BOSTON—Duration of epilepsy before treatment has no predictive value for epilepsy remission or intractability, reported Dr. Elson So, MD, at the 63rd Annual Meeting of the American Epilepsy Society. However, a number of historical clinical biomarkers, such as the time required to achieve seizure control, the number of medications tried to control seizures, the type of epilepsy (idiopathic/cryptogenic vs symptomatic), and age at seizure onset do have an impact on remission and intractability rates, according to Dr. So, Professor of Neurology at the Mayo Clinic in Rochester, Minnesota.
Remission Rates in Epilepsy
About 75% of patients with epilepsy achieve one-year remission within two to four years of antiepileptic drug (AED) treatment. “A majority of patients who are going to be seizure free will become seizure free within 13 months of starting treatment,” Dr. So said. “Many studies show that early treatment response is an important feature of those patients who are eventually going to be seizure free.”
One study found that the chance of becoming seizure free in the long term is higher when seizures could be controlled within one to four years of AED treatment. However, a separate study found that the duration between the first seizure and treatment does not affect the chance of remission.
“How soon you start the treatment doesn’t seem to have as much impact on eventual remission as how easy it is for you to control seizures,” said Dr. So. “I’m not advocating for delaying treatment. We all know that we treat seizures promptly for several reasons, many of them being the immediate negative consequences of seizure attacks.”
Dr. So reported that if only one or two seizures occurred within six months of the index seizure, the probability of maintaining a one-year remission is much higher than if more seizures had occurred. Another finding indicated that the chance of seizure freedom is better for those who required only one AED to gain the initial seizure control.
A review study found a number of consistent historical biomarkers for epilepsy remission, including idiopathic epilepsy, normal physical examination, and early response to treatment, according to Dr. So. “Are there any EEG biomarkers for remission?” he questioned. “I’m sorry to say, none.”
Intractability and Epilepsy
“We know that 10% of children may develop medical intractability in the first two years following seizure onset, [and] 10% to 25% in the long term,” Dr. So stated. “For seizures that are not controlled within two years of starting treatment, there is a 50% reduced chance of long-term remission.”
One study found that the time it takes to achieve early seizure control has a very important effect on long-term remission. Those who take a longer time to achieve seizure control following AED initiation will have a higher chance of epilepsy intractability in the long term. “Those who have taken five or more years to gain initial seizure control had a much higher probability of drug resistance in the long run than those who had taken a shorter time to achieve the initial seizure control,” Dr. So reported.
Pretreatment seizure frequency was observed in another study to be an important risk factor for uncontrolled epilepsy. A high number of pretreatment seizures is associated with greater risk for uncontrolled epilepsy. “This is one of the reasons we should not delay treatment,” Dr. So commented.
A separate study found that the presence of an early epilepsy risk factor (ie, neonatal seizures, febrile seizures, head injury resulting in at least 30 minutes of loss of consciousness or meningoencephaltitis) is predictive of intractability two years after temporal lobe epilepsy onset. The study also showed that the presence of MRI temporal lobe abnormality is associated with four times higher risk for epilepsy intractability. In another study, IQ was an important factor, as the proportion of patients with uncontrolled seizures was higher in those with an IQ of less than 70 than in those with an IQ of higher than 70.
“But most importantly, failure of the first AED to control temporal lobe seizures is associated with 94 times greater risk for epilepsy intractability than successful use of the first AED,” Dr. So stated. “Furthermore, Dlugos and colleagues found that the positive predictive value of having failed the first AED for intractability is about 90%. The negative predictive value of this factor is about 95%. Either the absence or presence of this factor has a high clinical value.”
In one study, focal EEG slowing was found to have some predictive value for epilepsy intractability (rate ratio [RR], 2.3). Other risk factors identified in the study were cryptogenic or symptomatic generalized epilepsy syndrome (RR, 3), higher initial seizure frequency (RR, 1.4) and neonatal or acutely provoked status epilepticus (RR, 5.9).