Cementing an Understanding of Managing Seizures in Elders With Epilepsy

Rebecca O'Dwyer, MD

At the 2021 American Epilepsy Society (AES) Annual Meeting, December 3-7, in Chicago, Illinois, an enlightening presentation by Rebecca O’Dwyer, MD, highlighted the frequent and atypical clinical presentations of epilepsy in older adults and ways that clinicians can improve quality of life and seizure control in the later stages of disease.

O’Dwyer, an assistant professor of neurology at Rush University Medical Center, noted that as society continues to age overall, the management of these patients becomes even more crucial. She pointed to recent literature, which has suggested that only about 37% of older patients are accurately diagnosed with epilepsy after symptom onset.

"There’s a lot of older adults who are being labeled with some other neurologic disorder, and in fact, they actually have epilepsy. Why is this? Why is this such a problem?" she said. "Some of it is just lucid awareness. Again, there is public perception that epilepsy is something that occurs in younger adults or children and that when you come to a certain age you cannot have epilepsy."

She went on to discuss the differences in clinical manifestations of seizures for this age group, adding that standard tools like electroencephalograms (EEGs) used for diagnosis are known to be less sensitive in patients aged 65 years and older. Seizures can also be more subtle for older patients and thus may be missed more often by family members or other medical providers. O’Dwyer explained that her experiences with patients in her clinic made her recognize the importance of taking a detailed history of stereotypical behaviors that may not bring the seizure into traditional sense.

READ MORE: Ganaxolone Associated With Decreased Seizure Frequency in Patients With CDD, LGS

Other potential causes that can be misdiagnosed as epilepsy include syncope, atrial fibrillation, transient ischemic attack, and transient global amnesia, among many others, O’Dwyer mentioned. She stressed that “sometimes when you come to the diagnosis of epilepsy it’s often one of exclusion, rather than one of inclusion. This is where I’ve worked closely with cardiologists and internists to make sure that we rule out other possible causes of these paroxysmal events.”

In older adults, most seizures tend to be the result of an underlying neurologic disorder, and if that disorder remains untreated, it becomes increasingly more difficult to treat the seizures. Stroke, neurodegenerative disorders, tumors, and trauma account for about half of all seizures seen in patients aged 65 years and older. O’Dwyer harped on stroke, which she mentioned is the No. 1 cause of seizures in older adults, while citing a notable study by Lossius et al published in Epilepsia in 2006.

In that study, patients were prospectively assessed 7-8 years after stroke or until death. Among 484 patients with ischemic strokes, post stroke epilepsy developed in 12 (2.5%) and 15 (3.1%) patients during the first year and 7-8 years after stroke, respectively, equating to a prevalence of 3.1%. A multivariate analysis showed that scores of less than 30 at admission on Scandinavian Stroke Scale was a significant predictor for developing post stroke epilepsy (OR, 4.9; P = .004).¹

"On the flip side, when you do diagnose someone older with new onset epilepsy, even in the absence of stroke, you should work them up for a stroke,” O’Dwyer noted. “Because we know that within the first 4 weeks after their first seizure, the likelihood that they could have a stroke is 3 times higher."

The other vague etiologic source for seizures in this older age group were neurodegenerative disorders. During her presentation, O’Dwyer discussed the increased prevalence of seizures in patients with Alzheimer disease (AD) and other dementia-related disorders, such as Lewy body dementia. Literature has shown that while these patients are at a higher risk for epilepsy, low dose antiseizure medications may help improve cognition. “You could say in this age group that epilepsy is actually a curable cause of dementia,” O’Dwyer mentioned.

One notable study, LEV-AD clinical trial (NCT02002819), showed that treatment with levetiracetam (Keppra; UCB Pharma) did not improve cognition in patients with AD; however, a subset of those who had AD with epileptiform activity demonstrated improved performance on tasks of spatial memory and executive function. These patients (n =9) had improvements on the Stroop interference naming subscale (net performance vs placebo, 7.4 points [95% CI, 0.2-14.7 points]; F = 5.54; Cohen f = 0.83; P = .046), whereas those without epileptiform activity showed no change in performance (net difference vs placebo, –0.3 points [95% CI, –4.5 to 3.9 points; P = .88 [P = .04 vs participants with epileptiform activity]).²

O’Dwyer referenced a graphic from her colleagues who work in geriatrics that showed the natural kinds of healthy aging decline in cognitive function over time and how they compare with those of neurodegenerative disorders. If a patient has underlying dementia and they take an initial hit, their cognitive starts to decline. Once a patient takes a second hit, or seizure, as an epileptologist, there are ways to help maintain a positive trajectory and ensure their cognition does not drop off, she said.

The amount of cognitive reserve, and several other factors, including exposure to other substances, renal function, liver function, use of drugs or alcohol, nutritional status, and more, all are taken into consideration when managing older patients. The problem with antiseizure medications as O’Dwyer noted, is the adverse effects.

"The common [adverse] effects that we see in the elderly that are susceptible to the [adverse] effects of ASMs are sedation, dizziness, hyponatremia, and cardiac conduction abnormalities,” she said. “When you’re prescribing medications to these older adults, the mantra of going low and slow is what you must adhere by, because they’re exquisitely susceptible to the [adverse] effects. The worst that that can happen is make someone dizzy who’s on a blood thinner and then they fall."

Most of the time, these pivotal trials that help lead to FDA decisions exclude older patients for these adverse effect risks. O’Dwyer stressed that while there has been an increased effort to study these medications in this age group, there remains a need for new clinical trials. She also discussed issues such as polypharmacy, which can be a major challenge in the care of this age group.

"Having a pharmacist is key," she said. "Our pharmacist is able to sit down with them and go through each medication 1 by 1, asking about [adverse] effects, beta indications, and then partnering with their primary care physician or geriatrician to nail down which is necessary and what is not. Because sometimes it’s the antiseizure medication that gets the blame for the sedation or dizziness when it’s not that medication. It could be the 2 unnecessary beta-blockers the patients on."

At the end of her presentation, she reemphasized the challenges in this patient population, mainly from a diagnostic perspective. “I think it is necessary to diagnose accurately because it has huge implications for the patient's prognosis, and, in that process, you need to be able to accurately diagnose the etiology and even in some cases preempt something about etiology of realigning technology. The treatment is difficult. There are lots of nuances, it takes a lot of time and requires a multidisciplinary approach that involves not only the caregiver, but also their primary care physician and other team members like harnessing social worker,” she said.

For more coverage of AES 2021, click here.

REFERENCES

1. Amatniek JC, Hauser WA, DelCastillo-Castaneda C, et al. Incidence and predictors of seizures in patients with Alzheimer disease. Epilepsia. 2006;47(5):867-72. Doi:10.1111/j.1528-1167.2006-00554.

2. Vossel K, Ranasinghe KG, Beagle AJ, et al. Effect of levetiracetam on cognition in patients with Alzheimer disease with and without epileptiform activity. JAMA Neurol. Published online September 27, 2021. doi:10.1001/jamaneurol.2021.3310