Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Early work in the field established that the 5 alpha-reduced metabolite of progesterone 3 alpha-OH-5 alpha-pregnan-20-one (allopregnanolone or 3 alpha,5 alpha-THP) is a potent positive modulator of the GABA(A) receptor (GABAR), the receptor mediating the effects of the primary inhibitory transmitter in the brain. This steroid acts in a manner similar to sedative drugs, such as the barbiturates, both in terms of potentiating GABA-induced inhibition in vitro and in behavioral assays, by reducing anxiety and seizure susceptibility. Because sedative compounds exhibit withdrawal properties that result in behavioral hyperexcitability, our laboratory has more recently investigated the effect of prolonged application and rapid removal (i.e. 'withdrawal') of this steroid, administered in vivo to female rats. Withdrawal from 3 alpha,5 alpha-THP produces a state of increased anxiety and lowered seizure threshold, similar to withdrawal from other GABA-modulatory drugs such as the benzodiazepines and alcohol. Hormone withdrawal also produced increases in the alpha 4-containing GABAR, an effect correlated with insensitivity of the GABAR to modulation by the benzodiazepine class of tranquilizers, as would normally occur under control conditions. In addition, changes in intrinsic channel properties, including a marked acceleration in the decay rate was also observed as a result of declining levels of 3 alpha,5 alpha-THP. Such a change would result in less inhibitory total current, and the resulting increase in neuronal excitability could then underlie the observed behavioral excitability following hormone withdrawal. These results suggest that actions of this steroid on a traditional transmitter receptor in the brain lead to alterations in GABAR subunit composition that result in changes in the intrinsic channel properties of the receptor and behavioral excitability. These results may have implications for endogenous fluctuations in this hormone which may accompany premenstrual dysphoric disorder.
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PMID:Withdrawal properties of a neuroactive steroid: implications for GABA(A) receptor gene regulation in the brain and anxiety behavior. 1196 Jun 30

Delirium Tremens is quite rare in children and it is usually caused by withdrawal or abstinence from alcohol, barbiturates and other major tranquilizers. The usual symptoms of Delirium Tremens include severe altered mental status with confusion, delusions, hallucinations, and severe agitation. Although psychosis is a recognized manifestation of Phenytoin toxicity, visual hallucinations are not. This study reports the case of a 4-year-old male with febrile seizures plus syndrome who developed acute complex visual hallucinations and psychomotor agitation early after therapy with intravenous Phenytoin was administered. These visual hallucinations mimicked those linked to Delirium Tremens and were not associated with an encephalopathy or other known neuropsychiatric side effects of this drug. Moreover, the hallucinations occurred while serum Phenytoin concentrations were below therapeutic range. We made an extensive investigation in order to exclude a non-convulsive Status Epilepticus, a Central Nervous System infection, a metabolic disorder, an underlying psychiatric disease and a possible drug toxicity. The temporal relationship between initiation of Phenytoin and onset of visual hallucinations and resolution of symptoms with withdrawal of Phenytoin suggests that the visual disturbances were probably due to that antiepileptic drug.
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PMID:Phenytoin-induced visual disturbances mimicking Delirium Tremens in a child. 2072 59

Objective: As a treatment for cases of developmental disorder accompanied with epilepsy, the author examined the efficacy and tolerability of combined administration of levetiracetam (LEV) on the cases. Methods: There were 21 participants (male-to-female-ratio was 16 to 5, 6 in their 10s, 7 in their 20s, 7 in their 30s and 1 in their 40s) to whom LEV was prescribed from October 2011 to December 2014. The effect was classified as loss of seizure, effective (more than 75% reduction in the number of seizures, more than 50% reduction in the number of seizures), unchanged (no change), and aggravation (increase in the number of seizures). Results: The study included 19 autistic spectrum disorder (ASD) cases (13 with profound intellectual disability, 5 with severe intellectual disability, and 1 with high functioning autism), 1 borderline intelligence case, and 1 attention deficit/hyper activity disorder (AD/HD) case. By classification of epilepsy seizure, there were 15 symptomatic localization-related epilepsy cases and 6 generalized epilepsy cases. The initial dose of LEV was an average of 488.1 mg/day, and the maintenance dose was an average of 1,714.2 mg/day. The average duration of administration was 2 years and 3 months. In terms of the response rate, there were 11 cases of loss of seizure (52.4%), 4 cases of more than 75% reduction in the number of seizures, (19.0%), and 3 cases of more than 50% reduction in the number of seizures (14.3%). The overall response rate was 85.7% (18 cases). 14.3% was unchanged (3 cases). No aggravation case was observed. There was only one case of dizziness in the initial period, but all cases continued taking LEV. The kinds of anticonvulsant agent could be adjusted from 2.5 at the beginning of LEV administration to 1.5. Emotional stability was also observed. Some cases could stop taking tranquilizers. Conclusions: LEV showed high response rate and tolerability on the cases of ASD and other developmental disorder accompanied with epilepsy. Administration of this drug led to reduction in the number of concomitant medications, which indicates the possibility that LEV may contribute to enhancing compliance.
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PMID:Experience with levetiracetam to epilepsy cases in neurodevelopmental disorders. 3001 Mar 7


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