Abstracts

Hypothalamic hamartomas (HH) produce a syndrome characterized by epilepsy, precocious puberty and cognitive and behavioral difficulties. Seizures that occur in association with HH are gelastic ([laquo] laughing seizures [raquo]) and more rarely dacrystic ([laquo] crying seizures [raquo]). Complex partial and generalized seizures may also be seen. The seizures are often very difficult to control, requiring polytherapy and surgical procedures.
Topiramate (TPM) is a widely used antiepileptic drug, sometimes very helpful in patients with refractory epilepsy.
We present two patients with HH in whom seizures were worsened by TPM.
: A man born in 1973 was first seen in 1991 with a history of poorly described seizures in early childhood. These seizures stopped in 1986 under carbamazepine (CBZ) monotherapy. There was no precocious puberty and no developmental delay. In 1994, there was a recurrence of complex partial seizures starting with a feeling of anxiety followed by fall. In 1998, a dacrystic seizure was observed by a neurologist. Vigabatrin (VGB) was then added to CBZ. In 2002, a brain MRI revealed a HH. At that moment, the patient was only presenting dacrystic seizures at the frequency of 20 per month. Phenobarbital (PB) was tried without any improvement in seizure frequency. At the end of year 2002, topiramate (150 mg per day) was added to CBZ (1500 mg per day), VGB (1500 mg per day) and PB (150 mg per day). There was a dramatic worsening in seizure frequency with one dacrystic seizure every 10 minutes, as recorded in the video-EEG monitoring unit. In January 2003, TPM was removed with an immediate return to baseline seizure frequency of about 20 seizures per month.
: A boy born in 1992 developped gelastic seizures at the age of 2 years. He was developmentally delayed. There was no precocious puberty. A HH was found at brain MRI. He was treated with valproic acid (VPA) and VGB. In 1996, a partial resection of the HH was surgically performed. Cognitive performances improved but seizure frequency was still several seizures per day. Multiple drug trials were done, including CBZ, lamotrigine, clobazam, and phenytoin. In 1998, he was presenting 6 or 7 seizures per day characterized by laughing followed by clonic movements of the right arm without loss of consciousness. TPM (200 mg per day) was then added to CBZ (1000 mg per day) and generalized seizures appeared at the frequency of 2 per day. A new surgical procedure was performed in 1999. There was a decrease in frequency of generalized seizures but they were still present. In 2000, TPM was stopped and generalized seizures disappeared. Multiple gelastic seizures still occurred daily.
Paradoxical or selective aggravation of seizures has been described for all antiepileptic medications. In these 2 cases of HH, TPM clearly increased seizure frequency in one patient and induced a new seizure type (generalized) in another. TPM may worsen seizures associated with HH.