Valproic acid induced encephalopathy – 19 new cases in Germany from 1994 to 2003 – A side effect associated to VPA-therapy not only in young children

Gerstner, Thorsten; Buesing, Deike; Longin, Elke; Bendl, Claudia; Wenzel, D.; Scheid, Brigitte; Goetze, G.; Macke, A; Lippert, G; Klostermann, W.E.M.; Mayer, Geert; Augspach-Hofmann, Regine; Fitzek, Sabine; Haensch, Carl-Albrecht; Reuland, Markus; Koenig, Stephan A.

doi:10.1016/j.seizure.2006.05.007

Cited by 96 publications

(58 citation statements)

References 32 publications

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“…Both of the patients we describe also had supratherapeutic VPA levels, but VHE is a welldocumented potential complication of the use of VPA in the medical literature, and it may occur in people with normal VPA levels. 1 Because of the wide spectrum of symptoms associated with VHE, physicians should consider hyperammonemia in the differential diagnosis of any patient taking VPA who shows changes in behavior, cognition, or orientation.…”

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confidence: 99%

Valproate-associated Hyperammonemic Encephalopathy

Wadzinski¹,

Franks²,

Roane³

et al. 2007

The Journal of the American Board of Family Medicine

113

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The use of valproic acid (VPA) (also known as Depakote, Depakene, and others) frequently results in elevated plasma ammonia. In some people, hyperammonemia may be clinically significant, resulting in hyperammonemic encephalopathy, which may be severe. Valproic acid-induced hyperammonemic encephalopathy may occur in people with normal liver function, despite normal doses and serum levels of VPA. We describe 2 cases of valproic acid-induced hyperammonemic encephalopathy in patients with supratherapeutic VPA levels, although the condition has been described in people with normal VPA lev- Valproic acid (VPA) is effective in the treatment of seizure disorders, bipolar disorder, migraine headache prophylaxis, neuropathic pain, restless legs syndrome, dementia-related agitation, and social anxiety disorder, among other conditions. VPA has numerous drug interactions and toxicities; severe toxicities include hepatic damage, pancreatitis, teratogenicity, thrombocytopenia, and hyperammonemia. Here we depict 2 case reports of VPAinduced hyperammonemic encephalopathy (VHE), both occurring in patietns with no history of underlying liver disease. In one instance, the patient was able to function, but with significant cognitive limitations. In the second case, the patient was comatose. Both of the patients we describe also had supratherapeutic VPA levels, but VHE is a welldocumented potential complication of the use of VPA in the medical literature, and it may occur in people with normal VPA levels.1 Because of the wide spectrum of symptoms associated with VHE, physicians should consider hyperammonemia in the differential diagnosis of any patient taking VPA who shows changes in behavior, cognition, or orientation. Case ReportsCase 1 A 51-year-old woman was transferred from a psychiatric hospital to an emergency department to evaluate the recent deterioration in her mental status. She had been admitted to the psychiatric hospital for an exacerbation of posttraumatic stress disorder and was placed on extended-release VPA at 1,000 mg nightly. After 7 days of treatment she was no longer responsive to verbal stimuli. Her medical history was significant for migraine headaches, posttraumatic stress disorder, and major depression. Her medications included topiramate (for migraine prophylaxis), quetiapine, and VPA. In the emergency department, she was nonresponsive to verbal or painful stimuli; her vital signs were normal. Her pupils were equal at 5 mm and her ammonia level was 232 mol/L (N ϭ 10 to 47); her VPA level was 145 g/mL (N ϭ 50 to 100); and aspartate aminotransferase and alanine aminotransferase were normal at 17 IU/L and 19 IU/L, respectively. The remainder of laboratory tests, including all liver tests, were normal. For the first 24 hours, the patient remained nonresponsive; her This article was externally peer reviewed.

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confidence: 99%

Valproate-associated Hyperammonemic Encephalopathy

Wadzinski¹,

Franks²,

Roane³

et al. 2007

The Journal of the American Board of Family Medicine

113

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“…Full recovery is anticipated in most patients [9]. In symptomatic patients whose mental status is altered and is not due to seizure activity dosage adjustment or discontinuation of valproate may be necessary [10].…”

Section: Discussionmentioning

confidence: 99%

Valproic Acid Toxicity Induced by Lacosamide: A Rare Case Report

Kumar

Chandran

Reghu

2017

Asian J Pharm Clin Res

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“…Although these latter metabolites have a minor role, they can be highly toxic in patients on chronic therapeutic dosing or after an acute overdose. 4-en-VPA has been incriminated in the development of cerebral edema, hepatotoxicty, and hyperammonemia [8,19,29,[31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48].…”

Section: How Is Valproic Acid Metabolized?mentioning

confidence: 99%

“…Despite the controversies, reports of fatal subarachnoid hemorrhage, pulmonary hemorrhage, and pancytopenia from the therapeutic use of VPA have been documented. This has influenced many anesthesiologists and surgeons to stop VPA-treatment before surgery to avoid bleeding complications [35,59,77,78].…”

Section: What Occurs With Valproic Acid Toxicity?mentioning

confidence: 99%

Case files of the Children’s Hospital of Michigan Regional Poison Control Center: The use of carnitine for the management of acute valproic acid toxicity

Katiyar

Aaron

2007

J. Med. Toxicol.

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A 28-year-old African-American male was found unresponsive outside of his girlfriend's house around 7 o'clock in the morning. He spent the night at the girlfriend's house and was last witnessed to be awake about 12 hours earlier. The girlfriend and her family were unable to awaken the patient and called emergency medical services (EMS). There was no history of headache, dizziness, fever, chills, nausea, vomiting, seizures, trauma, depressive thoughts, or suicidal ideation. When EMS arrived, they administered 6 mg of naloxone intramuscularly without effect, and the patient was transported to the emergency department (ED).After arriving in the ED, the cardiac monitor displayed a narrow-complex rhythm with a rate of 85-90 per minute. His initial vital signs were: heart rate 91/min; blood pressure 148/80 mmHg; respiratory rate 24/min; temperature 35.1°C (95.1°F) rectally; and pulse oximetry 100% on non-rebreather face mask oxygen. A fingerstick glucose determination was 106 mg/dL.Physical examination revealed a well developed, well nourished individual who was obtunded and unresponsive. His pupils were 2 mm, unreactive to light, and without nystagmus. He had diffuse bilateral wheezing, regular heart rate without any murmurs, and decreased bowel sounds. The patient had warm skin with good distal pulses in all extremities and no cyanosis, erythema, or edema. There was no clonus or hyperreflexia, and the gag reflex was intact.His past medical history was only pertinent for an old gunshot wound to the head. He developed a seizure disorder and was taking divalproex, 500 mg BID. Reportedly, he was allergic to carbamazepine and phenytoin. The patient smoked cigarettes, but the family stated that he had no history of alcohol or illicit drug use.A 12-lead electrocardiogram showed a sinus rhythm with a rate of 92 bpm, a PR interval of 134 msec, a QRS duration of 90 msec, and a QTc of 601 msec. A head CT and chest radiograph were unremarkable. Laboratory tests were obtained.

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Valproic acid induced encephalopathy – 19 new cases in Germany from 1994 to 2003 – A side effect associated to VPA-therapy not only in young children

Cited by 96 publications

References 32 publications

Valproate-associated Hyperammonemic Encephalopathy

Valproate-associated Hyperammonemic Encephalopathy

Valproic Acid Toxicity Induced by Lacosamide: A Rare Case Report

Case files of the Children’s Hospital of Michigan Regional Poison Control Center: The use of carnitine for the management of acute valproic acid toxicity

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