Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical course of a 9-year-old diagnosed with attention-deficit hyperactivity disorder, obsessive-compulsive disorder, and Tourette's disorder and treated with a combination of methylphenidate, clonidine, and fluoxetine is described. The patient experienced over a 10-month period, signs and symptoms suggestive of metabolic toxicity marked by bouts of gastrointestinal distress, low-grade fever, incoordination, and disorientation. Generalized seizures were observed, and the patient lapsed into status epilepticus followed by cardiac arrest and subsequently expired. At autopsy, blood, brain, and other tissue concentrations of fluoxetine and norfluoxetine were several-fold higher than expected based on literature reports for overdose situations. The medical examiner's report indicated death caused by fluoxetine toxicity. As the child's adoptive parents controlled medication access, they were investigated by social welfare agencies. Further genetic testing of autopsy tissue revealed the presence of a gene defect at the cytochrome P450 CYP2D locus, which results in poor metabolism of fluoxetine. As a result of this and other evidence, the investigation of the adoptive parents was terminated. This is the first report of a fluoxetine-related death in a child with a confirmed genetic polymorphism of the CYP2D6 gene that results in impaired drug metabolism. Issues relevant to child and adolescent psychopharmacology arising from this case are discussed.
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PMID:Fluoxetine-related death in a child with cytochrome P-450 2D6 genetic deficiency. 1075 79

There has been much debate about the nosologic forms of electrical status epilepticus during sleep (ESES) that can occur in a number of syndromes. The pathogenesis of ESES is unknown, and the natural course is variable. It is debatable whether these age-specific epileptic syndromes belong to the same spectrum of disorders with different severity but a common denominator of sleep-related hypersynchronization of generalized paroxysmal epileptic discharges. This report describes 18 children with medically refractory seizures, gradual deterioration in language skills, fine-motor incoordination, behavioral changes, psychologic and intellectual regression of different degrees, and the ESES phenomenon. Most exhibited clinical and electroencephalographic responses to intravenous or oral benzodiazepines, especially if initiated within the first 2 years of seizure onset. Seizure remission was nearly complete with cessation of seizures and marked improvement in language and fine-motor skills, behavior, and intellectual function in those with an idiopathic etiology. Therapeutic trials with benzodiazepines should be given to all children with the ESES phenomenon. Sleep electroencephalographic monitoring is recommended in all young children with epilepsy and language or psychologic deterioration so that the brain dysfunction can be reversed at a critical and vulnerable period of early life.
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PMID:Spectrum of epileptic syndromes with electrical status epilepticus during sleep in children. 1091 29

Adenosine is an endogenous modulator that has an inhibitory effect on neuronal activity. The aim of this work was to investigate the role of aminophylline, an adenosine receptor antagonist, on the long-term effects of status epilepticus (SE) in the developing brain. Four groups of rats at the postnatal age of 12 days were intraperitoneally administered with saline, aminophylline (50 mg/kg), lithium-pilocarpine (Li-PC) (3 mEq/kg-60 mg/kg), and Li-PC plus aminophylline, respectively. The four groups were tested for spatial memory using the Morris water maze task at P80 and motor performance by the Rotarod test at P100. The brains were then analyzed with cresyl violet stain for histological lesions and evaluated for mossy fiber sprouting with the Timm stain. At the acute stage, all rats subjected to Li-PC developed SE and no seizures were elicited in the saline-treated or aminophylline-treated rats. The seizure duration was longer in the Li-PC plus aminophylline group (346.9+/-32.7 min) as compared with that in the Li-PC group (265.2+/-9.8 min). The difference of mortality was not significant. Rats without seizures exhibited no motor imbalance, spatial deficits, or morphological changes. The rats with Li-PC-induced SE demonstrated spatial memory deficits without motor incoordination or morphological changes. However, the rats subjected to Li-PC plus aminophylline exhibited motor impairment and morphological changes, including neuronal cell loss in CA1 area and increased mossy fiber sprouting in CA3 area. In addition, the rats of Li-PC plus aminophylline had greater spatial memory deficits than that seen in rats with Li-PC. We concluded that an adenosine receptor antagonist, such as aminophylline, had synergistic effects on the SE-induced long-term deficit of cognition and motor performance in the developing brain. The present study may provide experimental evidence and lead to novel therapeutic interventions.
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PMID:Aminophylline exacerbates status epilepticus-induced neuronal damages in immature rats: a morphological, motor and behavioral study. 1207 43