Fluvoxamine, a selective serotonin reuptake inhibitor which modulates serotoninergic activities, is a useful drug for patients with an autistic disorder. Genetic variation of the serotonin receptor may influence the efficacy of fluvoxamine treatment. We studied the correlation between clinical responses to fluvoxamine and serotonin receptor gene polymorphism (5-HT2AR) in children with an autistic disorder. Eighteen patients completed a 12-week double-blind, placebo-controlled, randomized crossover study. Clinical global impression (CGI) by child neurologists and interviews for parents were assessed after 12 weeks of fluvoxamine treatment. Behavioral assessments consisting of 20 items by newly created Behavioral Assessment Scale (BAS) were obtained before as well as 6 and 12 weeks after treatment. For genotyping of 5-HT2AR, 102 T/C polymorphism was analyzed by the PCR method. Seven cases of T/T, 6 of T/C and 5 of C/C were identified. The patients with the genotype T/C responded more favorably when estimated by CGI and parents'report at 12 weeks of treatment. Although not significant statistically (p=0.0578), the number of improved BAS items in these patients were larger after fluvoxamine than placebo treatment. On analyses of individual BAS items, the patients with the genotype C/C showed improvement of unnatural facial expression, which was significant at 6 weeks, but not at 12 weeks, of fluvoxamine treatment. In the patients with the genotype T/C, eye movements and emotional changes were significantly improved at 12 weeks of treatment. Our results suggested that genetic polymorphism of 102T/C in the 5-HT2AR gene may have influence on the response to fluvoxamine treatment for patients with an autistic disorder. Because of the small numbers of subject studied here, further studies are needed. The methods of fluvoxamine treatment, such as appropriate dosage and treatment duration, should also be clarified.
Delirium in children associated with high fever is defined as an acute and transient confusional state. Clinically it is most important to differentiate delirium from encephalitis or encephalopathy. Electroencephalographic (EEG) tracings were obtained from 17 children with fever and delirium, consisting of 12 boys and 5 girls, aged from 2 to 13 years. The initial recording was done from 2 to 36 hours (mean: 15 hours) after the last episode of delirium. The causes of fever were upper respiratory infections in 14 patients, acute bronchitis in 1, measles in 1 and exanthema subitum in 1. The body temperature ranged from 38.0 to 41.0 t, when delirium was noticed by their parents. On 15 EEG tracings obtained during waking, the alpha rhythm showed a frequency normal for age, but it was interrupted by posterior slow waves in 2 of them. Eight tracings showed abnormal occipital delta activities. These slow waves were blocked by eye opening, and disappeared within 1 to 5 days. Two of the 6 tracings during sleep showed high voltage irregular slow wave bursts mixed with spikes lasting for 7 minutes, which also disappeared within 1 to 2 days. Our results indicate that EEG is useful in differentiating delirium from encephalitis or encephalopathy; in delirium, the occipital delta waves are blocked by eye opening and abnormal activities disappear within a few days.
We report two male patients with juvenile myoclonic epilepsy. They had been diagnosed as having partial epilepsy for three years. They had various myoclonic seizures characterized by truncal and head torsion, stepping backward, and inability to reach objects, as well as asymmetric myoclonic jerks of the upper extremities. For early diagnosis of juvenile myoclonic epilepsy, it is important to take account of the variability of myoclonic seizures.
Three patients with severe motor and intellectual disabilities presented deterioration of the activities ofdaily living, which was revealed to be caused by prolonged non-convulsive status epilepticus (NCSE). Theircondition improved by the treatment with antiepileptics. Case 1, a 4-year-old girl with profound psychomotor retardation and past history of West syndrome of unknown etiology, became unable to sit and eat orally above age of two years. EEG showed continuous generalized slow spike and wave bursts indicating NCSE. Continuous intravenous infusion of midazolam abolished EEG abnormalities of NCSE, and she regained the ability of oral feeding. Case 2, a 3-yearold boy with Angelman syndrome and past history of West syndrome, presented decreased mental response, poororal intake and somnolence. EEG showed continuous slow spike and wave bursts, indicating NCSE. High-dose phenobarbital therapy and continuous intravenous injection of vitamin B6 were effective, and remarkably improved his psychomotor activities. Case 3, a 3-year-old boy with Lennox-Gastaut syndrome, developed decreased psychomotoractivity and loss of vocalization and walking. He could not sit by himself and became nearly bed-ridden. EEG showed very frequent generalized spike and wave bursts, showing NCSE. Continuous infusion of thiopental diminishedNCSE, and he could walk again. Psychomotor deterioration in patients with severe motor and intellectual disabilities may be caused by NCSE, which should not be overlooked.
We report two unrelated cases of Costello syndrome, presenting with poor postnatal growth, mild mental retardation, poor feeding, curly hair, coarse characteristic face, loose skin, hypotonia, and cardiac involvement. Nasal papilloma and acanthosis nigricans were the most characteristic features of this syndrome. Both cases had atrial fibrilation from infancy to early childhood. One patient had hypertonia in the lower extremities and pes equinovarus, while the other had hypotonia and pes planovalgus.
We present the effects and adverse effects of dichloroacetate (DCA) in a girl with mitochondrial disorder. Oral administration of DCA 50 mg/kg per day, reduced the elevated levels of lactate to below the normal range. Treatment with DCA ameliorated electroencephalogram abnormalities, but caused the adverse effects with hepatomegaly and decreased activity, which were improved by reduction or withdrawal of DCA. The decreased activity may bean adverse effect on the central nervous system. The dosage of DCA should be adjusted for each patient.
We present here a 5-year-old girl with acutencephalitis with refractory, repetitive partial seizures (AERRPS), a new clinical entity defined by the following five criteria: 1. acute encephalitis with a prolonged acute phase of more than 2 weeks, 2. persistent partial seizures with identical phenotype both in the acute and recovery phase, 3. seizures frequently evolving into convulsive status especially during the acute phase, 4. extremely intractable, and 5. no causative lesion or agent is identified. Interestingly, her seizures had completely diminished from the fifty-sixth day of her illness with concomitant appearance of choreo-ballistic involuntary movements. After the 120th day of the illness, seizures evolved again, though the involuntary movements persisted. This transient disappearance of intractable seizures might provide a clue to the pathophysiology of seizures in AERRPS.
Hypothalamic hamartomas are associated with precocious puberty and gelastic epilepsy. The seizures are often refractory to antiepleptic medications. The treatment of hamartoma is not well established. We report a 3-year-6-month-old boy was admitted because of intractable seizures occurring several times a day. The findings on magnetic resonance imaging and his characteristic seizure led to the diagnosisofhypothalamic hamartoma. The seizures were resistant to multiple antiepileptic drugs, and persisted for about 3 years, during which his cognition deteriorated. Focal radiosurgery by a gamma knife of the hamartoma successfully controlled the seizures with noneurological complications, and his mental function improved.