Cognitive outcomes following vagus nerve stimulation, responsive neurostimulation and deep brain stimulation for epilepsy: A systematic review
Introduction
Cognitive deficits in patients with epilepsy are highly prevalent and contribute significant burden on quality of life to patients and their families (Gowers and William, 1881; Jokeit and Ebner, 2002; Kleen et al., 2013; Loughman et al., 2014; Smith et al., 2002). Deficits can affect the whole range of cognitive functions including attention, memory, executive function, IQ and language (Gowers and William, 1881; Jokeit and Ebner, 2002; Kleen et al., 2013; Loughman et al., 2014; Smith et al., 2002). Cognitive dysfunction in epilepsy patients is related to a multitude of factors, including etiology of epilepsy, permanent effects of seizure activity, antiepileptic drugs (AEDs), and surgical management (Bermudez et al., 2019; Cochrane et al., 1998; Copeland et al., 2017; Donos et al., 2018; Hermann et al., 2010; Holmes, 2015; Jokeit and Ebner, 2002; Kleen et al., 2013, 2011). Therefore, balancing ongoing cognitive decline from seizures with cognitive sequelae from surgery remains a challenge.
With the long-term cognitive impact of the traditional anterior temporal lobectomy (ATL) well studied, research into strategies to optimize seizure outcomes with minimal cognitive impact has been a priority. Selective approaches, including selective amygdalohippocampectomy (SAH), have been designed to remove epileptogenic mesial temporal structures while sparing temporal cortex in order to minimize cognitive impact. Studies have reported better cognitive outcomes following SAH versus ATL, but results have been mixed, with one meta-analysis finding no significant difference in IQ (Hu et al., 2013; Tanriverdi et al., 2010).
Less invasive still are electrical neurostimulation techniques including deep brain stimulation (DBS), vagus nerve stimulation (VNS), and responsive neurostimulation (RNS). Nondestructive, reversible and programmable, these techniques precisely target neural structures to modulate seizure activity while minimizing adverse effects. Although the indications for these techniques differ from those of resective surgery, they are thought to offer alternative surgical approaches to epilepsy with lesser adverse cognitive impact.
With cognitive outcomes a major factor in guiding management of epilepsy for both clinicians and patients alike, quantification of cognitive outcomes is of utmost importance. However, data for these newer techniques are few and mixed; heterogenous surgical technique, neuropsychological testing and reporting lead to difficulties in comparing studies.
The objective of this systematic review was to investigate neuropsychological outcomes following VNS, DBS and RNS for epilepsy.
Section snippets
Protocol and registration
The protocol for this study was registered on PROSPERO (registration number: CRD42020184432).
Eligibility criteria
Studies were selected that reported neuropsychological outcomes for adult and pediatric patients that underwent vagus nerve stimulation, deep brain stimulation, and responsive neurostimulation for epilepsy. All study designs were considered, with a minimum limit of five patients, and 6 months of follow up postoperatively. Studies with a selective population including exclusively syndromic epilepsy were
Study selection
The database searches yielded 8443 studies including 2575 duplicates. After excluding 5110 studies based on the abstract, 758 underwent full-text review. In total, 29 studies matched the inclusion criteria and were included. PRISMA flow diagram of identification, screening, eligibility, and inclusion of studies is shown in Supplementary information 1 (Moher et al., 2009).
Study characteristic
Nineteen studies investigated the effects of chronic stimulation (11 VNS, 6 DBS, 2 RNS). Of these, two were the open-label
Discussion
Cognitive dysfunction in epilepsy is highly prevalent, and related both to seizure frequency and disease duration (Wang et al., 2019b). A third of patients with epilepsy are refractory to medication and continue to experience seizures during long unsuccessful trials of multiple AEDs before being considered for surgery. While the two goals of epilepsy treatment – medical or surgical – are to reduce seizure frequency while minimizing adverse effects, both modalities are known to contribute to
Funding
No funding was received for this work.
Declaration of Competing Interest
The authors report no declarations of interest.
Acknowledgements
None.
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