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Variation in access to specialist services for neurosurgical procedures in adults with epilepsy in England, a cohort study

Open AccessPublished:December 26, 2022DOI:https://doi.org/10.1016/j.seizure.2022.12.006

      Highlights

      • Despite NICE guidance, visits to neurosurgery clinics remain uncommon and are seldom followed by surgical interventions.
      • Access to tertiary centres and neurosurgical procedures in adults with epilepsy in England, varies by region and CCGs.
      • Access to neurosurgical procedures is delayed, particularly if a person’s initial visit is not at a tertiary epilepsy centre.
      • VNS use remains low, although it is higher in people with learning disability, who are less likely to have resective surgery.

      Abstract

      Purpose

      To understand if primary consultation at tertiary epilepsy centres (TEC) in England impacts access to neurosurgical procedures (resective surgery, vagus nerve stimulator [VNS], deep brain stimulator [DBS]).

      Methods

      Adults with epilepsy, and with a first neurology outpatient visit (index) between 01/01/2013 and 31/12/2015, were followed using English Hospital Episode Statistics from index date to 31/12/2019. Analyses were stratified by geographic location, learning disability record, and whether the index or follow-up visits were at a TEC.

      Results

      84,093 people were included, with mean 5.5 years of follow-up. 12.4% of the cohort had learning disability (range 10.1%-17.4% across regions). TEC consultations varied by National Health Service regions and Clinical Commissioning Groups. 37.5% of people (11.2%-75.0% across regions) had their index visit at a TEC; and, of those not initially seen at a TEC, 10.6% (6.5%-17.7%) subsequently attended a tertiary centre. During follow-up, 11.1% people (9.5%-13.2%) visited a neurosurgery department, and 2.3% of those (0.9%-5.0%) then underwent a neurosurgical procedure, mainly VNS implantation. Median time from index date to first visit at a neurosurgery centre was 7 months (range 6-8 months across regions) and 40 months to procedure (36.5-49 months, 37.0 months in people with index visit at a TEC and 49.0 months otherwise). People with learning disability were less likely to have resective surgery (<0.5% versus 1.0% in those without) and more likely to undergo VNS implantation (5.8% versus 0.8%).

      Conclusion

      Although clinically recommended for suitable individuals, neurosurgical procedures in epilepsy remain uncommon even after consultation at a TEC. Geographical variation in access to TECs was present.

      Keywords

      Abbreviations:

      ASM (Anti-seizure medication), CCG (Clinical Commissioning Group), CT (Computed tomography), DBS (Deep brain stimulation), DRE (Drug resistant epilepsy), HES (Hospital Episode Statistics), ILAE (International League Against Epilepsy), IQR (Interquartile range), MRI (Magnetic resonance imaging), NHS (National Health Service), NICE (National Institute for Health and Care Excellence), NSC (Non-specialist centre), SD (Standard deviation), TEC (Tertiary epilepsy centre), vEEG (Video electroencephalogram), VNS (Vagus nerve stimulation)

      1. Introduction

      Despite numerous pharmacological options for people with epilepsy, the goal of seizure freedom without side-effect burden remains elusive for a large proportion of individuals. Treatment with anti-seizure medications (ASMs) typically starts with one ASM, whereafter the regimen is adapted with changes to drug and dose until seizures are controlled and the treatment is tolerated [
      • Park K.M.
      • Kim S.E.
      • Lee B.I.
      Antiepileptic drug therapy in patients with drug-resistant epilepsy.
      ].
      People who do not attain seizure freedom with the first or second ASM have markedly reduced chances of successful pharmacological treatment with subsequent new medications and increased likelihood of developing drug-resistant epilepsy (DRE) [
      • Chen Z.
      • Brodie M.J.
      • Liew D.
      • Kwan P.
      Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study.
      ]. DRE is defined by the International League Against Epilepsy (ILAE) as “as failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom”. DRE is associated with serious consequences, including neuropsychological decline, decreased quality of life, and increased risk of death [
      • Callaghan B.
      • Choi H.
      • Schlesinger M.
      • Rodemer W.
      • Pollard J.
      • Hesdorffer D.C.
      • et al.
      Increased mortality persists in an adult drug-resistant epilepsy prevalence cohort.
      ,
      • McLachlan R.S.
      • Rose K.J.
      • Derry P.A.
      • Bonnar C.
      • Blume W.T.
      • Girvin JP.
      Health-related quality of life and seizure control in temporal lobe epilepsy.
      ]. The prevalence of DRE is estimated as approximately 30% (95% confidence interval between 19% and 42%), a proportion which has remained relatively constant over the past decades [
      • Chen Z.
      • Brodie M.J.
      • Liew D.
      • Kwan P.
      Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study.
      ,
      • Sultana B.
      • Panzini M.A.
      • Veilleux Carpentier A.
      • Comtois J.
      • Rioux B.
      • Gore G.
      • et al.
      Incidence and prevalence of drug-resistant epilepsy: a systematic review and meta-analysis.
      ]; and a higher incidence of DRE in adults than in children has been observed (34% versus 15%) [
      • Kalilani L.
      • Sun X.
      • Pelgrims B.
      • Noack-Rink M.
      • Villanueva V.
      The epidemiology of drug-resistant epilepsy: A systematic review and meta-analysis.
      ].
      In people with DRE, several non-pharmacological options exist. These include resective surgery, corpus callosotomy, and the implantation of neuromodulation devices (vagus nerve stimulator [VNS] or deep brain stimulator [DBS]) and dietary therapy [
      • Jetté N.
      • Sander J.W.
      • Keezer M.R.
      Surgical treatment for epilepsy: the potential gap between evidence and practice.
      ,
      • Schoeler N.E.
      • Cross J.H.
      Ketogenic dietary therapies in adults with epilepsy: a practical guide.
      ]. Approximately two-thirds of people with intractable temporal lobe epilepsy, and half of people with focal neocortical epilepsy, have been shown to achieve seizure freedom following resective surgery [
      • Englot D.J.
      • Chang E.F.
      Rates and predictors of seizure freedom in resective epilepsy surgery: an update.
      ]. For VNS, 45%-65% of individuals demonstrate at least a halving and, in some cases up to 100% reduction, in seizure frequency within 6 months of initiating treatment [
      • Toffa D.H.
      • Touma L.
      • El Meskine T.
      • Bouthillier A.
      • Nguyen D.K.
      Learnings from 30 years of reported efficacy and safety of vagus nerve stimulation (VNS) for epilepsy treatment: a critical review.
      ]. The 2012 National Institute for Health and Care Excellence (NICE) clinical guideline 137 (applicable at the time of data capture for this study) recommended prompt referral to tertiary services for people with uncontrolled epilepsy to assess suitability for resective surgery or alternatives, and the recently updated guidance 2022 further strengthens support for this approach [

      Overview | epilepsies: diagnosis and management | guidance | NICE [Internet]. NICE; [cited 2021 Dec 1]. Available from: https://www.nice.org.uk/guidance/cg137.

      ,

      Referral to tertiary specialist services | Epilepsies in children, young people and adults | Guidance | NICE [Internet]. NICE; [cited 2022 May 25]. Available from: https://www.nice.org.uk/guidance/ng217/chapter/3-Referral-to-tertiary-specialist-services.

      ]. The NICE guidelines recommend considering VNS as an adjunctive treatment for people who are refractory to ASMs and are not suitable for resective surgery. This includes people whose epilepsy disorder is dominated by focal seizures (with or without secondary generalisation) or generalised seizures [

      Overview | epilepsies: diagnosis and management | guidance | NICE [Internet]. NICE; [cited 2021 Dec 1]. Available from: https://www.nice.org.uk/guidance/cg137.

      ,

      Project information | Epilepsies in children, young people and adults | Guidance | NICE [Internet]. NICE; [cited 2022 Mar 3]. Available from: https://www.nice.org.uk/guidance/indevelopment/gid-ng10112.

      ].
      An alternative neuromodulatory approach is DBS implantation, which has been available in England since 2012. Deep brain simulation has been reviewed under NICE interventional procedures guidance [

      Deep brain stimulation for refractory epilepsy | 2012 Guidance IPG416 | NICE [Internet]. NICE; [cited 2022 Jul 15]. Available from: https://www.nice.org.uk/guidance/ipg416.

      ,

      NHS England. Clinical commissioning policy: deep brain stimulation for refractory epilepsy (all ages). NHS England Reference: 170036P [Internet]. 2018. Available from: https://www.england.nhs.uk/wp-content/uploads/2018/03/d04-deep-brain-stimulation-for-refractory-epilepsy.pdf.

      ]. Anterior thalamic stimulation targets can be considered in people with a diagnosis of refractory epilepsy and under specific arrangements, although routine use of DBS for epilepsy is not commissioned by the National Health Service (NHS) England Specialised Services Commissioning [

      NHS England. Clinical commissioning policy: deep brain stimulation for refractory epilepsy (all ages). NHS England Reference: 170036P [Internet]. 2018. Available from: https://www.england.nhs.uk/wp-content/uploads/2018/03/d04-deep-brain-stimulation-for-refractory-epilepsy.pdf.

      ].
      Despite NICE clinical guidance on the management of people with DRE, though, access to non-pharmacological treatment options is limited and is seldom considered early in the treatment pathway [
      • Lhatoo S.D.
      • Solomon J.K.
      • McEvoy A.W.
      • Kitchen N.D.
      • Shorvon S.D.
      • Sander J.W.
      A prospective study of the requirement for and the provision of epilepsy surgery in the United Kingdom.
      ]. Low rates of referral for epilepsy surgery have been reported in the United Kingdom (UK) [
      • Lhatoo S.D.
      • Solomon J.K.
      • McEvoy A.W.
      • Kitchen N.D.
      • Shorvon S.D.
      • Sander J.W.
      A prospective study of the requirement for and the provision of epilepsy surgery in the United Kingdom.
      ], as well as elsewhere [
      • de Flon P.
      • Kumlien E.
      • Reuterwall C.
      • Mattsson P.
      Empirical evidence of underutilization of referrals for epilepsy surgery evaluation.
      ,
      • Burneo J.G.
      • Shariff S.Z.
      • Liu K.
      • Leonard S.
      • Saposnik G.
      • Garg A.X.
      Disparities in surgery among patients with intractable epilepsy in a universal health system.
      ,
      • Solli E.
      • Colwell N.A.
      • Say I.
      • Houston R.
      • Johal A.S.
      • Pak J.
      • et al.
      Deciphering the surgical treatment gap for drug-resistant epilepsy (DRE): a literature review.
      ]. There are claims that neurosurgery for people with DRE remains one of the least used evidence-based treatments in modern medicine [

      Samanta D., Ostendorf A.P., Willis E., Singh R., Gedela S., Arya R., et al. Underutilization of epilepsy surgery: Part I: a scoping review of barriers. Epilepsy Behav 2021;117:107837. Apr.

      ]. Given the adverse consequences of uncontrolled epilepsy, variation in referral and access to potential non-pharmacological options for people with DRE may have a detrimental effect on clinical outcomes, and increase the burden on the healthcare system.
      In this context, we investigated referral to neurology and neurosurgery departments for adults wih epilepsy in England, and access to epilepsy neurosurgical procedures including resective surgery, VNS and DBS, depending on people's pathway of care either via a tertiary epilepsy centre (TEC) or a non-specialist centre (NSC). We hypothesised that the causes of variation in access may include the organisational structure of the NHS at a regional and Clinical Care Commissioning Group (CCG) level, differences in clinical practice or individual clinical characteristics for example, the presence of a learning disability.

      2. Material and methods

      2.1 Study design, setting and participants

      We designed a cohort study extracting data from the Hospital Episode Statistics (HES) database (Copyright © 2023, NHS Digital. Re-used with the permission of NHS Digital. All rights reserved. This data is provided under licence via Harvey Walsh Ltd from NHS Digital, Data Sharing Agreement: DARS-NIC-05934-M7V9K), a data warehouse containing records of all people admitted as inpatients, seen as outpatients or who visit Accident and Emergency services at hospitals funded by the NHS across England; with data stored on hospital diagnoses, procedures, treatment, healthcare resource use and associated costs [

      Hospital episode statistics (HES) [Internet]. NHS digital. [cited 2021 Nov 27]. Available from: https://digital.nhs.uk/data-and-information/data-tools-and-services/data-services/hospital-episode-statistics.

      ]. The HES database contains records of NHS-funded and private-funded people treated by an NHS provider and the records of non-English residents treated in hospital settings. The database also contains the records of admissions to independent (non-NHS) providers where treatment is funded by the NHS. Disease diagnoses in HES are recorded using the International Classification of Diseases 10th revision (ICD-10) codes; and interventions, procedures and procurement for treatment are recorded using the Office of Population Censuses and Surveys Classification of Interventions and Procedures version 4 (OPCS-4) codes. Our study observation period included all HES records dated between 31/12/2011 and 31/12/2019.
      The study population comprised people with both (i) a visit to a neurology outpatient department (treatment speciality code 400, the first ever neurology visit during the observation period and flagged as a “first visit”) at ≥18 years of age between 01/01/2013 and 31/12/2015 inclusive (index date); and (ii) a recorded diagnosis of epilepsy (ICD10 codes G400-G419) anywhere in their HES records during the study observation period. Code lists are provided as supplementary material. The first outpatient visit to a neurosurgery department post index date was also extracted to define attendance at neurosurgery. People with a record of brain tumour (ICD-10 codes C710-C718) on or prior to the neurosurgery first visit were excluded. The hospital visits may have been to see a neurologist, a neurosurgeon or other relevant clinical expert(s), for example, a multidisciplinary team, to assess the possibility of neurosurgical procedures, to conduct investigations, or to perform a procedure. All people were followed from index date to the end of study period on 31/12/2019, i.e., before the impact of the COVID-19 pandemic affected NHS practice.

      2.2 Variable definitions

      Procedures and investigations extracted included those performed at TECs and NSCs. Procedures comprised a first code for either resective surgery, VNS or DBS implantation specifically performed for a diagnosis of epilepsy, and recorded during an inpatient admission in the period between an individual's first neurosurgery visit and the end of follow-up. Investigations were extracted in people undergoing a procedure from the index date up to the date of the first procedure and comprised telemetric video electroencephalogram (vEEG) during an elective admission to either neurology or neurosurgery (speciality code 150 or 400), and, as an inpatient or out-patient at neurology or neurosurgery, computed tomography (CT) of the head or magnetic resonance imaging (MRI).
      To investigate geographic variation at a regional level in England, analyses were stratified by seven geographic regions based on the NHS Region of residence of people at index date: East of England, London, Midlands, North East and Yorkshire, North West, South East, and South West and further sub-divided by CCG.
      No published list of TECs in England was available; therefore a TEC was defined as a hospital with both neurology and neurosurgery departments that could offer outpatient and inpatient care, in accordance with NHS England Specialised Services Commissioning requirements for epilepsy neurosurgical procedures [

      NHS commissioning » Specialised services [Internet]. [cited 2022 Apr 6]. Available from: https://www.england.nhs.uk/commissioning/spec-services/.

      ]. TECs were assigned to an NHS region based on the geographical location of the centre. A TEC visit was defined as a neurology or neurosurgical visit at a centre identified as being a TEC.
      Individuals were identified as having a learning disability if they attended a learning disability clinic (treatment function code 700) or had a recorded diagnosis of learning disability (see code list in Appendix) at any time in their outpatient or inpatient records during the study observation period.

      2.3 Data analysis

      All analyses were performed (i) for the total study population, and stratified by (ii) NHS region; (iii) individual's history of a learning disability; and (iv) index visit at a TEC. To evaluate geographical variation more precisely, the percentage of people attending a TEC either at index date or during follow-up was also estimated by CCGs. Categorical variables were summarised using frequency counts and percentages, overall and specifically in those attending neurosurgery, whenever relevant. Continuous variables were summarised using counts, arithmetic mean and standard deviation (SD) if normal, or median and interquartile range (IQR) if non-normal (based on Kolmogorov-Smirnov tests). Visits to a neurosurgical department, and procedures were also described in terms of time to access. Categorical comparisons were performed using Chi-square tests. Medians for time-to variables were compared across strata using either the Mann-Whitney U-test for binary comparisons of TEC versus NSC, and comparing comparing people with versus without learning disability; or the Kruskal-Wallis test for tests of differene across regions (as distributions were not normal).

      3. Results

      The study population comprised 84,093 people (Supplementary Fig. 1) with a mean age of 49 years (SD: 20) and mean follow-up of 5.5 years (SD: 0.9). A subset of 1,988 (2.4%) people did not have geographical information available and were excluded from analyses by NHS region and CCGs. Demographic characteristics; and descriptions of access to TEC, neurosurgery departments, and procedures, are described by NHS region in Table 1.
      Table 1Access to adult epilepsy services after a first visit to neurology between 2013 and 2015, overall and stratified by NHS Region.
      England region
      England1East of EnglandLondonMidlandsNorth East & YorkshireNorth WestSouth EastSouth Westp-value
      Variable84,093915211,43015,82914,04112,88411,3327,437
      Follow-up post-index date, years5.5 (0.9)5.5 (0.9)5.6 (0.9)5.5 (0.9)5.6 (0.9)5.4 (0.9)5.5 (0.9)5.5 (0.9)
      Descriptive characteristics
         Age, mean (SD)49 (20)51 (20)49 (20)50 (20)49 (19)49 (19)50 (20)50 (20)
         Female, %49.7%49.7%50.2%50.6%49.2%48.8%50.4%48.9%
         Learning disability, %12.4%11.0%10.1%11.4%17.4%,11.8%12.5%12.6%
      Attendance at a TEC:
         For an outpatient neurology visit at index, % (N)37.5% (31,508)11.2% (1,029)28.3% (3,232)24.5% (3,874)57.0% (8,009)75.0% (9,662)25.9% (2,937)21.5% (1,599)<0.0001
         For an outpatient neurology visit at index or follow-up, % (N)44.1% (37,060)18.6% (1,701)38.0% (4,342)32.7% (5,172)62.7% (8,808)79.4% (10,233)31.4% (3,561)26.6% (1,977)<0.0001
         Outpatient visit a neurosurgery department at index or follow-up, % (N)11.1% (9,347)9.5% (873)12.3% (1,404)10.7% (1,689)11.3% (1,587)13.2% (1,706)9.8% (1,110)10.2% (760)<0.0001
          Outpatient visit a neurosurgery department at index or follow-up, % (N) in those ever attending a TEC14.3% (5,313)19.5% (331)16.7% (726)16.0% (825)13.0% (1,141)13.1% (1,344)12.8% (457)16.5% (327)<0.0001
         Time from index neurology visit to first neurosurgery visit (months), median (IQR)7 (2-27)6 (2-24)6 (2-27)6 (2-24)7 (2-26)8 (2-29)7. (2-26)8 (2-30)0.001
      Epilepsy procedures in people seen at neurosurgery department, N (%)
      At least one procedure212 (2.3%)8 (0.92%)20 (1.4%)42 (2.5%)34 (21%)26 (1.5%)30 (2.7%)38 (5.0%)<0.0001
         Resective surgery285 (0.91%)<512 (0.85%)8 (0.47%)13 (0.82%)15 (0.878%)13 (1.2%)8 (1.1%)0.292
         VNS2121 (1.3%)<57 (0.50%)31 (1.8%)20 (1.3%)12 (0.70%)15 (1.4%)29 (3.8%)<0.0001
         DBS210 (0.11%)<5<5<5<50<5<5NA3
         Time from index neurology visit to first procedure (months), median (IQR)40 (27-53)48.5 (40-62)49 (35-63)38 (26-50)39 (27-53)36.5 (27-53)45.5 (28-51)47 (27-54)0.161
      1The England column includes 1988 people with missing region of residence. 2Numbers when fewer than 5 people in a cell are suppressed; a p-value is not presented for DBS due to the small cell counts. DBS, deep brain stimulation; IQR, interquartile range; N, number of people; NA: Not available; SD, standard deviation; TEC, tertiary epilepsy centre; VNS, vagus nerve stimulation.
      The index visit was at a TEC in 37.5% of individuals, with wide variation across regions ranging from 11.2% in East of England to 75.0% in the North West (Table 1). Overall, 44.1% of people visited a TEC either at or post the index date, varying by region (18.6%-79.4%) and across CCGs (Fig. 1). Of people first seen at a TEC, almost all had a further visit at a TEC during follow-up (90.4%, range across regions: 88.6%-94.4%), whilst people seen at an NSC at index were unlikely to subsequently attend a TEC during follow-up (10.6%, range: 6.5%-17.7%). The proportion of the study population seen in neurosurgical departments was consistently higher for people who ever attended a TEC at index (13.5% versus 9.7%) across NHS regions, except in the North West region (Table 2 and Supplementary Table S1).
      Fig. 1
      Fig. 1Visit at a TEC at or post-index date by Clinical Commissioning Groups in England
      Percentage of people attending a TEC post-index date in each CCG, with overlay of NHS regions. Each CCG is colour-coded according to the percentage of people with epilepsy attending a TEC.
      Table 2Access to adult epilepsy services after a first visit to neurology between 2013 and 2015, overall and stratified by NHS Region and by access to a tertiary epilepsy centre.
      First neurology visit
      VariableTEC, N (%)NSC, N (%)p-value
      Number of people, %31,508 (37.5%)52,585 (62.5%)
      Attendance at a TEC during follow-up, %90.4%10.6%<0.0001
      Attendance at neurosurgery department during follow-up, %13.5%9.7%<0.0001
      In people attending neurosurgery department, N42405107
         At least one procedure, %3.1%1.6%<0.0001
         VNS, %1.7%1.0%<0.0001
         Resective surgery, %1.3%0.55%<0.0001
         DBS, %0.1%<5
      Time from index neurology visit to first neurosurgery visit (months), median (IQR)7 (2-26)7 (2-27)0.10
      Time from index neurology visit to first procedure (months), median (IQR)37 (24-50)49 (34-58)<0.0001
      DBS, deep brain stimulation; IQR, interquartile range; N, number of individuals; NSC, non-specialist centre; SD, standard deviation; TEC, tertiary epilepsy centre; VNS, vagus nerve stimulation.
      In total, 11.1% of people visited a neurosurgery department during follow-up (range 9.5% to 13.2% by region), and this rose to 14.3% (12.8%-19.5%) in people attending a TEC at index or post-index visit. Among people who made at least one visit to a neurosurgery department, 2.3% underwent a procedure during follow-up (0.25% overall): 1.3% for VNS, 0.91% for resective surgery and 0.11% for DBS (Table 1). The median time for people from index visit at any neurology department to first visit at a neurosurgery department was 7 months (IQR: 2-27 months), and was similar in people attending and not attending a TEC at index date. The median time from index date to undergoing a surgical procedure was 40 months (IQR: 27-53 months). The shortest average times from index date to surgery were in the North West (36.5 months), and the longest were in London (49 months) and East of England (48.5 months). Those with a first visit at a TEC had both a higher chance of having a neurosurgical procedure (3.1% if seen at a TEC versus 1.6% if the index visit was at an NSC), and the median time to surgery was on average 1-year shorter (37 months versus 49 months). For VNS specifically, the proportion undergoing implantation was 1.7% in those with index visit at a TEC and 1.0% in those with index visit at an NSC; and for resective surgery the proportions were 1.3% and 0.55%.
      In people having VNS implantation during follow-up, 48.5% had a prior record of vEEG, 41.9% had an MRI and 11.0% had a CT. In those undergoing resective surgery, 45.8% of people had a recorded vEEG investigation, 49.0% of people had a MRI in 49.0% , and 50.0% of people had a CT (Supplementary Table S2).
      In our study, 12.4% of participants (10.1%-17.4% by regions) had learning disability (Table 3) , see Supplementary Table S3 for regional stratification). Among people with learning disability, attendance at a TEC during follow-up was slightly higher than in people without a record of learning disability (46.9% versus 43.7%). By contrast, attendance at a neurosurgery department was lower in people with learning disability (9.1% versus 11.4% in people without). People with learning disability were more likely to undergo VNS implantation than people without a learning disability (5.8% versus 0.79% of those with a neurosurgical appointment; 0.53% versus 0.090% in the entire study population) and less likely to undergo resective surgery (0.52% versus 0.95% of those seen in neurosurgery; 0.048% versus 0.11% out of the entire study population) compared to people without learning disability, although absolute numbers remained low. The patterns of regional variation when stratified by history of learning disability were similar to that observed in the overall study population.
      Table 3Access to adult epilepsy services after a first visit to neurology between 2013 and 2015, overall and stratified by NHS Region and by people’s history of learning disability.
      Learning disability
      VariableYesNoP-value
      Number of people, %10,456 (12.4%)73,637 (87.6%)
      Attendance at a TEC during follow-up (%)46.9%43.7%<0.0001
      Attendance at a neurosurgery department (%)9.1%11.4%<0.0001
      In people attending neurosurgery department, N9558,392
         At least one procedure, %6.6%1.8%<0.0001
         Resective surgery, %0.52%1.0%<0.0001
         VNS, %5.8%0.8%<0.0001
         DBS, %0.31%0.083%NA
      Time from index neurology visit to first neurosurgery visit (months) Median (IQR)11 (3-33)6 (2-26)<0.001
      Time from index neurology visit to first procedure (months) Median (IQR)39 (21-51)40 (28-54)0.12
      Numbers with fewer than 5 people in a cell are suppressed and a Chi-square result is not presented for these variables due to the small cell counts. DBS, deep brain stimulation; IQR, interquartile range; N, number of people; SD, standard deviation; TEC, specialist epilepsy centre; VNS, vagus nerve stimulation; % N: percentage of the study population; % neurosurgery: percentage of people restricting denominator to population with a neurosurgery visit during follow-up.

      4. Discussion

      This large study of all adults in England with epilepsy and a first neurology visit between 01/01/2013 and 31/12/2015, who had on average 5.5 years of follow-up, demonstrates large regional variations in access to a TEC, referral to neurosurgery and rates of VNS implantation.
      Our study findings highlight the low rates of adoption of neurosurgical options for people with epilepsy in England within 4-7 years from diagnosis. Within regions and overall, the percentage of people undergoing either resective surgery, VNS or DBS was very small (0.25% overall).
      Overall 44.1% of people visited a TEC at index or during follow-up, although we observed large NHS regional and CCG-level variations, indicating a lack of uniformity in pathways of care acros England. Over a third of individuals had their index visit at a TEC neurology department. Only a small minority not seen at a TEC at their index visit were later referred to a TEC (10.6%). According to NICE clinical guidance and existing evidence, people who develop DRE should be prioritised for referral to a TEC, therefore our findings may indicate that access to a TEC is sometimes governed by local NHS referral pathways rather than clinical need [

      Referral to tertiary specialist services | Epilepsies in children, young people and adults | Guidance | NICE [Internet]. NICE; [cited 2022 May 25]. Available from: https://www.nice.org.uk/guidance/ng217/chapter/3-Referral-to-tertiary-specialist-services.

      ,
      • Guery D.
      • Rheims S.
      Clinical management of drug resistant epilepsy: a review on current strategies.
      ]. People attending a TEC at index were more likely to attend a neurosurgery department during follow-up, although there was regional variation, and their time from index visit at the neurology department to neurosurgery was around a year shorter.
      Individuals attending a TEC at index visit had similar rates of neurosurgical procedures to those who started their journey at a NSC, showing that TEC access was not a strong determinant of undergoing a neurosurgical procedure in our study. Furthermore, regional variation in TEC attendance did not visibly correlate with the proportion of those undergoing neurosurgical procedures in a region.
      Only 11% of people with epilepsy in our cohort had an appointment at a neurosurgery department during the follow-up period, which is lower than may be expected assuming a prevalence of DRE of approximately 30% in adults in England [
      • Kalilani L.
      • Sun X.
      • Pelgrims B.
      • Noack-Rink M.
      • Villanueva V.
      The epidemiology of drug-resistant epilepsy: A systematic review and meta-analysis.
      ]. Fewer than 3% of adults with epilepsy seen in a neurosurgery clinic underwent an operation during follow-up, a finding consistent across regions. It is possible that this low percentage is partially due to the relatively short follow-up of our study with a median follow-up of 5.5 years (IQR: 0.9), with a median time from index appointment to surgical procedure of over 3.3 years (40 months). The start of our study period was chosen to correspond to the publication of the NHS England Commissioning Policy on VNS in 2013 [

      N.H.S. Commissioning Board. Clinical commissioning policy: vagal nerve stimulation for epilepsy. Reference NHSCB/D04/P/d. Crown copyright 2013; 2013.

      ]; and the end was determined to be prior to the onset of the COVID-19 pandemic which substantially altered access to healthcare. Previously, it has been reported that the average time from first epilepsy diagnosis to resective surgery can exceed 20 years in some people; although the best outcomes are achieved when surgery is performed within 5 years after diagnosis [
      • Jordan B.
      • Ingrid O.
      • Kristina M.
      • Ramsay Karin W.
      Epilepsy duration and seizure outcome in epilepsy surgery: a systematic review and meta-analysis.
      ]. Therefore our observation of very low rates of resective surgery during our study period is perhaps indicative of a lack of provision at a time when individuals are likely to benefit most from the procedure. The causes of the treatment gap that arise with delayed neurosurgical referrals have been previously investigated and shown to include an array of factors including a lack of knowledge among physicians, inequitable access to specialist epilepsy centres and the inherent complexity of pre-surgical investigations. Biases, either conscious or unconscious, may also influence choosing surgical candidates, for example socioeconomic characteristics or presence of a learning disability [
      • Solli E.
      • Colwell N.A.
      • Say I.
      • Houston R.
      • Johal A.S.
      • Pak J.
      • et al.
      Deciphering the surgical treatment gap for drug-resistant epilepsy (DRE): a literature review.
      ,

      Samanta D., Ostendorf A.P., Willis E., Singh R., Gedela S., Arya R., et al. Underutilization of epilepsy surgery: Part I: a scoping review of barriers. Epilepsy Behav 2021;117:107837. Apr.

      ,
      • Hrazdil C.
      • Roberts J.I.
      • Wiebe S.
      • Sauro K.
      • Vautour M.
      • Hanson A.
      • et al.
      Patient perceptions and barriers to epilepsy surgery: evaluation in a large health region.
      ]. Importantly, people with shorter waits to surgical assessment have been shown to have more favourable seizure outcomes, while early diagnosis and access to specialist neurology services and treatments are significant factors in achieving seizure control [
      • Lewis A.K.
      • Taylor N.F.
      • Carney P.W.
      • Harding KE.
      What is the effect of delays in access to specialist epilepsy care on patient outcomes? A systematic review and meta-analysis.
      ,

      Fahoum F., Boffini M., Kann L., Faini S., Gordon C., Tzadok M., et al. VNS parameters for clinical response in Epilepsy. Brain Stimul. 2022;15(3):814–821. May.

      ], especially in children[
      • Jain P.
      • Arya R.
      Vagus nerve stimulation and seizure outcomes in pediatric refractory epilepsy: systematic review and meta-analysis.
      ].
      Up to 50% of people assessed at a neurosurgery department are not suitable for resective surgery [
      • Polkey C.E.
      Selection of patients with chronic drug-resistant epilepsy for resective surgery: 5 years’ experience.
      ] although eligibility for VNS is likely to be higher given its broader indications for use in people with DRE. The proportion of people undergoing surgical intervention in our study (0.25% of the overall cohort) remains very small compared to the total epilepsy population; and hence relative to the expected proportion of people with DRE who may be eligible for non-pharmacological options. This may indicate either (i) inappropriate levels of referral to neurosurgery, (ii) a long delay for some individuals (beyond the 7 years of our sudy follow-up), and/or (iii) a lack of access to resective surgery or neuromodulation options.
      Previous analyses of adult epilepsy procedures across the UK reported low and decreasing rates in resective surgery from 422 to 242 between 2000 and 2011, with an increase in VNS implantation over the same period from 159 to 226 procedures [
      • Lhatoo S.D.
      • Solomon J.K.
      • McEvoy A.W.
      • Kitchen N.D.
      • Shorvon S.D.
      • Sander J.W.
      A prospective study of the requirement for and the provision of epilepsy surgery in the United Kingdom.
      ,
      • Neligan A.
      • Haliasos N.
      • Pettorini B.
      • Harkness W.F.J.
      • Solomon J.K.
      A survey of adult and pediatric epilepsy surgery in the United Kingdom.
      ]. In our study population which included people with epilepsy first visiting a neurology department in 2013-2015, 121 people were implanted with VNS between 2013 and 2019, and 85 underwent resective surgery, representing 1.43 people per 1000 for VNS and 1.04 per 1,000 for resective surgery.
      A decline in surgical procedures has been reported elsewhere in Europe and North America [
      • Jehi L.
      • Friedman D.
      • Carlson C.
      • Cascino G.
      • Dewar S.
      • Elger C.
      • et al.
      The evolution of epilepsy surgery between 1991 and 2011 in nine major epilepsy centers across the United States, Germany, and Australia.
      ], although a survey of 16 European centres reported an increase up to 2013 [
      • Baud M.O.
      • Perneger T.
      • Rácz A.
      • Pensel M.C.
      • Elger C.
      • Rydenhag B.
      • et al.
      European trends in epilepsy surgery.
      ]. A drop in the rates of surgical interventions might be surprising given the published evidence on the superiority of resective and non-resective epilepsy surgery procedures over continued medical treatment alone, for people with DRE [
      • Jetté N.
      • Sander J.W.
      • Keezer M.R.
      Surgical treatment for epilepsy: the potential gap between evidence and practice.
      ]. Reasons for a decline in the number of UK adult epilepsy surgeries are multiple [

      Neligan A., Haliasos N., Pettorini B., Harkness W.F., Solomon J.K.. A survey of adult and pediatric epilepsy surgery in the United Kingdom. Epilepsia 2013;54(5):e62-e65.

      ]. Hesitancy in identifying and referring surgical candidates and the introduction of new ASMs have been proposed as possible reasons [
      • de Flon P.
      • Kumlien E.
      • Reuterwall C.
      • Mattsson P.
      Empirical evidence of underutilization of referrals for epilepsy surgery evaluation.
      ,
      • Burneo J.G.
      • Shariff S.Z.
      • Liu K.
      • Leonard S.
      • Saposnik G.
      • Garg A.X.
      Disparities in surgery among patients with intractable epilepsy in a universal health system.
      ,
      • Solli E.
      • Colwell N.A.
      • Say I.
      • Houston R.
      • Johal A.S.
      • Pak J.
      • et al.
      Deciphering the surgical treatment gap for drug-resistant epilepsy (DRE): a literature review.
      ]. Misconceptions about epilepsy surgery are reported as a major factor [
      • Solli E.
      • Colwell N.A.
      • Say I.
      • Houston R.
      • Johal A.S.
      • Pak J.
      • et al.
      Deciphering the surgical treatment gap for drug-resistant epilepsy (DRE): a literature review.
      ,
      • Hrazdil C.
      • Roberts J.I.
      • Wiebe S.
      • Sauro K.
      • Vautour M.
      • Hanson A.
      • et al.
      Patient perceptions and barriers to epilepsy surgery: evaluation in a large health region.
      ]] but are outside the scope of this study.
      VNS was more frequently implanted in people with learning disability than in those without, although this may be expected as people with learning disability may be less likely to be candidates for resective surgery, and, the use of VNS was low even in this population. Very few people with an underlying learning disability had resective epilepsy surgery, and absolute numbers were lower than expected based on cohort size. Importantly, the recently updated NICE guideline states that people with genetic abnormalities or learning disability should not be excluded from referral to a tertiary centre for the consideration of surgery [

      Referral to tertiary specialist services | Epilepsies in children, young people and adults | Guidance | NICE [Internet]. NICE; [cited 2022 May 25]. Available from: https://www.nice.org.uk/guidance/ng217/chapter/3-Referral-to-tertiary-specialist-services.

      ], and this may lead in the future to an increase in people with learning disability being referred for neurosurgical assessment.
      The strength of this study is that it provides large-scale real-world evidence about the clinical management of people with epilepsy across England.. Due to its coverage, access to HES provides accesss to comprehensive sample of people living in England and diagnosed with epilepsy, consequently, the study results may inform public health decisions at a national level.
      Given the reported prevalence of DRE and its associated mortality and morbidity, the reasons for low rates of surgical intervention both in people seen at NSCs or at a TEC, and for patterns of regional variation in access to neurosurgery referrals and procedures, require further investigation. For this, an assessment of how many patients have DRE would be needed, but that is outside the scope of this research study.
      The study is subject to limitations.
      The identification of a TEC was made assuming that hospitals with both neurology and neurosurgery departments that could offer outpatient and inpatient care provided TEC services to people with epilepsy, however misclassification may have occured if some hospitals with both services were not organised as a TEC. A visit to neurology or neurosurgery departments was assumed to be for epilepsy, as the study population has a history of epilepsy and procedures had a linked epilepsy diagnosis code; however, some individuals may have been referred for other reasons such as diagnostic uncertainty, access to neuropsychological assessment or another specialist setting. Similarly, we were not able to ascertain the reason for attendance at a TEC. An identification of DRE status was out-of-scope in this study as its determination would require additional data linkage to a primary care dataset to review numbers of medications prescribed over the duration of the study.
      The average delay between diagnosis of DRE and epilepsy surgery has been previously reported consistently across countries at approximately 20 years in adults and 5 years in children [
      • Solli E.
      • Colwell N.A.
      • Say I.
      • Houston R.
      • Johal A.S.
      • Pak J.
      • et al.
      Deciphering the surgical treatment gap for drug-resistant epilepsy (DRE): a literature review.
      ]. Our study follow-up ranged 4 to 7 years, therefore, it may have been insufficient to identify all indivduals undertaking neurosurgical procedures after being referred to neurology departments and thoseidentified may have had more severe disease or other characteristics not captured in this study. Follow-up ceased in 2019 to avoid the COVID-19 pandemic influencing results, which means this study may not capture most recent clinical practice. Given the impact of COVID-19 on the healthcare of people with epilepsy in the England, though, the pandemic is likely to have resulted in fewer procedures and longer delays to operative assessment [
      • Thorpe J.
      • Ashby S.
      • Cross J.H.
      • Sander J.W.
      • Newton C.
      • Hanna J.
      • et al.
      The impact of COVID-19 on epilepsy care: perspectives from UK healthcare workers.
      ,
      • Thorpe J.
      • Ashby S.
      • Hallab A.
      • Ding D.
      • Andraus M.
      • Dugan P.
      • et al.
      Evaluating risk to people with epilepsy during the COVID-19 pandemic: preliminary findings from the COV-E study.
      ].
      As this study is based on electronic health records, it is restricted to those data that are routinely recorded. The low proportion of people with investigations prior to surgery may be due to under-recording and warrants further exploration. While the HES data can follow people across English NHS settings, those who leave the English NHS (due to relocation or death) are not always identified, so may continue to contribute to follow-up time. There may have been under-recording of learning disability if the diagnosis was made in primary care rather than secondary care, and therefore was not recorded in HES; however both clinical codes and referral to services were searched to minimise under-ascertainment. Finally, the study is predominantly descriptive and did not directly compare variables with adjustment for potential confounders.

      5. Conclusion

      In conclusion, rates of access to TEC vary across the country; which warrants further investigation. Assessment for surgical interventions are recommended for people with DRE, which is estimated to affect as many as 30% of people with epilepsy. Our data show that a very small minority of people with epilepsy undergo a surgical intervention within the first 4-7 years after their first visit to a neurologist, suggesting a large treatment gap and delays to clinically effective options.

      Funding

      The work was supported by LivaNova PLC (registered in England and Wales with registered no. 09451374), with its registered office address at 20 Eastbourne Terrace - London - W2 6LG.
      Highlights
      • 1.
        Despite NICE guidance, visits to neurosurgery clinics remain uncommon and are seldom followed by surgical interventions.
      • 2.
        Access to tertiary centres and neurosurgical procedures in adults with epilepsy in England, varies by region and CCGs.
      • 3.
        Access to neurosurgical procedures is delayed, particularly if a person’s initial visit is not at a tertiary epilepsy centre.
      • 4.
        VNS use remains low, although it is higher in people with learning disability, who are less likely to have resective surgery.

      Declaration of Competing Interest

      JM, FB, VD and MD are employees of LivaNova PLC. SB and JW are employees of Harvey Walsh Ltd., which is part of OPEN Health Ltd, and MA is employee of OPEN Health Ltd. GCH is employed by Gillian Hall Epidemiology Ltd which received funding from OPEN Health Ltd. for scientific input into the study. AS is supported by the Oxford NIHR Biomedical Research Centre.

      Appendix. Supplementary materials

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