NASHVILLE, Tennessee ― Focusing on related sleep issues for sufferers with refractory temporal lobe epilepsy (TLE) improves cognition, outcomes of a brand new, double-blind, randomized managed trial counsel.
Examine findings present important enchancment in REM sleep and language scores for sufferers with TLE who took the cholinesterase inhibitor donepezil and higher slow-wave-sleep and reminiscence scores for many who took the sleep help zolpidem.
The outcomes are “intriguing and stunning” and may encourage clinicians to “search for sleep abnormalities” in sufferers with uncontrolled epilepsy, research investigator Garima Shukla, MBBS, MD, DM, professor, Division of Neurology, Division of Medication, Queens College, Kingston, Ontario, Canada, informed Medscape Medical Information.
Daytime sleepiness could possibly be a purple flag in these sufferers, though it may imply they simply have treatable sleep apnea, mentioned Shukla. “But when they’ve very poor slow-wave sleep, we may strive rising its proportion by prescribing zolpidem.”
The findings have been offered right here on the American Epilepsy Society (AES) 2022 Annual Assembly.
Sleep, Cognitive Disturbances Frequent
Sleep disturbances and cognitive disturbances are widespread amongst sufferers with TLE. Government perform is affected in virtually all sufferers with refractory epilepsy, and it is “tremendous widespread” that TLE sufferers have reminiscence disturbances, mentioned Shukla.
The research included 108 sufferers with refractory TLE who have been awaiting surgical procedure. The sufferers, who had no extreme comorbidities, have been randomly assigned to 3 teams; the ultimate quantity in every group was 36.
Sufferers in group 1 obtained donepezil 10 mg within the morning and a placebo at evening. (Donepezil is used to deal with reminiscence loss related to Alzheimer’s illness.)
These in group 2 obtained a placebo within the morning and zolpidem 6.25 mg at evening. Group 3 sufferers obtained a placebo within the morning and once more at evening.
The imply age of the sufferers was 25.4, 27.1 and 27.6 years, and the share of males was 63.8%, 72.2%, and 63.8% in teams 1, 2, and three, respectively.
In all teams, sufferers had been experiencing about three seizures per thirty days. The median variety of antiseizure medicines was two in group 1 and three in each teams 2 and three.
Researchers evaluated sleep utilizing the Pittsburgh Sleep High quality Index, the Epsworth Sleepiness Scale, and video polysomnography and electroencephalography.
To evaluate government perform, they used the Path A & B, Stroop, and ahead and backward Digit Span assessments. For reminiscence, they used the Weschler Reminiscence Scale, and for language, the Western Aphasia Battery. They performed follow-up evaluations at 6 months.
The outcomes confirmed important enchancment within the proportion of speedy eye motion (REM) sleep in group 1 (from 14.81 at baseline to 18.21 at 6 months). On this group, the variety of sufferers whose REM sleep proportion was lower than 15 dropped considerably ― from 29 (of 36) to 10.
In group 2, sleep onset latency considerably improved, and the share of N3 (slow-wave) sleep stage elevated considerably ― from 25.27 to twenty-eight.74.
Concerning cognitive outcomes, backward Digit Span was considerably improved for sufferers in group 1. On this group, there was additionally a major discount within the time taken for Stroop A take a look at, and there was important enchancment in language.
In group 2, there was a major enchancment in verbal and visible reminiscence scores. There have been no important adjustments in group 3.
The rise in REM sleep proportion in group 1 strongly correlated with elevated language and government perform scores. Equally, in group 2, the rise in N3 sleep proportion strongly correlated with a rise in verbal reminiscence scores.
On the idea of those observations, giving a small dose of zolpidem to a affected person with “acceptable” REM sleep however little or no slow-wave sleep might enhance the affected person’s non-REM sleep, mentioned Shukla. “By enhancing non-REM sleep proportion, we’ll presumably assist reminiscence consolidation.”
Shukla sees this research as “a stepping-stone” to bigger, multicenter trials testing “the impact of zolpidem via its affect on enhancing non-REM sleep proportion consolidation and its affect on reminiscence.”
This concept veers considerably from the normal concept that REM sleep performs a better function in reminiscence consolidation, she mentioned. “We really discovered it correlates very nicely with language, which we have now additionally seen in a few of our anecdotal case studies.”
Sufferers whose language scores are very poor are “the inhabitants I’d choose to focus on REM sleep via donepezil,” mentioned Shukla.
Commenting for Medscape Medical Information, Daniel Goldenholz, MD, PhD, assistant professor, Harvard Beth Israel Deaconess Medical Heart, praised the research design.
“It permits for comparability between completely different therapies, in addition to a placebo management group,” mentioned Goldenholz, who added, “There seems to be good follow-up” as nicely.
The truth that remedy might present some cognitive profit for sufferers with TLE is “very encouraging,” he mentioned.
He famous many sufferers with TLE complain of reminiscence or language issues. “So, this can be a main concern.”
Nevertheless, he cautioned about unintended effects. “Placing all temporal-lobe epilepsy sufferers who say that they’ve reminiscence issues or language issues on these medicines may have some critical penalties.”
The research was funded by a Division of Well being Analysis grant from the federal government of India. Goldenholz is on the advisory board for epilepsy AI, Eyzs and Magic Leap.
American Epilepsy Society (AES) 2022 Annual Assembly: Summary 1.229. Offered December 3, 2022.
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