Mitigating Valproate-Induced Hyperammonemia: A Case Report on the Role and Benefits of Levocarnitine Supplementation

Case Diagnosis: Valproate-Induced Hyperammonemia

Case Description or Program Description: Two patients, both with a history of traumatic brain injury (TBI), were admitted to rehab on valproate. Patient A is a 54-year-old man who required valproate for agitation and Patient B is a 72-year-old man who required valproate for seizure management. Both patients developed hyperammonemia in the setting of valproate use and required levocarnitine, however both remained asymptomatic and had no worsening mentation or concern for toxic metabolic encephalopathy.

Setting: Acute inpatient rehabilitation.

Assessment/Results: Patient A’s agitation gradually improved, resulting in the discontinuation of both valproate and levocarnitine to reduce polypharmacy. However, his agitation quickly returned, necessitating discharge on both valproate and levocarnitine. Patient B, however, had an increase in his ammonia levels from 55 to 123 micromol/L overnight. The sudden increase raised concern for impending mental deterioration, encephalopathy, or nephrotoxicity. Patient B was ultimately placed on lactulose and had his valproate switched to lacosamide, after which his ammonia stabilized and he was able to be discharged without levocarnitine.

Discussion (relevance): Valproate is frequently used in TBI patients, so it is important to note that it can increase ammonia levels by disrupting the urea cycle via the inhibition of N-acetyl glutamate. Hyperammonemia in patients without hepatic dysfunction is often asymptomatic but can become neurotoxic at high levels, potentially leading to valproate-induced hyperammonemic encephalopathy (VHE). Levocarnitine can be beneficial through its proposed mechanism of increasing levels of N-acetyl glutamate.

Conclusions: Ammonia levels should be monitored for patients on valproate given its potential neurotoxicity in patients with preexisting TBIs, and should be considered as a reason for mental status decline, regardless of whether there is concurrent liver disease. Lactulose has historically been used as a medication to stimulate ammonia release via defecation, but levocarnitine may offer an alternative for patients where lactulose is contraindicated or with refractory hyperammonemia.