A Case of Valproate-Induced Hyperammonemic Encephalopathy

Zafar, Faraaz; Billadeau, Beau M; Ahmed, Ahsen U

doi:10.7759/cureus.9114

Cited by 3 publications

(5 citation statements)

References 8 publications

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“…Manual search of reference lists and gray literature did not identify additional studies. After screening and assessing for eligibility, 240 studies were included with the remaining articles being excluded for meeting the exclusion criteria 6,7,12–245 . Among the excluded 350 articles, 37 were literature reviews, 5 were pharmacokinetically related, 41 were VPA overdose related, and 267 articles were unable to clearly answer our objectives listed.…”

Section: Resultsmentioning

confidence: 99%

Valproic Acid–Associated Hyperammonemia

Wong

Fan

Wan

et al. 2023

J Clin Psychopharmacol

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BackgroundHyperammonemia is an adverse effect that poses clinical uncertainty around valproic acid (VPA) use. The prevalence of symptomatic and asymptomatic hyperammonemia and its relationship to VPA concentration is not well established. There is also no clear guidance regarding its management. This results in variability in the monitoring and treatment of VPA–induced hyperammonemia. To inform clinical practice, this systematic review aims to summarize evidence available around VPA-associated hyperammonemia and its prevalence, clinical outcomes, and management.MethodsAn electronic search was performed through Ovid MEDLINE, Ovid Embase, Web of Science, and PsycINFO using search terms that identified hyperammonemia in patients receiving VPA. Two reviewers independently performed primary title and abstract screening with a third reviewer resolving conflicting screening results. This process was repeated during the full-text review process.ResultsA total of 240 articles were included. Prevalence of asymptomatic hyperammonemia (5%–73%) was higher than symptomatic hyperammonemia (0.7%–22.2%) and occurred within the therapeutic range of VPA serum concentration. Various risk factors were identified, including concomitant medications, liver injury, and defects in carnitine metabolism. With VPA discontinued, most symptomatic patients returned to baseline mental status with normalized ammonia level. There was insufficient data to support routine monitoring of ammonia level for VPA-associated hyperammonemia.ConclusionsValproic acid–associated hyperammonemia is a common adverse effect that may occur within therapeutic range of VPA. Further studies are required to determine the benefit of routine ammonia level monitoring and to guide the management of VPA-associated hyperammonemia.

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Section: Resultsmentioning

confidence: 99%

Valproic Acid–Associated Hyperammonemia

Wong

Fan

Wan

et al. 2023

J Clin Psychopharmacol

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“…An enzyme, N-acetyl glutamate synthetase (NAGS), forms N-acetyl glutamate (NAG) from acetyl CoA and glutamate [2]. Direct inhibition of CPS-I by VPA is thought to be the primary mechanism of VPA-induced hyperammonemia [2,10]. Furthermore, VPA metabolism occurs in the liver via glucuronic acid conjugation and mitochondrial beta-and cytosolic omega-oxidation.…”

Section: Discussionmentioning

confidence: 99%

“…The other metabolite of VPA, en-VPA, decreases the acetyl CoA available for NAG production by forming valproyl-CoA (VP-CoA) (2). VP-CoA has also been implicated to directly inhibit the activity of NAGS, resulting in VPA-induced hyperammonemia [2,10]. Prior literature suggests that genetic defects in two essential urea cycle enzymes, CPS-I and ornithine transcarbamylase (OTC), could contribute to VPA-induced hyperammonemia [1,10].…”

Section: Discussionmentioning

confidence: 99%

“…VP-CoA has also been implicated to directly inhibit the activity of NAGS, resulting in VPA-induced hyperammonemia [2,10]. Prior literature suggests that genetic defects in two essential urea cycle enzymes, CPS-I and ornithine transcarbamylase (OTC), could contribute to VPA-induced hyperammonemia [1,10]. This explains why VPA-induced hyperammonemia occurs only in a subset of patients [10].…”

Section: Discussionmentioning

confidence: 99%

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A Case of Valproic-Acid Induced Hyperammonemic Encephalopathy

Iqbal¹,

Kummamuru²,

Dasari³

et al. 2021

Cureus

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Valproic acid (VPA), an antiepileptic medication, is known to cause hyperammonemia, which may be asymptomatic or can present with encephalopathy. VPA-induced hyperammonemic encephalopathy (VHE) is a serious but reversible condition, which requires high clinical suspicion for diagnosis. It may occur acutely or after chronic use of VPA. We present the case of a 44-year-old male who was on long-term VPA therapy for a seizure disorder. He presented to the emergency department with the complaint of two episodes of seizures two days before admission. On arrival, the patient was confused and tearful and was unable to recollect the events leading to the seizure. The initial complete metabolic panel, liver function tests, urinalysis, and serum VPA levels were observed to be normal. However, there was a marked elevation in ammonia levels. VPA was suspected to be the inciting agent of hyperammonemic encephalopathy, and, therefore, it was discontinued. The patient was started on oral lactulose and prescribed a different antiseizure medication (i.e., lamotrigine). His ammonia levels decreased gradually, and his condition improved. Thus, it was concluded that the patient had developed VHE. At the time of discharge, he was stable and had no confusion or seizures. This case report evaluates his presentation and discusses the possible pathogenesis of VHE.

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“…Ammonia level greater than 4 times the upper limit of normal is an indication for hemodialysis. 2,3 Here we present a case of hyperammonemia encephalopathy in a young male.…”

Section: Introductionmentioning

confidence: 97%

Valproate Induced Hyperammonemic Encephalopathy

Qayyum

Yousafzai

Iqbal

et al. 2022

J Ayub Med Coll Abbottabad

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Valproate is a commonly prescribed anticonvulsant drug. It has a potential to cause hyperammonemia even in the presence of normal liver function tests. This hyperammonemic state can lead to encephalopathy referred as Valproate induced hyperammonemic encephalopathy (VHE). Here we present a case of valproate induced hyperammonemic encephalopathy in a young male caused by initiation of valproate therapy.

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A Case of Valproate-Induced Hyperammonemic Encephalopathy

Cited by 3 publications

References 8 publications

Valproic Acid–Associated Hyperammonemia

Valproic Acid–Associated Hyperammonemia

A Case of Valproic-Acid Induced Hyperammonemic Encephalopathy

Valproate Induced Hyperammonemic Encephalopathy

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