Tonic-clonic seizure following combined treatment of mycophenolate mofetil and acyclovir

Abstract

Dear Editor, We have read about the anti-herpetic synergistic effect of combined treatment with mycophenolate mofetil (MMF) and acyclovir in patients with herpetic eye disease [1]. However, we encountered unexpected neuronal toxicity with this combination. A 55-year-old man was brought to the emergency department on the day of his discharge after he experienced a generalized tonic–clonic seizure. Two days before, he had undergone penetrating keratoplasty on his left eye. Fortunately, he had the seizure just in front of the hospital while he was on his way home. His vital signs were stable except mild hypertension; 157/82 mmHg. He had two additional generalized tonic–clonic seizures with loss of consciousness, as documented by a neurologist at the emergency department. The first documented seizure spontaneously subsided, but the second documented attack lasted for 1 min, and subsided after the neurologist ordered intravenous administration of lorazepam 5 mg. A computed tomography scan of the head showed no evidence of acute intracranial involvement. An electroencephalogram did not show epileptiform discharge in his brain. He denied history of seizure or general medical illness, except his eye problem. He had had recurrent herpetic keratitis in both eyes and subsequent opacity in his left eye. Three years before, he had undergone penetrating keratoplasty, but had experienced graft rejection after 6 months. One year before, he had undergone a second penetrating keratoplasty, but had experienced graft rejection again after 3 months. This operation was his third penetrating keratoplasty. Before the first penetrating keratoplasty, he had been treated with oral acyclovir (400 mg b.i.d.) for 2 months. After the first penetrating keratoplasty, he had continued with oral acyclovir and started an oral steroid (30 mg q.d.) for 1 month. After tapering of the oral steroid therapy, he continued oral acyclovir until rejection. After the second penetrating keratoplasty, he had been treated with oral acyclovir and an oral steroid, and the oral steroid was replaced with oral cyclosporine (100 mg b.i.d.). In the intervening period, he was treated with both oral steroid and cyclosporine with acyclovir. After the third penetrating keratoplasty, he had been treated with oral acyclovir (400 mg b.i.d.) and oral steroid (30mg q.d.), andMMF 1000mg (b.i.d.). On the second day after initiation of this combination, he had three sequential generalized tonic–clonic seizures with loss of consciousness. The patient had not experienced seizure attacks with any of the other previous combinations. After discontinuation ofMMF, he did not suffer anymore seizures, and did not require any anti-epileptic medication. However, he experienced graft rejection in his left eye again. In this patient, MMF or combination ofMMF and acyclovir or oral steroid must have caused the seizures, because he did not suffer from seizures before initiation or after discontinuation of MMF combined with oral acyclovir and steroid or even cyclosporine. The neurotoxicity of immunosuppressant drugs has been reported, especially in anti-metabolites [2] such as methotrexate [3]. No study has reported neurotoxicity of MMF [4, 5]; in fact there was a report of improvement of K. M. Lee :M. K. Kim :W. R. Wee : J.-h. Lee Department of Ophthalmology, Seoul National University College of Medicine, Seoul, South Korea