Weathering the Storms & Minding the (Perception) Gaps pt3 (Or, Getting to the Nub)

So, in pt3a, I made a pinky promise. Sub-dividing, giving this part, the part which relates to post or inter-ictal notes made, back in October last year, and what they referred to, its own space is intended to highlight, to focus on where this series began, why I started writing it, full of command defiance, hypervigilance and procrastination. Warts and all.

Pts1-3a explored the concepts of perception gaps from a few different angles, but the one that matters most, to me at least, arising from which the others became emergent properties, through neurodivergent and interictal osmosis, is the one covered here. I’d be happy for you to ignore the previous three parts, if you just read this.

Of course, context matters, or why else have three foregoing parts. Amidst it all, among the observed gaps in perceptions of time, of calendars and festive days, of literal gaps in them which create collective and individual gaps in our perceptions, somewhere lies a nub to get to.

They are gaps in giving and community, in welfare and support, underlined and highlighted, ad infinitum. The self-same gaps in perception signified in the email received, that first event thrusting its way into unguarded consciousness, I finally got around to explaining (at least to some extent) in pt3a.

It quoted and interpreted the findings of a comprehensive survey, carried out between July and September last year, in which, as an academic and self-employed professional, working in the third sector, with refractory, high daily seizure frequency epilepsy, I took part. They made for some grim reading, even for someone involved in legal advocacy for people with epilepsy, providing representation at employment and housing tribunals/legal proceedings, as well as being involved in academic research on the social model of disability as it applies to circumstance impacting neurological conditions.

Regardless of how realistic my academic and professional areas of interest make me about how epilepsy is perceived socially and how that impacts the lives of people with epilepsy, the key findings, of the survey, were stark. They hit me like the proverbial smack in the face with a wet fish.

Just so we’re clear, for anyone facing or living with neurological or mental disability, that too can constitute disabling circumstance, as you may have gathered from pt3a.

The survey focussed on work and consulted both people with epilepsy, to gather their experience, and employers, ‘to understand their attitudes towards people with epilepsy’.

Where it provided reasoning for surveying employers should probably have added some significant caveats. Whilst it summarised attitudes and some reasoning for them, it did very little in terms of explicitly ‘understanding’ them, particularly on behalf of people with epilepsy.

There are other past and recent surveys which might provide a bit more towards engendering that but, as with this survey, it is to be found as much in what isn’t said as in what is. We’ll get into it but, first a short, sharp blast of Epilepsy Action’s key survey findings about people with epilepsy in the workplace.

Bear in mind, whilst casting your perception (complete with all of its attendant gaps) over them, most of these relate to the 42% of people with epilepsy who are able to, or need to despite not really being ‘able’, seek or find employment. Probably also best borne in mind alongside the uncomfortable fact that people with epilepsy are paid 11.8% less than their non-disabled peers. Just because.

So, the scores on the doors? Read em and weep, or whatever your coping strategy is, then do…something?

• 42% of employers admitted they would be unlikely to employ someone with epilepsy to save their company potential challenges, even though they know this is legally discriminatory.
• Almost two thirds of respondents with epilepsy have experienced unequal treatment or discrimination at work because of it.
• Two in five respondents with epilepsy say their employer outright refused to provide reasonable adjustments, even when requested and legally required of them by the Equality Act 2010.
• Over a third (36%) have had their colleagues, manager or employer make derogatory (and thus also legally discriminatory) comments about their epilepsy.
• One in three have been directly and/or systemically bullied at work because of their condition, either by their employer, manager or colleagues.
• Likewise, nearly a third have been subjected to disciplinary proceedings for having seizures.

Following on from publishing the findings of their research, Epilepsy Action, in line with their campaigning aims, launched a petition to call on the UK Government to strengthen employment law, to make it fit for purpose, in terms of equalities provision. To do that, any legislation, or interpretation of it, should also ensure employers are properly punished for discriminating against disabled people generally and people with epilepsy specifically.

It is not a big ask. For people with epilepsy to be able to work without fear of being discriminated against, being bullied or treated unfairly ‘just’ because of their disabling medical condition.

Currently employment tribunal payments are made up of amounts allocated based on loss of earnings and missed opportunity. In theory, disability discrimination compensation awards are uncapped. In practice, the average award, across the UK, is just £13,500.

This clearly does not create enough of a deterrent to stop discrimination against people with epilepsy in the workplace, as borne out by the survey’s findings. Accordingly, Epilepsy Action’s petition, launched nearly four months ago alongside an awareness raising campaign regarding it, calls upon government to ensure that the Equality Act 2010 (and Disability Discrimination Act 1995 in NI) is fit for purpose by:

• Introducing minimum fines for any employer found guilty of discriminating against disabled employees. The minimum fine should be a percentage of the employer’s annual turnover.
• Ensuring that proceeds of these fines are given to the victims of discrimination to provide more meaningful compensation than awards currently being provided through the Tribunals service.

Epilepsy is the single most prevalent neurological condition across the UK. Demographics vary from country to country in incidence (the number of new cases) and prevalence (the overall number).

Overall, across the UK, just over 9 in every 1000 people have epilepsy. This means an estimated 633,000 people living with epilepsy.

When looking at constituent countries, there are slight differences. In England, the prevalence figure is just under 9 (8.85) in every 1000. In Scotland, it is just over 10 (10.13), in Wales, over 11 (11.4), in NI, over 12 (12.08).

This is also reflected in terms of incidence. Across the UK, there are/will be around 43 new cases of epilepsy in every 100,000 people, in one year.

In England, it is 37 people per 100,000; in Scotland, 48; in Wales 55 and in NI, 46. Overall, this means there are 28,313 new cases of epilepsy each year in the UK, or 79 a day.

Wigglesworth et al (whose comprehensive study, published in February 2023, these figures are drawn from) also found the prevalence and incidence of epilepsy in the UK is similar to that of other ‘high income’ countries, with peaks at younger and older ages and a ‘dip’ in the middle. They also noted a connection between ‘more deprived’ areas and a higher level of epilepsy. People in ‘the most deprived areas’ of the UK are, in excess of a third, more likely to have epilepsy than those in the ‘least deprived areas’.

So, the DWP report, there are 16 million disabled people across the UK. Some of those counted will also be people with epilepsy. It is worth noting, in relation to this, that where seizures are managed by medication or other treatment, for a person with epilepsy, they are not counted by the DWP as disabled.

This is wrong and relies upon a significant gap in perception, that people with epilepsy are only disabled by seizures. We’ll come back to that but, for now, it best serves the focus of this blog, as well as the lived experience of people with epilepsy, whilst allowing for some degree of crossover, to consider the 633,000 people with epilepsy as disabled, to greater and lesser degrees, through circumstance.

All of those people will have varying numbers of family and friends, partners, neighbours, work colleagues, wider social networks (IRL or virtual) and carers. Overall, thats a sizeable Venn diagram of cross demographics from which to draw support for a petition.

Any petition registered with the UK Government and Parliament website, which Epilepsy Action’s is, which gathers 100,000 signatures will be considered for a debate in Parliament. Reaching the 100,000 threshold means petitions are almost always debated.

The Petitions Committee are only likely not to put a petition, which meets the threshold, forward if the issue has been debated recently or there is a debate scheduled for the near future. Neither is the case with Epilepsy Action’s petition.

So, what’s stopping it being debated, given the seriousness of the issues its stated aims apparently hope to address? Well, as of the time of writing, some four months after it and the attendant awareness raising campaign were launched, it had only collected 1834 signatures.

Some of the reasons for this lack of overt support lie in perception gaps between people’s understanding of epilepsy and the reality of living with it. Sometimes this is as true of partners and relatives, friends and carers as it is of people with no experience of caring for people with epilepsy. The fear of seeing someone you love or care for in life threatening circumstance does not necessarily make it more likely you will understand what they are living through. Your perceptions are guided primarily by fear and risk management.

Whilst some of those fears may be absolutely grounded in experience, they are also supported, augmented, amplified by other unfounded fears, such as those rooted in perceptions of the legal status of people with epilepsy as a danger to themselves and others, often exploited by employers. Fears, perceptions and the discriminatory attitudes, towards people with epilepsy, which emerge from them are also rooted in deep, long held social and cultural prejudices.

Despite laudable aims, the petition appears to be faltering due to the very fears underlying discriminatory practice and attitudes highlighted in the survey, which gave rise to it, and which it hopes to address. Is there a hate crime of collective and individual meta-discrimination? Rhetorical as the question is (hint, there isn’t!), there bloody well should be!

The lie behind perception gaps exposed by this frustrating situation can also be explained and underlined by findings of an earlier study (Homes et al, 2018). Some of these were also highlighted in a later study by Angelini Pharma, sponsors of the #50millionsteps campaign.

We’ll return to them but note for now that their involvement brings us appropriately back to corporate charity washing, covered in pt3a. Unsurprisingly, Angelini also produce one of the latest anti-seizure medications to enter UK pharmaceutical and medical markets. It is currently seeing the highest and fastest growing rates of new prescriptions for epilepsy treatment across the UK.

We’ll also come back to ‘anti-seizure medications’ (ASM’s or AED’s, ‘anti epilepsy drugs’, as they were/are more commonly and, as the slight detour we are about to take should make clear, wrongly referred to) as an aspect of perception gaps in public understanding of epilepsy and disabling circumstance relating to it.

Let’s clarify a few things before proceeding.

The International League Against Epilepsy (founded in 1909, with the goal of improving the lives of people with epilepsy through academic and clinical research) gave its existing and clarifying definition of epilepsy back in 2005. It states that epilepsy is characterised by ‘an enduring predisposition (of the brain) to generate epileptic seizures and by the neurobiological, cognitive, psychological and social consequences of this condition’. These fundamental aspects of definition carried forward into a 2014 revision, which also began to refer to epilepsy as a ‘disease’ rather than a ‘disorder’, as it did previously.

This change was made specifically to underline that the disabling circumstance typified for people with epilepsy does not relate only to seizures but involves ‘a more lasting derangement of normal function’. It is a matter of lived experiential fact that, for a majority of people affected by epilepsy, challenges of the interictal state (ie those related to the consequences of seizures) are often more distressing than those directly related to the seizures themselves.

This means a comprehensive understanding of the disability related to epilepsy must not only take account of seizure manifestations and injuries but also of the physical and psychological/ emotional consequences of seizures for a person with epilepsy. It is almost impossible to assess these without also taking into account the particularities of epilepsy diagnosis and treatment, the first line approach to which is predominantly via medication.

Understanding of disability related to epilepsy, like all disability (as highlighted by the UN Convention on the Rights of Persons with Disabilities) remains incomplete and is an evolving concept. ILAE’s 2005 definition (and subsequent revisions to it) attempts to take account of the social model of disability as applied to epilepsy and as provided for in the UN’s approach to it. As such, understanding of disabling circumstance, as it relates to epilepsy, must remain cognisant of its social dimensions.

Epilepsy is not only disabling due to seizures typical of it but also through perceptions of them held by people experiencing them (as well as the ongoing and extended pre, post and interictal manifestations engendered) and due to perceptions (as well as gaps in them based on attendant disparities between perceived understanding and actual knowledge) held and acted upon by those around them and by society at large.

In 2018, analysis of extensive and comprehensive responses from the UK public to a stratified survey based on the Attitudes and Beliefs About Living with Epilepsy (ABLE) scale, by Holmes et al, explored the extent of unhelpful gaps in societal perceptions of epilepsy, as disabling circumstance not related to clinical aspects of seizures themselves or any attributes of those affected by them.

On the surface, some of their findings may seem encouraging. Analysis of survey responses found that, on the whole, the UK public has a relatively positive attitude towards epilepsy. There were, however, significantly troubling aspects to these findings, which appear counterintuitive to and undermine any encouraging elements.

A clear inverse relationship between self-reported knowledge about epilepsy and evidence of such knowledge was identified. The gaps in perception represented by this are particularly relevant to the lived experience of stigma and discrimination experienced by people living with epilepsy.

Real-life consequences of these gaps (as well as how people respond to gaps in their perception based on risk – see pts 2 & 3a of this series) mean it is difficult to reach those with the greatest need to learn more about epilepsy, since they perceive themselves (wrongfully, based on factual evidence of understanding or knowledge) as well informed about epilepsy as a disease. Educational efforts made, whilst facing these difficulties in ‘targeting’, are also complicated by the fact that higher level of (actual, not perceived) knowledge about epilepsy are also associated with greater risk and safety concerns. In turn, these are associated with the highest levels of stigma.

The 2018 study sought to redress an imbalance in understanding UK public perceptions of and attitudes towards epilepsy. Prior related research focussed on experience of stigma by people with epilepsy. Comprehensive research evidence of the associated negative societal attitudes prevalent in the UK was at best limited and at worst non-existent.

Researchers in the US developed the ABLE scale to measure public attitudes toward epilepsy and people with epilepsy. This is used longitudinally to measure changes in public perception, tracking changing attitudes over time.

Applying the same approach in the UK has the same potential to assist future planning on how to improve awareness and understanding of epilepsy, as well as to evaluate success, or not, of any such attempts. As a seminal study of its kind in the UK, Holmes et al hoped it would establish a baseline from which to develop further study and analysis.

As aspects of this, they noted that evidence of public attitudes should contribute meaningfully to the debate on internal perceptions of stigma. Consequently, they hoped that by using research like theirs as a basis for creating, strengthening and implementing policies to promote access to information and knowledge would help reduce stigma (and perceptions of it) surrounding people living with epilepsy.

Significant to this, the study found:

• Less than half of people understand epilepsy and seizure type prevalence, seizure first-aid and other epilepsy manifestations.
• More than a quarter of people do not know that people with epilepsy are protected by the Equality Act.
• Perceived knowledge (ABLE item ‘I believe I know a lot about epilepsy’) negatively predicted actual knowledge (knowledge test score). People who strongly agreed with the ABLE statement had a significantly lower test score than people who did not strongly agree with the statement.
• Statistically significant differences in attitudes were observed across age categories, with progressively more negative attitudes expressed with increasing age.
• Men had more negative attitudes on all scales
• People in employment had significantly lower risk and safety concerns but more fear, social avoidance and negative stereotyping compared to people not in paid employment.
• Risk and safety concerns were significantly lower for people with less perceived risk-based considerations (eg, people who had never been married or in a civil partnership and people with no children)

Several of these findings appear of particular significance and relevance to how stigma applied to people with epilepsy manifests. They are moving parts which interact with each other, culturally and socially influenced by statistically significant demographic factors. Taken in separation or interactively, they all relate to and arise from gaps in public perception.

As referred to above, 20% of people believe they know a lot about epilepsy and, of particularly relevant interest, an overwhelming majority of those people had a significantly lower knowledge base than the other 80% of people. Cumulative research in other fields (psychology, neuropsychology, sociology etc) indicates strongly that people who express a belief that they are more knowledgeable (generally and on specific subjects) and have a perception of themselves as better informed are more likely to display higher evidence gaps between their perceived and actual knowledge.

Noting this, Holmes et al assert that it, amongst all of their findings, most warrants further research in the context of epilepsy.

Also significant in their study, when assessing the relationship between stigma and knowledge, an incorrect response to the most commonly known items was associated with the greatest stigma. Almost inversely, association between attitude and knowledge in the domain of risk and safety indicates higher knowledge is associated with being more risk averse.

The study’s most negative findings relate to risk and safety in work and role expectations. Risk and safety at work, as well as in other public spaces, for people with epilepsy and for people around them, were found to be of highest concern to the UK public. These also gave rise to the highest levels of stigma and perceptions of it.

Analysis of the findings asserts that future agendas should ‘focus on improving knowledge, addressing risk and safety concerns, and dispelling misconceptions’. These assertions could, of course, be perceived as entirely congruent with the aims of UK based epilepsy charities, like Epilepsy Action, who co-funded the research.

Just a few short years after making them, gaps in perception of them became apparent and widened further. Epilepsy Action provided general support and supplementary data for publication of Angelini Pharma’s survey (conducted on their behalf by SWG), published in March 2021.

They became involved, however unwittingly, in Angelini’s marketing ‘blitz’ for the release of adjunct ASM/AED Cenobamate and licensing for its use, across the EU and in the UK, between 2021 and 2022. Chief Executive Philip Lee even wrote an article, based on the survey’s findings, for Pharma Times, which self-identifies as ‘the UK’s leading pharmaceutical magazine, tracking the trends and issues that affect the industry’.

For the sake of clarity and necessary distinction, that’s the pharmaceutical industry, not the charity or health care industries.

Neither of these things precludes the accuracy or efficacy of the survey’s findings. They may (and I would argue such things almost always do) direct what use those findings are put to.

The survey focussed on epilepsy and inclusion in society. It highlighted some of the clear discrimination people living with epilepsy in the UK face.

Amongst a number of discriminatory societal barriers emphasised by the survey (and Lee’s article), employment and access to it were underlined as particularly significant. In the article, Epilepsy Action, in relation to the survey’s findings, noted how people living with epilepsy ‘can encounter a number of challenges in…(and accessing)…the workplace, such as concern about disclosing their condition…(and)…how colleagues may react to seizures or factors that trigger a seizure’.

Before going on to highlight some of Angelini’s findings and data synchronous with them collected by Epilepsy Action contemporaneously, it is worth re-emphasising a few simple and well-established facts about people with epilepsy and employment.

Despite being the single (when considered under an umbrella which does not homogenise varying types) most common neurological condition, people living with epilepsy are, according to the Office for National Statistics, significantly less likely to be in work than the general population. The unemployment rate of 66% is also significantly higher than for people with most other disabilities. Those who are employed are paid 11.8% less than non-disabled workers.

So, of the estimated 633,000 people living with epilepsy in the UK, only 215,220 are in paid employment. For the other 417,780 people, significant barriers to accessing work opportunities are not rooted in the restrictions placed upon them by living with epilepsy alone but these are significantly exacerbated and compounded by ill-founded perceptions of it. Congruous with other data gathered and referred to herein, Angelini’s survey found that amongst people living with epilepsy:

• 38% would be afraid of losing their job because of their epilepsy and perceptions of it.
• 30% would be afraid to tell colleagues about their condition.
• 26% would be afraid to tell friends.
• 18% would be afraid to tell family.

The survey also revealed a significantly large gap in knowledge around seizures. This appeared, familiarly, rooted in misconceptions around epilepsy, which arise as a result of assumptions people form around it, or from inaccurate depictions in the media.

According to other research by Epilepsy Action, 73% of people in the UK believe epilepsy is characterised by just one symptom – convulsions (nb, this taxonomically describes one type of seizure).

Misunderstanding of epilepsy, in this general sense, extends further. One third of people, according to Epilepsy Action, said epilepsy does not impact mental health, whereas it disproportionately does. People with epilepsy are significantly more likely to to experience chronic anxiety and/or depression, leading to persistent suicidal ideation. These are also significantly exacerbated and compounded by the side effect profile of almost all AEDs/ASMs.

One in four people think epilepsy has no extended impact on a person’s life, other than having seizures. 52% of people state they would feel afraid if they witnessed someone having a seizure.

All related data highlights a significant societal disconnect and subsequent exclusion of people with epilepsy. This is based wholly in poor understanding of, as well as ill-founded perceptions around, epilepsy, leading to equally significant stigma and discrimination against people with epilepsy.

According to other Epilepsy Action surveys, more than half of people living with epilepsy wish people knew the impact of their condition goes far beyond seizures. One in five said their single biggest wish was for better public awareness that there are many different seizure types.

The Angelini survey also found significant numbers of the UK public understand people living with epilepsy face discrimination. 59% of respondents agreed that people living with epilepsy often face discrimination in the UK. This figure increased to 62% among people who personally know someone with epilepsy.

Quoting these surveys, studies and reports is building to a point, or points, and I will get there, honest (again) guv…

…the essential treatment goal for epilepsy, as determined by clinicians, is freedom from seizures. The global and national ‘disease burden’ of epilepsy is high. Lived experience of an epilepsy diagnosis confers significant disability on a person. This includes physical, psychological and socially disabling circumstance. These are proven to negatively impact self-esteem, family environment, relationships, leisure and working life.

Long-term outcomes for patients who have not responded to at least two ASMs/AEDs show they remain without significant improvement for more than two decades, or chronically, despite the recurring availability of many ‘new’ drugs.

A persistent fact of clinical trials and wider rollout of ASMs/AEDs, since records began, also remains that 35-40% of people with epilepsy do not and will not achieve freedom from seizures despite medical treatment. The probability of achieving the goal of seizure freedom decreases significantly with each failed treatment.

With one or two notable exceptions, almost all ASMs/AEDs are administered with long titration periods, testing for tolerance against efficacy. Almost all also have very similar side effect profiles and incidence/prevalence.

Most common among these are physically and cognitively disorienting or impairing, alongside high incidences of impaired cognitive function, anxiety, depression and suicidal ideation. These are all also common symptoms of epilepsy itself, which are then compounded by medical treatment, as well as being compounded further if or when adjunct treatment (ie, addition of a new drug alongside another tolerated one, which is either only partially improving seizure management or is not improving it at all, thus the perceived need to add another treatment) is considered.

It is not uncommon for balance of titration and tolerance (gradually building up dosage) against efficacy, introducing one prescribed drug, to take 4-6 months. This can result in improved seizure management or acknowledging a lack of efficacy or tolerance. If the latter two prove to be the case, a similar period is necessary to reverse titration, gradually withdrawing the initial drug, often whilst another is introduced with increasing titration, with side effects, dependency and withdrawal all creating confusing physical, psychological and neuropsychological impacts, whilst seizures, with all attendant extended cognitive and neurological disruption, persist.

For significant numbers of people, this will happen more than twice, as NHS clinicians are provided with few approved ‘tools’ to manage seizures, with medication being the default. This is despite it being a recurring feature of new drug trials, over time, that more than a third of people will not respond to this type of treatment. Given the long titration period and the persistence of clinicians trying ‘new’ medication or combinations of them, this can result in many years of attempting to manage seizures this way, with all attendant issues, resulting in significant and compound decreases in quality of life not always directly linked to seizures or epilepsy but to attempts to treat them.

All of these things (titration periods, side effect profile, compound impacts, percentage and probability of efficacy) remain true, in terms of lived experience for people with epilepsy, of Angelini Pharma’s new treatment drug, Cenobamate (branded in the UK and EU as Ontozry, and in the US as Xcopri). What differed, alongside clinical differences in how and where in the brain active molecules bind, was in how Angelini marketed their drug.

They actively worked with social care providers and epilepsy-based charities, alongside marketing to clinicians in a more familiar pattern, prior to release and licensing rollouts, to create a receptive market of end-users. This brought about a superficial veneer of considering both the social and medical models of disability in relation to epilepsy and their drug.

In the UK, this meant, epilepsy charities provided effective cover, or charity washing, alongside Angelini’s own commissioning of surveys and promotion of social media based epilepsy awareness raising campaigns, for Angelini’s profits. This appears to have been particularly true of Epilepsy Action.

The charity released a statement, in January 2022, following licensing for use of cenobamate in the UK (England, Wales and NI, with Scotland/SIGN following suit in February 2022) by the National Institute for health and Care Excellence (NICE), recommending use of cenobamate for treating focal onset seizures, with or without secondary generalisation, in adults with drug resistant or hard to treat epilepsy, in the NHS.

The NICE recommendation was based on evidence from two clinical trials showing the effectiveness of cenobamate. The larger of the two produced evidence that it reduced focal seizures by at least half in nearly two-thirds (65.2%) of people taking the largest dose (400mg). the most common side effects noted during the trial were sleepiness, dizziness and tiredness.

Daniel Jennings, senior policy and campaigns officer at Epilepsy Action, said:

‘We are very pleased that NICE has recommended cenobamate for use in treating people with focal onset seizures, particularly as a treatment for people whose seizures are currently uncontrolled. Epilepsy Action was involved with NICE’s appraisal process and supported proposals to recommend this treatment.

We know that with the right treatment the number of people whose seizures are controlled could increase significantly. Many people with uncontrolled or hard-to-treat epilepsy have tried a large number of medications without success. We welcome any new treatments that could offer people with epilepsy a better quality of life’.

There are two, almost oxymoronic, assertions made here. The first relates to Epilepsy Action being ‘very pleased that NICE recommended cenobamate for use’, having been involved with…(the)…appraisal process and supported proposals to recommend this treatment. The second relates to the seemingly obvious and anodyne assertion that Epilepsy Action ‘welcome any new treatments that could offer people with epilepsy a better quality of life’.

Reading this, you may of course wonder why these two aspects of the statement are referred to as ‘assertions’. A useful primer for understanding what follows, as a deconstruction of them, and which should help underscore them as, at least partially unfounded, assertions, may be to return to (or to read of you haven’t previously) pt3a, before continuing here. As always, context is everything and everything is context, right?

SIGN guidelines, used by the NHS in Scotland (whereas the NICE guidelines, referred to, are used in England and Wales), are more often than not largely in line with NICE guidelines. Where they are most often not is in where they provide context highlighting differing health related or medical challenges based on the demographics or particularities of the geographical areas where they are used. Sometimes this context also highlights issues which are not as considered as they should be for all areas and demographics.

This is the case with how SIGN guidelines for treatment of epilepsy differ from those provided by NICE. The appropriate national clinical guidelines, for reference given considerations made here, can be found at ‘SIGN 143 – Diagnosis and management of epilepsy in adults’ and ‘NICE guideline [NG217] – Epilepsies in children, young people and adults’.

It is also worth noting that SIGN explicitly acknowledges that its epilepsy guidelines conform to and utilise ILAE terms of reference. NICE does not.

Context provided by SIGN, relevant to considerations here, but also not explicitly provided by NICE, is as follows:

• ‘The low number of epilepsy specialists in previous decades means that many people with epilepsy across the UK have been diagnosed and treated by non-specialists in both primary and secondary care’
• ‘Epilepsy carries a small but significant risk of mortality which is increased where seizure control is incomplete’

• ‘Adherence to guideline recommendations will not ensure a successful outcome in every case, nor should they be construed as including all proper methods of care or excluding other acceptable methods of care aimed at the same results’

• ‘The crucial decision whether or not to start antiepileptic drug (AED) treatment must take into account the relative risks of recurrent seizures (including the small but important risk of SUDEP) and the commitment to long-term medication with potential adverse side-effects’

• ‘Complementary therapy is increasingly popular with patients, who may use this in addition to conventional medication…There is no consistent evidence to support, or definitively exclude, the use of any particular type of complementary to improve seizure frequency in patients with epilepsy.’
• ‘The effect of AED withdrawal on the risk of seizure recurrence has not been adequately studied.’

• ‘Antiepileptic drug adverse effects are common and a major cause of drug failure. Most are mild but a minority can be life-threatening. Accurate data on prevalence of adverse drug reactions (ADRs) with long-term AED treatment is scarce; almost all reports refer to short-term clinical trials and, as experience…has shown, long-term surveillance is needed to identify all ADRs.’

• ‘The law of diminishing returns may require patient and doctor to accept the persistence of some seizures once a range of treatment options has failed and where surgery is not an option. Adequacy of seizure control must be balanced with optimal quality of life.’

The penultimate of these contextualising statements, quoted directly from the SIGN guideline, provides the key to understanding the others, as well as the conflicting/conflicted nature of Epilepsy Action’s cenobamate press release, quoted above, including its reference to involvement in NICE’s ‘appraisal process’. As with the release of most drugs to market, particularly with what are referred to by both NICE and SIGN as AEDs, cenobomate was given a NICE recommendation following pre-release, short-term clinical trials. SIGN followed on from this recommendation and likewise recommended cenobomate for use in Scotland.

Where drugs appear to reduce seizure frequency in the short term, both NICE and SIGN guidelines ignore the fact highlighted by the ‘crucial decision’ referred to above. This short-term evidence will be used to gain the patient’s consent for a ‘commitment to long-term medication with potential adverse side-effects’. Whilst some of these are acknowledged as ‘life-threatening’, there is also an acknowledged lack of data/study regarding their emergence from long-term use.

When the balance of tolerance (ability to continue drug use despite side effects), reduction of seizure frequency and the patient’s quality of life is upset by continued usage, with tolerance and quality of life lessening, the only option available to doctor and patient is to reduce titration or to withdraw the drug entirely. And yet, the guideline also acknowledges ‘The effect of AED withdrawal on the risk of seizure recurrence has not been adequately studied’.

In line with this, SIGN also acknowledges that ‘the guideline development group was not able to identify sufficient evidence to answer all of the key questions raised in attempting to formulate guidance for treatment and care of people with epilepsy’. SIGN say the quiet bit, which NICE implies, out loud.

Following on from this, SIGN goes on to acknowledge other areas, aside from those mentioned above, where they make ‘Recommendations for Research’, some of which appear fundamental. Some of these are demographic specific but those which are general and seemingly foundational are:

• ‘What is the best first-line therapy for patients with focal seizures? (Comparison of new with old AEDs)
• ‘What is the best first-line treatment for patients with generalised seizures?’
• ‘What non-drug therapies and surgical interventions are most effective for different types of seizure?’
• ‘How should bone disease be screened for in those with epilepsy on AEDs?’
• ‘What are the optimum models of care for epilepsy in community, secondary and tertiary care?’

So, just to summarise, before returning to the key phrase in clinical guidelines, referred to above, and frequently used by care providers at all levels, as well as in almost all health care provision and health based third sector or charity-based provision, ‘quality of life’, the basis for proceeding with clinical intervention and drug-based medical treatment of epilepsy is as follows:

Treatment in the UK proceeds on the basis of NICE and SIGN guidelines, which also acknowledge this is and has been just as likely to be based on diagnosis by ‘non-specialists in both primary and secondary care’, as by specialist clinicians. Neither have evidence or data to support what is the best first-line drug treatment, whether seizures are focal, generalised or both.

They also have a lack of data to support what non-drug therapies and surgical interventions are most effective for different types of seizure. Likewise, they have a lack of data supporting recommendation, or definitive exclusion, of any other complementary therapy.

On these bases, drug treatment remains first-line, despite adverse drug reactions being ‘a major cause of drug failure’ and there being a distinct lack of study or recorded data of and for long-term side effects, with drugs recommended for long-term usage based on short-term clinical trials. Provision of community, secondary and tertiary care is largely focussed on seizure first aid and management of thus prescribed drug regimes alongside the emerging side-effects/ADRs which they cause. This continues, with charities and third sector providers embedded in provision, despite there being no evidence or data to support ‘optimum models of care for epilepsy’.

Some third sector provision of care becomes hybrid, in that it is initially provided for or funded by charities to other third sector organisations but uses NHS staff. One such provider is considered the ‘gold standard’ of care and treatment, including diagnosis, for epilepsy in Scotland, being the William Quarrier Scottish Epilepsy Centre, founded by the Quarriers epilepsy charity.

Clinicians (including diagnosing and prescribing neurologists) and care staff there operate on the same bases and lack of general study/evidence outlined above. They are able, via extensive video telemetry, to work with individual patients’ thus identified seizure patterns to attempt optimising treatment, including recommending neuropsychological support.

Where there is a lack of data or study of long-term effects of both seizures and drug-based treatment of them, there is a significant body of evidence supporting the long-term increasing co-morbidity of neuropsychological, psychological, psychiatric and general mental/emotional health and well-being issues for people with epilepsy. The focus of this is well summarised by Berg et al, in their 2017 study ‘Psychiatric and Behavioral Comorbidities in Epilepsy: A Critical Reappraisal’:

‘Beginning around 2000, studies started to raise…explanations. Specifically, investigators began reporting that psychiatric disorders and behavioral problems were already present at or near the time when people were first diagnosed with epilepsy and suggested these disorders predated the onset of seizures.

Other studies demonstrated higher rates of psychiatric diagnoses both before and after the diagnosis of epilepsy. This has been termed the “bi-directional” association between epilepsy and psychiatric comorbidity, and was recently employed in reference to autism spectrum and attention deficit hyperactivity disorders.

In all, the repeated findings that psychiatric diagnoses and behavioral problems predated the onset of epilepsy suggested that the psychiatric and behavioral disorders were not simply due to the reactions to epilepsy and its consequences but might, in some patients, actually be related to expression of the same underlying pathophysiology that is involved in the seizures (epilepsy) themselves. Much research has since been devoted to demonstrating this association in different populations. The notion of psychiatric and behavioral disorders as part of the spectrum of the expression of epilepsy has become generally accepted.

In theory, a disorder or associated dysregulation that drives a brain to have seizures could also affect other aspects of brain function including behavior and mood. This is because some epilepsies implicate common networks involved in the expression and regulation of mood. For instance, frontal-temporal dysfunction has been implicated in mood and anxiety disorders, including suicide related behavior and post-traumatic stress disorder.

It is likely that seizure foci in frontal or temporal regions as well as white matter changes affecting functions in or between those regions could disrupt those pathways. The epilepsies, however, are a diverse set of disorders, and studies should reflect the different specific diseases that are grouped together as epilepsy.’

What is not mentioned in the study’s findings, apropos as their conclusions may be, is that for a vast majority of people with epilepsy who are treated with drugs, it is not possible to tell the difference between a co-morbid psychiatric or behavioural ‘disorder’ as a bi-directional emergent property of a brain, or root epileptiform in it, pre-disposed towards seizures or as an ADR developed through long-term drug use. Regardless of which is the case or what balance there is between them, not being mutually exclusive, a significant. Body of evidence exists to confirm the following:

People with epilepsy are at a compound higher risk of mental heath issues, such as stress, anxiety or depression, by a factor of x3-x5 that of the general population. 87% of people with epilepsy have experienced significant co-morbid symptoms of mental health issues.

69% say the biggest impact on their mental health was feeling that epilepsy limited their independence. 59% worry about having seizures in front of other people.

Misplaced perception, stigma and lack of understanding also play a big part. Almost a third (29%) say people have shown negative attitudes towards their condition, which affected their mental health.

Nearly a quarter of people in the UK admit they would be scared to be in a room with someone with epilepsy ‘in case they had a seizure’. A further 24% say this would make them ‘uncomfortable’.

These unfounded perceptions and stigmas push people with epilepsy to feel even more anxious, misunderstood and lonely. 84% have experienced anxiety and exactly half (50%) of people with the condition report feeling isolated.

It is impossible to find a drug used to treat epilepsy which does not have listed among the side effects, based on short-term trials and likely to be significantly more prevalent if longer term surveillance of ADRs had been/is conducted, often given as ‘common’, anxiety, depression, mood disorders and/or suicidal ideation. This is true of cenobomate.

So, with all of that taken into account, what of the likely ability of clinicians, caregivers, family, friends and people with epilepsy themselves to assess a balance between seizure frequency, ADRs and quality of life? The basis for the unlikely target (at least for a persistent 30-35% of people who remain treatment resistant, with a significant proportion of people also learning to tolerate debilitating ADRs in pursuit of it) of freedom from seizures as the aim of epilepsy treatment is rooted in the presupposition that this will be an optimal improvement of quality of life, despite a distinct lack of evidence (particularly balanced against the negative effects of long-term drug use) to prove this in the longer term.

All of these factors must be considered by neuropsychologists or neuropsychiatrists (and in terms of working with the bi-directional co-morbidities developed alongside epilepsy, it should always be these, as clinicians with a neurological founding of practise or neurological speciality, in order to be able to treat the persistence of mood disorders rooted in a neurological condition, as well as treatment and societal perceptions of it, to not be counter intuitive) as they are by the head neuropsychologist at the William Quarrier Scottish Epilepsy Centre, Dr Iain Campbell.

This blog spoke to Dr Campbell regarding these issues, with a particular focus on the psychological and psychiatric impact of drugs used to treat seizures. Note the emphasis here, ‘to treat seizures’, not to treat epilepsy, as intimated by the commonly used acronym AED.

Dr Campbell never refers to AEDs. This is because his clinical practice over many years has shown that as many mood disorder comorbidities associated with epilepsy are likely to emerge from drug treatment as they are from epilepsy itself. The efficacy of drugs in pre-market, short-term trials, is determined only by their impact on seizure frequency, not any of the other clinically determined factors, supported by significant volumes of study, experienced by people with epilepsy. These are more often exacerbated by long-term drug use than alleviated by it.

A much more appropriate acronym is available and used by Dr Campbell, who encourages its use by other staff and patients. It is based on the predominant drug target of seizures to the wilfully exclusion of other debilitating effects/ADRs. It is far more appropriate and reflective of both the available evidence and the lived experience of people with epilepsy; it is ASMs, or Anti-Seizure Medications.

Understanding and studying long-terms ADRs and both the symptoms, as well as root causes of which they emergent properties, of types and co-morbidities experienced by people with it, are key to understanding what ‘quality of life’ means in the context of epilepsy. This is not exclusive to epilepsy as a medical and/or neurological condition and is also key to understanding the disabling circumstance associated with it and any other such conditions.

In 2019, Haraldstad et al published ‘A systematic review of quality of life research in medicine and health sciences’. It noted:

‘Quality of life (QOL) has become established as a significant concept and target for research and practice in the fields of health and medicine. Traditionally, biomedical and not QOL outcomes have been the principal endpoints in medical and health research. However, during the past decades, more research has focused on patients’ QOL, and the use of QOL assessments has increased.

Understanding QOL is important for improving symptom relief, care, and rehabilitation of patients. Problems revealed by patients’ self-reported QOL may lead to modifications and improvement in treatment and care or may show that some therapies offer little benefit. QOL is also used to identify the range of problems that can affect patients. This kind of information can be communicated to future patients to help them anticipate and understand the consequences of their illness and its treatment. In addition, cured patients and long-term survivors may have continuing problems long after their treatment is completed. These late problems may be overlooked without QOL assessment. QOL is also important for medical decision-making because QOL is a predictor of treatment success and is therefore of prognostic importance. For instance, QOL has been shown to be a strong predictor of survival. This prognostic ability suggests that there is a need for routine assessment of QOL in clinical trials.

Despite the importance of QOL in health and medicine, there is a continuing conceptual and methodological debate about the meaning of QOL and about what should be measured. There is no uniform definition of the concept; however, The World Health Organization (WHO) outlines one definition of QOL; “An individual’s perception of their position in the in the life in the context of the culture in which they live and in relation to their goals, expectations, standards and concerns”.

Moreover, the term health-related quality of life (HRQOL) is often described as: “A term referring to the health aspects of quality of life, generally considered to reflect the impact of disease and treatment on disability and daily functioning; it has also been considered to reflect the impact of perceived health on an individual’s ability to live a fulfilling life. However, more specifically HRQOL is a measure of the value assigned to duration of life as modified by impairments, functional states, perceptions and opportunities, as influenced by disease, injury, treatment and policy”.

QOL is a complex concept that is interpreted and defined in a number of ways within and between various disciplines. As a consequence, many different instruments are now used to assess QOL. These instruments were developed based mainly on empirical considerations and have not been developed from a definition or a conceptual model. Consequently, there is a lack of conceptual clarity about what QOL means and measures, which may pose a threat to the validity of QOL research.’

And concluded:

‘Knowledge about QOL is important for understanding the consequences of illness and treatment, and for medical decision-making across age groups and culture. QOL is an important endpoint in medical and health research, and QOL research involves a variety of target groups and research designs. However, based on the current evaluation of the methodological and conceptual clarity of QOL research, we conclude that many QOL studies in health and medicine have conceptual and methodological challenges. There is a need for improvements in this field, and researchers should pay closer attention to methodological and conceptual issues when planning QOL studies.’