Gait instability in valproate-treated patients: Call to measure ammonia levels

Abstract

Gait instability due to hyperammonemia and VPA treatment is probably under-recognized in many patients. It can develop when the VPA levels are within the reference range and with normal or slightly elevated liver enzymes.

Uncommon Movement Disorders in Chronic Hepatic Disease with Response to Rifaximin

“…The link between freezing and hyperammonemia has also been described in epileptic patients under valproate treatment. 12 It is conceivable that ammonia is toxic to basal ganglia and its gait networks, particularly in susceptible individuals as ours.…”

Valproic Acid–Associated Hyperammonemia

“…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.…”

Hyperammonemic Encephalopathy Associated with Perampanel: Case Report and Discussion

“…Hyperammonemic encephalopathy (HE) can manifest with variable symptoms ranging from mild to severe such as lethargy, fatigue, seizure exacerbation, altered behavior, insomnia, impaired consciousness, gait instability, and flapping tremor. 1,2,3 Valproate-induced HE has long been described, but can be under-recognized, as mild symptoms can mimic side effects of antiepileptic drugs (AEDs). Hyperammonemia may occur even if serum valproic acid (VPA) levels are within the reference range with normal or slightly elevated liver enzymes serum levels.…”

“…Hyperammonemia may occur even if serum valproic acid (VPA) levels are within the reference range with normal or slightly elevated liver enzymes serum levels. 2,3 Other AEDs have rarely been associated with HE. Adding Levetiracetam (LEV), Phenobarbital (PB), or Topiramate (TPM) to a patient already taking VPA has been reported to trigger HE.…”

“…Proposed mechanisms include inhibition of the hepatic mitochondrial enzyme carbamoyl-phosphate synthase-I, reduction of hepatic carnitine levels, and increased ammonia production in the kidneys. 2,3 TPM may cause increased ammonia levels by inhibition of carbonic anhydrase and cerebral glutamine synthetase. 7 Our patient was on TPM which might have influenced the increase in ammonia levels, nonetheless, he was previously on high-dose TPM for more than a decade without side effects.…”