Elsevier

Epilepsy & Behavior

Volume 126, January 2022, 108431
Epilepsy & Behavior

Vagus nerve stimulation for drug-resistant epilepsy induced by tuberous sclerosis complex

https://doi.org/10.1016/j.yebeh.2021.108431Get rights and content

Abstract

Objective

This study investigated the dynamic and long-term efficacy of vagus nerve stimulation (VNS) in patients with drug-resistant epilepsy (DRE) induced by tuberous sclerosis complex (TSC). In addition, the impact of VNS on cognition and emotion after a one-year follow-up was evaluated.

Methods

A total of 17 patients diagnosed with DRE induced by TSC were retrospectively recruited between 2008 and 2019. Dynamic changes in seizure frequency were observed in the responders (≥50% reduction of seizure frequency at last follow-up) and non-responders. Clinical characteristics and seizure outcomes were comprehensively analyzed to determine factors associated with seizure outcomes. The Wechsler intelligence scale was applied in a subgroup of six pediatric patients, whereas the Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) were assessed in a subgroup of nine patients to determine the impact of VNS therapy on cognitive performance and emotional state.

Results

The follow-up duration for the 17 patients who underwent VNS treatment ranged from 0.5 to 10 years (mean ± SD: 4.1 ± 3.2 years). Monthly seizures decreased significantly from three months to four years post-treatment (p < 0.05). At the last follow-up, 70.6% of the patients achieved at least a 50% reduction in seizure frequency, and three patients were completely seizure free. Comparatively, non-responder patients experienced deterioration of seizure frequency after the first year. Notably, after one-year follow-up the mean standard score of full-scale intelligence quotient increased from 67.33 to 69.5 (p = 0.078) while the mean, standard score of SDS decreased from 49.22 to 45.67 (p = 0.003) compared to preoperative neuropsychological evaluation results.

Conclusion

VNS is a safe and effective treatment for patients with DRE caused by TSC. Although early outcomes were encouraging, a follow-up of at least one-year was required to predict long-term outcomes in patients receiving VNS treatment. Moreover, VNS may improve depressive mood in patients with DRE caused by TSC. Further investigations are needed to validate the present results.

Introduction

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder attributed to TSC1 or TSC2 gene mutations. These mutations hyperactivate the rapamycin (mTOR) pathway. Dysregulated mTOR signaling has been found to cause disorders of the skin, eyes, kidneys, and heart [1]. In addition, dysregulated mTOR signaling affects neural progenitor cells (NPCs) in the fetal nervous system, causing abnormal cell differentiation, proliferation, growth, and migration. For instance, abnormal mTOR signaling has been shown to cause three characteristic encephalopathies: cortical tubers, subependymal nodules, and subependymal giant cell astrocytomas (SEGAs) [2].

Epilepsy is the most prevalent clinical symptom of TSC, occurring in about 90% of patients with TSC [3]. Most patients develop seizures during their first years of life, at the age of three months. However, in others, the first seizure might occur at adolescence or adulthood [2], [4]. Most patients with TSC experience developmental delay and neuropsychiatric symptoms [5], [6]. According to previous studies, early onset of seizures may be associated with significant cognitive deficits [7]. Therefore, effective treatment of TSC-induced epilepsy is essential not only for seizure control but also for normal intellectual development.

Although antiepileptic drugs (AEDs) are the first-line of treatment for epilepsy induced by TSC, at least 50% of patients with TSC-induced epilepsy develop drug resistance to AEDs [8]. If pre-surgical evaluation identifies localized epileptogenic foci, resective surgery is preferred than medication alone. For patients who cannot benefit from resective surgery or epileptic lesions cannot be localized, neuromodulation therapy such as vagus nerve stimulation (VNS) is recommended.

Currently, the benefits of VNS in patients with TSC-induced epilepsy are not well defined, especially, the dynamic and long-term efficacy remains unclear [9], [10], [11], [12]. This study presented the VNS therapeutic efficacy changes over time, and investigated the potential impact of VNS on cognition and emotion.

Section snippets

Subjects

A total of 17 patients diagnosed with TSC-induced drug-resistant epilepsy (DRE) were recruited at the Epilepsy Center of Sanbo Brain Hospital of Capital Medical University (Beijing, China) between 2008 and 2020. All patients were clinically diagnosed based on the TSC diagnostic criteria of 1998 or 2012 [13], [14]. Drug-resistant epilepsy was defined as the failure of two adequate AEDs deemed appropriate to the condition of patient [15]. In our comprehensive epilepsy center, each patient was

Demographics and clinical characteristics

Patient demographics and clinical characteristics are summarized in Table 1. The patients comprised seven females (41.2%) and ten males (58.8%), with mean age at VNS implantation of 11.4 years old (range: 0.9–30, SD: 8.4, median: 11). Before VNS implantation; the mean age at seizure onset was 3.7 years (range: 0.25–11, SD: 3.6, median: 3); the mean monthly seizure frequency was 154.5 (range: 0.33–600, SD: 167.6, median: 122) and the mean number of failed AEDs was 3.8 (range: 3–6, SD: 0.8,

Discussion

Based on the results of this study and other literature reports, VNS seems to be an effective and safe treatment for TSC-induced DRE [9], [10], [11], [12]. At the last follow-up, 70.6% of the patients had at least a 50% reduction in seizure frequency, and three patients achieved seizure-free status. Moreover, all patients experienced seizure frequency reduction within one year after the initiation of VNS treatment although a few patients experienced more frequent seizures later. Wechsler

Conclusion

Vagus nerve stimulation is an effective and safe treatment for patients with DRE caused by TSC. Seizure control by VNS tended to stabilize one year after surgery, thus, a follow-up of at least one year is required to determine the long-term effects of VNS therapy in patients. Moreover, VNS may improve depression in patients with DRE caused by TSC, further studies are needed to validate this finding.

Sources of financial support

This study was supported by funds from the Major Program of the National Natural Science Foundation of China (grant numbers 81790654, 81790650, 81790651 and 11932003) and Capital’s Funds for Health Improvement and Research (grant number 2020-4-8012).

Authorship statement

All persons who meet authorship criteria are listed as authors, and all authors confirm that they have participated sufficiently in the work to take responsibility for the content, including participation in the conception, design, analysis, writing, or revision of the manuscript. Furthermore, each author confirms that this material or similar materials have not been and will not be submitted to or published in any publication before its appearance in the Epilepsy & Behavior.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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