Valproate: An Unusual Cause of Hyperammonemic Encephalopathy

Abstract

Heuristics, or mental shortcuts, are an invaluable resource for quickly making diagnoses and treatment plans for the busy clinician. However, this can sometimes result in incorrect diagnoses unless the clinician actively reassesses his initial diagnosis. We highlight this concept in a patient who presented to the hospital with altered mental status. The patient was initially diagnosed with encephalopathy due to cystitis, but later found to have hyperammonemia due to valproic acid (VPA) toxicity. A 59-year-old female with COPD, hypertension, and bipolar disorder was admitted from a correctional facility with confusion, weakness and nausea. She displayed no signs of encephalopathy prior to her incarceration, which was one month before admission. History could not be obtained as the patient was somnolent. Physical examination revealed generalized abdominal tenderness and asterixis without other stigmata of liver disease. Significant lab results included leukocytosis of 16,000, acute kidney injury with a creatinine of 1.9, and an ALT elevation of 47. A head CT scan was unremarkable and a urinalysis showed pyuria. The patient was treated with IV antibiotics and hydration with a presumptive diagnosis of encephalopathy secondary to cystitis. Further investigation included TSH, ammonia, vitamin B12, RPR, HIV, and urine toxicity screens, of which an elevated ammonia level of 170 umol/L resulted. Given the encephalopathy, hyperammonemia and asterixis, hepatic dysfunction was suspected, but remaining LFTs were within normal range with negative hepatitis serologies. Furthermore, an abdominal USG noted hepatic steatosis without evidence of cirrhosis. It was later found that her dose of VPA was increased two months ago. Of note, the VPA level was within normal limits. VPA was then discontinued and lactulose and L-carnitine were initiated with gradual improvement of her encephalopathy, asterixis, somnolence, and tremor over two days. VPA may cause elevated plasma ammonia resulting in encephalopathy, asterixis and tremor. These symptoms may occur with normal levels mainly seen in chronic therapy, thus creating a misleading presentation suggestive of hepatic dysfunction despite normal LFTs leading to an extensive, yet unnecessary workup. Therefore, clinicians should be aware of these side effects and monitor serum ammonia and VPA levels in patients who present with unexplained encephalopathy or tremors while on VPA.