Valproic acid-induced hyperammonemic encephalopathy – a potentially fatal adverse drug reaction

Sousa, Cátia

doi:10.1186/2193-1801-2-13

Cited by 27 publications

(22 citation statements)

References 9 publications

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“…The period of time taken for symptoms to develop is longer than previously reported4; however, this may be owing to the lower dose of valproate involved in this case.…”

Section: Discussioncontrasting

confidence: 59%

Normoammonemic encephalopathy: solely valproate induced or multiple mechanisms?

Budhdeo¹,

Marquette

Singh

et al. 2014

BMJ Case Reports

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SUMMARYA 77-year-old woman presented with subacute onset progressive confusion, aggression, auditory hallucinations and delusions. In the preceding months, the patient had a number of admissions with transient unilateral hemiparesis with facial droop, and had been started on valproate for presumed hemiplegic migraine. Valproate was withdrawn soon after admission and her cognitive abilities have gradually improved over 3 months of follow-up. Valproate levels taken prior to withdrawal were subtherapeutic and the patient was normoammonaemic. EEG undertaken during inpatient stay showed changes consistent with encephalopathy, and low titre N-methyl-D-aspartate (NMDA) receptor antibodies were present in this patient. The possible aetiologies of valproate-induced encephalopathy and NMDA receptor-associated encephalitis present a diagnostic dilemma. We present a putative combinatorial hypothesis to explain this patient's symptoms. BACKGROUND

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“…The period of time taken for symptoms to develop is longer than previously reported4; however, this may be owing to the lower dose of valproate involved in this case.…”

Section: Discussioncontrasting

confidence: 59%

Normoammonemic encephalopathy: solely valproate induced or multiple mechanisms?

Budhdeo¹,

Marquette

Singh

et al. 2014

BMJ Case Reports

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“…However, it has well-described side effects affecting mainly the liver, pancreas and reproductive system 1. Valproate therapy may also result in a clinically significant rise in plasma ammonia levels leading to an encephalopathy which may prove fatal 2.…”

Section: Introductionmentioning

confidence: 99%

Reversible weakness and encephalopathy while on long-term valproate treatment due to carnitine deficiency

Al-Sharefi

Bilous

2015

BMJ Case Reports

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We describe a case of a 35-year-old woman who presented with bilateral leg weakness and encephalopathy while on long-term valproate therapy. She was diagnosed with valproate-induced encephalopathy due to carnitine deficiency. Clinical improvement occurred with oral carnitine supplementation. Our case report highlights the importance of considering carnitine deficiency in patients presenting with unexplained neurological signs while on long-term valproate treatment.

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“…The serum valproic acid level ranged 50 ~ 269.9 mg/L, which roughly corresponds to 0.5 ~ 2.5 mM [16] [17]. Our previous study has also shown that treatment with 2 mM VPA induced learning impairments in the adult zebrafish [18].…”

Section: Discussionmentioning

confidence: 76%

Valproic Acid Decreases Cell Proliferation and Color Preference in the Zebrafish Larvae

Lee¹,

Lee²,

Choi³

et al. 2017

JBM

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Valproic acid (VPA) is widely used as an antiepileptic drug or mood stabilizer. In this study, we evaluated the effects of treatment with 2 mM VPA for 3 h on cell proliferation in the telencephalic area of zebrafish larvae using bromodeoxyuridine (BRDU) to label dividing cells. It was demonstrated that 2 mM VPA exposure for 3 h at 2 and 3 days post-fertilization (dpf) larvae decreased cell proliferation in the telencephalic area of 5 dpf larvae. The reduced cell proliferation was not restored at 10 dpf larvae. The quantitative real-time PCR (qRT-PCR) data indicated that mRNA expression levels of WNT signaling pathway-related factors such as β-catenin, LEF1, and gsk3β were altered in the zebrafish larvae treated with 2 mM VPA at 2 and 3 pdf. It was also demonstrated that 2 mM VPA exposure affected color preference of the zebrafish larvae, reducing blue color preference at 5 dpf larvae. The altered color preference was restored at 10 dpf larvae. These results suggest that VPA exposure may cause molecular, cellular, and behavioral alterations in early developmental stage of the zebrafish.

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Valproic acid-induced hyperammonemic encephalopathy – a potentially fatal adverse drug reaction

Cited by 27 publications

References 9 publications

Normoammonemic encephalopathy: solely valproate induced or multiple mechanisms?

Normoammonemic encephalopathy: solely valproate induced or multiple mechanisms?

Reversible weakness and encephalopathy while on long-term valproate treatment due to carnitine deficiency

Valproic Acid Decreases Cell Proliferation and Color Preference in the Zebrafish Larvae

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