Cognitive Outcomes From Deep Brain Stimulation for Lennox-Gastaut Syndrome

Patients with LGS experienced reduced epilepsy severity and improved disability following DBS treatment.

Deep brain stimulation (DBS) treatment was associated with reduced epilepsy severity and improved disability among young adults with Lennox-Gastaut syndrome (LGS). However, changes in cognition among these patients were not statistically significance following treatment. These are the findings of a study published in Seizure: European Journal of Epilepsy.

The onset of LGS is seen during childhood. It presents as intractable seizures and is associated with severe cognitive and behavioral impairments. An emerging treatment to reduce seizure frequency for drug-resistant epilepsy, such as LGS, is DBS. For the study, researchers sought to evaluate potential cognitive outcomes from a DBS intervention, which can be difficult to ascertain among patients with baseline cognitive impairments.

The researchers used data from the Electrical Stimulation of the Thalamus in Epilepsy of Lennox-Gastaut phenotype (ESTEL) trial which was conducted at Austin Health in Melbourne, Australia and included 10 treated patients with electrographic seizures and 9 control individuals. After 3 months of blinded treatment, at least a 50% seizure reduction was experienced by 89% of individuals in the stimulation group, compared with no reduction for individuals in the control group (P =.05).

In the new study, researchers analyzed young adults (N=19) with LGS who underwent DBS of the thalamic centromedian nucleus (CM). The caregivers kept a seizure diary for 3 months prior to and 3 months following CM-DBS which was delivered in 2 phases. In phase 1, half of the participants received active and the other half received sham treatment, and in phase 2, all received unblinded active CM-DBS treatment. Cognitive function was evaluated using the National Institute of Health Toolbox Cognition Battery (NIHTB-CB) and adaptive skills were assessed using the Adaptive Behavior Assessment System–Third Edition (ABAS-3) instruments.

Longer periods of follow-up testing may capture further changes in cognition, with previous neuromodulation studies showing additional neuropsychological changes over time.

All participants were aged between 17 and 37 years and 13 were girls or women. At baseline, 6 participants had moderate impairment, 7 had severe impairment, and 7 had profound impairment. A total of 6 participants were non-verbal.

Cognitive, adaptive skills, epilepsy disability, quality of life, and depression scores tended to improve by 11.96%-50% from baseline but were not statistically significant. All but 1 caregiver rated their patient as having improved alertness following CM-DBS.

None of the age-adjusted NIHTB-CH (all P ³.07) or ABAS-3 (all P ³.17) scores improved significantly from baseline to follow-up. Among the NIHTB-CH components, 3 subscores improved (cognitive composite, reading, list sorting), 3 did not change (fluid composite, flanker, card sort), and 4 declined (crystalized composite, picture vocabulary, picture sequence memory, pattern recognition). For the ABAS-3 components, 6 subscores improved (overall raw score, home living, health and safety, leisure, self-care, self-direction), 6 did not change (general adaptive composite, conceptual, social, practical, community, functional academics), and 1 declined (communication).

Significant effects were observed when epilepsy severity and disability scores were converted into dichotomous categories of favorable and unfavorable changes, in which both epilepsy severity (P =.01) and disability (P =.004) improved after CM-DBS.

The major limitation of this study was the amount of missing data, as only 21% of participants completed all follow-up assessments.

Overall, the researchers found that DBS treatment was associated with reduced epilepsy severity and disability among young adults with LGS. When it came to improvements in formal measures of cognition, they were not statistically observed. “Longer periods of follow-up testing may capture further changes in cognition, with previous neuromodulation studies showing additional neuropsychological changes over time,” the researchers hypothesized.

They concluded, “Future clinical trials should be designed to incorporate LGS-specific outcome measures.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

References:

Dalic LJ, Warren AEL, Malpas CB, et al. Cognition, adaptive skills and epilepsy disability/severity in patients with Lennox–Gastaut syndrome undergoing deep brain stimulation for epilepsy in the ESTEL trial. Seizure. 2022;101:67-74. doi:10.1016/j.seizure.2022.07.0