From Cukurova University Medical Faculty, Department of Pediatric Neurology, Adana, Turkey.

Correspondence to: Faruk Incecik, Toros mah. BariÕ Manço Bulv. Gökçenbay-2 sitesi, B blok, kat: 8, no: 16, Adana, Turkey. E-mail: [email protected]

Manuscript received: March 5, 2007; Initial review completed: June 1, 2007;
Revision accepted: September 25, 2007.

Abstract:

Topiramate is a new antiepileptic drug, used for treatment of partial onset seizure and refractory seizures. Although it is well tolerated in children, some adverse effects including hypohidrosis and hyperthermia are reported. We present two children with epilepsy who were treated with topiramate and developed hypohidrosis and hyperthermia.

Key words: Adverse event, Epilepsy, Hyperthermia, Hypohidrosis, Topiramate.

Topiramate is a new antiepileptic drug, effectively used for partial onset seizures, infantile spasms, and refractory absence(1). Chemically it is a sulfamate-substituted monosaccharide and structurally resembles carbonic anhydrase inhibitors with a weak inhibitory effect in vitro. Topiramate has different mechanisms of action: (i) blockade of voltage-dependent sodium channel in the neuronal membrane, (ii) blockade of kainate type of glutamate receptor, (iii) enhanced g aminobutyric acid (GABA) activity at GABA receptors, and (iv) inhibition of carbonic anhydrase isoenzyme(2).

Topiramate is an effective drug, safe and tolerated well in children. Most common adverse effects are central nervous system related, such as somnolence, confusion, concentration difficulties, and behavioral change. Anorexia, weight loss, nephro-lithiasis, hypohidrosis, and acute glaucoma are also reported(3-5). We report hypohidrosis in two children who were administered topiramate.

Case 1: A five year-old girl was admitted to our clinic with complex partial epilepsy secondary to intracranial hemorrhage. In the past, she was treated with several antiepileptic drugs (AEDs). Because of poor seizure control, the medication was changed to oxcarbazepine and one month later to topiramate. Topiramate was started with initial dose of 1 mg/kg/day, and increased weekly up to 7 mg/kg/day. Topiramate was initially well tolerated, and the patient became seizure-free. Four months after reaching the target dose, she developed intermittent hyperthermia, which disappeared after bathing and cooling. Moreover, her mother noticed the loss of sweat despite high ambient temperature. There were no clinical or laboratory indicators of infection. Sweat test was performed with pilocarpine iontophoresis, however sweat could not be collected. Topiramate was stopped, and the sweat test was repeated after one month. The sweat chloride concentration was 60 mEq/L. Hyperthermia also disappeared after discontinuation of topiramate.

Case 2: A 7-year-old boy was admitted with symptomatic partial epilepsy secondary to phenylketonuria. He was medicated with oxcarbazepine. Because of poor seizure control on oxcarbazepine, topiramate was added in a dose of 1 mg/kg/day, and gradually increased to 6 mg/kg/day. Topiramate was well tolerated, and the child became seizure-free. Six months later, he developed daily hyperthermia, and felt tired after normal exercise. He also reported loss of sweating despite a high ambient temperature. Hyperthermia disappeared, and sweating became normal, after discontinuation of topiramate.

Physiologic sweating is a complex function regulated by the sympathetic system as well as factors and neurotransmitters localized in the periglandular nerves or within human sweat glands(6). In addition, isoenzymes of carbonic anhydrase I and II have been identified in human eccrine sweat glands(7). Although the mechanism of the hyperthermia and hypohidrosis associated with topiramate is not well known, it is speculated that the inhibition of carbonic anhydrase and sweat dysfunction may be responsible for this side effect(2). Topiramate might affect electrolyte channels or transporters in sweat glands as well as in neurons; however it is not clear whether the sodium channels in sweat glands are structurally similar to the neuronal channels. Topiramate also has an inhibitory effect on some carbonic anhydrase isoenzymes (II and IV)(2).

We conclude that topiramate may cause fever and decreased sweating, however these effects are reversible. Children treated with topiramate should be warned regarding these potential adverse effects, to facilitate early withdrawal of drug and symptomatic relief.