Randomized trial of high-dose pyridoxine in combination with standard hormonal therapy in West syndrome.

OBJECTIVE: To determine whether high-dose, oral pyridoxine in combination with standard adrenocorticotropic hormone (ACTH) therapy has superior effectiveness than ACTH therapy alone in increasing cessation of epileptic spasms for children with West syndrome. METHODS: This study was an open-label, randomized controlled trial with masked endpoint assessments. Eligible children with West syndrome, age ranged 3-18 months, were randomized into the intervention (n = 43) and the standard arm (n = 37) of therapy. The intervention group received oral pyridoxine at 100-300 mg/kg/day in addition to standard therapy of intramuscular ACTH at 150 IU/m2/day. Primary effectiveness outcome was a complete cessation of spasms at two weeks and sustained till six weeks. RESULTS: Comparison of effectiveness measures between intervention and standard groups were : complete cessation of epileptic spasms (48.8% vs 58.3%; group difference -9.6%; 95% confidence interval [CI] -30% to 12.3%; p = 0.4), median EEG scores (Q1-Q3) by Jeavons Score at six weeks [3 (1-5) vs 3 (1-5); p = 0.6], median motor scores (Q1-Q3) by DASII (Development Assessment Scales for Indian Infants) at 12 weeks [35 (29-49) vs 42 (34.3-63.8), p = 0.04], and median mental scores (Q1-Q3) by DASII at 12 weeks [35 (29.5-46) vs 41.5 (31.3-60), p = 0.02]. Adverse events were comparable in both arms. CONCLUSIONS: There was no evidence to suggest the superiority of high-dose pyridoxine in combination with ACTH versus ACTH alone for the treatment of West syndrome, considering the limitations of the study design.

Primary Hypokalemic Periodic Paralysis: Long-term Management and Complications in a Child.

Hypokalemic periodic paralysis (HPP) is a rare genetically determined neuromuscular disorder caused by mutation in skeletal muscles calcium and sodium channels. It presents with recurrent episodes of flaccid paralysis. A 9-year-old girl presented with recurrent episodic flaccid quadriparesis with complete recovery in-between the episodes. Investigations during the acute episode revealed marked hypokalemia with electrocardiogram changes. Next-generation sequencing showed pathogenic missense mutation in CACNA1S gene. She responded well to oral potassium supplementation, acetazolamide, and spironolactone therapy. Muscle weakness in HPP is reversible, and long-term management reduces frequency of paralysis and prevents permanent weakness.

Thiamine Responsive Pyruvate Dehydrogenase Complex Deficiency: A Potentially Treatable Cause of Leigh's Disease.

Pyruvate dehydrogenase complex (PDHC) deficiency is a rare metabolic disorder that affects tissues with high energy demand such as the central nervous system. The clinico-radiological phenotype of Leigh's disease is one of its common presentations. We present a 9-month-old boy with rapidly progressive infantile Leigh's disease. PDHA1 gene sequencing revealed a pathological homozygous missense mutation c.131A>G or p.H44R in exon 3 consistent with PDHC deficiency. H44R is among the five mutations (H44R, R88S, G89S, R263G, and V389fs) in E1α subunit that is thiamine-responsive. The child was initiated on thiamine, riboflavin, carnitine, coenzyme Q, and sodium benzoate supplementation. Mild recovery was noted at 6 months follow up as no further episodes of encephalopathy occurred. Thereafter, the child was treated with Ketogenic diet which resulted in increased levels of activity and alertness. Despite an improving course, the child had a sudden unexpected death at the age of 21 months.

Hyperhomocysteinaemia in children receiving phenytoin and carbamazepine monotherapy: a cross-sectional observational study.

OBJECTIVE: Long-term therapy with phenytoin and carbamazepine is known to cause hyperhomocysteinaemia. We evaluated the prevalence of hyperhomocysteinaemia in North Indian children receiving phenytoin or carbamazepine monotherapy for >6 months duration and the effect of folic acid supplementation on plasma homocysteine. METHODS: In this cross-sectional observational study we enrolled consecutive children aged 2-12 years with epilepsy who had received phenytoin or carbamazepine monotherapy for >6 months. Plasma total homocysteine, folic acid, vitamin B12 and antiepileptic drug concentrations were measured. Healthy age- and sex-matched controls were recruited. Children with homocysteine >10.4 µmol/L received folic acid supplementation for 1 month and homocysteine and folic acid concentrations were measured after 1 month follow-up. RESULTS: A total of 112 children receiving antiepileptic monotherapy for >6 months were enrolled. Hyperhomocysteinaemia was present in 54 children (90%) receiving phenytoin, 45 children (90%) receiving carbamazepine therapy and 17 (34%) controls (p<0.05). Mean plasma homocysteine concentrations were significantly higher (18.9±10.2 vs 9.1±3 µmol/L) and serum folic acid concentrations (10.04±8.5 ng/ml vs 12.6±4.8 p<0.001) and vitamin B12 concentrations (365±155 pg/mL vs 474±332 pg/mL, p=0.02) were significantly lower in the study group compared with the control group. Duration of antiepileptic drug therapy correlated significantly with elevated homocysteine and reduced folic acid concentrations (p<0.05). Supplementation with folic acid for 1 month led to a reduction in plasma homocysteine concentrations in the study group (from 20.9±10.3 µmol/L to 14.2±8.2 µmol/L, p<0.05). CONCLUSIONS: Phenytoin or carbamazepine monotherapy for >6 months duration is associated with hyperhomocysteinaemia in 90% of North Indian children. Elevated homocysteine concentrations were normalised in these children with folic acid supplementation.