Highlights
- •The determinants of cognitive impairment in epilepsy are known since long.
- •After 20–30 years of extensive research, neuropsychology still struggles with knowledge transfer to individual patient care.
- •Progress in regard to diagnostics, disease, and outcome monitoring is discussed.
- •National and international efforts for reaching a common diagnostics are outlined.
- •Proposals for indication of assessment and an evidence based test selection are made.
- •The impact of neuropsychology on safer surgery and drug treatment and on outcome prediction are discussed.
- •The necessity to assess and follow up patients from the beginning of epilepsy is pointed out.
Abstract
Some of the roots of current clinical neuropsychology go back to the early days of epilepsy surgery. Looking back a huge number of publications have dealt with cognition in epilepsy. The major factors driving this work were questions relating to surgery, antiepileptic drugs and, more recently, also to underlying pathology. However, most factors affecting cognition in epilepsy have been discerned many years ago. The body of neuropsychological literature in this field has accumulated much knowledge, raising the question why, apart from epilepsy surgery settings, neuropsychology has still not been fully integrated in the routine care of patients with epilepsy. This review on the occasion of Seizure’s 25th anniversary attempts to summarize clinically relevant diagnostic advances following a question guided, modular, and evidence-based approach. In doing so, we hope to attract the interest of readers to an exciting mode of assessment which does not only have theoretical but also practical relevance. The comorbidities of epilepsy are becoming an increasingly relevant topic. It is now widely accepted that, while epilepsy may be defined by the occurrence of epileptic seizures, these seizures represent only one of several possible sources of cognitive impairment. It is well-established that there are complex interactions between epilepsy, cognition and behavior, and that both seizures and problems with cognition or behavior may result from a common underlying pathology requiring treatment. With this review we aim to demonstrate that neuropsychology can make a highly valuable contribution to the care of individual patients by contributing to the diagnostic process and by serving as a tool for the monitoring of disease and treatment, thereby improving the quality and safety of patient care. On a national, European, and international level, first efforts are being made to homogenize diagnostics across epilepsy centers and countries in order to achieve a common language and core standards. This should improve communication within and outside the speciality, and help to generate the data required to allow the field to make further progress.
Keywords
1. Introduction
Nearly 30 years ago, Michael Trimble, in an article published in Epilepsia, described the cognitive hazards of seizure disorders, identifying the major factors to be considered with cognitive impairment in epilepsy in two groups of patients with this disorder, i.e. underlying brain damage, age at seizure onset, seizure type and frequency, as well as antiepileptic drugs (AEDs) [
[1]
].He was not the first to raise the question of what the reason for cognitive deficits in epilepsy may be, but this early study already revealed an understanding of the complex and multifactorial etiology of cognitive impairment and decline in epilepsy. The question of mental impairment and decline in epilepsy is old and was discussed as “epileptic dementia” in medical texts as early as at the turn of the 19th century [,
3
, 4
]. At that time, with reduced knowledge about the different structural, metabolic, and genetic causes of epilepsy, epileptic dementia was thought to manifest in 50% of all patients. Interestingly, the mental problems were mainly attributed to what was considered as non-lesional epilepsy in these days. While it should be pointed out that the term “dementia” is used differently today (when it specifically refers to progressive mental decline) these early writings demonstrate that, although seizures were the main focus of medical interest, cognitive and behavioral (personality) abnormalities were well-recognized and thought to be directly linked to the disorder.Stimulated by the success story of epilepsy surgery starting in 1935 [
[5]
] and by new antiepileptic drug developments from the 1960s and 70s, a large body of neuropsychological research on cognition and epilepsy has accumulated over the past decades [[6]
]. With an increasing understanding of the mechanisms underpinning the epilepsies, etiological models of cognitive impairment in the epileptic disorders became more elaborated, but the basic determinants are still the underlying static versus dynamic brain pathology, epileptic activity (both in terms of seizures and interictal epileptic dysfunction), psychiatric comorbidity and treatment effects [[7]
]. In addition, newer models underline the relevance of personal and sociocultural variables as well as, most importantly, the neurodevelopmental context (i.e. differences between the developing versus the ageing brain). Along with progress in brain imaging, neuropathology and genetics, the number of epilepsies with an unknown etiology has reduced significantly, prompting changes in seizure and epilepsy classifications but also the appreciation of the cognitive impairments in epilepsy [[8]
]. In contrast to a traditional epilepsy-centric view according to which cognitive impairments and behavioral problems are the result of having seizures, new etiological models increasingly consider neuropsychological problems as one of several comorbidities of epilepsy [9
, 10
]. Cognitive impairment can be the consequence of epilepsy but can precede the development of epilepsy as well, and epilepsy and cognitive impairment can both be comorbidties resulting from the same underlying pathology [[11]
]. The major consequence for clinical practice is that it is not sufficient to treat seizures to resolve the cognitive problems seen in patients with epilepsy. Neuropsychology represents an independent approach to the patient, his disorder and its underlying pathology and may call for therapeutic interventions other than those primarily directed at reducing the number of seizures.On the basis of this theoretical framework, what follows in this review is a discussion of the highly relevant question of how, thirty years after Michael Trimbles work, and after 80 years of epilepsy surgery, accumulated neuropsychological knowledge does or does not translate into the routine care of individual patients. We will consider this question in relation to neuropsychological diagnostics, monitoring of the disorder and its treatment, patient counseling, and therapeutic decision-making.
2. Advances in diagnostics
UCB and John Libbey sponsored a meeting in Toronto, Canada, on 3–6 November, 2010, involving 66 specialists from 13 countries representing expertise in adult and pediatric neuropsychology, psychiatry, and neurology; neuroimaging, cognitive neurosciences, electrophysiology, pharmacology, and other fields. The overarching idea and very practical aim of the meeting was to disseminate evidence-based neuropsychological practice in the care of children and adults with epilepsy around the world.
It became evident that standardized neuropsychological assessment has become an integrated and essential tool in the diagnostic and clinical evaluation of patients considering epilepsy surgery. However, there was a great heterogeneity of assessments and their application, and despite progress in other diagnostic fields and in the treatment of epilepsy, clinical neuropsychology in epileptology still appeared to be very focused on epilepsy surgery, especially temporal lobe surgery. There was little indication that it had secured a clear role in the routine care of patients with epilepsy outside epilepsy surgery evaluation. At that time Medline listed as many as 3000 publications under the search “epilepsy and cognition”. Thus, major developments in cognitive neuroscience and the vast number of clinical studies on epilepsy, cognition and mind, had obviously not found their way into routine clinical practice. One of the outcomes of the Toronto meeting was the publication in the Progress of Epileptic Disorders Series by John Libbey in 2011. This publication continues to be a very comprehensive compendium which provides an overview of the state of the art at that time [
[12]
].Following this publication and an inquiry of all members of the ILAE Neuropsychology Task Force, Bruce Hermann, Madison Wisconsin, who was one of the organizers of the Toronto meeting and the leader of the Task Force at that time, summarized the strategy for the future as listed in Table 1.
Table 1Future tasks for neuropsychology in epilepsy (as formulated in 2011).
1. Top priority: Definition of optimal cognitive and behavioral measures for screening epilepsy-related impairments in different types of epilepsy (i.e. epilepsies with different etiologies), and to define …
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2. Secondary aims were …
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Meanwhile the ILAE task force, now under the leadership of Sarah Wilson, University of Melbourne, Australia, has published a consensus paper on the indications for and expectations of neuropsychological assessment in routine epilepsy care [
[13]
]. The paper addresses what the role of neuropsychological assessment is, who should carry out a neuropsychological assessment, when people with epilepsy should be referred for neuropsychological assessment, and what can be expected from it. This consensus document provides an excellent structural framework for neuropsychology in epilepsy care. However it does not spell out which tests would be most appropriate to address the priorities listed above.Coincidentally in 2013 a pan-European project (E-pilepsy; www.e-pilepsy.eu) involving 13 epilepsy reference centers and 15 associated centers was initiated funded by the EU Agency for Health and Consumers. This collaboration aims to improve awareness and accessibility of surgery for epilepsy across the EU. Part of this project is the homogenization and dissemination of evidence-based best practice in imaging, EEG monitoring, and neuropsychology. Current practice has been reviewed, a literature search on best practice is being undertaken. The resulting conclusions will lead to the construction of a website for patient evaluation allowing multicenter use. Overviews on the present state of imaging and EEG-monitoring in the EU have been published [
14
, 15
], the data on neuropsychology have been evaluated and will soon be published. In concordance with older studies dating back 23 years [[16]
], 11 years [[17]
] and, more recently, 5 years [18
, 19
] the data continue to indicate that different centers (not to mention different countries) use a tremendous diversity of neuropsychological tests and examination protocols [[20]
]. There is, however, general consensus on which functional domains need to be considered but not on which tests should be chosen to undertake the assessments. More than 160 different tests are in use, no standardized protocols for dominance assessment and outcome prediction are in sight, and the choice of particular tests in epilepsy is still very much determined by general neuropsychological considerations and individual preferences rather than by published evidence in epilepsy. Language lateralization is now commonly done by fMRI but only two centers provided the requested decision tree for indication and surgical decision making according to the protocols. Nevertheless for neuropsychological assessment a core battery could be extracted from the inquiry, which, if confirmed by literature review, has the potential to be agreeable across centers (see Table 2). Unfortunately most EU-centers did not provide published evidence for use of their tests to answer specific epilepsy-related medical questions. Frequent use of individual tests, fMRI, or IAT paradigms thus rather reflects experience-based preferences (voting by the feet) than suitability and validity in patients with epilepsy.Table 2Frequent and recommended tests for use in epilepsy.
| Domain | Tests used across EU centers | Common data elements |
|---|---|---|
| Intelligence | Wechsler Adult Intelligence Scale (WAIS), Wechsler Intelligence Scale for Children (WISC) | Wechsler Adult Intelligence Test-Fourth Edition (WAIS-IV) or short form (WASI) |
| General performance level | Montreal Cognitive Assessment | |
| Development | Bayley Scales of Infant and Toddler Development (BSID), Vineland Adaptive Behavior Scales (VABS) | Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III), Mullen Scales of Early Learning (MSEL), Bayley Scales of Infant and Toddler Development (BSID) |
| Motor functions | Finger tapping, Luria motor sequences | |
| Attention, executive functions, working memory | Trail Making Test (TMT) A & B, Digit span, Corsi block-tapping test | Trail Making Test (TMT) A & B, Digit Span subtest from WAIS-IV/WISC-IV, Wisconsin Card Sorting Test (64 card version) |
| Verbal memory | Rey Auditory Verbal Learning Test (AVLT) | Rey Auditory Verbal Learning Test (AVLT) |
| Figural memory | Rey-Osterrieth Complex Figure Test (ROCFT) delayed recall | Brief Visuospatial Memory Test − Revised (BVMT-R), Rey-Osterrieth Complex Figure Test, Wechsler Memory Scale Visual Reproduction |
| Language | Boston Naming Test (BNT), phonemic & semantic fluency tests | Boston Naming Test (BNT), Controlled Oral Word Association (COWA), aka FAS, Animal Fluency, aka Animal Naming |
| Visual spatial functions | Rey-Osterrieth Figure (ROCFT) copy, WAIS Block Design | WAIS-IV or WASI block design |
| Adverse events | Adverse Event Profile (AEP) | Hague Side Effects Scale (HASES) |
| Mood, quality of life | Beck Depression Inventory (BDI), Quality of Life in Epilepsy (QOLIE), Child Behavior Checklist (CBCL) | Beck Depression Inventory (BDI), Quality of life in neurological disorders (Neuro-QoL), Child behavior Checklist (CBCL), Child depression inventory (CDI) |
| Language lateralization | fMRI: Word generation tasks, naming tasks | |
| IAT: Counting tasks, naming tasks, materialspecific memory tasks | ||
| Transient cognitive impairment | no test which would be shared |
Table 2 contains additional information provided by the so-called common data elements from the National Institute of Health (NIH, USA), a source of surveys, questionnaires, instruments, instrument items, and other methods of data collection, which provides the highest level of evidence in clinical studies and the best scientific basis for research in epilepsy (https://commondataelements.ninds.nih.gov/Doc/EPI/F1140_Overview_of_Recommended_Neuropsychology_Instruments.docx).
Positive is the overlap of the results of the EU survey with the NIH common data elements, indicating on where the efforts converge.
This is the place also to mention the work of the Bozeman Epilepsy Consortium in the US which addressed neuropsychologically relevant diagnostic questions in a multi-centric way [
[6]
]. The knowledge gained from group studies, however was not explicitly translated into individual diagnostics and prognostics.In terms of what an evidence-based diagnostic toolbox for use in epilepsy may look like, we recently proposed a strictly question-guided and modular diagnostic approach, which does not only provide descriptive information but should make a difference to patients, their treatment, and treatment outcomes [
[21]
] (see Table 3, references for the measures used in epilepsy can be found in Ref. [[21]
]).Table 3Question-guided modular neuropsychological evaluation.
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Having outlined recent developments aiming to achieve more homogeneous and evidence-based neuropsychological diagnostics in epilepsy, we will next discuss how neuropsychology can help improve individual patient’s care in terms of surgical and medical treatment.
2.1 Advances in presurgical diagnostics and outcome control of epilepsy surgery
Epilepsy surgery has been and continues to be one of the major driving forces for progress in neuropsychology in epilepsy [
[6]
]. In its beginnings, neuropsychology was used in the evaluation of patients with focal epilepsies to provide the localization and lateralization of cognitive dysfunctions and thus give hints to structural lesions and epileptic foci. This role changed very much with the improvement of neuroimaging. Nevertheless, and this is linked to the previous section of this review discussing diagnostics, measures are still needed which are sensitive to detect neuropsychological deficits associated with lesions or dysfunctional brain structures in different parts of the brain and which can be reliably used to monitor the effects of invasive treatments with the potential to damage the brain [[22]
]. Within certain limits such a diagnostics can detect dysfunction associated with the left vs. right hemisphere, frontal, central, parietal, occipital, temporal lobe or temporo–mesial structures. However, the choice, use and interpretation of tests of specific functions requires consideration of factors such as neurodevelopment [[23]
], processes of plasticity [24
, 25
], compensatory and restitutional processes [26
, 27
] and gender differences [[28]
]. Mental health problems and motivational factors need to be considered as well, the latter especially in children. In addition practitioners have to be aware that brain functions (and the neuropsychological test measuring them) are complex, hierarchically structured, and not independent of each other [[29]
].Meaningful neuropsychological assessment of patients with epilepsy cannot be limited to psychological performance diagnostics. Simple performance measurement may be related to everyday functioning but it is likely not to reveal detailed information about the impact of the disease, its pathological features or treatment on cognition. For simple performance diagnostics it would probably be sufficient to carry out a screening test like the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment (MOCA) [
[30]
], or (more complex and time consuming) a Wechsler intelligence battery [[31]
], or (even more time consuming) an additional Wechsler memory scale [[32]
]. However, if a patient is tested whilst exposed to a high load of AEDs with possible adverse effects on cognition, and no screening of cognitive drug effects has been performed, IQ testing may easily underestimate the patient’s capabilities [[31]
].Better imaging, more sophisticated invasive and noninvasive EEG, advanced surgical procedures and the monitoring of surgical outcomes with sensitive neuropsychological measures has resulted in increasingly selective and individually tailored surgical approaches aiming to restrict surgery to affected and non- or dysfunctional tissues while sparing non-affected and functional tissues. This is true for temporal as much as for extratemporal lobe surgery, especially since imaging of focal cortical dysplasia has improved.
Review articles are still inconclusive as to whether tailored versus extended standard resections are more successful in terms of patients achieving seizure freedom [
33
, 34
, 35
]. When considering meta-analytic studies aiming to address this question, however, one must take into consideration that they mix very different patient groups with very different starting conditions who are mostly not matched in terms of underlying pathology. In addition, different centers and different surgeons may have variable and individual surgical approaches, and they may be subject to a personal learning curve [[36]
]. These are all factors which have not been systematically taken into account. Under the proposition of a technically diligent surgery, the achievement of seizure freedom is presumably less closely related to the surgical approach than to the presurgical work up. If the epileptogenic lesion and zone can be clearly localized, selective surgery should be as successful as extended standard resections, and if the diagnostic situation is less clear a more extended resection might be advantageous.Early studies on the lateral extent of 2/3 anterior temporal lobectomy (ATL) and the comparison of 2/3 ATL and selective amygdalohippocampectomy in patients with pure mesial hippocampal sclerosis already provided evidence of the negative effects of the resection of functional tissues which were not involved in seizure generation [
[37]
]. Meanwhile several studies have demonstrated the relevance of the damage of the temporolateral neocortex for memory and language outcome after different surgical approaches, and there are other studies showing that the degree/volume of hippocampal resection correlates with postoperative loss in memory [[37]
]. Recent developments in regard to radiotherapy and highly selective stereotactic radiofrequency therapy have the potential further to improve patients’ functional outcomes without diminishing the chance of becoming seizure free [38
, 39
, 40
, 41
]. Similar trends are seen in extratemporal lobe surgery of developmental malformations [- Feng E.S.
- Sui C.B.
- Wang T.X.
- Sun G.L.
Stereotactic radiosurgery for the treatment of mesial temporal lobe epilepsy.
Acta Neurol Scand. 2016; (February 4 [Epub ahead of print])https://doi.org/10.1111/ane.12562
42
, 43
].In summary, the clear and simple message which comes across from these studies is that the resection or collateral damage of non-affected functional brain tissues has negative cognitive consequences. Severe postoperative memory decline in MRI negative and histopathologically negative patients may serve as particularly compelling proof of this principle [
[44]
]. In terms of the surgical target region, morphological integrity as determined by structural imaging and functional integrity as indicated by sensitive neuropsychological testing and functional imaging should be red flags. In addition, from a neuropsychological perspective, minimally invasive treatment with minimal collateral damage is preferable. It is unlikely that the historical refinement of neurosurgical approaches would have occurred without routine presurgical neuropsychological testing. Likewise it is unlikely that current and future surgical techniques (for instance thermocoagulation or brain stimulation) will be refined further (and that the quality of local surgical programmes can be assured) without neuropsychological assessment being a core feature of pre- and postsurgical assessment.Table 4 provides more details about procedures which can support the individual counseling of patients with regard to the benefit-risk-evaluation before temporal lobe surgery. It must be noted, however, that because of variations of surgeries and surgical approaches in combination with varying pathological conditions, no exact functional outcome prediction can be expected, not now, and probably also not in the near future. Furthermore, methods validated in one center cannot simply be transferred to other centers without matching of procedures including neuropsychological outcome measures.
Table 4Outcome prediction, patients counseling.
| 1. There are so-called regression-based prediction models which take patient characteristics and performance levels into consideration. This approach is elegant but requires a large, high-quality database and is difficult to transfer to other centers [45] |
| 2. Intracranial EEG measures, fMRI and the Wada test have been used for individual memory prognosis but this does not apply to all temporal lobe surgery approaches and again there is no standard to be used across centers 46 , 47 , 48 , 49 |
3. Rules of thumb inferred from publications, as there are …
|
4. Probabilities of significant individual declines in memory (not taking into consideration the degree of loss, different dependent measures or surgical procedures):
|
Thus, individual level counseling about the likely specific functional risks of epilepsy surgery is, at present, only possible on the basis of a collection of clinical markers in addition to classic neuropsychological assessment. On this basis some trend (better, unchanged, worse) can be formulated without excluding that it might come different. In this regard, other functional test modalities (for instance fMRI) do not yet allow clinicians to clearly delineate the specific risks of epilepsy surgery for individual patients in isolation. The study which derives a good prediction model in one cohort and which would show its value by prospective application in another cohort is still missing.
For extratemporal surgeries comparable data are not available, most likely because this group is too small and too heterogeneous. The principles, however, can be assumed to be the same.
2.2 Advances in monitoring antiepileptic drug (AED) treatment
Pharmacological treatment is the main therapeutic approach in epilepsy, controlling seizures in about 70% of the patients [
[61]
], and, unlike many other aspects affecting cognition, treatment is in under the direct influence of the physician. However, cognitive side effects of antiepileptic drugs are common. They can negatively affect tolerability, adherence, and long-term treatment retention. Patients’ willingness to accept side effects is very low even when seizure control is achieved, and psychiatric followed by cognitive side effects appear least acceptable [[62]
]. In addition, AED side effects represent a considerable economic burden [[63]
]. The occurrence and severity of adverse cognitive side effects of AEDs depends on the pharmacological agent, titration speed, dose, and, when given in combination therapy, on the total drug load and on potential interactions of concurrent drugs. As indicated by reviews there are drugs which are less likely or more likely associated with negative side effects, even when given in monotherapy [64
, 65
]. However, cognitive impairments in the context of AED pharmacotherapy cannot be considered as independent of the disease, in that they are mostly the result of a synergy of having epilepsy, being treated at all, and being treated with a specific drug or drug combination [[66]
]. In addition one may not forget that seizure control achieved by drug treatment can improve cognition through the cessation of seizures and interictal epileptic dysfunction [[67]
].Apart from specific effects of individual drugs, the total drug load appears to be a major determinant of cognitive adverse effects of AED. Drug load can be determined simply by counting the number of AEDs or by concurrent consideration of the given dose related to the average recommended dose of each drug which is called the defined daily dose (DDD). The two measures are largely interchangeable since both measures correlate well with cognitive measures sensitive to AED side effects [
[68]
].Tools are at hand which can be used for the monitoring of the cognitive impact of drug treatment in an individual patient. Subjective assessment of antiepileptic drug side effects, i.e. signaling the physicians’ interest, can already positively affect therapy decisions [
[69]
]. For objective assessment repeated testing is required, conducted before and after a new AED is added, when treatment is first initiated, with relevant dose changes, or during drug tempering or withdrawal. The indications and requirements for individual cognitive monitoring of antiepileptic therapies, available diagnostic tools and potential pitfalls are outlined in detail in a review by Witt and Helmstaedter [[70]
].Although some drugs are claimed to have specific effects on certain functional domains, like language/word fluency with topiramate, or phenobarbital, carbamazepine or valproic acid on memory, functions of psychomotor speed, alertness, or executive functions seem to be sensitive to adverse effects of AEDs in general [
[21]
]. Several computerized tests have been proven to be CNS drug sensitive, and some of these have also been validated for use in epilepsy [[71]
]. In addition there are many standard paper–pencil tests which are suitable for this purpose. Routinely used screening of individual patients allows for comparison of the effects of different drugs in natural in- or outpatient settings [[72]
]. Screening for negative cognitive antiepileptic drug effects is also useful as a first step before comprehensive (neuro-) psychological diagnostics is performed. Having ruled out that performance deficits were observed under the influence of drugs, one can continue with more extensive testing. Otherwise one would recommend to postpone a more elaborate testing until the antiepileptic regimen has successfully been optimized which again should be proven by a cognitive screening. Monitoring of drug effects is particularly recommended in new-onset epilepsies, this will be discussed in more detail in the next section of this review.2.3 The need for early assessment in new-onset epilepsy
A highly relevant question relating to the cognitive and behavioral comorbidities of epilepsy was raised recently when epidemiological studies indicated that depression and other behavioral problems are often present before the onset of epileptic seizures and that they may even represent a risk factor for the development of epilepsy [
73
, 74
]. Indeed, the co-occurrence of epilepsy and behavioral or mood problems is frequent at the onset of the seizure disorder and common underlying pathogenic factors should be considered. As with depression, cognitive impairment can be understood as a marker of a pathological condition which later, in the course of the underlying disease, may also lead to seizures. In this case seizures would also need to be considered as a symptom rather than the origin or cause of cognitive impairment.As it stands, in many adult and pediatric patients with new-onset epilepsies, cognitive impairments are already present before the initiation of AED therapy [
75
, 76
, 77
, 78
]. With regard to clinical practice this calls for early cognitive assessments in children, adolescents and adults with new-onset or newly diagnosed epilepsies before treatment is first started. The subsequent course of the disease and treatment effects can only be observed clearly if baseline observations were obtained. Another reason is that very often, in the course of the disease, when the patient’s and the physician’s focus shifts away from the primary issue of seizure control, issues around comorbidities will become more prominent. At that point the key question is whether the disorder, the underlying disease dynamic or treatment have caused the problems. The availability of a baseline assessment is obviously very helpful in this situation. In children a brief structured clinical interview conducted with parents can identify children with epilepsy who are at academic risk at the time of diagnosis. It has been shown that this risk persists up to five years later, indicating that early interventions after such a baseline examination may be useful [[79]
]. It is interesting and perhaps surprising that behavior and competence problems in children newly diagnosed with localization-related and idiopathic generalized childhood epilepsies do not tend to get progressively worse over the next 5- to 6-years [[80]
]. Others have demonstrated that application of a short screening of cognition (EpiTrack Junior) is very helpful in the objective assessment of children at epilepsy onset and over the course of the disorder while AEDs are administered. This study also found quite stable performance over time after AED treatment had been initiated [81
, 82
], providing further support to the idea that neuropsychological deficits are typically not progressive after the development of epilepsy, although they often precede it.The question whether epilepsy causes cognitive deterioration in adults has also been discussed controversially for a long time. Most studies relying on retrospective analyses give room for the speculation that a longer duration of epilepsy is associated with a worsening of cognitive functioning. We have led a detailed discussion about the complex relationship between age, duration and age at onset of epilepsy elsewhere [
83
, 84
] and have come to the conclusion that cognitive decline with chronic epilepsy is the exception, that cognition is mostly very stable over time, and that any significant decline should be considered an unexpected development calling for additional diagnostic efforts to identify the underlying pathology. Thus conditions in children and adults are not that different and early neuropsychological evaluation and monitoring is indicated for both patient groups.3. Outlook
In the light of 25th anniversary of Seizure—European Journal of Epilepsy, the scope of this article was to provide an overview of developments in the neuropsychology of epilepsy and the significance of these developments reflecting several decades of research at group level into current clinical practice and individual patient care. What is the value of great and high impact publications at group level if they cannot or are not applied and validated in individual care? Clinical neuropsychology is an exciting subject and we hope this review has demonstrated that it can be used to make a valuable contribution to the lives of patients with epilepsy and their treatment.
Obviously progress is gradual, and there is great heterogeneity of how neuropsychology in epilepsy is currently used in clinical practice. However, there are some positive developments. Hopefully, neuropsychologists will be able to agree to speak with one language based on best published evidence. This should lead to greater homogeneity of neuropsychological assessment and practice and better communication across centers and countries. A higher scientific esteem of clinical work and of studies which may not necessarily produce new results but which consolidate the role of neuropsychology in clinical practice by demonstrating the application of neuroscientific knowledge on individual patients should help speed up progress in the field—as would adequate payment of neuropsychological diagnostics, and better financial support for standardization, normalization, validation of tests and open source instruments.
Conflict of interest statement
J.-A.Witt has no conflict of interest in regard to the submitted work.
C. Helmstaeder receives license fees from UCB and EISAI, gets honoraries for talks and/or consulting from GW pharmaceuticals, UCB, EISAI, and is being funded by the Marga Boll Stiftung, and the EU (GA 2013 1203).
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Article info
Publication history
Published online: October 13, 2016
Accepted:
September 23,
2016
Received in revised form:
September 23,
2016
Received:
August 25,
2016
Footnotes
☆One of the authors of this paper is a member of the current editorial team of Seizure. The supervision of the independent peer review process was undertaken and the decision about the publication of this manuscript were made by other members of the editorial team.
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© 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
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