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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We reported a case of early infantile epileptic encephalopathy (EIEE) due to perinatal hypoxic-ischemic brain damage. This infant had frequent brief tonic seizures in series accompanied by apnea and bradycardia since two days after birth. Her EEG showed a typical suppression burst pattern. We administered PB. VPA and CZP, but could not control her seizures at all. Then, a thyrotropin releasing hormone (TRH) analog, in addition to PB and VPA, was administered intravenously (0.5 mg/day) to her. Three weeks after the administration of this TRH analog, her seizures ceased completely. We suggest that TRH analog therapy should be considered as one of therapeutics for EIEE whose prognosis is expected to be poor.
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PMID:[Effectiveness of TRH analog in a case of early infantile epileptic encephalopathy]. 212 Nov 73

Valproic acid is known to cause an increase in blood ammonia levels in humans at the usual clinical dose. In most patients, this increase is small and asymptomatic, but in some patients the increase is larger and is associated with encephalopathy. In this study, valproate also caused a small increase in blood ammonia level (from 50 to 83 mumol/l) in Wistar rats. Salicylate potentiated this increase in blood ammonia (greater than 210 mumol/l) when coadministered with valproate at a dose of salicylate which did not cause a significant increase when given alone. Other nonsteroidal anti-inflammatory drugs tested (ibuprofen and naproxen) did not potentiate valproate-induced hyperammonemia, and paracetamol actually appeared to decrease ammonia levels. The degree of hyperammonemia was dependent upon diet, and fasting decreased the level of hyperammonemia. In order to determine what component of the diet was responsible for this effect, protein, fat and carbohydrate were given by gavage, individually and also a mixture of the three. Only the mixture was able to increase the degree of hyperammonemia, even though the number of calories in the mixture and in each nutrient given individually was approximately the same. 2,4-Dinitrophenol, which like salicylate uncouples oxidative phosphorylation, potentiated valproate-induced hyperammonemia at a much lower dose than salicylate. Whether salicylate can potentiate hyperammonemia and lead to encephalopathy in some patients and therefore represents one of the risk factors for observed cases of valproate toxicity remains to be determined. Potentiation of hyperammonemia by salicylates is also consistent with the apparent association between salicylates and Reye's syndrome which is also characterized by hyperammonemia.
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PMID:Salicylate potentiates valproate-induced hyperammonemia in the rat. 311 9

Acute liver toxicity caused by carbamazepine is a well known though infrequent event. Severe toxicity with hepatocellular insufficiency is even more rare. A case is presented of a patient who suffered of partial epilepsy on treatment with valproate and carbamazepine, who was admitted because of severe acute liver insufficiency attributable to carbamazepine. He had started treatment with the latter drug two weeks earlier, when he developed fever, jaundice, rash and signs of encephalopathy in association with elevation in serum transaminases levels and a decrease in prothrombin index (24%). Discontinuation of both antiepileptic drugs, together with the usual supportive measures, was followed by a complete resolution. Valproate was restarted without complications. Liver biopsy suggested acute hepatitis of drug-related origin. Granulomas or steatosis were not found. The histologic picture together with the relation between carbamazepine administration and the development of hepatotoxicity allow us to dismiss valproate as the possible causal agent of this patient's disease. Therefore, we believe it was an acute hepatocellular failure secondary to carbamazepine.
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PMID:[Acute severe hepatic insufficiency caused by carbamazepine]. 839 72

Valproic acid is an anticonvulsant drug known to inhibit the glucuronidation of zidovudine (AZT) in human liver microsomes. Zidovudine is metabolized by glucuronidation to the inactive 5'-glucuronide with a short plasma half-life (1.0 +/- 0.2 hour). This case presentation confirms that valproic acid inhibits glucuronidation in vivo, and this is the first documented observation of increased cerebrospinal fluid levels of zidovudine because of an interaction with valproic acid in a patient with acquired immune deficiency syndrome (AIDS). The peak plasma AZT level for the control period was 119 ng/mL, which increased almost 3-fold to 344 ng/mL with valproic acid (1.5 g/day). The plasma AZT trough was 47 ng/mL, which also increased almost 3-fold to 124 ng/mL with valproic acid. The molar ratio of plasma 5'-glucuronide/AZT at the peak was reduced from 1.77 (control) to 1.07 with valproic acid. The 5'-glucuronide/AZT ratio at the trough was reduced markedly from 5.0 (control) to 0.93 with valproic acid, suggesting in vivo inhibition of glucuronidation. Cerebrospinal AZT levels, drawn 30 minutes after peak plasma levels, increased from 27 ng/mL for the control to 47 ng/mL with valproic acid, which paralleled the change in peak plasma concentrations. This interaction with valproic acid may contribute to higher AZT levels in the brains of patients with human immunodeficiency virus-related (HIV) encephalopathy.
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PMID:Valproic acid increases cerebrospinal fluid zidovudine levels in a patient with AIDS. 909 56

Based on small numbers of patients, it is possible to make the following suggestions rather than categorical statements. For myoclonic seizures and epilepsies which are not otherwise specified, valproate seems of proven efficacy. Ethosuximide may be a useful adjunct. The exact place of lamotrigine, which controls some myoclonia and makes them worse in other patients, requires further study. The findings are clearer when specific syndromes are considered. Valproate is the treatment of first choice for benign myoclonic epilepsy in infants, myoclonic astatic epilepsy, epilepsy with myoclonic absences, eyelid myoclonia with absences, juvenile myoclonic epilepsy and progressive myoclonus epilepsy. The addition of ethosuximide to valproate can be helpful to those with myoclonic absences, where this combination appears more beneficial than either valproate or ethosuximide alone and in eyelid myoclonia with absences. Lamotrigine can be effective therapy for juvenile myoclonic epilepsy and eyelid myoclonia with absences when used alone and, in conjunction with other antiepileptic drugs (AED) (usually valproate) for early myoclonic encephalopathy, myoclonic-astatic epilepsy and particularly, epilepsy with myoclonic absences. The myoclonia of infantile neuronal ceroid lipofuscinosis respond to lamotrigine. Severe myoclonic epilepsy of infants usually worsens with lamotrigine, but occasionally, children improve. Zonisamide added to clonazepam and valproate or a barbiturate, can reduce the cascade of myoclonia in progressive myoclonus epilepsies for at least 2 years, but relapse may occur thereafter.
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PMID:Myoclonus and epilepsy in childhood: a review of treatment with valproate, ethosuximide, lamotrigine and zonisamide. 947 47

Ornithine transcarbamylase deficiency is an X linked disorder and the most common inherited cause of hyperammonaemia. Fluctuating concentrations of ammonia, glutamine, and other excitotoxic amino acids result in a chronic or episodically recurring encephalopathy. A heterozygous female patient first presented with protein intolerance, attacks of vomiting, and signs of mental retardation in early childhood. At the age of 16 complex partial seizures occurred which were treated with sodium valproate. Seven days after initiation of valproate therapy, she developed severe hyperammonaemic encephalopathy with deep somnolence. The maximum concentration of ammonia was 480 micromol/l. After withdrawal of valproate, three cycles of plasma dialysis, and initiation of a specific therapy for the inborn metabolic disease, ammonia concentrations fell to normal values. The patient remitted, returning to her premorbid state. Valproate can cause high concentrations of ammonia in serum in patients with normal urea cycle enzymes and may worsen a pre-existing hyperammonaemia caused by an enzymatic defect of the urea cycle. Sufficient diagnostic tests for the detection of metabolic disorders must be performed before prescribing valproate for patients with a history of encephalopathy.
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PMID:Hyperammonaemic encephalopathy after initiation of valproate therapy in unrecognised ornithine transcarbamylase deficiency. 959 92

Valproic acid (VPA)-induced encephalopathy is a rarely considered side effect, with somnolence, reduced motor activity and severe deterioration of cognitive and behavioural abilities. In accordance with the increasing clinical importance of valproate clinical symptoms, causes and possibilities of treatment are reviewed by reporting on two cases of valproate-induced encephalopathy. In comparison to VPA intoxication, which is associated to increased VPA blood levels, the mechanisms of encephalopathy may include interactions of the hepatic enzymes, a direct toxic effect on the cerebral receptors, as well as drug interactions, a paradoxical epileptogenic effect and metabolic interactions. In most cases withdrawal of VPA produces regression of the symptoms within a few days; the role of L-carnitin or citrullin supplementation in clinical treatment remains unclear.
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PMID:[Encephalopathies caused by valproate]. 1006 84

A 24-years-old woman with epilepsy treated with valproic acid developed disorientation, acalculia, perseveration, slow responsiveness and loss of memory. The drug withdrawal induced a quick improvement of mental function. In this case, hyperammonemia, hypocarnitinemia, increased protein in cerebrospinal fluid were found. When the drug was discontinued, she had a dramatic improvement. Valproic acid caused encephalopathy because of metabolic abnormality in mitochondria in this case. In the cases of encephalopathy caused by valproic acid, the drug administration should be withdrawn, and appropriate measures had to be taken. In addition, elevation of ammonia in the blood, lactic acid and pyruic acid in the serum and cerebrospinal fluid, and decreased carnitine level in the serum will be useful to make a diagnosis of valproate-induced encephalopathy.
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PMID:[A case report of valproate encephalopathy]. 1065 74

A 28-year-old patient with a 5-year history of bipolar disorder developed signs of encephalopathy 2 weeks after the addition of valproic acid to his treatment regimen of doxepine, risperidone, and biperidene. The clinical signs were drowsiness, ataxic gait, asterixis, and a generalized epileptic seizure. Discontinuation of valproic acid gradually resulted in complete remission of these symptoms. Valproate encephalopathy has been described mainly in patients receiving anticonvulsant polytherapy. This complication might become more prevalent in psychiatric pharmacotherapy due to the increasing use of valproic acid.
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PMID:[Valproic acid in prophylaxis of bipolar disorder. A case of valproate-induced encephalopathy]. 1084 16

Long-term intragastric administration of the antiepileptic drug sodium valproate (Vuprol Polfa) to rats for 1, 3, 6, 9 and 12 months, once daily at the effective dose of 200 mg/kg body weight showed morphological evidence of encephalopathy, manifested by numerous nonspecific changes within Purkinje cell perikarya and their dendritic processes. The first ultrastructural abnormalities appeared after 3 months. They became more severe in animals with longer survival and were most pronounced after 12 months. The changes were maintained both 1 and 3 months after drug withdrawal. Mitochondria of Purkinje cell perikarya were most severely affected. Damage to mitochondria was accompanied by disintegration and fragmentation of granular endoplasmic reticulum, dilation of channels and cisterns of Golgi apparatus, enlargement of smooth endoplasmic reticulum elements including submembranous cisterns, and accumulation of profuse lipofuscin deposits. Frequently, Purkinje cells appeared as dark ischemic neurones, with focally damaged cellular membrane and features of disintegration. Swollen Bergmann's astrocytes were seen among damaged Purkinje cells or at the site of their loss. The general pattern of submicroscopic alterations of Purkinje cell perikarya suggested severe disorders in several intercellular biochemical extents, including inhibition of oxidative phosphorylation and abnormal protein synthesis, both of which could lead to lethal damage. Ultrastructural abnormalities within dendrites were characterized by damage to elements of smooth endoplasmic reticulum, which was considerably enlarged, with formation of large vacuolar structures situated deep in the dendroplasm. Mitochondrial lesions and alterations in cytoskeletal elements--disintegration of microtubules or even their complete loss--were also observed. The general pattern of abnormalities within the organelles and cytoskeletal elements of dendritic processes in Purkinje cells in the VPA chronic experimental model imply that there are disturbances in detoxication processes. Furthermore these changes were irreversible, as they were maintained after drug withdrawal.
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PMID:Ultrastructure of Purkinje cell perikarya and their dendritic processes in the rat cerebellar cortex in experimental encephalopathy induced by chronic application of valproate. 1184 40


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