Puneet Jain

Vincristine-induced Neuropathy in Childhood ALL (Acute Lymphoblastic Leukemia) Survivors Prevalence and Electrophysiological Characteristics

The prevalence and the burden of vincristine-induced neuropathy have been poorly documented in childhood acute lymphoblastic leukemia survivors. This cross-sectional study was carried out at a tertiary care center in northern India from October 2011 to June 2012. Eighty consecutive acute lymphoblastic leukemia survivors aged 5 to 18 years, within 3 years of completion of their chemotherapy, were enrolled. After clinical evaluation, detailed nerve conduction studies were performed and the reduced version of the Total Neuropathy Score was calculated. The mean age at the time of evaluation was 11.2 ± 3.2 years. 33.75% had neuropathy electrophysiologically. Symmetric motor axonal polyneuropathy was the most common pattern of involvement seen in 19 (23.8%) children. There was significant improvement with time, as revealed by lower prevalence of neuropathy with increasing interval following vincristine injection. 33.75% of the children had Reduced version of Total Neuropathy Score ≥ 1.

The Modified Atkins Diet in Refractory Epilepsy

The modified Atkins diet is a less restrictive variation of the ketogenic diet. This diet is started on an outpatient basis without a fast, allows unlimited protein and fat, and does not restrict calories or fluids. Recent studies have shown good efficacy and tolerability of this diet in refractory epilepsy. In this review, we discuss the use of the modified Atkins diet in refractory epilepsy.

Use of the modified Atkins diet in Lennox Gastaut syndrome.

There is scanty data regarding the efficacy and tolerability of the modified Atkins diet in children with Lennox-Gastaut syndrome. This study was a retrospective review of children with Lennox-Gastaut syndrome treated with the modified Atkins diet from May 2009 and March 2011. The diet was initiated in those children who persisted to have daily seizures despite the use of at least 3 appropriate antiepileptic drugs. Twenty-five children were started on a modified Atkins diet, restricting carbohydrate intake to 10 g/d. After 3 months, 2 patients were seizure-free, and 10/25 children had >50% reduction in seizure frequency. At 6 months, of 11 patients on the diet, 3 were seizure free and 8 had >50% reduction in seizure frequency. At 1 year, all 9 children on diet had >50% reduction in seizure frequency. The side effects of the diet were mild. The modified Atkins diet was found to be effective and well tolerated in children with Lennox-Gastaut syndrome.

Evaluation of a simplified modified Atkins diet for use by parents with low levels of literacy in children with refractory epilepsy: A randomized controlled trial

PURPOSE This study was planned to develop and evaluate a simple, easy-to-understand variation of the modified Atkins diet, for use by parents with low levels of literacy in children with refractory epilepsy. METHODS This study was conducted in two phases. In the first phase, a simplified version of the modified Atkins diet was developed. In the second phase this was evaluated in children aged 2-14 years who had daily seizures despite the appropriate use of at least two anticonvulsant drugs, in an open-label randomized-controlled-trial. Children were randomized to receive either the simplified modified Atkins diet or no dietary intervention for a period of 3 months with the ongoing anticonvulsant medications being continued unchanged in both the groups. Reduction in seizure frequency was the primary outcome-measure. Data was analyzed using intention to treat approach. Adverse effects were also studied. (Clinical trial identifier NCT0189989). RESULTS Forty-one children were randomly assigned to the diet-group, and 40 were assigned to the control-group. Two patients discontinued the diet during the study period. The proportion of children with>50% seizure reduction was significantly higher in the diet group as compared to the control group (56.1% vs 7.5%, p<0.0001). The proportion of children with 90% seizure reduction was also higher in the diet group (19.5% vs 2%, p=0.09). Six children in the diet group were seizure free at 3 months compared with two in the control group (p=0.26). At 3 months, 6 children had constipation and 5 had weight loss. CONCLUSION A simplified version of the modified Atkins diet was developed for use by parents with low levels literacy. This diet was found to be feasible, efficacious and well tolerated in children with refractory epilepsy.

The ketogenic diet and other dietary treatments for refractory epilepsy in children

The ketogenic diet is a high-fat, low-carbohydrate, and restricted protein diet that is useful in patients with refractory epilepsy. The efficacy of the ketogenic diet is better than most of the new antiepileptic drugs. Other modifications of the diet are also beneficial, such as the modified Atkins diet and the low glycemic index treatment. There is a lack of awareness of the ketogenic diet as a treatment modality for epilepsy amongst pediatricians and neurologists. In this review, the use of the ketogenic diet and other dietary treatments in refractory epilepsy is discussed. The Indian experience with the use of these dietary treatments is also briefly reviewed.

Idiopathic Harlequin Syndrome A Pediatric Case

Harlequin syndrome, Harlequin sign, Holmes-Adie syndrome, and Ross syndrome lie on a spectrum of partial dysautonomias affecting facial sudomotor, vasomotor, and pupillary responses. These syndromes have imprecise clinical boundaries and overlap syndromes are known. We report a 9-year-old girl who presented with anhidrosis over the right half of her face and the left side of her body, with compensatory hyperhidrosis on the contralateral side. She was noted to have bilateral tonic pupils and normal muscle stretch reflexes with other features suggestive of autonomic dysfunction. Investigations to rule out secondary causes were noncontributory. Her clinical presentation can be categorized as partial overlap between Harlequin syndrome and Holmes-Adie syndrome.

The Clinical Characteristics and Treatment Response in Children with West Syndrome in a Developing Country: A Retrospective Case Record Analysis

This study describes the clinical characteristics, treatment, and outcome of children with West syndrome in a tertiary care hospital in north India. Overall, 310 case records diagnosed from January 2009 to June 2012 were reviewed. The median age of onset of spasms was 5 months (interquartile range = 2.5-7 months). The predominant underlying etiology was perinatal cerebral ischemia (55%). Adrenocorticotropic hormone or oral steroids were received by 92% children, of whom 43% became seizure free. Median lag time for appropriate treatment initiation was significantly less in patients who became seizure free as compared to those with persisting seizures (11 vs 15 months, P = .001) soon after receiving treatment of choice. Later age at onset of spasms was associated with a favorable seizure outcome (P = .03). In a resource-limited setting, unawareness along with treatment costs and repeated visits to the hospital are significant obstacles to optimum management.

Diagnosis and management of epileptic encephalopathies in children.

Epileptic encephalopathies refer to a group of disorders in which the unremitting epileptic activity contributes to severe cognitive and behavioral impairments above and beyond what might be expected from the underlying pathology alone, and these can worsen over time leading to progressive cerebral dysfunction. Several syndromes have been described based on their electroclinical features (age of onset, seizure type, and EEG pattern). This review briefly describes the clinical evaluation and management of commonly encountered epileptic encephalopathies in children.

Prevalence of UGT1A6 polymorphisms in children with epilepsy on valproate monotherapy

BACKGROUND Valproate is a commonly used anticonvulsant drug. Uridine 5΄-diphospho (UDP)-glucuronosyltransferase (UGT) contributes to around 50% of valproate metabolism and its polymorphisms may be important for explaining the considerable variation in valproate levels in patients with epilepsy. AIM This study was aimed to analyze the genetic polymorphisms of UGT1A6 in Indian children with epilepsy and their potential influence on the pharmacokinetics of valproate. SETTING AND DESIGN This cross-sectional study was carried out in the Department of Pediatrics, All India Institutes of Medical Sciences (AIIMS), New Delhi, between March 2011 and July 2012. MATERIALS AND METHODS Children aged 3-12 years diagnosed with epilepsy on valproate monotherapy for at least 1 month were enrolled. They underwent a detailed clinical examination. The UGT1A6 polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Random samples were checked by genetic sequencing. The steady-state plasma concentrations of valproate were measured by High Performance Liquid Chromatography (HPLC) and associated with UGT1A6 polymorphisms. RESULTS A total of 80 children were studied. The prevalence of UGT1A6 T19G was as follows: TT (45%), TG (38.8%), and GG (16.3%); that of UGT1A6 A541G was: AA (48.8%), AG (38.8%), and GG (12.5%); and that of UGT1A6 A552C was: AA (43.8%), AC (40%), and CC (16.3%). The association between valproate doses or standardized serum valproate concentration and the various UGT1A6 genotypes could not be studied reliably in this small study population. CONCLUSIONS The frequencies of UGT1A6 geneotypes and alleles were reported in the study population.

Menkes disease - An important cause of early onset refractory seizures.

Context: Menkes disease is an X-linked multisystem disorder characterized by early onset of cerebral and cerebellar neurodegeneration, fair skin, hypopigmented sparse hair and connective tissue abnormalities. Aims: We aimed to evaluate the clinical, electrophysiological and radiological features of children with Menkes disease seen at our institute. Setting/Design: The medical records of children diagnosed with Menkes disease admitted in the pediatric neurology ward or attending the special pediatric neurology clinic at a tertiary care and a referral hospital in North India, from January 2010 to December 2012, were retrospectively reviewed. The clinical data of each case was subsequently summarized and reported. Statistical analysis used: Descriptive statistics were used. Results: During the study period, 1174 children were seen. Out of these, 6 cases were diagnosed as Menkes disease on the basis of clinical phenotype, low serum copper and ceruloplasmin and supportive neuroimaging. All the children were males and had disease onset within 3 months of age, with 4 children presenting in the neonatal period. Global developmental delay and refractory seizures were the predominant clinical symptoms. Two children had symptomatic West syndrome. Other seizure semiologies included tonic-clonic (4), myoclonic (2) and tonic seizures (1). The electroencephalographic abnormalities included hypsarrythmia (2) and multifocal epileptiform discharges (3). The salient radiological features included white matter changes, temporal lobe abnormalities, global atrophy, subdural hygromas and tortuous cerebral blood vessels. Conclusions: Menkes disease should be suspected in a case of refractory early onset seizures especially in the presence of subtle clinical clues. The neuroimaging findings may further support the diagnosis.