In a startling case, a 79-year-old woman developed severe life-threatening symptoms leading to hyperammonemic encephalopathy after being treated with sodium valproate, a medication commonly used for managing epilepsy. The case report, detailed in the “Rinsho Shinkeigaku” journal (Clinical Neurology), serves as a stark reminder of the importance of monitoring patients on valproic acid monotherapy for signs of hyperammonemia, even in the absence of other predisposing factors.
According to the report, published on May 28, 2019, the patient, diagnosed with epilepsy following multiple episodes of loss of consciousness, began treatment with 800 mg of sustained-release sodium valproate in June 2016. Within days, she experienced a loss of appetite, followed by a disturbance of consciousness, and was subsequently admitted to the hospital.
Upon examination, her serum valproic acid (VPA) concentration was found to be at 128.3 μg/ml, while her serum ammonia level was alarmingly high at 404 μmol/l. These symptoms and laboratory findings were consistent with valproic acid-induced hyperammonemic encephalopathy, a rare but severe condition that can develop in patients receiving VPA therapy.
The patient’s condition escalated rapidly, resulting in cerebral edema and status epilepticus, indicating uncontrolled seizures. Despite aggressive interventions, including continuous hemodiafiltration and administration of levocarnitine for suspected systemic carnitine deficiency, the patient was left with severe neurological dysfunction.
The case was brought to light by Dr. Hidetada Yamada and his colleagues from the Department of Neurology at Hiroshima Prefectural Hospital, along with the Department of Neurology at Hiroshima University Hospital. Their findings illustrate a critical medical oversight: the need for stringent monitoring of ammonia levels in patients treated with VPA, even those on monotherapy without other medications that could influence serum ammonia levels.
Valproic acid is widely utilized in the treatment of generalized epilepsy due to its effectiveness in controlling seizures. However, VPA-induced hyperammonemic encephalopathy is an adverse event characterized by elevated blood ammonia levels, which can result in altered mental status, cerebral edema, and ultimately severe neurological damage or death.
The pathophysiology behind VPA-induced encephalopathy is not fully understood, but it is believed to involve a disruption in the urea cycle as well as secondary carnitine deficiency. VPA’s interference with the metabolism can lead to the accumulation of ammonia in the blood, crossing the blood-brain barrier and causing encephalopathy.
Numerous factors can predispose someone to develop hyperammonemic encephalopathy while on VPA therapy, including genetic mutations affecting the urea cycle, liver dysfunction, and concomitant medications that affect carnitine metabolism or increase ammonia levels. In this case, however, the patient developed the condition while on VPA monotherapy.
The case report, accessible via the Digital Object Identifier (DOI) 10.5692/clinicalneurol.cn-001254, serves as a critical reminder for healthcare providers to maintain vigilance for hyperammonemia symptoms in patients taking valproic acid. Rapid identification and management of this adverse reaction are imperative to prevent irreversible neurological damage or death.
In response to this case and similar reports, recommendations for healthcare professionals include monitoring ammonia levels before initiating valproic acid therapy and conducting regular follow-ups, particularly in elderly patients or those with underlying metabolic susceptibilities.
The report’s authors stress the importance of considering alternative antiepileptic medications in patients with known risk factors for hyperammonemia. Additionally, supplementation with carnitine, a compound involved in fatty acid metabolism and potentially depleted by VPA, may also be recommended, particularly in patients showing signs of hyperammonemic encephalopathy.
References
1. Verrotti, A., Trotta, D., Morgese, G., & Chiarelli, F. (2002). Valproate-induced hyperammonemic encephalopathy. Metabolic Brain Disease, 17(4), 367-373. DOI: 10.1023/A:1021918104123
2. Carr, R. V., Winesett, S. P., & Menkes, J. H. (1982). Valproic acid-induced hyperammonemic encephalopathy successfully treated with peritoneal dialysis. Pediatric Neurology, 76(5), 690–692. DOI: 10.1016/0009-9236(92)90066-B
3. Lheureux, P. E. R., & Hantson, P. (2009). Carnitine in the treatment of valproic acid-induced toxicity. Clinical Toxicology, 47(2), 101-111. DOI: 10.1080/15563650902752376
4. Zaccara, G., Franciotta, D., Perucca, E. (2007). Idiosyncratic adverse reactions to antiepileptic drugs. Epilepsia, 48(7), 1223-1244. DOI: 10.1111/j.1528-1167.2007.01041.x
5. Hamer, H. M., Knake, S., Schomburg, U., & Rosenow, F. (2000). Valproate-induced hyperammonemic encephalopathy in the presence of topiramate. Neurology, 54(1), 230-232. DOI: 10.1212/WNL.54.1.230
Keywords
1. Valproic Acid Side Effects
2. Hyperammonemic Encephalopathy Treatment
3. Epilepsy Drug Complications
4. Ammonia Toxicity From Medication
5. Sodium Valproate Adverse Reactions
This case underscores the delicate balance healthcare providers must maintain when prescribing medications, particularly those with known significant side effects such as valproic acid. Vigilance in monitoring and swift action in response to adverse reactions can make the difference between recovery and enduring neurological deficits.