New AAN/AES Guideline on First Unprovoked Seizure in Adults
They classified unprovoked seizures into two broad categories: a seizure of unknown etiology or a seizure in relation to a demonstrated pre-existing brain legion or progressive central nervous system disorder. They identified two prognostic class I and 8 prognostic class II studies addressing the probability than an adult with an unprovoked first seizure would have recurrent seizure.
The analysis showed that the cumulative incidence of seizure recurrence increases over time, with most occurring within the first 1 to 2 years after the initial seizure and the greatest risk in the first year — for example 32% at 1 year and just 46% by 5 years.
The risk for seizure recurrence about doubles under certain circumstances. For example, a prior brain insult such as a seizure was associated with an increased relative rate of seizure recurrence at 1 to 5 years of 2.55 (95% confidence interval [CI], 1.44 – 4.51) compared with that in patients with seizures of unknown cause.
Strong evidence also suggests that having an EEG showing signs of epilepsy is associated with increased risk. The relative rate increase for seizure recurrence at 1 to 5 years was 2.16 (95% CI, 1.07 – 4.38) compared with patients without such EEG abnormalities.
There was moderate evidence for other factors increasing the recurrence risk. Having abnormal brain imaging results had a hazard ratio at 1 to 4 years of 2.44 (95% CI, 1.09 – 5.44) compared with not having imaging abnormalities. And having a nocturnal seizure had an odds ratio at 1 to 4 years of 2.1 (95% CI, 1.0 – 4.3) compared with a seizure while awake.
“If the seizure has a focal onset, that already says that there may be some faulty wiring, so if you don’t see any focal onset; the EEG is completely normal; and the MRI is completely normal, in those situations the likelihood of a recurrent seizure goes down to about 20% or 25%,”
Many people would accept that 25% risk but others would consider it too high, she said. She pointed out that if a patient decides to start medication, and comes off that medication later, they might still face that 25% risk.
However, she pointed out that mediations today are less “toxic” than they were in the past. “It used to be a really big decision to go on a medication; now, the good news is that we have medications that are really well tolerated.”
But unfortunately these newer medications still don’t change the underlying disease. “They treat the symptoms, which in many cases is just as good. If you can take a pill every day and not have seizures.”
The review found moderate evidence that immediate treatment can lower the risk for another seizure within the first 2 years after a first unprovoked seizure.
There was an absolute risk reduction in seizure recurrence of 35% (95% CI, 23% – 46%) for immediate vs delayed AED treatment in pooled 2-year data in adults presenting with an unprovoked first seizure.
As for seizure remission over the longer term — over 3 years — the review showed that compared with delaying treatment until a second seizure occurs, immediate AED treatment is unlikely to improve the chance of attaining sustained seizure remission.
While seizure recurrence can cause such serious psychological and social consequences as loss of driving privileges and limitations on employment, one controlled class II study comparing immediate AED treatment with treatment deferred until after a seizure recurrence found no significant difference in standard 2-year quality-of-life measures.
The new guideline comes at a time when the current standard definition of epilepsy is changing. The International League Against Epilepsy has proposed the definition be expanded to encompass people with an unprovoked seizure and at least a 60% risk for seizure recurrence over the next 10 years.
“It used to be that you needed to have two seizures to have epilepsy,” said Dr French. “Many clinicians have been trained that a single seizure is not epilepsy and therefore should not be treated.”
According to the guideline, the incidence of adverse events from AEDs in adults initially treated with a single AED for an unprovoked first seizure is reportedly 7% to 31%. The adverse events appear to be mild and many are reversible when doses are lowered or patients are switched to another AED. At the time of the studies, AEDs included phenytoin, phenobarbital, carbamazepine, valproic acid, and lamotrigine.
The authors pointed out that the newer AEDs may have fewer and different adverse events.
They stressed the importance of patients appreciating how long they may need to be receiving an AED and the risks of AED discontinuation.
The guideline was endorsed by the American Neurological Association and the World Federation of Neurology. A 2007 practice guideline addressed the evaluation of an unprovoked first seizure in adults.
Because neurologists are not always the first clinicians to see patients following a first unprovoked seizure, the new guideline “needs to be promoted and available to all physicians,” including primary care and emergency department doctors, said Dr Krumboltz.
Dr French stressed that a first seizure may not be a convulsion but could be small spells of confusion or strong feelings of déjà vu that can often be missed. She told the story of a 50-year-old women presenting with confusion and feelings of déjà vu. She was sent to an internist, a psychiatrist, and finally a neurologist before MRI found a brain tumor.
An estimated 150,000 adults present annually with an unprovoked first seizure in the United States.
Marijuana Compound May Reduce Seizures in Severe Epilepsy
A new study shows a mean reduction in seizures of over 50% in 3 months among some patients with epilepsy taking cannabidiol (CBD).
Results of an open-label, multicenter trial of a liquid product that is 99% cannabidiol (Epidiolex; GW Pharmaceuticals), the major nonpsychoactive ingredient in marijuana, showed that treatment provided seizure relief in children with Dravet syndrome and Lennox-Gastaut syndrome (LGS) who had been resistant to at least eight antiepileptic drugs.
“I think this is an important study,” and it’s “definitely the largest” study of a pure medical marijuana product, commented lead investigator Orrin Devinsky, MD, director, New York University (NYU) Epilepsy Center, and professor, neurology, NYU. “It looks very, very promising but until we get blinded data, we have to be humble,” he said.
The full results will be presented next week during the American Academy of Neurology (AAN) 67th Annual Meeting.
CBD is a component of Cannabis sativa with anticonvulsant activity in preclinical models of epilepsy, independent of activity at known endogenous cannabinoid receptors, the authors write. Ten centers have independent US Food and Drug Administration (FDA)–approved open-label Expanded Access Programs and have treated children and young adults with treatment-resistant epilepsies using pure CBD.
Data have been collected on demographic characteristics, seizure counts, and safety through case report forms and tabulated in this series of open-label trials, the authors note. Eligibility was determined and documented in protocols specific to each site after FDA and institutional review board review.
This new analysis included patients aged 2 to 26 years (mean age, about 10.5 years) with uncontrolled seizures enrolled at NYU, Children’s Hospital of Philadelphia (CHOP), and eight other centers across the United States. Patients with Dravet syndrome and LGS represented two of the larger epilepsy groups, although the study also included patients with over 10 other conditions, some genetically related.
Study patients had tried an average of more than eight antiseizure medications and experienced an average of two seizures per day.
The children took CBD in liquid form in a daily dose titrated up to 25 mg per kg.
Data were collected on 213 patients with treatment-resistant epilepsies for safety evaluation. One hundred twenty-three patients had at least 12 weeks of continuous exposure and were included in efficacy calculations.
At month 3, the median percentage reduction in total seizures (convulsive and nonconvulsive) among 123 patients was 48% and the responder rate (50% or greater reduction) was 48%. Seizure freedom was seen in 10% of these patients.
In 93 patients with month 4 data, the median percentage reduction in seizures was 52% and the responder rate was 52%.