Case Presentation:
We present a 43 year old man with history of neuro‐sarcoidosis resulting in generalized tonic‐clonic seizures and ischemic stroke with residual aphasia and left sided forearm weakness. The patient presented to the emergency department three times over a course of one month, with complaints of nausea, vomiting and new partial seizures, characteristically different from his baseline seizures. At each visit, serum valproate and phenytoin levels were obtained and found normal, phenytoin dose was increased with the presumption that patient was having breakthrough seizures. On his third visit, he had developed worsening nausea, vomiting, a new symptom of waxing and waning confusion, worsening of his expressive aphasia and disturbance of sleep‐wake cycle. Physical exam revealed a hemodynamically stable patient, disoriented to time, place and person with marked aphasia. Anti‐epileptic drug levels were repeated and were again within normal limits. Basic serum chemistry and liver function tests were normal. No infectious etiology was identified. CT scan and subsequent MRI of brain were at baseline with stable neuro‐sarcoidosis associated lesions. On further work‐up serum ammonia level was found elevated (186 micromole/L; normal 11‐32). A presumptive diagnosis of VHE was made and valproic acid was stopped. The patient’s mental status returned to baseline within a period of 24 hours with a corresponding fall in the serum ammonia level. He was discharged home in a stable condition. Of note, our patient had been on valproate therapy since 1998 when he was first diagnosed of epileptic seizures and this was the first time he had symptoms associated with hyperammonemia.
Discussion:
Acute confusional state is a common clinical presentation in hospital medicine, especially in patients with history of epilepsy. Post‐ictal confusion is usually the foremost diagnosis. Valproic acid is a widely used anti‐epileptic agent that has long been associated with hyperammonemia. Most case reports of this rare side effect have been described in context of acute intoxication and there are only a few reports about valproate induced hyperammonemic encephalopathy (VHE) in patients on chronic valproate therapy. No current guideline is available regarding screening and monitoring for hyperammonemia with chronic valproate therapy. The incidence of hyperammonemia with no clinical symptoms on valproate therapy is around 20‐30 %. However, the incidence of VHE is a rare albeit potentially life threatening event.
Conclusions:
VHE is a rare yet potentially life threatening complication as it can precipitate cerebral edema and death. It is reversible if recognized early. . Hospitalists need to be aware of this side effect as this is an important differential of a commonly encountered presentation. Any patient on valproate therapy presenting with either acute confusion or change in the characteristic of baseline seizures should be evaluated for VHE. Studies have revealed no correlation between valproate dose, serum levels and the degree of hyperammonemia.