Jithangi Wanigasinghe

Epilepsy in hemiplegic cerebral palsy due to perinatal arterial ischaemic stroke

Aim  The aim of this study was to describe the frequency, risk factors, manifestations, and outcome of epilepsy in children with hemiplegic cerebral palsy (CP) due to perinatal arterial ischaemic stroke (AIS).

The efficacy of moderate-to-high dose oral prednisolone versus low-to-moderate dose intramuscular corticotropin for improvement of hypsarrhythmia in West syndrome: a randomized, single-blind, parallel clinical trial.

BACKGROUND The role of therapy on improvement of hypsarrhythmia has not been systematically assessed. This study was performed to assess the efficacy of oral prednisolone and intramuscular adrenocorticotrophin hormone in improving hypsarrhythmia in West syndrome. METHOD Children (2 months-2 years), with previously untreated West syndrome, were randomized to receive 40-60 IU every other day of intramuscular adrenocorticotrophin hormone or 40-60 mg/day of oral prednisolone for 14 days. Children with tuberous sclerosis were excluded. Improvement of hypsarrhythmia was assessed blindly using a hypsarrhythmia severity scale before and after completion of therapy. Adverse effects were assessed on day 14 using symptom diary. (Clinical trial registry identifier: SLCTR/2010/010.) RESULTS From 92 newly diagnosed West syndrome infants, 48 were randomized to receive prednisolone and 44 to receive adrenocorticotrophin hormone. Eighty infants completed the posttreatment evaluation according to specifications. The hypsarrhythmia severity score, significantly improved with hormonal therapy for 2 weeks (10.45 ± 2.65 vs 3.45 ± 2.67); P < 0.01. When individual treatment arms were compared using mean differences in the improvement of scores, improvement in prednisolone arm (7.95 ± 2.76) was significantly greater than that in the adrenocorticotrophin hormone arm (6.00 ± 2.61); P < 0.01. Both forms of therapy were tolerated well. Frequent crying, irritability, weight gain, increased appetite, and abdominal distension were more common (but not statistically significant) with prednisolone. CONCLUSIONS Hypsarrhythmia severity score improved significantly with both hormonal therapies, but this improvement was significantly better with oral prednisolone than intramuscular adrenocorticotrophin hormone. This is the first ever documentation of a superior therapeutic role of oral steroids in West syndrome.

Randomized, Single-Blind, Parallel Clinical Trial on Efficacy of Oral Prednisolone Versus Intramuscular Corticotropin on Immediate and Continued Spasm Control in West Syndrome

OBJECTIVE A single-center, single-blind, parallel-group, randomized clinical trial was performed to test the null hypothesis that adrenocorticotropic hormone is not superior to high-dose prednisolone for treatment of newly diagnosed West syndrome. METHODS Newly diagnosed infants with West syndrome were randomized to receive 14 days of oral prednisolone (40-60 mg/day) or a synthetically prepared intramuscular long-acting adrenocorticotropic hormone (40-60 IU/every other day [0.5-0.75 mg]) according to the United Kingdom Infantile Spasm Study protocol. They were blindly evaluated for infantile spasm remission by day 14, electroclinical remission (spasm cessation + resolution of hypsarrhythmia on a 30-minute electroencephalograph) by day 14 and continued spasm freedom for 28 days. RESULTS Ninety-seven patients were enrolled in the study, with 48 of them receiving prednisolone and 49 receiving ACTH. There was no significant difference in the baseline characteristics or risk factors for the two treatment groups. By day 14, cessation of infantile spasms occurred in 28/48 (58.3%) infants on prednisolone compared with only 18/49 (36.7%) infants given adrenocorticotropic hormone (P = 0.03) and electroclinical remission in 21 on prednisolone compared with nine on adrenocorticotropic hormone (P = 0.007). Sustained spasm control for 28 consecutive days following electroclinical remission occurred in 15 children on prednisolone compared with six on adrenocorticotropic hormone (P = 0.008). The total number of days required for spasm cessation was significantly less in those treated with prednisolone (3.85 days ± 2.4) compared with adrenocorticotropic hormone (8.65 days ± 3.7) (P = 0.001). Among patients who did not achieve remission, there was a non-significant trend toward greater quantitative reduction of spasms with prednisolone than with adrenocorticotropic hormone (P = 0.079). CONCLUSION Synthetic adrenocorticotropic hormone of 40-60 IU/every other day did not yield superior rates of electroencephalographic or clinical remission when compared with prednisolone of 40-60 mg/day. Significantly, more patients achieved electroclinical remission when treated with prednisolone than with adrenocorticotropic hormone.

An international pilot study of an internet‐based platform to facilitate clinical research in epilepsy: The EpiNet project

Purpose:  We created an epilepsy patient database that can be accessed via the Internet by neurologists from anywhere in the world. The database was designed to enroll and follow large cohorts of patients with specific epilepsy syndromes, and to facilitate recruitment of patients for investigator‐initiated clinical trials.

First contiguous gene deletion causing biotinidase deficiency: The enzyme deficiency in three Sri Lankan children

We report three symptomatic children with profound biotinidase deficiency from Sri Lanka. All three children presented with typical clinical features of the disorder. The first is homozygous for a missense mutation in the BTD gene (c.98_104 del7insTCC; p.Cys33PhefsX36) that is commonly seen in the western countries, the second is homozygous for a novel missense mutation (p.Ala439Asp), and the third is the first reported instance of a contiguous gene deletion causing the enzyme deficiency. In addition, this latter finding exemplifies the importance of considering a deletion within the BTD gene for reconciling enzymatic activity with genotype, which can occur in asymptomatic children who are identified by newborn screening.

Parental concerns towards children and adolescents with epilepsy in Sri Lanka—Qualitative study

PURPOSE Social, cultural, psychological and many other factors significantly impact the lives of epileptic children and their families. Parental concerns towards their children are less known in south Asian children with epilepsy. We aimed to identify the parental concerns regarding their children and adolescents with epilepsy in Sri Lanka. METHODS We carried out qualitative study in 3 districts of Sri Lanka, comprising 16 in-depth interviews with parents of children and adolescents with epilepsy and 3 focus group discussions with primary caregivers of epileptic children and key informants (schoolteachers, public health staffs). Content analysis of the interview data was performed. RESULTS Parental concerns were spread among seven themes that emerged from the content analysis. These concerns were about the childs functioning in areas such as physical, behavioural, psychological and social, education, concerns related to anti-epileptic therapy and epilepsy as a disease. Parents were more concerned about their childs safety, educational achievements and future prospects in terms of employment and marriage. Unpredictability of seizures, fear of stigma and unawareness of epilepsy were the main reasons voiced by the parents for having such concerns. Increased concern and perception of vulnerability was seen among parents whose children had epilepsy and co-morbid illness. CONCLUSIONS Parental concerns towards their children and adolescents show a multidimensional construct. Unpredictability of seizures, fear of stigma and unawareness of epilepsy were identified as key influential factors in moulding the parental concerns.

Treatment-responsive, reversible, autoimmune encephalitis in a child

The recent recognition of anti-N-methyl-D-aspartate receptor (NMDAR) antibody encephalitis has added to the growing list of treatment-responsive, reversible, autoimmune CNS disorders [1]. NMDAR-antibody encephalitis is characterised by a multistage progression from psychosis, memory deficits, seizures and language dysfunction to a state of coma often associated with movement disorders, dysautonomia and breathing instability [2]. Although first described as a paraneoplastic syndrome associated with ovarian teratomata in young women, NMDAR-antibody encephalitis is increasingly recognised in children, often unassociated with tumours [3-5]. This is the first report of NMDAR-antibody encephalitis from Sri Lanka.

Infantile-Onset Myelin Protein Zero–Related Demyelinating Neuropathy Presenting as an Upper Extremity Monoplegia

We describe an infant with an early-onset demyelinating neuropathy who presented with an upper extremity monoplegia and progressive asymmetric weakness. Neurophysiologic testing revealed a generalized severe neuropathy with marked slowing of nerve conduction. The disproportionate severity and asymmetry of upper extremity involvement at presentation was atypical of inherited neuropathies, and an initial diagnosis of chronic inflammatory demyelinating polyneuropathy was considered. Nerve biopsy showed severe depletion of large myelinated fibers without inflammatory cells, and focally folded myelin sheaths were seen on electron microscopy. Genetic testing revealed a de novo heterozygous mutation in the myelin protein zero gene.

Multiple subcutaneous folds in oculocerebrorenal syndrome of Lowe

A 3-months old infant born to non-consanguineous parents was evaluated for hypotonia and developmental delay. He had a cataract in left eye, congenital glaucoma and megalocornea in right eye with no other dysmorphism. Anterior fontanelle was widely open. He was hypotonic with diminished tendon reflexes. Hypermobility was noted around both elbows and knees. There were unusual multiple skin folds with generalised increase in subcutaneous tissue noted in the limbs (Figure 1). His weight was between mean and -1SD.

Corrigendum to “First contiguous gene deletion causing biotinidase deficiency: The enzyme deficiency in three Sri Lankan children” [Mol. Genet. Metab. Rep. 2 (2016) 81–84]

[This corrects the article DOI: 10.1016/j.ymgmr.2015.01.005.].