Pratibha Singhi

Risperidone in Children With Autism: Randomized, Placebo-Controlled, Double-Blind Study

Some open-label studies suggest that risperidone can be useful in the treatment of certain target symptoms in children with autism. We aimed to study whether the use of risperidone in comparison with placebo improved functioning in children with autism with regard to behavior (aggressiveness, hyperactivity, irritability), social and emotional responsiveness, and communication skills. We conducted a randomized, double-blind, placebo-controlled trial with 40 consecutive children with autism, whose ages ranged from 2 to 9 years, who were receiving either risperidone or placebo given orally at a dose of 1 mg/day for 6 months. Autism symptoms were monitored periodically. The outcome variables were total scores on the Childhood Autism Rating Scale (CARS) and the Childrens Global Assessment Scale (CGAS) after 6 months. Of the 40 children enrolled, 39 completed the trial over a period of 18 months; 19 received risperidone, and 20 received placebo. In the risperidone group, 12 of 19 children showed improvement in the total Childhood Autism Rating Scale score and 17 of 19 children in the Childrens Global Assessment Scale score compared with 0 of 20 children for the Childhood Autism Rating Scale score and 2 of 20 children for the Childrens Global Assessment Scale score in the placebo group (P < .001 and P = .035, respectively). Risperidone also improved social responsiveness and nonverbal communication and reduced the symptoms of hyperactivity and aggression. Risperidone was associated with increased appetite and a mild weight gain, mild sedation in 20%, and transient dyskinesias in three children. Risperidone improved global functioning and social responsiveness while reducing hyperactivity and aggression in children with autism and was well tolerated. (J Child Neurol 2006;21:450—455; DOI 10.2310/7010.2006.00099).

Albendazole therapy in children with focal seizures and single small enhancing computerized tomographic lesions : a randomized placebo-controlled double blind trial

BACKGROUND Single small enhancing computerized tomographic (CT) lesions (SSECTLs) are common in children with focal seizures. These are considered to represent solitary cysticercus granulomas. Controversy exists regarding their treatment. OBJECTIVE To evaluate the efficacy of albendazole in cases of focal seizures with SSECTLs. DESIGN Randomized, placebo-controlled, double blind trial. SETTING Pediatric service of Nehru Hospital, PGIMER, an urban tertiary care teaching hospital. SUBJECTS 63 children between 2 and 12 years of age with focal seizures for <3 months and SSECTLs. INTERVENTION All children were randomly assigned to receive either albendazole (15 mg/kg/ day) or placebo for 28 days. CT scan was done at 1 and 3 months after beginning treatment. Codes opened after 6 months of inclusion in the study showed that 31 had received albendazole and 32 had received placebo. All children were followed up for at least 15 months. RESULTS Disappearance of lesions on CT scan was noted in 41% of albendazole vs. 16.2% of placebo patients after 1 month of follow-up (P < 0.05) and 64.5% of albendazole- vs. 37.5% of placebo-treated patients after 3 months of follow-up (P < 0.05). During the first 4 weeks of therapy seizure recurrence was seen in 9.7% of albendazole vs. 3.2% of placebo-treated children (odds ratio, 3.32; 95% confidence interval, 0.33 to 33.8). After 4 weeks seizure recurrence was seen in 31.3% of placebo-treated children vs. 12.9% of albendazole-treated children (odds ratio, 3.07; 95% confidence interval, 1.18 to 11.15). CONCLUSIONS Albendazole therapy results in significantly faster and increased resolution of solitary cysticercus lesions (SSECTLs) and appears to reduce the risk of late seizure recurrences.

Clinical Spectrum of 500 Children With Neurocysticercosis and Response to Albendazole Therapy

Neurocysticercosis is a major cause of neurologic illness worldwide. Its manifestations are variable, and somewhat different when it occurs in children. Controversy exists regarding anticysticercal therapy. The clinical, laboratory, and radiographic features of 500 consecutive children with neurocysticercosis were studied; the children were then followed prospectively and their response to albendazole therapy was analyzed. Diagnosis of neurocysticercosis was based primarily on neuroimaging. Computed tomographic (CT) scans, neurocysticercosis serology, chest radiographs, and Mantoux tests were done in all children, and magnetic resonance imaging scans in 10%. All children with multiple lesions, and some randomly allocated children with single, small, enhancing CT lesions received albendazole. CT scans were repeated after 3 to 6 months. There were 272 boys and 228 girls, age range 16/12 to 126/12 years. Seizures were present in 94.8% of cases; 83.7% had focal seizures. Features of raised intracranial pressure were seen in 30% of patients and focal neurodeficit in 4%. Single lesions were seen in 76% of the children, with perilesional edema in 57.4%. Thirty-four children who had multiple cysts and received albendazole underwent serial CT evaluation. Four showed disappearance of lesions and 22 had reductions in the size or number, to give an overall improvement rate of 76%. Serial CT studies were available on 176 children with single lesions, 90 of whom received albendazole. Improvement (disappearance or reduction in the size of lesions) was observed in 91% (82 of 90) of albendazole-treated children versus 85% (73 of 86) of untreated children. This difference was not significant. No significant side-effects of albendazole were reported. These data indicate that partial seizures and single parenchymal cysts are the most frequent clinical and neuroradiographic manifestations of neurocysticercosis in children. Although albendazole therapy should be considered, especially in children with multiple lesions, many children with isolated neurocysticercosis will improve without antiparasitic therapy. (J Child Neurol 2000;15:207-213).

Continuous midazolam versus diazepam infusion for refractory convulsive status epilepticus.

The objective of this study was to compare the efficacy of continuous midazolam and diazepam infusion for the control of refractory status epilepticus. An open-label, randomized control study was undertaken at the Pediatric Emergency and Intensive Care Service of a multidisciplinary teaching and referral hospital. Subjects included 40 children, 2 to 12 years of age, with refractory status epilepticus (motor seizures uncontrolled after two doses of diazepam, 0.3 mg/kg per dose, and phenytoin infusion, 20 mg/kg). Either continuous midazolam (n = 21) or diazepam infusion (n = 19) in incremental doses was administered. The primary outcome measure was the proportion of children in each group with successful control of refractory status epilepticus. The secondary outcome measure was the time to control seizure activity, recurrence of seizure after initial control, if any, the frequency of hypotension, and the need for ventilation. The two groups were similar in age (mean ± SD = 4.9 ± 43.6 months) and etiology. Twenty-three (57.5%) patients had acute central nervous system infection. Refractory status epilepticus was controlled in 18 (86%) and 17 (89%) patients in the midazolam and diazepam groups, respectively (P = not significant). The median time to seizure control was 16 minutes in both groups, but in the midazolam group, seizures recurred in more children (57% versus 16% in diazepam group; P < .05). The maximum dose (mean ± SD) of midazolam and diazepam required was 5.3 ± 2.6 μg/kg/min and 0.04 ± 0.02 mg/kg/min, respectively. About half of the patients needed mechanical ventilation and 40% had hypotension in both groups, but the mortality was higher in the midazolam group (38%) as compared to the diazepam group (10.5%, P < . 1 > .05). Continuous midazolam and diazepam infusions were equally effective for control of refractory status epilepticus. However, midazolam was associated with more seizure recurrence and higher mortality in refractory status epilepticus predominantly caused by central nervous system infections. (J Child Neurol 2002;17:106-110).

Intravenous sodium valproate versus diazepam infusion for the control of refractory status epilepticus in children: a randomized controlled trial.

An open-label, randomized controlled study was conducted at a tertiary care teaching hospital to compare efficacy and safety of intravenous sodium valproate versus diazepam infusion for control of refractory status epilepticus. Forty children with refractory status epilepticus were randomized to receive either intravenous sodium valproate or diazepam infusion. Refractory status epilepticus was controlled in 80% of the valproate and 85% of the diazepam patients. The median time to control refractory status epilepticus was less in the valproate group (5 minutes) than the diazepam group (17 minutes; P < .001). None of the patients in the valproate group required ventilation or developed hypotension, whereas in the diazepam group 60% required ventilation and 50% developed hypotension after starting diazepam infusion. No adverse effects on liver functions were seen with valproate. It is concluded that intravenous sodium valproate is an effective alternative to diazepam infusion in controlling refractory status epilepticus in children and is free of respiratory depression and hypotension.

Topiramate in the prophylaxis of pediatric migraine: a double-blind placebo-controlled trial.

Several large, randomized controlled trials have demonstrated the efficacy of topiramate in migraine prophylaxis in adults. However, there are limited data about the use of topiramate in migraine prophylaxis in children. We conducted this single-center, double-blind, placebo-controlled trial to evaluate the efficacy and safety of topiramate in the prophylaxis of migraine in children. A total of 44 children with migraine were randomized using random number tables to receive topiramate (n = 22) or placebo (n = 22). The total duration of treatment was 4 months, including a baseline period of 1 month during which topiramate was titrated weekly in 25-mg increments to 100 mg/d in 2 divided doses or to the maximum tolerated dose. The titration was followed by a 12-week maintenance phase during which topiramate was given in 2 divided doses. The primary outcome measures were the reduction in the mean migraine frequency and severity of headache. Secondary outcome measures included the number of times analgesics were required for a month for acute attacks and functional disability. Functional disability was measured by comparing school absenteeism and Pediatric Migraine Disability Assessment Scale (PedMIDAS). The decrease in mean (±SD) monthly migraine frequency from 16.14 (±9.35) at baseline to 4.27 (±1.95) at the end of the study in the topiramate group was significantly greater as compared with a decrease from 13.38 (±7.78) to 7.48 (±5.94) at the end of the study in the placebo group (P = .025). The difference in number of rescue medications used for topiramate and placebo was not statistically significant (P = .059). There was a statistically significant decrease in the PedMIDAS score from 50.66 (±32.1) to 10.42 (±6.39) at the end of the study in the topiramate group compared with a decrease from 42.66 (±27.5) to 23.7 (±19.1) at the end of 4 months in the placebo group (P = .003). The decrease in school absenteeism was significant with topiramate compared with placebo (P = .002). Weight loss, decreased concentration in school, sedation, and parasthesias were important side effects with topiramate. Most of these side effects were mild to moderate and were not significant enough to cause dropout from the study.

Epilepsy in Children With Cerebral Palsy

To study the spectrum of epilepsy in children with cerebral palsy, 105 consecutive children with cerebral palsy and active epilepsy, between 1 and 14 years of age, were studied prospectively. A detailed history and examination, electroencephalography (EEG), and computed tomography (CT) were done in all cases. The social quotient was assessed using the Vineland Social Maturity Scale. A retrospective cohort of 452 cases of cerebral palsy was studied to find the prevalence of epilepsy in cerebral palsy. A control group of 60 age-matched children with cerebral palsy but no epilepsy was also studied for comparison of the social quotient. Of the 105 children, 65 were male, 40 of 105 (38%) had a history of birth asphyxia. The mean age of onset of seizures was 18.9 months; 64 (60.95%) had seizure onset before 1 year of age. Children with myoclonic seizures (P < .05) and infantile spasms (P < .01) had seizure onset significantly early in life. Generalized seizures were the most common, followed by partial seizures, infantile spasms, and other myoclonic seizures. Seizures were controlled in 45 (58.1%) children, and polytherapy was required in 40 children. EEG and CT abnormalities were seen in 70.5% and 61% of the children. Seizure control was achieved in 74% of the patients with a normal to borderline social quotient compared with 48.7% with a social quotient less than 70. Social quotient values had a positive correlation with age of onset of seizures (P < .01) and with better control of seizures (P < .01). Of the cohort of 452 children, 160 (35.4%) had epilepsy. The maximum incidence (66%) was seen in children with spastic hemiplegia, followed by quadriplegia (42.6%) and diplegia (15.8%). Epilepsy in cerebral palsy is seen in about one third of cases; it is often severe and difficult to control, particularly in children with mental retardation. (J Child Neurol 2003; 18: 174—179).

Clinical Spectrum of Cerebral Palsy in North India—An Analysis of 1000 Cases

One thousand children with cerebral palsy (CP) were reviewed to study their clinical profile, etiological factors and associated problems. Spastic quadriplegia constituted the predominant group (61 per cent), followed by spastic diplegia (22 per cent). Dyskinetic CP was present in 7.8 per cent of the cases. Acquired CP, particularly secondary to nervous system infections, constituted a significant proportion of cases. The clinical spectrum of CP is different in developing countries compared with developed countries. Associated problems were present in a majority (75 per cent) of cases, of which mental retardation was the commonest (72.5 per cent). Comprehensive assessment and early management of these problems are emphasized, which can minimize the extent of disabilities.

A randomized trial of fully intermittent vs. daily followed by intermittent short course chemotherapy for childhood tuberculosis.

Fully intermittent short course chemotherapy regimens have been used successfully in adults but not in children. We report the results on 76 children with tuberculosis, excluding central nervous system tuberculosis and primary pulmonary complex. Isoniazid, rifampin and pyrazinamide were used for treatment. They were randomly allocated to Regimen A (52 doses) and Regimen B (94 doses). Overall efficacy of both schedules was greater than 95% in 27 children with lymphatic, 43 with pulmonary and 6 with disseminated tuberculosis. Compliance in 10 children after 2 to 4 months of therapy was poor because rapid improvement was mistaken by parents for cure. Two children died, probably of underlying lung disease. Follow-up for up to 2 years did not reveal any case of relapse or recurrence of the disease. Therapy for 6 months involving administration of only 52 or 94 doses of drugs was found to be economical, effective and safe for treating children with tuberculosis.

Corticosteroids Versus Albendazole for Treatment of Single Small Enhancing Computed Tomographic Lesions in Children With Neurocysticercosis

Single small enhancing computed tomographic (CT) lesions representing cysticercus granuloma are a common cause of focal seizures in children. Controversy exists regarding the efficacy of various modalities of treatment. We conducted a randomized prospective trial to evaluate the efficacy of corticosteroids, albendazole, and corticosteroids with albendazole in children with focal seizures and single small enhancing CT lesions. The study population consisted of 133 children with focal seizures of recent onset (< 3 months) and single small enhancing CT lesions who presented to the Neurocysticercosis Clinic of Pediatric Neurology Services at the Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, an urban teaching and tertiary care hospital in Chandigarh, North India. All children were randomly assigned to receive corticosteroids (group S), albendazole (group A), or both corticosteroids and albendazole (group SA) for 28 days. CT was done at 3 and 6 months after enrollment in the study. Of the 133 patients enrolled, 23 were lost to follow-up. Of the remaining 110 patients, 38 patients were in group S, 37 in group A, and 35 in group SA. All children were followed up for at least 18 months. Disappearance of the lesion on CT scan was noted in 52.6% of patients in group S, 59.5% in group A, and 62.9% in Group SA (P > .1) at the 3-month follow-up. After the 6-month follow-up, disappearance of the lesion was noted in 76.3% in group S, 75.7% in group A, and 74.2% in group SA (P > .1). Twenty-three patients had seizure recurrence while on antiepilepsy drugs: 36.8% of patients in group S, 13.5% in group A, and 11.4% in group SA (P < .05). Seizure recurrence after antiepilepsy drug withdrawal was seen in seven children (three in group S and two each in groups A and SA). In conclusion, there was no significant difference in resolution of CT lesions in the three therapy groups at 3 and 6 months of follow-up. Children in the corticosteroid group had significantly more seizure recurrences while on antiepilepsy drugs. (J Child Neurol 2004;19:323-327).