Puneet Jain

High dose (4 mg/kg/day) versus usual dose (2 mg/kg/day) oral prednisolone for treatment of infantile spasms: An open-label, randomized controlled trial

OBJECTIVES This study aimed to test the hypothesis that high-dose prednisolone (4 mg/kg/day) may be more efficacious than usual-dose (2 mg/kg/day) prednisolone for spasm resolution at 14-days in children with infantile spasms. METHODS This was a randomized, open-label-trial conducted at a tertiary-level-hospital from February-2012 to March-2013. Children aged 3-months to 2-years presenting with infantile spasms in clusters (at least 1 cluster/day) with hypsarrhythmia or its variants on EEG were enrolled. The study participants were randomized to receive either high-dose prednisolone (4 mg/kg/day) or the usual-dose (2 mg/kg/day) prednisolone. The primary outcome measure was the proportion of children who achieved spasm freedom for 48-h at day-14 after treatment initiation as per parental reports in both the groups. The adverse effects were also monitored. The study was registered with the clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT01575639). RESULTS Sixty-three children were randomized into the two groups with comparable baseline characteristics. The proportion of children with spasm cessation on day-14 was significantly higher in the high-dose group as compared to the usual-dose group (51.6% vs. 25%, p=0.03). The absolute risk reduction was 26.6% (95% confidence interval 11.5-41.7%) with number needed to treat being 4. The adverse effects were comparable in both the groups. CONCLUSIONS High-dose prednisolone (4 mg/kg/d) was more effective than low-dose prednisolone (2mg/kg/d) in achieving spasm cessation at 14-days (as per parental reports) in children with infantile spasms.

Seroconversion Following Killed Polio Vaccine in Neonates

The study was carried out to evaluate the efficacy of IPV in neonates and to study the additive effect of IPV or OPV at birth on seroconversion with three subsequent doses of OPV. Addition of IPV or OPV at birth to the conventional OPV schedule resulted in significantly higher seroconversion rates than in the controls, who received three doses of OPV. Three doses of IPV beginning from birth resulted in significantly better seroconversion rates than in the control group. Children receiving 3 doses of IPV showed significantly greater seroconversion rates against type III polio virus than those receiving IPV/OPV at birth followed by 3 doses of OPV. The difference in the seroconversion rates against the other virus types was not significant.A significantly greater number of children who received some vaccine at birth (IPV or OPV) were protected against poliomyelitis by 6 weeks age as compared to those who received no immunization at birth. The study recommends that seroconversion rates following three doses of IPV are satisfactory. Addition of IPV or OPV at birth to the conventional schedule markedly increases the seroconversion rates. Immunization can be started at birth to ensure early protection against poliomyelitis.

Transient restricted diffusion of corpus callosum and subcortical white matter following febrile status epilepticus.

We describe the case of a 4½-year-old girl with prolonged febrile status followed by abnormal behavior and loss of speech. Interesting findings on diffusion-restricted imaging were noted. The clinicoradiologic possibilities are discussed.

Complete Bilateral Ophthalmoplegia with Unilateral Facial Palsy in a Child with Anti-GQ1b Syndrome

The classical phenotype of Miller Fisher syndrome is characterized by ophthalmoplegia, ataxia and areflexia. However, less extensive forms have been described. The authors report a 14-y-old boy with positive anti-GQ1b antibodies with unusual clinical findings. He presented with headache, double vision and vomiting for 7 d. Examination revealed complete opththalmoplegia, right lower-motor-neuron facial palsy, no limb weakness or cerebellar signs and normal fundus. CSF examination and MRI brain were normal. Electrophysiological studies showed normal limb nerve conduction studies, low CMAP amplitude of right facial nerve, abnormal blink reflex and negative repetitive-nerve-stimulation test. Anti-GQ1b antibodies were positive. The child was managed conservatively with gradual complete recovery. The patients with positive anti-GQ1b antibodies who do not demonstrate the full complement of the Miller Fisher syndrome triad have been reported previously. However, unilateral facial palsy has not been reported previously. This report further expands the phenotypic spectrum of anti-GQ1b syndrome.

Pontocerebellar hypoplasia type 1 with a milder phenotype in a two-year-old girl.

The rare association of pontocerebellar hypoplasia with anterior horn cell involvement has been classified as pontocerebellar hypoplasia type 1. Its classic phenotype is usually severe. However, the pontocerebellar hypoplasia type 1 may have wider variability in clinical and radiological features. There may be a genetic heterogeneity as well. We described here a young girl with relatively milder clinical phenotype with cerebellar atrophy with absent pontine involvement, further adding to the clinical phenotype.

Hypomyelination With T2-hypointense Globi Pallidi in a Child With Fucosidosis

A 4-year-old boy presented with progressive neurodegeneration, mild coarsening of facies and spasticity. The classical neuroimaging guided the subsequent investigation of enzyme assay which confirmed the diagnosis of fucosidosis.

Teaching Video NeuroImages: Perioral myoclonia with absences in a 12-year-old boy

A previously normal 12-year-old boy presented with 2 episodes of generalized tonic-clonic seizures in the past month. The parents also noticed brief episodes of twitching of the mouth for the last 2 years, which increased in frequency after treatment with oxcarbamazepine. Examination and neuroimaging were normal. The seizure semiology (see the video on the Neurology® Web site at www.neurology.org) and EEG (figure) were suggestive of perioral myoclonia with absences. Brief episodes of absences (2–9 seconds) with perioral myoclonia, infrequent generalized tonic-clonic seizures, and frequent occurrence of absence status epilepticus should suggest the diagnosis.1 The interictal EEG may reveal focal abnormalities that may lead to a misdiagnosis of a focal epilepsy. The seizures may be treatment-resistant and oxcarbamazepine must be avoided.2

Vitamin B12 Deficiency in Children With Infantile Spasms: A Case-Control Study:

There have been few case reports showing association of vitamin B12 deficiency with infantile spasms. We planned this study to see if there was an association of serum vitamin B12 deficiency in children with development of infantile spasms. Cases included children with infantile spasms of ages 6 months to 3 years. The controls were children in the same age group who had global developmental delay but no history of epileptic spasms. Mean serum vitamin B12, serum homocysteine, and urinary methylmalonic acid levels were measured in both groups and compared. Children with infantile spasms had lower mean serum vitamin B12 levels (354.1 pg/mL; standard deviation 234.1 pg/mL) as compared to children with global developmental delay without spasms (466.7 pg/mL; standard deviation 285.5 pg/mL) (P value < .05). Mean serum homocysteine level (13.9 vs 7.8 μmol/L, P = .02) and mean urinary methylmalonic acid level (68.1 mmol/mol of creatinine vs 26.1 mmol/mol of creatinine, P = .03) were elevated in children with infantile spasms than in controls. Fourteen children (35.0%) with infantile spasms were vitamin B12 deficient compared with 3 (7.50%) controls (P = .005). Thus, vitamin B12 deficiency may have an association with infantile spasms. More studies are needed before recommending routine measurement of serum B12 levels in children with infantile spasms.

Fixation-off Sensitivity in Idiopathic Childhood Occipital Epilepsy of Gastaut

A 7-year-old boy presented with episodic blindness for the last 2 months with occipital paroxysms and fixation-off sensitivity on electroencephalography (EEG). The clinico-EEG features were suggestive of idiopathic childhood occipital epilepsy of Gastaut. The interesting phenomenon of fixation-off sensitivity is discussed.

Bilateral frontoparietal polymicrogyria.

Two male siblings, aged 4.5 and 10 y respectively, of a nonconsanguinous family, presented with delayed milestones and epilepsy. The older sibling had frequent seizures since 7 y of age. Seizures were generalized-tonic-clonic and were poorly controlled on valproate, phenytoin and clobazam. His younger sibling had seizures (myoclonic and generalized tonicclonic) since 2.5 y of age with partial response to valproate, levetiracetam and clobazam. The inter-ictal EEG showed multifocal epileptiform discharges in the older sibling and infrequent bilateral frontal spike-wave-discharges in the younger sibling. The examination of both the siblings revealed a normal head circumference, bilateral esotropia, pseudobulbar palsy andmild spasticity. Magnetic-Resonance-Imaging of the brain is shown as Fig. 1. One female sibling died (probable aspiration) at 3 y of age. She had global-developmental-delay and spasticity but no seizures. She was not investigated. There are three other female siblings who are alive and healthy. All coding exons 2–14 and exon/intron junctions in the gene GPR56 were sequenced. Both the siblings showed homozygous nucleotide mutation c.739_745 del (CAGGACC) leading to a protein variation p. Q247Cfs74. Both the parents were heterozygous for the same mutation. Polymicrogyria is a malformation-of-cortical-development characterized by excessive gyration and abnormal cortical structure and lamination. The various regional polymicrogyria syndromes reported include bilateral perisylvian polymicrogyria, bilateral frontal polymicrogyria, bilateral frontoparietal polymicrogyria (BFPP), bilateral parasagittal parietooccipital polymicrogyria and unilateral multilobar polymicrogyria [1]. BFPP is a recently described entity caused by mutations in G protein-coupled receptor 56 gene (GPR56). It has been rarely reported from India [2]. GPR56 gene may be critical for the preplate neurons, which are the earliest born neurons in the cortex with roles in cortical development and patterning [3]. Most patients present in infancy with severe hypotonia, ‘pseudomyopathic’ presentation and strabismus with normal serum creatine kinase levels. They later exhibit mental and motor retardation with pyramidal signs, epilepsy, language impairment, cerebellar signs and eye movement abnormalities. The neuroimaging shows bilateral polymicrogyria with P. Jain : S. Sharma : S. Aneja Division of Pediatric Neurology, Department of Pediatrics, Lady HardingeMedical College and Associated Kalawati Saran Children’s Hospital, New Delhi, India