Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the light of three case histories, other personal observations and the literature, the clinical and electroencephalographical differences between absences in the limited sense and continuous LENNOX petit-mal state are described and the problems of the latter discussed. As a rule, petit-mal state is diagnosed as such in young people or adults, and practically never before the 10th year of life. In about two thirds of cases, its clinical symptomatology consists of a twilight condition lasting some hours to a few days, coupled with inertia and apathy. The remaining third of the patients usually experience milder disturbances, e.g. in the form of concentration difficulties, tiredness, and (more rarely) severe forms including lethargy. The EEG correlate of a petit-mal state is made up of continuous bilaterally synchronous, frontally marked (less frequently with exclusively frontal localization), usually irregular spike waves or poly-spike waves, which frequently occur in only rudimentary forms and register a frequency of 2 1/2-4 c/sec. For the treatment of petit-mal state, benzodiazepines and in particular clonazepam (Rivotril) (1-2 mg i.v.) are recommended. During the interval condition the same therapy as with an absence epilepsy, e.g. succinimides or dipropylacetate (Depakine) is administered. Anti-grand-mal remedies, especially hydantoins, may trigger petit-mal status.
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PMID:[The petit-mal-status]. 1 55

The rapid-cycling variant of bipolar disorder constitutes about 15%-20% of all bipolar patients, and 72%-82% of these patients exhibit less than adequate response to lithium therapy. Valproate's spectrum of efficacy was examined in 78 patients with rapid-cycling bipolar disorder in a prospective, open, 15.8-month trial. Thirty patients received valproate monotherapy and 48 received combination therapy. Treatment assignment was nonrandomized and based on prior treatment history. A marked acute response was seen in 54% of the patients with mania, 87% of those with mixed states, and 19% of those with depression. Marked prophylactic responses were seen in 72% of manic patients, 94% of mixed states patients, and 33% of depressed patients. In addition, moderate acute antimanic responses were observed in another 31% of the patients, prophylactic antimanic responses in 17%, acute antimixed state responses in 0%, prophylactic antimixed state responses in 0%, acute antidepressant responses in 25%, and prophylactic antidepressant responses in mixed states in 34%. Pattern analysis was conducted to examine the spectrum of efficacy of valproate in various cells (e.g., the cohort of patients who had an acute antimanic response to the drug). Pattern analysis showed that 40% of the patients with a marked prophylactic antimanic response had a marked antidepressant response to valproate. However, among the patients with a marked antidepressant response to valproate, 91% had a marked antimanic response. The most common side effects of valproate in our study, as in earlier studies, were gastrointestinal problems (nausea, stomach cramps, diarrhea), tremors, lethargy, and hair thinning.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Spectrum of efficacy of valproate in 78 rapid-cycling bipolar patients. 154 18

A 20 year old woman with complex partial seizures from childhood developed a stuporous state when her anticonvulsant therapy was substituted by VPA. She recovered when treated orally with clonazepam. This case was compared with others in the literature for which the origin of the stuporous state have been hypothesized.
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PMID:[State of confusion induced by valproic acid and reversed after administration of clonazepam]. 393 22

All individuals receiving valproic acid therapy in an institution for the mentally retarded were evaluated for hyperammonemia. Of these 19 adults, 6 had persistent and 5 others had intermittent hyperammonemia. The hyperammonemic patients were asymptomatic, except that 2 had occasional lethargy. Hyperammonemia was detected more often in younger adults and in those treated with multiple anticonvulsants, especially phenytoin. Valproate-induced hyperammonemia is probably the result of depletion of mitochondrial acetyl CoA and decreased production of N-acetylglutamate, the obligatory activator of the first enzyme of the urea cycle, carbamyl phosphate synthetase I. Anticonvulsant-mediated microsomal enzyme induction may also contribute.
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PMID:Valproic acid-induced hyperammonemia in mentally retarded adults. 642 25

In 11 patients with complex partial epileptic seizures stuporous states were observed during treatment with valproate (VPA) (2 cases), with VPA and phenobarbitone (PB) (4 cases), or with VPA, PB and a third anti-epileptic drug (5 cases). Based on 3 characteristic cases, an attempt is made to define the role of VPA, the nature of the stuporous states, and the origin of digestive disorders which often herald the onset of behavioural disorders. Several clinical studies have suggested the direct responsibility of VPA even if the adverse effects are potentiated by many other anti-epileptic drugs. Stuporous states are not due to VPA overdose and do not depend on the mode of administration. No correlation has been found between electroclinical signs and plasma or CSF levels of the different anti-epileptic drugs. Reported data and the present cases suggest a paradoxical epileptogenic role for VPA on complex partial seizures: there exists a close similarity of electroclinical findings between spontaneous epileptic seizures and stuporous states during DPA treatment. Digestive disorders appear to result from a central mechanism and not from digestive tract intolerance. In some cases, it is likely that partial seizures with digestive symptoms and signs do occur.
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PMID:[Stuporous states during treatment with sodium valproate. Pathogenetic hypotheses]. 679 80

The efficacy of valproic acid in the treatment of intractable chronic daily headache, unresponsive to traditional prophylactic medications, was examined prospectively in 16 patients. Dosage of the medication was adjusted to maintain serum valproic acid levels between 50 and 100 micrograms/mL, provided there were no significant side effects at that level. Valproic acid prophylaxis was of some benefit in only 2 of 16 patients. One of these two patients discontinued therapy due to side effects. Eight of the 16 patients reported side effects which included nausea, diarrhea, anorexia, lethargy, sleepiness, confusion, blurred vision, and decreased libido. In conclusion, valproic acid was not effective in controlling chronic daily headache in the majority of patients in whom conventional therapy had failed, and 50% of patients reported side effects. There is a significant disparity in the reported efficacy of this drug in treating chronic daily headache. This disparity is most likely due to the poorly-defined nature of this variety of headache. It is, therefore, recommended that more stringent definition of this disorder be developed before therapeutic regimens are evaluated.
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PMID:Valproic acid treatment of chronic daily headache. 853 Feb 78

An 18-year-old male suffered from familial progressive myoclonic epilepsy from the age of 7 years. In addition to seizures, there was a marked decline in school performance. At the age of 14 years, sodium valproate was started as add-on therapy; 2 weeks later he was hospitalized in a stuporous state. The serum level of valproate was within the therapeutic range. Cognitive evaluation disclosed moderate mental retardation. No metabolic abnormalities were detected. Valproate was discontinued and during the 4 following months, a slow but significant improvement was documented in cognitive functions. Repeated assessment was within the range of mild mental retardation. Initially, magnetic resonance imaging (MRI) showed mild cortical atrophy. A subsequent MRI study performed 2 years later was normal.
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PMID:Reversible cortical atrophy and cognitive decline induced by valproic acid. 1072 94

Malignant neuroleptic syndrome is a complication of antipsychotic medication use. Clozapine use is also associated with polyserositis and eosinophilia. We report a 17 years old female treated with clozapine, valproic acid, lithium carbonate and lorazepam that consulted in the emergency room for confusion, lethargy, catatonia, rigidity, myalgya and fever. Complete blood count showed eosinophilia. An abdominal CAT scan showed ascites and pleural effusion. Clozapine was discontinued and bromocriptine was started. One week after admission, the patient remained febrile and liver enzymes were elevated. Valproic acid was discontinued. Inflammatory parameters stated to subside and the patient was discharged afebrile days after admission.
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PMID:[Malignant neuroleptic syndrome and polyserositis associated to clozapine use: report of one case]. 1634 74

Valproate-induced hyperammonemic encephalopathy (VHE) is an unusual complication characterized by a decreasing level of consciousness, focal neurological deficits, cognitive slowing, vomiting, drowsiness, and lethargy. We have thoroughly reviewed the predisposing factors and their screening, the biochemical and physiopathological mechanisms involved, the different treatments described, and those that are being investigated. Etiopathogenesis is not completely understood, although hyperammonemia has been postulated as the main cause of the clinical syndrome. The increase in serum ammonium level is due to several mechanisms, the most important one appearing to be the inhibition of carbamoylphosphate synthetase-I, the enzyme that begins the urea cycle. Polytherapy with several drugs, such as phenobarbital and topiramate, seems to contribute to hyperammonemia. Hyperammonemia leads to an increase in the glutamine level in the brain, which produces astrocyte swelling and cerebral edema. There are several studies that suggest that treatment with supplements of carnitine can lead to an early favorable clinical response due to the probable carnitine deficiency induced by a valproate (VPA) treatment. Development of the progressive confusional syndrome, associated with an increase in seizure frequency after VPA treatment onset, obliges us to rule out VHE by screening for blood ammonium levels and the existence of urea cycle enzyme deficiency, such as ornithine carbamoyltransferase deficiency. Electroencephalography (EEG) is characterized by signs of severe encephalopathy with continuous generalized slowing, a predominance of theta and delta activity, occasional bursts of frontal intermittent rhythmic delta activity, and triphasic waves. These EEG findings, as well as clinical manifestations and hyperammonemia, tend to normalize after VPA withdrawal.
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PMID:Valproate-induced hyperammonemic encephalopathy. 1677 19

Valproic acid (VPA) is used to manage a variety of conditions, including simple and complex absence seizure disorder, bipolar disorder, and migraine prophylaxis. The clinical manifestations of VPA overdose range in severity from mild confusion and lethargy to severe coma and death. The treatment of VPA toxicity is mainly supportive. There is no specific antidote or guidelines for managing VPA intoxication. Anecdotal reports describe the efficacy of naloxone and L-carnitine, but the data are insufficient to make strong conclusions. Various extracorporeal techniques for managing VPA toxicity have been described, but none has prevailed as standard therapy. We report a patient with VPA overdose who was treated successfully with hemoperfusion with activated charcoal and L-carnitine. The VPA level of the patient exceeded 1000 microg/mL and was normalized after 3 rounds of hemoperfusion. The patient was injected with L-carnitine at a maximum of 600 mg/kg per day for 5 days without complications.
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PMID:A case of hemoperfusion and L-carnitine management in valproic acid overdose. 1835 83


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