370 pilot study in the use of melatonin for children with neurological disorders and sleep problems

1
Abstracts A21 mean 5.5 months (SD=2.65). Before and after helmet treatment the parents were asked to score the severity of deformity on a rating scale O-10 (0 = severely abnormal; lO=normal) and to indicate when an improvement was noticed after onset of the helmet treatment. Results: In 38 of the 39 infants an improvement of the shape of the skull was reported by the parents (Wilcoxon’s signed ranks test; p < 0.05). Improvement was observed within 5.9 weeks (mean, SD=3.97) after starting helmet treatment. The degree of improvement was inversely correlated to the pre-treatment score (Pearson corr: -0.702, p=O.Ol). Neither the time of onset of helmet treatment (corr.coeff.0.05) nor the duration of treatment (corr.coeff.0.181) was correlated to the degree of improvement of the skull deformity. No severe side-effects or intolerance to the device were reported. Conclusion: The status of this therapy should be com- pared with the natural course and/or spontaneous improvement of the non-synostotic posterior skull deformity for final conclusions. However, improvement was observed on average even after 5.9 weeks, which does support the interpretation of our results that a helmet device seems to be a safe and effective treatment for non-synostotic posterior plagiocephaly in infants. 370 Pilot study in the use of melatonin for children with neurological disorders and sleep problems V WONG,’ S F PANG’ ‘Division of Neurodevelopmental Paediatrics, Department of Paediatrics, ‘Department of Physiology, The University of Hong Kong, Hong Kong Melatonin is a hormone secreted by the pineal gland with a diurnal rhythm, being low level in the daytime with peaks at night. Its circulating levels correlate well with urinary 6-hydroxy-melatonin sulphate levels. The determination of urinary 6-hydroxy-myelatonin has been used as a non-invasive technique for monitoring human circadian rhythmicity. Melatonin plays an important role in the regulation of diurnal and seasonal rhythms in animals and humans. In humans, melatonin has been used for 15 years in the treatment of disorders of circadian rhythm including jet lag and sleep disorders. The use of melatonin in regulating the human sleep-wake cycle and the re- entrainment of circadian rhythm by promoting sleep in humans have been well documented. In animal research, melatonin also has an anticonvulsant effect. There are scanty reports in humans concerning the use of melato- nin as an anticonvulsant. The relationship of melatonin and seizure might be mediated by the following mechanisms: (1) altered brain GABAergic neurotrans- mission, (2) interaction of melatonin with benzodiazepinic brain receptors, through tryptophan metabolite activity, or (3) acting as a free-radical scavenger. Children with severe neurological disabilities usually had sleep problems. The objective of this pilot study was to assess the efficacy of melatonin in improving the sleep pattern of these children and to observe any secondary beneficial effect on seizure freqency per se. During the period June 1998 to January 1999, 12 children (8 boys, 5 girls) with multiple neurological disorders were included in the study if they had severe sleep problems. The mean age was 6 years 4 months (range = 13 months to 16 years). Ten children (83%) had intractable epilepsy. Neurological disorders included cerebral palsy (3), autism (2), cortical blindness (5), mental retardation [ll; mild (I), moderate (4), severe (8)], lissencephaly and schizencephaly (l), tuberous sclerosis 91), Walker- Warburg syndrome (1) and Angelman syndrome (1). All children had multiple neurological problems. The sleep problems had been quite severe so that the children’s behaviour deteriorated and the quality of life of the parents was affected. A sleep diary was kept for a few days prior to the melatonin trial. Most children had delayed sleep onset and short sleep cycles with frequent awakenings. Oral melatonin - 1 mg was given, and increased to 36mg if it failed to improve sleep onset and increase the sleep duration. The sleep diary was monitored during the trial. The sleep response was graded as follows: grade 1: > 90% improvement in sleep pattern [n=9 children (75%)]; grade 2: 50- < 90% improvement (n=3, 17%) and grade 3: no improvement (n=l). The complete failure occurred in a 5-year-old severely mentally retarded boy with intractable infan- tile spasm, cortical blindness, spastic tetraplegia and lissencephaly/schizencephaly. For those with grade 1 response, the effect was seen immediately after one oral dose of melatonin, 1 mg. It was not necessary to increase the dose in those with grade 1 response. The parents were very satisfied with the marked improvement of sleep pattern in those with grade 1 response. When the sleep-wake cycle was re-established, most of these parents stopped melatonin with no untoward effect. They resumed oral melatonin when there was a relapse of the sleep disturbance, which was rare. For those with grade 2 to 3 response, the maximum dose of melatonin tried was 6 mg. The lack of response in one case might be related to inadequate dosage for that particular child. As the exact dosage of melatonin use is unknown, and melatonin is relatively safe, one can try to increase the dosage further depending on the clinical response. Even the frequency of epileptic seizures decreased in those who were on the same anticonvulsant regime, especially in the child with Angelman syndrome and another with unexplained encephalopathy and infantile spasm. Thus, oral melatonin is worth a therapeutic trial in those children with multiple neurological problems and sleep disorders. Future research should concentrate on sleep- wake EEG analysis and assaying of serum melatonin levels to titrate the response more objectively. 198 Use of traditional Chinese medicine (tongue acupuncture) in children with neurological disorders: Pilot study of 100 cases V WONG,’ j G SUN,’ Q MA,’ E YANG,’ C Y YEUNG,’ R LIZ ‘Department of Paediatrics, The University of Hong Kong; 2 The Jockey Club, MRI Engineering Centre, The University of Hong Kong; ‘Radiology Department, St Paul’s Hospital, Hong Kong

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Page 1: 370 Pilot study in the use of melatonin for children with neurological disorders and sleep problems

Abstracts A21

mean 5.5 months (SD=2.65). Before and after helmet treatment the parents were asked to score the severity of deformity on a rating scale O-10 (0 = severely abnormal; lO=normal) and to indicate when an improvement was noticed after onset of the helmet treatment.

Results: In 38 of the 39 infants an improvement of the shape of the skull was reported by the parents (Wilcoxon’s signed ranks test; p < 0.05). Improvement was observed within 5.9 weeks (mean, SD=3.97) after starting helmet treatment. The degree of improvement was inversely correlated to the pre-treatment score (Pearson corr: -0.702, p=O.Ol). Neither the time of onset of helmet treatment (corr.coeff.0.05) nor the duration of treatment (corr.coeff.0.181) was correlated to the degree of improvement of the skull deformity. No severe side-effects or intolerance to the device were reported.

Conclusion: The status of this therapy should be com- pared with the natural course and/or spontaneous improvement of the non-synostotic posterior skull deformity for final conclusions. However, improvement was observed on average even after 5.9 weeks, which does support the interpretation of our results that a helmet device seems to be a safe and effective treatment for non-synostotic posterior plagiocephaly in infants.

370 Pilot study in the use of melatonin for children with neurological disorders and sleep problems V WONG,’ S F PANG’ ‘Division of Neurodevelopmental Paediatrics, Department of Paediatrics, ‘Department of Physiology, The University of Hong Kong, Hong Kong

Melatonin is a hormone secreted by the pineal gland with a diurnal rhythm, being low level in the daytime with peaks at night. Its circulating levels correlate well with urinary 6-hydroxy-melatonin sulphate levels. The determination of urinary 6-hydroxy-myelatonin has been used as a non-invasive technique for monitoring human circadian rhythmicity. Melatonin plays an important role in the regulation of diurnal and seasonal rhythms in animals and humans.

In humans, melatonin has been used for 15 years in the treatment of disorders of circadian rhythm including jet lag and sleep disorders. The use of melatonin in regulating the human sleep-wake cycle and the re- entrainment of circadian rhythm by promoting sleep in humans have been well documented. In animal research, melatonin also has an anticonvulsant effect. There are scanty reports in humans concerning the use of melato- nin as an anticonvulsant. The relationship of melatonin and seizure might be mediated by the following mechanisms: (1) altered brain GABAergic neurotrans- mission, (2) interaction of melatonin with benzodiazepinic brain receptors, through tryptophan metabolite activity, or (3) acting as a free-radical scavenger.

Children with severe neurological disabilities usually had sleep problems. The objective of this pilot study was to assess the efficacy of melatonin in improving the sleep pattern of these children and to observe any secondary beneficial effect on seizure freqency per se. During the

period June 1998 to January 1999, 12 children (8 boys, 5 girls) with multiple neurological disorders were included in the study if they had severe sleep problems.

The mean age was 6 years 4 months (range = 13 months to 16 years). Ten children (83%) had intractable epilepsy. Neurological disorders included cerebral palsy (3), autism (2), cortical blindness (5), mental retardation [ll; mild (I), moderate (4), severe (8)], lissencephaly and schizencephaly (l), tuberous sclerosis 91), Walker- Warburg syndrome (1) and Angelman syndrome (1). All children had multiple neurological problems. The sleep problems had been quite severe so that the children’s behaviour deteriorated and the quality of life of the parents was affected. A sleep diary was kept for a few days prior to the melatonin trial. Most children had delayed sleep onset and short sleep cycles with frequent awakenings. Oral melatonin - 1 mg was given, and increased to 36mg if it failed to improve sleep onset and increase the sleep duration. The sleep diary was monitored during the trial. The sleep response was graded as follows: grade 1: > 90% improvement in sleep pattern [n=9 children (75%)]; grade 2: 50- < 90% improvement (n=3, 17%) and grade 3: no improvement (n=l). The complete failure occurred in a 5-year-old severely mentally retarded boy with intractable infan- tile spasm, cortical blindness, spastic tetraplegia and lissencephaly/schizencephaly. For those with grade 1 response, the effect was seen immediately after one oral dose of melatonin, 1 mg. It was not necessary to increase the dose in those with grade 1 response. The parents were very satisfied with the marked improvement of sleep pattern in those with grade 1 response. When the sleep-wake cycle was re-established, most of these parents stopped melatonin with no untoward effect. They resumed oral melatonin when there was a relapse of the sleep disturbance, which was rare. For those with grade 2 to 3 response, the maximum dose of melatonin tried was 6 mg. The lack of response in one case might be related to inadequate dosage for that particular child. As the exact dosage of melatonin use is unknown, and melatonin is relatively safe, one can try to increase the dosage further depending on the clinical response. Even the frequency of epileptic seizures decreased in those who were on the same anticonvulsant regime, especially in the child with Angelman syndrome and another with unexplained encephalopathy and infantile spasm. Thus, oral melatonin is worth a therapeutic trial in those children with multiple neurological problems and sleep disorders. Future research should concentrate on sleep- wake EEG analysis and assaying of serum melatonin levels to titrate the response more objectively.

198 Use of traditional Chinese medicine (tongue acupuncture) in children with neurological disorders: Pilot study of 100 cases V WONG,’ j G SUN,’ Q MA,’ E YANG,’ C Y YEUNG,’ R LIZ ‘Department of Paediatrics, The University of Hong Kong; 2 The Jockey Club, MRI Engineering Centre, The University of Hong Kong; ‘Radiology Department, St Paul’s Hospital, Hong Kong