Topiramate-induced hyperammonemic encephalopathy in a patient with mental retardation: A case report and review of the literature

Abstract

Hyperammonemia is an uncommon side effect of topiramate (TPM) that has only been reported when it is used as an adjunct to valproate. We report a patient with mental retardation who developed reversible encephalopathy from TPM. Ammonia level was monitored during the course of TPM treatment. This patient had recurring, reversible elevations in serum ammonia levels that coincided with the administration of TPM. To our knowledge, symptomatic hyperammonemia has not been reported to occur with TPM monotherapy.

Hypoxic respiratory failure due to hyperammonemic encephalopathy induced by concurrent use of valproic acid and topiramate, a case report and review of the literature

“…This number could be higher if patients are taking sedatives and other antiepileptic medications like lamotrigine, topiramate and risperidone [ 13 ]. Carnitine deficiency and urea cycle enzyme abnormalities also expose patients for valproate and topiramate induced hyperammonemic encephalopathy [ [2] , [3] , [4] ]. Our patient was on topiramate in addition to the valproic acid but she was not checked for carnitine deficiency or urea cycle enzyme defect.…”

“…This results in decreased beta-oxidation of fatty acids, which in turn results in reduced levels of Acetyl Co-A. This decrease in Acetyl Co-A ultimately disrupts the urea cycle resulting in ammonia accumulation [ 2 ]. The less common mechanism is that valproic acid stimulates kidney tubule glutaminase that subsequently enhances glutamine uptake into renal cortical cell mitochondria.…”

“…The conversion of glutamine ultimately leads to increased ammonia production [ 4 ]. The cytosolic ammonia accumulated within astrocytes and neuronal cells which is conjugated with glutamine by glutamine synthetase is responsible for the oxidative stress and subsequently leads to mitochondrial swelling and cytosolic edema [ 2 , 14 ]. Availability of electroencephalogram recordings may help improve diagnostic validity, but it is unlikely to facilitate differentiation of VPA from other causes of encephalopathy [ 13 ].…”

“…The mainstay of VHE treatment is discontinuation of VPA, which leads to complete recovery in most patients [ [1] , [2] , [3] , [4] ]. We decreased the dose of both valproate and topiramate in our patient but patient's clinical condition didn't improve.…”

“…Valproic acid (VPA) is widely used for the treatment of epilepsy, migraine, and a variety of psychiatric symptoms, including bipolar disorder, borderline personality disorder, and alcohol withdrawal. VPA has been used effectively to reduce agitation and aggression in both acute and post-acute traumatic brain injury patients, as well as a variety of other neuropsychiatric syndromes, including dementia and mental retardation [ [2] , [3] , [4] ]. Valproate is associated with severe idiosyncratic adverse effects, the most notable being valproate-induced hyperammonemic encephalopathy (VHE), which is seen in up to 0.9% of patients taking valproate [ 5 ].…”