasians but much less so in Chinese. In a setting of a University Hospital Metabolic Clinic in Hong Kong, over 100 patients with IMDs have been seen during a period of 13 years (from 1997 to 2010). The data were used to define the spectrum of diseases in the Southern Chinese population. Comparison with other populations revealed a unique spectrum of common IMDs. Furthermore, the incidence of the common IMDs was estimated by using population carrier frequencies of known recurrent mutations. Locally common diseases (their estimated incidence) include (1) glutaric aciduria type 1 (∼1/60,000), (2) multiple carboxylase deficiency (∼1/60,000), (3) primary carnitine deficiency (∼1/60,000), (4) carnitine-acylcarnitine translocase deficiency (∼1/60,000), (5) glutaric aciduria type 2 (∼1/22,500), (6) citrin deficiency (∼1/17,000), (7) tetrahydrobiopterin-deficient hyperphenylalaninaemia due to 6-pyruvoyl-tetrahydropterin synthase deficiency (∼1/60,000), (8) glycogen storage disease type 1 (∼1/150,000). In addition, ornithine carbamoyltransferase deficiency and X-linked adrenoleukodystrophy are common X-linked diseases. Findings of the disease spectrum and treatment outcome are summarised here which may be useful for clinical practice. In addition, data will also be useful for policy makers in planning of newborn screening programs and resource allocation.

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.

Could Vitamin C deficiency have a role in shaken baby syndrome

Unexplained subdural hematoma in infants, with or without retinal hemorrhages and skeletal fracture, has been considered by some to be pathognomic for non-accidental injury (Fig. 1). However, there is increasing concern that the exact pathogenesis of these findings is not well understood. Dr Clemeston has proposed that some of these cases of presumed shaken baby syndrome (SBS) were due to vitamin C deficiency, and has recommended that plasma ascorbic acid and whole blood histamine should be included in the diagnostic workup of all cases of suspected SBS. 1

Diagnosing Wilson's disease in a 5-year-old child

A previously healthy 5-year old Chinese boy was admitted with fever and vomiting. There was no abdominal pain, diarrhoea, tea-coloured urine, history of recent travel, or known hepatitis contact. There were no signs of chronic liver disease and the liver was not enlarged. The rest of the physical examination, including examination of the eyes and central nervous system, was normal. Liver function tests on admission revealed only a mildly elevated serum alanine transaminase of 152 IU/L (normal range <58 IU/L). Other haematological and biochemical tests were normal: haemoglobin 12.1 g/dL, white blood cell count 7.2 × 10 9 /L, platelet count 480 × 10 9 /L, total protein 70 g/L, albumin 37 g/L (normal range 36–48 g/L), total bilirubin 10 μ mol/L (normal range <15 μ mol/L), alkaline phosphatase 250 IU/L (normal range 130–380 IU/L) and γ -glutamyltransferase 78 U/L (normal range <100 U/L). Coagulation study was normal with prothrombin time 10 s, international normalized ratio 0.97 (normal range 0.9–1.1) and activated partial thromboplastin time 33.3 s (normal range 26.2–40.1 s). Creatinine phosphokinase was 99 U/L (42–218) suggesting that the elevated ALT was not of muscle origin. The patient was managed with intravenous fluid rehydration and discharged 3 days later. However, on subsequent follow up, he continued to show elevated serum transaminases, despite being entirely asymptomatic. A viral hepatitis serology screen showed that hepatitis B surface antigen, immunoglobulin M (IgM) antibody to hepatitis A virus, antibody to hepatitis B-core antigen immunoglobulin M, antibody to hepatitis C virus and Epstein-Barr virus viral capsid antigen antibody IgM were all negative. Shell vial culture for cytomegalovirus in urine was also negative. A screen for autoimmune hepatitis was negative for antimitochondria, antinuclear and antismooth muscle antibody. An abdominal ultrasound revealed fatty infiltration of the liver with no focal lesions. The biliary tree was not dilated and there were no enlarged lymph nodes. A metabolic work-up was subsequently carried out after the common causes of elevated liver enzymes were excluded. Serum α 1 -antitrypsin was 1.35 g/L (normal range 0.83–1.99 g/L). The α 1antitrypsin phenotype was not checked. Serum ferritin was 438 pmol/L (normal range 47–708 pmol/L). Both serum copper and caeruloplasmin were low at 3.9 μ mol/L (normal range 10.7–25.2 μ mol/L) and 0.02 g/L (normal range 0.21– 0.53 g/L), respectively. Twenty-four-hour urine copper output was elevated at 11.9 μ mol/day (normal range <1.0 μ mol/day). Gas chromatographic analysis of urinary organic acids showed no abnormal pattern. A percutaneous liver biopsy showed intact hepatic lobular architecture with minimal portal fibrosis, minimal portal lymphocytic infiltrate and scanty lobular lymphocytic infiltrate. Marked para-lobular macroand microvesicular fatty change was seen. Both orcein stain for copper-associated protein and rhodanine stain for copper were negative. The liver copper content was elevated at 947 μ g/g dry weight of liver (normal liver 19.0–50.8 μ g/g) confirming the diagnosis of Wilson’s disease. The patient was then started on oral zinc acetate therapy at 25 mg twice daily (2.5 mg/kg/day), which he tolerated well. Serum transaminase levels returned to normal levels of 33 IU/L (normal range <58 IU/L) 3 months after the commencement of zinc therapy.

Unexplained subdural hematoma in young children

Reply to letter by Anselm C W Lee ‘Unexplained subdural hematoma in young children’, Pediatrics International 45: 220. Dr Lee suggests that making the diagnosis of so-called abusive head injury in young children is never easy because perpetrators hardly ever admit what they have done. Our report discusses the possibility that the ‘abusive head injury’ may not in fact be abusive, that the ‘perpetrators’ may in fact be innocent bystanders and that they are therefore not able to admit what they have not done. It is imperative that we understand that the conviction that subdural hemorrhage (plus retinal hemorrhage and no adequate explanation of injury) is the result of severe shaking is no more than a favored but unproven hypothesis. 1 The size of our series and the absence of any fatalities does not alter this fact. We willingly admit that we do not know or understand the cause of these tragic events. We also willingly admit that our hypothesis that more trivial injury may be a cause in some cases is also unproven. We therefore re-iterate our conclusion that much more information on this very sensitive and serious issue is required, and that these data be collected with an open mind. What are needed in Hong Kong and elsewhere are large well-designed prospective case-control studies that can give a clearer picture of possible risk factors, a better understanding of etiology, more precise estimates of incidence and better documentation of mortality and longterm outcomes.

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.