Northern epilepsy syndrome: clinical course and the effect of medication on seizures

We describe the clinical course and treatment of 19 patients with the Northern epilepsy syndrome, an autosomal recessively inherited epilepsy with associated mental deterioration. The clinical course could be divided into three successive stages. The first stage continued from the onset of epilepsy until puberty. Seizures began at a mean age of 6.6 years and consisted predominantly of generalized tonic-clonic convulsions (GTC) and, transiently, also of complex partial seizures (CPS). Until puberty, seizure frequency increased in most patients from one attack in 1-2 months to one to two attacks weekly. Seizures did not respond to phenytoin (PHT) or carbamazepine (CBZ), were transiently controlled by valproate (VPA) and phenobarbital (PB), but were effectively treated only by clonazepam (CZP). Mental deterioration began 2-5 years after the onset of epilepsy and was most rapid before adulthood, a time when the seizures were also most frequent. The second stage is marked by fewer seizures, further mental deterioration, and less rapid progression. All patients were demented (I.Q. < 70) by age of 30 years. The first signs of motor clumsiness also appeared then. The third stage was one of permanent disability and usually began in middle age. Seizures were few, but the patients were clumsy and had marked equilibrium difficulties.