Asymptomatic Hyperammonemia in Children Treated With Valproic Acid

Altunbaşak, Şakìr; Baytok, Vildan; Tasouji, M.; Hergüner, Özlem; Burgut, Refik; Kayrın, Levent

doi:10.1177/088307389701200709

Cited by 39 publications

(38 citation statements)

References 19 publications

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“…13 Thus, we do not believe that levels of ammonia need to be monitored in all patients treated with VA, although they should be monitored in those who develop neurological symptoms. On the other hand, mild elevations in the level of ammonia that did not cause any symptoms have been observed in patients treated with VA in whom medication did not need to be discontinued.…”

Section: Discussionmentioning

confidence: 98%

Valproate-induced hyperammonaemic encephalopathy in a neonate: Treatment with carglumic acid

Colomer

García

López

et al. 2014

Anales de Pediatría (English Edition)

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Section: Discussionmentioning

confidence: 98%

Valproate-induced hyperammonaemic encephalopathy in a neonate: Treatment with carglumic acid

Colomer

García

López

et al. 2014

Anales de Pediatría (English Edition)

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“…Those of hyperammonemic encephalopathy are less elucidated. Hyperammonemia is frequently observed in children treated by VPA, but rarely results in encephalopathy [1]. Cases of hyperammonemic encephalopathy without signs of hepatic dysfunction have been described in adults after normal or excessive intake of VPA [2][3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Comparison of clinical, magnetic resonance and evoked potentials data in a case of valproic-acid-related hyperammonemic coma

et al. 2004

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Magnetic resonance (MR) multimodality evoked potentials (MEPs) and clinical findings were correlated in a 47-year-old epileptic man in whom parenteral valproic acid (VPA) therapy induced severe comatose hyperammonemic encephalopathy without biological signs of hepatotoxicity (or hepatocytic dysfunction). Although the plasma VPA level remained within a normal therapeutic range, the ammoniemia increased to a toxic peak level at 411 micromol/l 24 h after symptom onset, requiring VPA therapy discontinuation. Brain MR monitoring demonstrated early cytotoxic edema evolving into delayed vasogenic edema and final brain atrophy. Concomitantly to abnormalities within the brainstem on MR images, an increase in brainstem conduction at MEPs and clinical disturbance of brainstem reflexes were observed at the initial phase of the disease course. Later, the resolution of the MR and MEPs abnormalities paralleled the clinical recovery of the reflexes.

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“…Our previous study established that high‐dose VPA therapy, concomitant use of hepatic enzyme inducers, and concomitant use of topiramate (TPM) were risk factors for an increase of the blood ammonia level in adult patients with epilepsy who were treated with VPA (Yamamoto et al., ). There have also been some reports regarding the risk of hyperammonemia in pediatric patients with epilepsy (Coulter & Allen, ; Batshaw & Brusilow, ; Murphy & Marquardt, ; Ohtani et al., ; Haidukewych et al., ; Laub, ; Iinuma et al., ; Thom et al., ; Kondo et al., ; Altunbaşak et al., ; Sharma et al., ). Verrotti et al.…”

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confidence: 99%

Risk factors for hyperammonemia in pediatric patients with epilepsy

et al. 2013

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SUMMARYPurpose: To identify risk factors for hyperammonemia in pediatric patients with epilepsy. Methods: A total of 2,944 pediatric patients (ages 0-15 years) were classified into the following three groups: a group without drug treatment (n = 445, group I), a group receiving antiepileptic drugs other than valproic acid (VPA) (n = 673, group II), and a VPA-treated group (n = 1,826, group III). Hyperammonemia was defined as a plasma ammonia level exceeding 100 lg/dl with reference to the standard range and previous reports. Key Findings: The mean ammonia level of groups I, II, and III was 36.0, 56.0, and 86.8 lg/dl, respectively, and the incidence of hyperammonemia was 1.6%, 7.7%, and 31.7%, respectively. In each group, the mean ammonia level of patients aged 3 years or younger was significantly higher than that of patients aged 4-15 years. In group II, concomitant use of topiramate and zonisamide were risk factors for hyperammonemia (adjusted odds ratio [OR] 3.9, 95% confidence interval [CI] 1.7-9.2, and OR 3.5, 95% CI 1.9-6.5, respectively). In group III, the ammonia level increased in a VPA dose-dependent manner. At a VPA dose of 30 mg/kg, there was 4.3-fold increase in the incidence of hyperammonemia. The other significant risk factors identified were female gender (OR 1.3, 95% CI 1.0-1.6), symptomatic generalized epilepsy (OR 1.4, 95% CI 1.1-1.8), and the concomitant use of phenytoin (OR 4.7, 95% CI 3.3-6.9), phenobarbital (OR 2.2. 95% CI 1.6-3.2), acetazolamide (OR 6.6, 95% CI 2.5-17.2), topiramate, or zonisamide. Significance: A young age and concomitant use of carbonic anhydrase inhibitors are associated with an increased risk of hyperammonemia regardless of whether the patient is taking VPA. In patients receiving VPA, concomitant use of phenytoin and/or phenobarbital enhances the risk of hyperammonemia. An increase in ammonia can be caused by multiple factors. Our results may help clinicians to avoid problems of hyperammonemia. KEY WORDS: Hyperammonemia, Epilepsy, Children, Risk factor, Valproic acid, Phenytoin.Hyperammonemia is a frequent problem associated with antiepileptic drugs (AEDs) that can lead to vomiting, aggression, ataxia, and exacerbation of seizures. Acute hyperammonemia can also cause cerebral edema and severe brain damage (encephalopathy), whereas chronic hyperammonemia due to metabolic disorders is associated with developmental delay and intellectual disability (Cagnon & Braissant, 2007;Lichter-Konecki, 2008). Among the AEDs, valproic acid (VPA) is recommended as a first-line treatment for generalized epilepsy. Although VPA can cause an increase of the blood ammonia level, VPA therapy is rarely associated with hyperammonemic encephalopathy.The exact relationship between symptoms and the ammonia level remains unclear. Murphy and Marquardt (1982) reported that patients with hyperammonemia not exceeding 240 lg/dl were asymptomatic. In contrast, Coulter and Allen (1981) recommended reducing the VPA dose when the ammonia level exceeded 100 lg/dl. Our data (see later) indicate that hyperammo...

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Asymptomatic Hyperammonemia in Children Treated With Valproic Acid

Cited by 39 publications

References 19 publications

Valproate-induced hyperammonaemic encephalopathy in a neonate: Treatment with carglumic acid

Valproate-induced hyperammonaemic encephalopathy in a neonate: Treatment with carglumic acid

Comparison of clinical, magnetic resonance and evoked potentials data in a case of valproic-acid-related hyperammonemic coma

Risk factors for hyperammonemia in pediatric patients with epilepsy

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