Complex executive functions assessed by the trail making test (TMT) part B improve more than those assessed by the TMT part A or digit span backward task during vagus nerve stimulation in patients with drug-resistant epilepsy.

Introduction: There is a paucity of clinical studies examining the long-term effects of vagus nerve stimulation (VNS) on cognition, although a recent study of patients with drug-resistant epilepsy (DRE) treated with VNS therapy demonstrated significant improvement in executive functions as measured by the EpiTrack composite score. The present study aimed to investigate performance variability in three cognitive tests assessing executive functions and working memory in a cohort of DRE patients receiving VNS therapy during a follow-up duration of up to 5 years. Methods: The study included 46 DRE patients who were assessed with the Trail Making Test (TMT) (Parts A and B) and Digit Span Backward (DB) task prior to VNS implantation, 6 months and 12 months after implantation, and yearly thereafter as a part of the clinical VNS protocol. A linear mixed-effects (LME) model was used to analyze changes in test z scores over time, accounting for variations in follow-up duration when predicting changes over 5 years. Additionally, we conducted descriptive analyses to illustrate individual changes. Results: On average, TMT-A z scores improved by 0.024 units (95% confidence interval (CI): 0.006 to 0.042, p = 0.009), TMT-B z scores by 0.034 units (95% CI: 0.012 to 0.057, p = 0.003), and DB z scores by 0.019 units per month (95% CI: 0.011 to 0.028, p < 0.001). Patients with psychiatric comorbidities achieved the greatest improvements in TMT-B and DB z scores among all groups (0.0058 units/month, p = 0.036 and 0.028 units/month, p = 0.003, respectively). TMT-A z scores improved the most in patients taking 1-2 ASMs as well as in patients with psychiatric comorbidities (0.042 units/month, p = 0.002 and p = 0.003, respectively). Conclusion: Performance in all three tests improved at the group level during the follow-up period, with the most robust improvement observed in TMT-B, which requires inhibition control and set-switching in addition to the visuoperceptual processing speed that is crucial in TMT-A and working-memory performance that is essential in DB. Moreover, the improvement in TMT-B was further enhanced if the patient had psychiatric comorbidities.

Longitudinal EpiTrack assessment of executive functions following vagus nerve stimulation therapy in patients with drug-resistant epilepsy.

OBJECTIVE: To investigate executive functions and attention with repeated EpiTrack evaluations in a group of DR patients with drug-resistant epilepsy (DRE) receiving vagus nerve stimulation (VNS) during a follow-up duration of up to 5 years. METHODS: The study involved 33 patients with DRE who were assessed with EpiTrack as a part of the clinical VNS protocol. Evaluations were scheduled prior to VNS implantation and then at 6 months, 12 months, and yearly thereafter. However, the COVID-19 pandemic disrupted follow-up. Therefore, changes in EpiTrack total scores over time were analyzed using a linear mixed-effects (LMEs) model to compensate for the variation in follow-up duration when predicting EpiTrack total score changes over 5 years. RESULTS: The median follow-up time was 29 months. During each month, the EpiTrack total score was predicted to increase by 0.07 units (95% confidence interval [CI]: 0.01-0.12, P = 0.02), corresponding to a change from a baseline score of 27.3 (severe impairment) to a score of 28.9 (mild impairment) at 2 years and a score of 31.5 (almost normal) at 5 years. In the group of patients with psychiatric comorbidities, the EpiTrack total score increased by 0.14 units per month (P = 0.003), which was 3.5-fold higher than the increase of patients without psychiatric comorbidities. For the patients taking 1-2 antiseizure medications (ASMs), the EpiTrack total score increased by 0.11 units per month (P = 0.005), which was almost quadruple the rate of patients taking 3-4 ASMs. SIGNIFICANCE: Based on EpiTrack total scores, the LME model predicted a four-point improvement in executive functions among patients with DRE at 5 years after the initiation of VNS, representing a clinically meaningful change. DRE patients with comorbid depression seemed to experience the most cognitive benefits. In addition, better cognitive outcomes were achieved if the patient took less than three ASMs. PLAIN LANGUAGE SUMMARY: Executive functions and attention may improve during vagus nerve stimulation therapy in patients with drug-resistant epilepsy. Epilepsy patients who have depression or use fewer than three antiseizure medications are likely to benefit cognitively more from the treatment.

EpiTrack is a feasible tool for assessing attention and executive functions in patients with refractory epilepsy.

OBJECTIVE: The purpose of this cross-sectional retrospective study was to utilize EpiTrack to assess cognitive performance within the domain of attention and executive functions in patients with refractory epilepsy in consideration for treatment interventions either with antiepileptic drug (AED) changes and/or neuromodulation therapies. We also aimed to identify the relevant clinical and treatment factors possibly affecting EpiTrack performance. METHODS: The patient group consisted of 95 consecutive refractory epilepsy patients who were evaluated with EpiTrack. Based on their EpiTrack performance, the patients could be categorized as cognitively unimpaired, mildly, or severely impaired. The patients were also divided into three groups based on the planned treatment modification: AED group (n = 38) with only AED treatment, vagal nerve stimulation (VNS) group (n = 40) and deep-brain stimulation (DBS) group (n = 17). However, the effect of planned interventions was not the subject of this study. We retrospectively reviewed the medical records for detailed clinical characterization. RESULTS: EpiTrack performance was severely impaired in 48 (50.5%), mildly impaired in 22 (23.2%) and unimpaired in 25 (26.3%) of the patients. The DBS group had significantly lower EpiTrack scores (mean (SD) and median, 25.5 (4.81) and 27.0, respectively) compared to the AED group (28.6 (6.2) and 30.0, respectively, p = 0.049). Sixty-three (66.3%) of the whole study population had more than 2 AEDs. When comparing EpiTrack scores between patient groups based on the number of AEDs administered, there was a trend toward better performance in EpiTrack with 2 AEDs as compared to 3-4 AEDs. CONCLUSIONS: Deficits in attention and executive functions were frequent among patients with refractory epilepsy. Deficits were evident in all three treatment groups being most severe in the DBS group reflecting the patient selection. Furthermore, the effect of AED burden on executive functions was remarkable since two thirds of the patients had more than two AEDs and the deficits were more prominent among those with a higher AED burden. These results highlight the benefits of a feasible screening tool such as EpiTrack for assessing attention and executive functions when optimizing the treatment effects of neurostimulation therapies on cognition, and when evaluating the impacts of the AED burden.