Terrence Thomas

The Demographic, Clinical, and Magnetic Resonance Imaging (MRI) Features of Transverse Myelitis in Children

The authors collected demographic, clinical, and neuroimaging data prospectively on 38 children with transverse myelitis. One child died during the illness. The female:male ratio was 1.2:1 for children under age 10 years and 2.6:1 over age 10 years. Twenty-eight (74%) reported a prodromal event. Twenty-two patients (58%) had longitudinally extensive transverse myelitis, 9 (24%) had focal lesions, and 5 (13%) had both. Twenty of 33 with brain imaging (61%) had brain lesions; 7 fulfilled McDonald criteria for dissemination in space. Seven of 22 (36%) tested had cerebrospinal fluid oligoclonal banding, 6 of whom had brain lesions. Serum neuromyelitis optica IgG antibodies were absent in all 20 of the children for whom this test was available. At follow-up (mean 3.2 ± 2.0 years), 16% are wheelchair-dependent, 22% have persisting bladder dysfunction, and 13% have been diagnosed with multiple sclerosis.

Association of carbamazepine-induced severe cutaneous drug reactions and HLA-B*1502 allele status, and dose and treatment duration in paediatric neurology patients in Singapore

Objectives To determine the association between severe cutaneous drug reactions (SCDR), HLA-B*1502 allelism, carbamazepine dose and treatment duration in a Singapore paediatric population. Method Case–control study of SCDR with carbamazepine and HLA-B*1502. We recruited 32 cases, 5 with Steven Johnson Syndrome/Toxic Epidermolytic Necrolysis (SJS/TEN) (2 Chinese, 3 Malay), 6 with hypersensitivity syndrome (HSS) (5 Chinese, 1 Indian), 11 with minor drug reactions (9 Chinese, 2 Malay) and 10 controls (7 Chinese, 2 Malay, 1 Indian). HLA-B*1502 allelism was assayed. HLA-B*1502 status and the type of drug reaction were compared using univariate analysis. The time-span from treatment onset to reaction and the dose-time to reaction association in the 3 groups were analysed. Results HLA-B*1502 was positive in: 5/5 (SJS/TEN), 0/6 (HSS), 1/11 (minor drug reactions) and 1/10 controls. OR for SJS/TEN in HLA-B*1502-positive patients relative to that in HLA-B*1502-negative patients was estimated by exact logistic regression to be 27.20 (95% CI 2.67 to ∞). Median treatment duration (days) until allergic reactions was 12 (range 11–13), 16 (range 10–37) and 11 (range 0–63) for SJS/TEN, HSS and minor drug reactions, respectively. Median dose at onset of reactions was 6.2 mg/kg/day (range 4.6–7.4), 9.8 mg/kg/day (range 7.7–12.2) and 6.7 mg/kg/day (range 3.6–20.0) for the 3 groups, respectively. Conclusions HLA-B*1502 positivity increases the odds of carbamazepine-induced SCDR in Singapore children of Chinese and Malay ethnicity. Adverse drug reactions to carbamazepine occurred within 2 weeks and at low doses.

Pediatric transverse myelitis

Pediatric acute transverse myelitis (ATM) is an immune-mediated CNS disorder and contributes to 20% of children experiencing a first acquired demyelinating syndrome (ADS). ATM must be differentiated from other presentations of myelopathy and may be the first presentation of relapsing ADS such as neuromyelitis optica (NMO) or multiple sclerosis (MS). The tenets of the diagnostic criteria for ATM established by the Transverse Myelitis Consortium Working Group can generally be applied in children; however, a clear sensory level may not be evident in some. MRI lesions are often centrally located with high T2 signal intensity involving gray and neighboring white matter. Longitudinally extensive ATM occurs in the majority. Asymptomatic lesions on brain MRI are seen in more than one-third and predict MS or NMO. The role of antibodies such as myelin oligodendrocyte glycoprotein in monophasic and relapsing ATM and their significance in therapeutic approaches remain unclear. ATM is a potentially devastating condition with variable outcome and presents significant cumulative demands on health and social care resources. Children generally have a better outcome than adults, with one-half making a complete recovery by 2 years. There is need for standardization of clinical assessment and investigation protocols to enable international collaborative studies to delineate prognostic factors for disability and relapse. There are no robust controlled trials in children or adults to inform optimal treatment of ATM, with one study currently open to recruitment. This review provides an overview of current knowledge of clinical features, investigative workup, pathogenesis, and management of ATM and suggests future directions.

Multiple sclerosis in children.

Multiple sclerosis (MS) is being increasingly diagnosed in children and adolescents. Clinical and magnetic resonance imaging (MRI) features of MS in the pediatric population are similar to adult-onset disease, with some important distinctions. Case vignettes, recently published clinical definitions, and an approach to disorders considered in the differential diagnoses are provided in this article. Immunomodulatory therapies approved for use in adults with MS are safe and well-tolerated in children, although monitoring of liver function is of particular importance. Finally, this article presents recent research studies performed in an MS population for whom disease onset occurs in unique temporal proximity to the events involved in MS pathogenesis.

Focal status epilepticus and progressive dyskinesia: A novel phenotype for glycine receptor antibody-mediated neurological disease in children.

BACKGROUND Antibody-associated disorders of the central nervous system are increasingly recognised in adults and children. Some are known to be paraneoplastic, whereas in others an infective trigger is postulated. They include disorders associated with antibodies to N-methyl-d-aspartate receptor (NMDAR), voltage-gated potassium channel-complexes (VGKC-complex), GABAB receptor or glycine receptor (GlyR). With antibodies to NMDAR or VGKC-complexes, distinct clinical patterns are well characterised, but as more antibodies are discovered, the spectra of associated disorders are evolving. GlyR antibodies have been detected in patients with progressive encephalopathy with rigidity and myoclonus (PERM), or stiff man syndrome, both rare but disabling conditions. CASE REPORT We report a case of a young child with focal seizures and progressive dyskinesia in whom GlyR antibodies were detected. Anticonvulsants and immunotherapy were effective in treating both the seizures and movement disorder with good neurological outcome and with a decline in the patients serum GlyR-Ab titres. CONCLUSION Glycine receptor antibodies are associated with focal status epilepticus and seizures, encephalopathy and progressive dyskinesia and should be evaluated in autoimmune encephalitis.

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome may have a hypothalamus-periaqueductal gray localization.

BACKGROUND Anatomical localization of the rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome has proved elusive. Most patients had neuroimaging after cardiorespiratory collapse, revealing a range of ischemic lesions. PATIENT DESCRIPTION A 15-year-old obese boy with an acute febrile encephalopathy had hypoventilation, autonomic dysfunction, visual hallucinations, hyperekplexia, and disordered body temperature, and saltwater regulation. These features describe the ROHHAD syndrome. Cerebrospinal fluid analysis showed pleocytosis, elevated neopterins, and oligoclonal bands, and serology for systemic and antineuronal antibodies was negative. He improved after receiving intravenous steroids, immunoglobulins, and long-term mycophenolate. Screening for neural crest tumors was negative. CONCLUSION Magnetic resonance imaging of the brain early in his illness showed focal inflammation in the periaqueductal gray matter and hypothalamus. This unique localization explains almost all symptoms of this rare autoimmune encephalitis.

Use of Magnesium Sulfate Infusion for the Management of Febrile Illness-Related Epilepsy Syndrome A Case Series

Febrile illness-related epilepsy syndrome is a catastrophic epileptic encephalopathy that is highly refractory to most antiepileptic drugs leading to high morbidity and mortality. The authors report the use of a pediatric infusion protocol of continuous intravenous magnesium sulfate for the control of seizures in 2 children with febrile illness-related epilepsy syndrome refractory to multiple antiepileptic drugs in a pediatric intensive care unit of a tertiary care children’s hospital. Both patients, 2 and 16 years of age, respectively, were treated with continuous magnesium sulfate infusion. Serum magnesium concentrations ranging from 2.1 to 5 mmol/L were achieved. Seizure reduction and cessation were noted in 1 patient with magnesium more than 3.0 mmol/L. No significant adverse effects were observed. Magnesium sulfate infusions can be safely used in pediatric refractory status epilepticus. Magnesium sulfate can be considered in the management of children with febrile illness-related epilepsy syndrome.

Childhood Transverse Myelitis and Its Mimics

Childhood transverse myelitis is an acute inflammatory disorder of the spinal cord with a risk of permanent disability. A timely and accurate diagnosis is imperative, and the radiologist needs to discern between a variety of extra-axial and spinal cord abnormalities that produce similar symptoms but require vastly differing treatments. This article presents the range of imaging characteristics seen in childhood transverse myelitis and the differentiation from its mimics.

PO-0845 Acute Necrotising Encepholopathy In Childhood – Epidemiology, Radiological Findings And Outcomes

Background and aims Acute necrotizing encephalopathy in childhood (ANEC) is a disease characterised by acute encephalopathy and radiological features of bilateral thalamic necrosis. Medium and long term morbidity is not well described. We describe the mortality and morbidity outcomes in our paediatric cohort with this disease. Methods This is a retrospective ten-year series. Children aged one month to 18 years diagnosed with ‘ANEC’ were collated from Neurology and Radiology databases. 18 fulfilled clinical criteria of acute encephalopathy. All were scored with Mizuguchi’s radiological checklist by two paediatric neurologists and one radiologist. 11 cases scored unlikely were excluded. Data analysis focused on discharge and follow-up outcomes. Results 7 patients were analysed. The median age was 3.7 years. All were previously well with normal development. All had impaired consciousness at presentation with preceding fever and prodrome. Typical radiology showed bilateral thalamic involvement with/without areas of haemorrhage and necrosis. Causative organisms included Influenza A H1N1, Human Herpes Virus 6 and Metapneumovirus. All were treated with steroids, immunoglobulin or both. Outcomes were evaluated at discharge and follow-up and divided into good or poor (including death). One passed away from brainstem death. All had neurological deficit at discharge: 50% mildly affected; 50% severely affected. 00% in the former group restored normal neurological function on follow-up. In the latter, two responded well to rehabilitation but one remained severely impaired. Conclusions ANE mortality at our institution is 14%. Morbidity of survivors at discharge is 100%. Long term follow up morbidity however, improves to 50% with half achieving normal neurological function at follow up.

Mycophenolate mofetil in paediatric autoimmune or immune-mediated diseases of the central nervous system: clinical experience and recommendations

To gather data on mycophenolate mofetil (MMF) in paediatric autoimmune/immune‐mediated central nervous system (CNS) conditions, focusing on safety and factors that may affect MMF efficacy.