Sheffali Gulati

Use of the modified Atkins diet for treatment of refractory childhood epilepsy: A randomized controlled trial

The aim of this study was to evaluate the efficacy of the modified Atkins diet in a randomized controlled trial in children with refractory epilepsy.

Intranasal versus intravenous lorazepam for control of acute seizures in children: A randomized open-label study

Purpose:  Intravenous lorazepam is considered the drug of first choice for control of acute convulsive seizures. However, resource or personnel constraints necessitate the study of alternative routes and medications. This study compared the efficacy and adverse effects of intranasal versus intravenous lorazepam in children aged 6–14 years who presented with acute seizures.

Epilepsy in children with Down syndrome

This review discusses the various aspects of epilepsy in Down syndrome (DS) from the perspective of paediatric neurology. DS is the most common genetic cause of mental retardation (MR) with a reported prevalence of epilepsy of 1–13%. Infantile spasms (IS) or West syndrome (WS) is the most frequent epilepsy syndrome in children with DS. IS occur in 0.6–13% of children with DS, representing 4.5–47% of seizures in these children. Curiously, these patients have electroencephalographic (EEG) characteristics of idiopathic rather than symptomatic WS. Despite a lack of consensus on therapeutic approach, no significant difference has been reported among the different regimens with regards to achieving clinical remission or EEG normalisation. It appears that DS patients have better seizure control compared to other patients with symptomatic IS, and early initiation of appropriate treatment may contribute to the prevention of late seizure development and better developmental outcome. Lennox-Gastaut syndrome (LGS) also exhibits some distinctive features in children with DS including later onset and high incidence of reflex seizures. Other seizure types including partial and generalised tonic clonic seizures have also been described in children with DS. There is a high rate of EEG abnormalities in children with DS, even among children without epilepsy, however, no patterns specific to DS have been identified and EEG does not correlate with outcome. Various cellular and molecular mechanisms contribute to epileptogenesis in DS and offer an interesting field of study.

Duchenne muscular dystrophy: prevalence and patterns of cardiac involvement.

In about 10% cases of Duchenne muscular dystrophy (DMD), death is due to cardiac dysfunction. The recognition of cardiomyopathy in DMD is thus important.Objective: To assess cardiac involvement in DMD patients by clinical, radiographic, electrocardiographic (ECG) and echocardiographic monitoring and correlate clinical parameters, CPK levels, presence of gene deletion and steroid therapy with cardiac involvement.Methods: Thirty patients beyond 6 years age, with DMD in advanced stage disease/non-ambulatory were recalled. A detailed clinical evaluation, CPK levels, gene deletion studies were carried out. Cardiac investigations included Chest X-ray, 12 lead ECG and echocardiography.Results: Nineteen patients were non-ambulatory at the time of enrollment. Symptoms or signs suggestive of cardiac dysfunction were seen in only 10%. Gene deletion was identified in 70.3%. Around one-third patients had cardiomegaly. ECG abnormalities were present in 93.3% patients and commonest abnormality was R> 4 mm in V1. Ejection fraction (EF) < 55% was observed in 64.2% and EF < 50% in 17.8%.Conclusion: Cardiomyopathy of DMD is characterized by lack of symptoms and few physical signs. Presence of subtle changes like sinus tachycardia may suggest early cardiac involvement. Thus echocardiography is required for evaluation of cardiac dysfunction. Presence of gene deletion was associated with higher CT ratio. Older children have been found to have higher heart rates. No other significant correlation with clinical parameters, CPK levels, genotype and steroid therapy was observed. Early detection possibly leads to appropriate treatment thus reducing the morbidity.

Portal hypertension in north Indian children

Etiological factors associated with portal hypertension in children influence the decision about therapy and the prognosis. This cross-sectional observational study was performed at a tertiary care centre in northern India from January, 1990 to December, 1994. Children below the age of 14 years with suspected portal hypertension were prospectively assembled into a cohort to determine the etiology and clinical profile of portal hypertension. Of the 115 patients with portal hypertension, 76.5% had extrahepatic portal hypertension (EHPH). Remaining 23.5% of the cases had intrahepatic and post-hepatic causes of portal hypertension. Children with EHPH had a significantly earlier onset of symptoms as compared to those with intrahepatic portal hypertension (p = 0.002) and bled significantly more frequently (p = 0.00). Forty per cent of patients with chronic liver disease (CLD) never had jaundice. History suggestive of potential etiological factors could be elicited in only 7% of EHPH patients. The commonest site of block in splenoportal axis was at the formation of the portal vein. An inverse relation of bleeding rates with duration of illness was seen in EHPH. Of the 10 CLD patients in whom liver biopsy could be done, cirrhosis was present in 6 patients.Understanding the natural history of EHPH and portal hypertension due to other etiologies may have significant implications in choosing the appropriate intervention and predicting the outcome.

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.

Folic acid supplementation prevents phenytoin-induced gingival overgrowth in children

Objective: Gingival overgrowth is an important adverse effect of phenytoin (PHT) therapy, occurring in about half of the patients. This study aimed to evaluate the effect of oral folic acid supplementation (0.5 mg/day) for the prevention of PHT-induced gingival overgrowth (PIGO) in children with epilepsy aged 6–15 years on PHT monotherapy for 6 months. Methods: This was a randomized, double-blind, placebo-controlled trial conducted at a tertiary level hospital from May 2008 to June 2009. Children aged 6–15 years started on PHT monotherapy within last 1 month were eligible for inclusion. Preexisting gingival overgrowth, use of other folic acid antagonists, and macrocytic anemia were exclusion criteria. Trial subjects were randomized to receive either folic acid or placebo. The primary outcome measure was incidence of any degree of gingival overgrowth after 6 months of PHT monotherapy. The trial was registered with clinicaltrials.gov (NCT00781196). Results: A total of 120 children were recruited, 62 and 58, respectively, in folic acid and placebo arms. The 2 arms were comparable at baseline. Twenty-one percent of patients in the folic acid arm developed PIGO, as compared with 88% receiving placebo (p < 0.001). Absolute risk reduction of PIGO by folic acid was 67% (95% confidence interval 54%–80%), and relative risk reduction was 0.76. Conclusions: Oral folic acid was found to decrease the incidence of PIGO in children on PHT monotherapy, in a statistically significant and clinically relevant manner. Classification of evidence: This study provides Class I evidence that folic acid supplementation, 0.5 mg/day, is associated with prevention of gingival overgrowth in children taking PHT monotherapy.

Prevalence of MTHFR C677T Polymorphism in North Indian Mothers Having Babies with Trisomy 21 Down Syndrome.

Recent studies have evaluated possible links between polymorphisms in maternal folate metabolism genes and Down syndrome. Some of these studies show a significantly increased prevalence of the C677T polymorphism of the 5,10-methylene tetrahydrofolate reductase (NADPH) gene (MTHFR) among mothers who have had babies with Down syndrome. This study examined the prevalence of the MTHFR C677T polymorphism among 104 north Indian mothers of babies with Down syndrome and 109 control mothers. The prevalence of MTHFR C677T polymorphism observed among mothers of babies with Down syndrome was 28% compared to 35% in controls (C677T/T677T). There was no significant difference between the two groups (p = 0.294). Mean homocysteine level in mothers of children with Down syndrome was lower than the level in the controls. Our data suggests that the MTHFR C677T polymorphism is not associated with an increased risk of Down syndrome in the north Indian population. Homocysteine levels in our study were higher when compared to other studies. Methylcobolamin and folate deficiency or use of random samples for homocysteine determination could possibly account for this observation.

Surgery for Drug-Resistant Epilepsy in Children

BACKGROUND Neurosurgical treatment may improve seizures in children and adolescents with drug‐resistant epilepsy, but additional data are needed from randomized trials. METHODS In this single‐center trial, we randomly assigned 116 patients who were 18 years of age or younger with drug‐resistant epilepsy to undergo brain surgery appropriate to the underlying cause of epilepsy along with appropriate medical therapy (surgery group, 57 patients) or to receive medical therapy alone (medical‐therapy group, 59 patients). The patients in the medical‐therapy group were assigned to a waiting list for surgery. The primary outcome was freedom from seizures at 12 months. Secondary outcomes were the score on the Hague Seizure Severity scale, the Binet–Kamat intelligence quotient, the social quotient on the Vineland Social Maturity Scale, and scores on the Child Behavior Checklist and the Pediatric Quality of Life Inventory. RESULTS At 12 months, freedom from seizures occurred in 44 patients (77%) in the surgery group and in 4 (7%) in the medical‐therapy group (P<0.001). Between‐group differences in the change from baseline to 12 months significantly favored surgery with respect to the score on the Hague Seizure Severity scale (difference, 19.4; 95% confidence interval [CI], 15.8 to 23.1; P<0.001), on the Child Behavior Checklist (difference, 13.1; 95% CI, 10.7 to 15.6; P<0.001), on the Pediatric Quality of Life Inventory (difference, 21.9; 95% CI, 16.4 to 27.6; P<0.001), and on the Vineland Social Maturity Scale (difference, 4.7; 95% CI, 0.4 to 9.1; P=0.03), but not on the Binet–Kamat intelligence quotient (difference, 2.5; 95% CI, ‐0.1 to 5.1; P=0.06). Serious adverse events occurred in 19 patients (33%) in the surgery group, including hemiparesis in 15 (26%). CONCLUSIONS In this single‐center trial, children and adolescents with drug‐resistant epilepsy who had undergone epilepsy surgery had a significantly higher rate of freedom from seizures and better scores with respect to behavior and quality of life than did those who continued medical therapy alone at 12 months. Surgery resulted in anticipated neurologic deficits related to the region of brain resection. (Funded by the Indian Council of Medical Research and others; Clinical Trial Registry–India number, CTRI/2010/091/000525.)

Status epilepticus in indian children in a tertiary care center

Objective: To study the clinical profile, immediate outcome and possible risk factors of SE in pediatric age group admitted to pediatric intensive care unit (PICU) in a tertiary care center.Methods: A retrospective study of case records of 451 neuroemergency patients admitted in PICU in a tertiary care center between January 1993 to April 2000, out of which 30 patients had status epilepticus. They were evaluated for their clinical presentation, laboratory parameters, treatment profile and immediate outcome.Results: The age group varied from 1 to 120 months with mean of 56.6±46.5 months. Seventeen patients were less than 60 months. Sixteen patients (53.3%) presented with SE as first presentation without prior history of seizure activity. Nine patients died (30%) during hospital course. Seizure duration >45 minutes (p-0.001) and presence of septic shock (p-0.001) were associated with significantly more mortality.Conclusion: There is a need to abort seizure activity at the earliest and this improves immediate outcome.