Epilepsy Q&A: Answers to 6 Not-So-Easy Questions

Clinicians face numerous challenges in epilepsy management: determining whether seizures are partial or generalized, choosing antiepileptic drugs, identifying surgery candidates, treating psychiatric comorbidities, and providing effective patient education.

However, help in meeting those challenges comes from new research findings almost on a daily basis.

Find the latest epilepsy developments on the pages that follow and test your knowledge by answering these not-so-easy questions.

Please turn the page for Question 1.

1: What Are the First Seizure Clinical Variables and Risk?

• A new guideline on how to treat a first seizure released by the American Academy of Neurology and the American Epilepsy Society could change the approach doctors take in treating a first seizure.

• Epilepsy is defined as 1 or more seizures with a high likelihood of recurrence, not resulting from another immediately triggering cause, such as low blood sugar, according to The International League Against Epilepsy.

• Taking epilepsy drugs immediately after a first seizure may reduce the risk of having another seizure, the guideline found.

• The decision to treat after a first seizure is complex because doctors must consider the risks and benefits for each patient.

• The guideline stated that adults with an unprovoked first seizure should be informed that their seizure recurrence risk is greatest early, within the first 2 years.

• The guideline noted that patients should be advised that the risk of antiepileptic drug adverse events may range from 7% to 31% and that they probably are predominantly mild and reversible.

Question 1:

Q: According to the AAN/AES guideline, what clinical variables are associated with increased seizure recurrence risk?

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A: The variables associated with increased seizure recurrence risk include a prior brain insult, an EEG with epileptiform abnormalities, a significant brain-imaging abnormality, and a nocturnal seizure.

2: What Matters to Children Who Have Epilepsy?

• Canadian researchers studied child mental health, parental support, and social support of children with epilepsy as they relate to quality of life (QOL). The primary outcome of child-reported QOL was measured using the Child Epilepsy QOL Questionnaire.

• From the child's perspective, epilepsy-specific QOL is strongly related to his or her mental health and social support but not to seizures.

• Child mental health and peer support exhibit direct associations with QOL. Parental support has both direct and indirect associations.

• Estimated verbal intelligence exerts its strongest association with QOL through mental health.

• Seizure status exhibits a weak relationship to QOL only through mental health.

Question 2:

In the assessment of QOL in children with epilepsy aged 8 to 14 years, what should be the areas of focus?

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A: Mental health and social support should be the areas of focus in assessment of children with epilepsy. Controlling seizures is insufficient care.

3: What’s Up With Epilepsy Drugs?

• Eslicarbazepine, ezogabine, and parampanel are 3 recent entries into the medical armamentarium for treating epilepsy.

• “Blue person syndrome” has been seen with ezogabine. Up to 6% of study patients taking this drug developed a bluish hue to their lips, fingernail beds, and retinas. Because of this adverse effect, ezogabine is reserved for intractable epilepsy cases.

• Eslicarbazepine appears to be a useful and safe medication.

• Parampanel carries a blackbox warning from the FDA because of possible neuropsychiatric adverse events, including aggression, hostility, irritability, and even homicidal thoughts.

• Most antiepileptic drugs are similar in efficacy. Initial treatment should be based on the seizure syndrome; if unknown, then seizure type.

• If seizures are mixed or generalized, consider lamotrigine, levetiracetam, topiramate, zonisamide, clobazam, or valproic acid.

Question 3:

Q: What are the most dangerous adverse effects of valproic acid?

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A: Valproic acid has adverse effects on the unborn child in women who are of childbearing age and not using effective contraceptive therapy.

4: Detect Attention Problems in Children With Epilepsy?

• The rate of attention-deficit/hyperactivity disorder (ADHD) is higher in children with epilepsy (28% to 70%) than in typically developing children (5% to 10%).

• Because attention is multidimensional, researchers aimed to characterize the profile of attention difficulties in children with epilepsy.

• The epilepsy group performed worse than the typically developing group on timed and complex attention aspects of attention. Performance on simple visual and simple auditory attention tasks was comparable.

• Children with epilepsy were 12 times as likely as typically developing children to have clinically elevated symptoms of inattention as rated by parents, although ratings were a weak predictor of attention performance.

• The attention problems in pediatric epilepsy may be under-recognized.

• Children with epilepsy had difficulty with complex attention and rapid response, not simple attention. They may not exhibit difficulty until later in primary school when demands increase.

Question 4:

Q: Because parent report with standard ADHD screening tools may under-detect attention difficulties in children with epilepsy, what alternative is recommended?

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A: Monitoring through direct neuropsychological performance is recommended to detect attention difficulties in children with epilepsy.

5: What Adverse Effects of Cannabidiol Treatment?

• A medicinal liquid form of marijuana created with cannabidiol shows promise as a treatment for children with severe epilepsy who are refractory to other treatments.

• In preclinical models of epilepsy, cannabidiol showed anticonvulsant activity independent of activity at known endogenous cannabinoid receptors.

• Ten centers have independent, FDA-approved open-label Expanded Access Programs and have treated children and young adults who have treatment-resistant epilepsies with pure cannabidiol.

• Etiologies included Dravet and Lennox-Gastaut syndromes (LGS) and more than 10 other conditions.

• The number of seizures decreased by an average of 54% (Dravet syndrome, by 53%; LGS, a 55% reduction in the number of atonic seizures).

• Cannabidiol showed reductions in seizure frequency across multiple drug-resistant epilepsy syndromes and seizure types and was generally well tolerated.

Question 5:

Q: What are the most likely adverse effects with the use of cannabidiol to treat children with severe epilepsy?

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A: Adverse effects in children with severe epilepsy treated with cannabidiol include drowsiness, diarrhea, tiredness, and decreased appetite.

6: What Risk Factors for Autism Spectrum Disorders in Children With Infantile Spasms?

• Infantile spasms are associated with autism spectrum disorders in up to 35% of cases.

• In a post hoc analysis of their randomized control trial, researchers tried to determine whether rapid diagnosis and treatment of infantile spasms could limit the incidence of ASD while identifying risk factors related to ASD outcome.

• ASD was observed only in children who had symptomatic infantile spasms.

• Early diagnosis and treatment did not prevent ASD as an outcome of infantile spasms.

• Patients at risk for ASD could be identified early and could benefit from early intervention to improve their long-term outcome.

Question 6:

Q: What are other clinical risk factors for autism spectrum disorders in children with infantile spasms?

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A: Other clinical risk factors for autism spectrum disorders in children with infantile spasms include chronic frontotemporal epileptic activity and being of non-white origin.