Clinical Aspects and Cognitive Rehabilitation in People with Epilepsy

Epilepsy is one of the most widespread neurological disorders in Italy, so much so that it has been recognized as a “social disease” since 1965 (Ministry of Health Decree of 5/11/1965). To date, according to the latest data, the prevalence of active epilepsy (i.e., in treatment and/or with seizures in the last 2-5 years) is around 6.4 cases per 1,000 inhabitants, with an annual incidence rate of 61.4 per 100,000 inhabitants [1]. Applying this estimate to our national territory, people with the active disease in Italy turn out to be more than 500,000, with about 36,000 new cases each year. Specifically, the prevalence of memory problems in cases of epilepsy has been estimated at 20-50% the majority of patients who have undergone a neuropsychological examination report memory difficulties in daily life, most studies, which have dealt with cognitive aspects and epilepsy, have examined patients with focal epilepsy and Temporal Lobe Epilepsy (TLE). Hermann and coworkers, in their studies, report three different cognitive phenotypes in patients with temporal epilepsy: 47 percent with minimal cognitive impairment, 24 percent with memory impairment, and 29 percent with deficits in memory, executive functions, and in the speed of information processing [2]. Learning and memory deficits in patients with left temporal epilepsy are mainly verbal in nature in contrast to patients with right temporal epilepsy who manifest mainly deficits in visual memory, but not verbal memory [3].

Cognitive rehabilitation, aims at, the use of intervention strategies or technique that intends to manage, circumvent, reduce cognitive deficits and in the last decade, has been put into practice to treat patients with epilepsy, with the aim of restoring patients’ ability to cope with daily routines. Studies conducted from 2002 to 2017 have shown that cognitive rehabilitation programs are effective for patients with focal seizures and therefore should be incorporated into comprehensive care programs. This review aims to deepen knowledge about the disease by reviewing the clinical and neuropsychological characteristics of the patient with epilepsy, to rehabilitation treatment. It also aims to deepen knowledge about the stigma present toward patients with epilepsy, both in social and hospital settings, by proposing interventions approved by the scientific literature, aimed at preventing and/or reducing stigma and consequently helping to improve quality of life.

During the period before Hippocrates, epilepsy was called a “sacred disease” as it was believed to be a divine punishment [4]. In the period of the Middle Ages, dominated by religious obscurantism, diseases of the central nervous system were pervaded by a metaphysical view devoid of scientificity because of the ignorant view of the Catholic church. Epilepsy being, characterized by an unpredictable and uncontrollable nature was interpreted by the man of the Middle Ages as a demonic manifestation, requiring intolerant intervention practices: violent rites of exorcism, exile, burial of live women during gestation or castration of epileptic men [4]. With Hippocrates, in the fifth century B.C., epilepsy took on the definition of a brain pathology that he describes in his treatise “On Sacred Disease.” According to The Greek physician, epilepsy was caused by the imbalance of the somatic humors (blood, black bile, white bile, phlegm), in particular the excessive secretion of phlegm, induced by colds, resulted in an excess of mucus in the brain, resulting in obstruction of the ventricular system [5]. It was not until the 19th century that there was a first formulation of epileptic seizure, by John Hughling Jackson, who, despite the absence of instruments capable of measuring cerebral electrical activity, defined it as “the result of an occasional, excessive and disordered discharge of nerve tissue.”

Jackson also hypothesized that epileptic seizures did not always involve loss of consciousness, but could manifest as focal symptoms observable, for example, in jerking contraction of the arm [6]. Jackson’s hypotheses, were refuted in 1929, when German psychiatrist Hans Berger, introduced electroencephalography and made the first electroencephalographic recording on a human, giving rise to the diagnosis of epileptic phenomena [6].

Epidemiology of epilepsy: Epilepsy after headache represents the second most common chronic neurological condition [7]. The disorder is more common than Parkinson’s Disease, Multiple Sclerosis, Cerebral Palsy and Muscular Dystrophy, which is the reason why it is identified as a social disease by Ministerial Decree No. 249/65. The prevalence of epilepsy is about 1 percent and the incidence (number of new cases in a specific population in a defined time interval) varies from 40 to 70 new cases /100,000 population/ year in industrialized countries and from 100 to 190 new cases/ 100,000 population/ in developing countries [7]. The incidence of epilepsy appears to be age-related and has a bimodal distribution with two peaks, the first in the first year of life and the second in old age, over 75 years. The risk of recurrence three years after the first seizure is 80%. Remission, under drug treatment, is observed in 70-80% of cases, which may be followed, under careful observation, by discontinuation of therapy with possible relapse in 17-50% of cases [7].

Seizures are defined by the ILAE as the transient occurrence of signs/symptoms due to abnormal, excessive, or hypersynchronous electrical activity in the brain. According to the most recent classification, the main distinction is according to the brain area involved by the epileptogenic focus, i.e., the aggregate of neurons from which the discharge originates; thus, one can have seizures with focal, generalized, or unknown onset. These in turn are divided into motor or nonmotor seizures, which can lead to different manifestations [8,9]. Although in the common imagination epilepsy is often associated with seizures, typical of generalized tonic-clonic seizures (also called “big bad”), this can announce itself with quite different symptoms such as behavioral arrest, automatisms, dejavu, sensory hallucinations, and sudden changes in mood, typical of focal seizures; or as loss of contact with the outside world and motor arrest, typical of generalized absence seizures. Epidemiological data show that the incidence of focal rather than generalized seizures is higher [10]. One reason epilepsy education is difficult is the complexity and nuanced knowledge required to recognize and deal with different forms of seizures. At the same time, however, the diagnosis of an epilepsy and the location of the epileptogenic focus relies heavily on the witness’s description of the event. Obtaining an appropriate account of the events from a witness is a crucial component of patient assessment, particularly because most seizures do not last long enough to be identified by first responders and patients are unable to provide useful information because they present to the emergency in a post-ictal and confused state with no memory of the event.

Although assessment tools such as EEG or brain imaging can help, they are not always diagnostic [11], it is important to investigate seizure risk factors or look for clinical signs that suggest a seizure has occurred, knowing the semiological details can direct identification of the most appropriate treatment. A seizure in the real world is a very dramatic event for a first-time witness, and the emotional impact can affect the details of observation. In addition, witnesses often do not spontaneously provide all the necessary information without being asked [11]. The cognitive alterations described in epileptic patients are related to problems with attention, concentration, slower processing speed, language difficulties, deficits in executive functions, and memory problems [12]. To these alterations must be added the subjective perception of patients, which is usually related to problems of psychomotor retardation, attention disorders or language difficulties (naming and verbal fluency). However, the main complaint refers to memory loss, which seems to be independent of the type of epilepsy or its control, both pharmacological and surgical [13].

The prevalence of memory problems in cases of epilepsy has been estimated at 20-50% and more than half of patients referred for neuropsychological examination report memory difficulties in daily life. The nature and severity of cognitive impairment not only result from the type and extent of brain damage but also from a combination of positive and negative effects, personality, behavioral changes, motivation, compliance, family support, and the physical environment. Several studies [14,15] confirmed that there is no correlation between patients’ subjective perception and objective performance on standardized memory tests, on the contrary, they found correlations between affective-emotional state (anxiety and depression) and certain personality traits (neuroticism) with the level of subjective disorder, so that patients who report memory disorders are more likely to suffer from depression or anxiety than those who do not report memory difficulties. In a study in which, prior to neuropsychological evaluation, patients were asked openly about possible cognitive difficulties, a 53% coincidence was found between the results and their complaints, most of which referred to difficulties with memory, access to vocabulary (feeling of „tongue tip”) and concentration (when reading, studying or performing calculations).

On the other hand, 80% of them were able to maintain a normalized working life despite the tests detecting some type of cognitive alteration in 91% of them, although some authors consider the severity of these alterations to be moderate, their impact on the functioning in patients’ daily lives can be very relevant in specific activities such as driving, or when the affected functions were already vulnerable, such as memory [16,17]. In addition, behavioral and emotional alterations may appear, such as irritability and hyperactivity to those already mentioned on mood.

One of the most studied epilepsies from a neuropsychological point of view is temporal lobe epilepsy due to the high incidence of cognitive, emotional and psychiatric disorders it entails. Most studies on cognition and epilepsy deal with patients with focal temporal lobe epilepsy, as the features of temporal epilepsy seem better understood than other types of focal epilepsies due to the high incidence with which the disorder manifests. Engel in 2001 estimated that 60% of adult patients with partial epilepsy also suffer from temporal epilepsy [18]. In addition, it is one of the most studied epilepsies due to the high incidence of cognitive, emotional and psychiatric disorders. The International League against epilepsy (ILAE) has distinguished temporal lobe epilepsies into:
a. Mesial Temporal Lobe Epilepsy (mTLE);
b. Lateral Temporal Lobe Epilepsy (iTLE);

Mesial Temporal Lobe Epilepsy (mTLE) is a focal disorder in which patients suffer from frequent seizures that impair consciousness, extensive neurocognitive deficits, and reduced quality of life [19]. In mesial epilepsy, seizures occur in the hippocampus, amygdala and parahippocampal gyrus, while seizures in lateral temporal lobe epilepsy arise in the neocortex. Seizures in mesial temporal lobe epilepsy are characterized by the presence of auras with ascending epigastric sensation or abdominal discomfort and déjà vu, jamáis vu and fear and may be accompanied by an unpleasant olfactory or gustatory perception. In addition, the seizures can occur in isolation or be followed by the progressive alteration of the state of consciousness and oro-food (chewing, swallowing, tongue and lip movements) and manual automatisms. Pallor, redness and tachycardia are common in seizures and the duration of the seizures tends to be longer than in the case of lateral temporal seizures and it is rare for them to generalize to a bilateral seizure.

The crisis in the lateral temporal lobe originates with an initial auditory aura, for example a buzzing, which can only be perceived through an ear suggesting that the crisis begins in the contralateral hemisphere, but visual auras may also occur during the crisis, contrary to what happens with mesial temporal crises of shorter duration. In addition, the crisis can spread and present motor features such as upper limb dystonia, facial spasms or grimaces. Generalization of seizures is more common than in mesial temporal lobe epilepsy.

The most frequent cognitive deficits in patients with temporal lobe epilepsy include:
a. Long-term storage deficit;
b. Memory material recall deficit;
c. Learning difficulties;
d. Attention deficits;
e. Naming deficit;
f. Visuospatial deficits;
g. Deficit of executive functions

In particular, declarative memory is largely impaired, due to the involvement of the temporo-limbic system, even if episodic memory is more so than semantic memory [20]. Learning and memory deficits in patients with left temporal epilepsy are mainly verbal in nature, unlike patients with right temporal epilepsy who mainly manifest deficits in visual memory, but not in verbal memory [20]. Studies have shown an association between the type of memory disorder (verbal and nonverbal) and the side of the epileptic focus (left and right).

Jambaqué et al. [21] have shown that subjects with a right epileptic focus, compared to subjects with a left focus, show a more pronounced impairment of visual memory than verbal memory deficits [21]. However, recent studies, conducted with 43 subjects (21 with left focus and 22 with right focus), have shown that memory disorders are not affected by hemispheric specialization [22]. The authors administered a battery of memory tests to 43 subjects with temporal lobe epilepsy concluding that only memory related to face recognition is lower in the group of subjects with the right focus compared to the group with the left focus. Regardless of the location of the epileptic focus, cognitive alterations are a frequent consequence of different forms of epilepsy, with an association that has been described in the literature [23,24]. According to Rijckvorsel [25] cognition can be defined as the brain’s ability to process information accurately and to program behavior, solve problems, memorize information, or focus attention. On a higher level, it involves dealing with complex situations creatively by transcending immediate circumstances to anticipate future actions. In adults, the disorders are more frequently affected by memory functions, ideomotor slowdown and attention deficit, while in children and adolescents cognitive disorders are more frequent and are associated with learning difficulties, language problems and difficulties in social and professional adaptation [25].

Strauss [26] identified the main risk factors that contribute to cognitive decline:
a. Age at onset;
b. The frequency of seizures (primary predictor in memory and language);
c. The etiology;
d. The duration;
e. The use of antiepileptic drugs

In 2020 Englot, Morgan & Chan [27] observed that despite seizures in mTLE (Medial Temporal Lobe) having focal origin in the hippocampus or amygdala, mTLE patients show cognitive deficits extended beyond temporal lobe function, such as decline in executive function, cognitive processing speed and attention, as well as a widespread decrease in neocortical metabolism and functional connectivity. Given previous observations that mTLE patients exhibit impairments in alertness and that seizures can disrupt the long-range activity and connectivity of subcortical brain structures involved in the regulation of alertness, they propose that the subcortical activation networks underlying alertness play a critical role in mediating the cognitive effects of focal mTLE.

Non-pharmacological cognitive therapies, like other types of treatment, base their theoretical assumptions on brain plasticity [28]. The etymology of the word plasticity comes from the Greek „plassein” and literally means to shape. Since the seventies it has been demonstrated that reorganizational processes, affecting the central or peripheral nervous system, can occur both for physiological dynamics related to learning and for pathological dynamics, allowing the reorganization and recovery, in the short and long term, of lost or damaged functions. The first observations date back to Ramon y Cajal who in the nineteenth century wrote that learning to be such required the formation of new connections between neurons [6]. However, for more than a century the brain has been regarded as rigid, unchanging, and genetically determined. According to this view, which has its roots in the concept of predetermined epigenesis, the environment has no influence on the functioning and development of the individual, because it is the genetic configuration that predisposes the development of functions and only subsequently of behaviors, these patients suffering from the disease were considered unable to functional recovery [29]. The traditional view has been progressively questioned by the evidence of patients who show functional recovery following a neurological injury. Thanks to the development, in the sixties, of non-invasive tools for the study of the nervous system and brain activity, it has been confirmed that the brain is a dynamic and plastic organ, capable of modifying itself both structurally and functionally. The understanding of neuroplastic processes originates from in vitro studies on experimental animal models and only later, with the advent of neuroimaging, have they also been investigated in humans. The modern vision, on the other hand, supports the interdependence between the genetic dimension and the environmental dimension in the structuring of the individual, demonstrating the groundlessness of the traditional paradigm.

Before the 1980’s, the structure of the receptive field and the topography of the adult were considered stable and resistant to sensory deprivation or enrichment. This view has changed since the 1980’s, when it was shown that the neural pathways of adult primates reorganize following injury to peripheral nerves, and empirical evidence of this modifiability comes from studies on primates that have undergone limb amputation or deafferentation as a result of which the primary somatosensory cortex has been reorganized [30]. Similarly, in humans, the somatotopic organization of the somatosensory cortex and its reorganization following injury have been demonstrated through magnetoencephalographic studies. Merzenich is considered the father of the concept of plasticity and has studied the process through animal models demonstrating that cortical reorganization is associated with long-term enhancement of neurons [30].

Cognitive rehabilitation has been used to treat patients with epilepsy since the last decade. Pathologies that benefit from cognitive rehabilitation interventions include cerebral stroke, dementia, head trauma and epilepsy [31]. Neuropsychology in the area of epilepsy studies the relationship between epilepsy and upper cortical functions, cognitive deficits, relationships with symptoms, differential diagnosis, psychiatric comorbidity, pharmacotherapy, associated social decline and neurorehabilitation interventions understood both as cognitive recovery and as compensation for the deficit [31]. Cognitive rehabilitation has been defined as „any intervention strategy or technique that intends to rehabilitate patients and their families aimed at managing, bypassing, and reducing cognitive deficits precipitated by brain injury” [32]. Therefore, rehabilitation is aimed at compensating for impaired functions, improving the patient’s life and strengthening residual capacities. Patients with epilepsy often face a wide range of limitations in autonomy, school, social situations and employment, mainly due to the cognitive deficits caused by the disorder, particularly in memory and attention.

A testimony comes from a 29-year-old patient suffering from epilepsy in the left temporal lobe who reports: „I can no longer find the words I want to say and write. When I speak I often use wrong words which make my speech incomprehensible. Friends and colleagues start laughing and I get angry.” In most patients with epilepsy, more than one cognitive domain such as language, psychomotor speed, verbal speed, episodic memory and executive functions seems to be impaired, but memory and attention are the two domains that are most frequently affected by the disorder. In addition, the nature and severity of cognitive deficits depend not only on the extent and nature of the brain damage or dysfunction, but also on personality characteristics (e.g., neurotic), the patient’s psychological reactions (e.g., anxiety and depression), the patient’s environment (physical), and last but not least, the patient’s expectations (e.g., return to work or education) [12].

The neuropsychologist, after documenting the patient’s cognitive and behavioral deficits, proceeds to plan a rehabilitation program planned on the needs of each individual with the ultimate goal of functional recovery of the affected areas. In cases of severe impairment of brain tissue, compensatory strategies are adopted, which recruit new areas and replace the compromised ones, in this case we speak of functional replacement rather than functional recovery. In functional replacement, functionally intact areas perform tasks normally performed by damaged areas. Ponds, identified the three central aspects of neuropsychological intervention:
a. Psycho-education to the effects of brain damage in a realistic perspective and cognitive difficulties;
b. The impact of personality changes and emotional reactions;
c. Individual perception of cognitive disorders.

In reference to personality changes, these include behavioral problems (impulsivity and low tolerance for frustration), lack of understanding (and consequently poor motivation), symptoms of depression and anxiety, acceptance problems, personality traits such as neuroticism, rigidity or compulsiveness, and dysfunctional thought patterns such as catastrophic reactions or the desire that only returning to the situation before the deficit can be satisfying. These problems strongly interfere with learning and should therefore be taken into account before rehabilitation begins. In addition, for some patients there is a large discrepancy between the severity of memory impairments observed as indicated with memory tests and the severity and impact of these memory problems in daily life. With reference to the individual perception of cognitive disorders, it emerges that the beliefs and perceptions that the patient holds about his memory strongly influence the activities in which he will engage or how he will perform a memory task. If these memory beliefs are deficient, it is very likely that the patient will invest less effort (or inefficient allocation of effort) into daily memory tasks, which could lead to lower memory performance.

The more specific aspects of the program have to do with:
a. what memory problems should be trained;
b. what are the best strategies to use;

Memory training must be differentiated from subject to subject and the objectives must be built together with the patient. For example, „general improvement of memory to the level it was before my accident” is not a good training goal, but learning the names of nursing staff may be. The goals should always be tailor-made, small, as concrete as possible and fully tailored to the patient’s needs and wishes. Of course, it is possible to learn a general strategy for remembering names, but only after repeated practice will the patient generalize this strategy to other „name situations” than the one for which he or she was trained. As a general rule, it could be said that patients alone have a lot of difficulty applying learned strategies beyond the training situation or beyond the training period. Most memory patients share many common memory problems. The main methods of neuropsychological memory rehabilitation in patients with epilepsy are:
a. The development of strategies (relearning);
b. Repetition of cognitive tasks (re-education);
c. Use of external aids;
d. Error-free learning;
e. Cognitive support;
f. Mnemontechnics;

Strategizing (relearning) involves the use of verbal strategies, such as depth of information encoding, processing, and recall through the use of cues. In relation to relearning, recent studies have shown that patients with left temporal lobe epilepsy benefit from strategies such as semantic processing and coding, while patients with right temporal epilepsy would benefit from cue-based recall. The second method, the repetition of cognitive tasks (re-education) is based on the learning of mnemonic rules, such as: „choosing and organizing information strengthens memory”, „greater intervals of learning seem to improve memory” and „repetition improves memory”. Errorless learning aims to reduce errors during the mnestic coding phase of the information being learned, facilitating correct answers. Cognitive support (scaffolding) aims to bridge the gap between what can be achieved independently and the goal to be achieved. The technique must offer patients support or support from the operator, control and autonomy, feedback and metacognitive training based on the representation of information (graphs, images and simulations). Finally, mnemonics, strategies and techniques used to promote learning, aim to enhance the processes of storing information.

Mnemonics include

Mental imagery which induces the patient to create and store images containing verbal information, recalled in the form of images verbal elaboration which, through associations, facilitates the mnestic coding and the method of loci. Recently, rehabilitation approaches defined as „ecological”, which simulate everyday life situations, have also been adopted with epileptic patients. Yang and collaborators used simulations as a rehabilitation tool in 2010, during the simulations, the patient simulated driving the car while electroencephalographic activity was recorded to study the triggering of seizures caused, for example, by driving and lay the foundations for a rehabilitation path. In general, the memory deficits seen in patients with epilepsy are less severe than in severely brain damaged patients or those with dementia or Korsakoff syndrome. In addition, unlike, for example, patients with frontal lobe damage or those with specific neuropsychological disorders such as anosognosia, patients with epilepsy generally retain sufficient insight into their daily possibilities and deficits, since epilepsy is a chronic disease, it is possible to assume that memory problems will worsen over time. A final aspect to consider in the design of the intervention is that during a memory treatment seizures can also interfere with progress or cause temporary interruption of treatment. Cognitive rehabilitation has been applied to treat patients with epilepsy in the last decade with the aim of compensating for impaired functions, improving the patient’s quality of life and strengthening residual abilities. Between 2002 and 2017, studies were carried out on patients with temporal lobe epilepsy with the aim of demonstrating the effectiveness of rehabilitation programs aimed at improving cognitive functions such as memory and attention, which are the most affected domains.

Studies have shown that the pathophysiological and clinical characteristics of the disorder can provide specific indications for the structuring of rehabilitation programs. In particular, cognitive rehabilitation programs that use compensatory strategies and a holistic approach that includes: cognitive exercises specifically training for visual or verbal memory and attention, group therapy aimed at psychoeducation and the teaching of compensatory strategies, occupational therapy and sociotherapy are effective. The holistic approach, compared to the single technique, has the advantage of simultaneously addressing the cognitive and behavioral problems that cause psychosocial disabilities. The studies in the literature converge in considering the personalization of the rehabilitation intervention and the therapeutic alliance between the patient and the staff central in order to obtain good results.

An educational intervention on how to behave in the face of comitial seizures would not only make potential witnesses better prepared to witness the event and handle it but, in the event that EMS intervention is needed, it would give them the opportunity to help more quickly identify treatment for that patient through their observations. The most recent studies have analyzed knowledge about epilepsy exclusively within school environments, promoting educational interventions for teachers and pupils in order to eliminate distrust around the disease that causes social maladjustment in the affected child with consequent influences not only in his or her school performance but also in his or her growth [33-35]. Nevertheless, people with epilepsy should feel comfortable in whatever context they find themselves, without the fear of being ostracized for their condition. Most importantly, they have the right to live their lives without being constantly dependent on their caregiver, knowing that they are safe outside their care. The multi-component intervention aims to consider the patient from a psychological perspective, as well as a strictly neuropsychological one, also considering the patient’s emotional reactions. Cognitive rehabilitation programs have been shown to be effective in patients with epilepsy in the domains of memory and attention and should be incorporated into comprehensive care programs [36].

1. Fiest KM, Sauro KM, Wiebe S, Patten SB, Kwon CS, et al. (2016) Prevalence and incidence of epilepsy: A systematic review and meta-analysis of international studies. Neurology 88(3): 296-303.
2. Hermann B, Seidenberg M, Fong C (2017) Cognitive phenotypes in temporal lobe epilepsy. Journal of the International Neuropsychological Society 13(1):12-20.
3. Muldoon SF, Costantini J, Webber WRS, Lesser R, Bassett DS (2018) Locally stable brain states predict suppression of epileptic activity by enhanced cognitive effort. NeuroImage: Clinical 18: 599-607.
4. Panayiotopoulos CP (2010) A clinical guide to epileptic syndromes and their treatment. (2^nd edn), Springer Publishers, UK.
5. (1996) Hippocrates, as quoted in Opera di Hippocrates, Untet, Turin.
6. Kandel ER, Schwarz J, Jessell T (2000) Principles of neural science. (4^th edn), McGraw Hill Professional, USA, pp. 1-1414.
7. Berardelli A (2019) The Neurology of wisdom. Esculapio Publishing Company, Italy.
8. Fisher RS, Cross JH, French JA, Higurashi N, Hirsch E, et al. (2017) Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia 58(4): 522-530.
9. Fisher SR, Cross HJ, D’Souza C, French JA, Haut SR, et al. (2017) Instruction manual for the ILAE 2007 operational classification of seizure types. Epilepsia 58(4): 531-542.
10. Kotsopoulos IA, Merode T, Kessels FG, Krom MC, Knottnerus JA (2002) Systematic review and meta-analysis of incidence studies of epilepsy and unprovoked seizures. Epilepsia 43(11): 1402-1409.
11. Muayqil TA, Alanazy MH, Almalak HM, Alsalman HK, Abdulfattah FW, et al. (2018) Accuracy of seizure semiology obtained from first-time seizure witnesses. BMC Neurology 18(1): 135.
12. Ponds RW, Hendriks M (2006) Cognitive rehabilitation of memory problems in patients with epilepsy. Seizure 15(4): 267-273.
13. Uijl SG, Uiterwaal CSMP, Aldenkamp AP, Carpay JA, Doelman JC, et al. (2006) A cross-sectional study of subjective complaints in patients with epilepsy who seem to be well-controlled with anti-epileptic drugs. Seizure 15(4): 242-248.
14. Hendriks M, Aldenkamp AP, Vlugt HV (2004) Neuropsychological assessment of memory functions in epilepsy. Acta Neurol Scand 110: 291-300.
15. Hendriks MPH, Aldenkamp AP, Vlugt HV, Alpherts WCJ, Vermeulen J (2002) Memory complaints in medically refractory epilepsy: Relationship to epilepsy- related factors. Epilepsy Behav 3(2): 165-172.
16. Aldenkamp AP, Hendriks MPH (2000) Managing cognitive and behavioural consequences of epilepsy. In: Baker GA, Jacoby A (Eds.), Quality of life in epilepsy. Harwood Academic Publishers, UK, pp. 12-31.
17. Aldenkamp AP, Alpherts WCJ, Dekker MJA, Overweg J (1990) Neuropsychological aspects of learning disabilities in epilepsy. Epilepsia 31(4): 9-20.
18. Engel J Jr (2001) A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: Report of the ILAE task force on classification and terminology. Epilepsia 42(6): 796-803.
19. Englot J, Morgan V, Chang C (2020) Impaired vigilance networks in temporal lobe epilepsy: Mechanism and clinical implications. Epilepsy 61(2): 189-202.
20. Helmstaedter C, Reuber M, Elger CE (2002) Interaction of cognitive aging and memory deficits related to epilepsy surgery. AnnNeurol 52(1): 89-94.
21. Jambaque I, Dellatolas G, Dulac O, Ponsot G, Signoret JL (1993) Verbal and visual memory impairment in children with epilepsy. Neuropsychol 31(12): 1321-1337.
22. Gonzalez LM, Anderson VA, Wood SJ, Mitchell LA, Harvey AS (2007) The localization and lateralization of memory deficits in children with temporal lobe epilepsy. Epilepsia 48(1): 124-132.
23. Aldenkamp AP, Alpherts WCJ, Dekker MJA, Overweg J (1990) Neuropsychological aspects of learning disabilities in epilepsy. Epilepsia 31(4): 9-20.
24. Hermann B, Seidenberg M, Lee E, Fong C, Rutecki P (2017) Cognitive phenotypes in temporal lobe epilepsy. Journal of the International Neuropsychological Society 13(1): 12-20.
25. Rijckevorsel K (2006) Cognitive problems related to epilepsy syndromes, especially malignant epilepsies. Seizure 15(4): 227-234.
26. Strauss E, Sherman E, Spreen O (2006) A compendium of neuropsychological tests: Administration, norms, and commentary. (3^rd), Oxford University Press, USA, pp. 1-1240.
27. Englot J, Morgan V, Chang C (2020) Impaired vigilance networks in temporal lobe epilepsy: Mechanism and clinical implications. Epilepsy 61(2): 189-202.
28. Giovagnoli AR, Parente A, Tarallo A, Casazza M, Franceschetti S, et al. (2014) Self-rated and assessed cognitive functions in epilepsy: Impact on quality of life. Epilepsy Res 108(8): 1461-1468.
29. Ramachandran VS, Rogers-Ramachandran D (1996) Synaesthesia in phantom limbs induced with mirrors. Proc Biol Sci 263(1369): 377-386.
30. Merzenich MM, Kaas JH, Wall J, Nelson RJ, Sur M, et al. (1983) Topographic reorganization of senosry cortical areas 3b and 1 in adult monkeys following restricted deafferentation. Neuroscience 8(1): 33-55.
31. Patrikellis P, Messinis L, Kimiskidis V, Gatzonis S (2023) Neuropsychology of epilepsy surgery and theory-based practice: An opinion review. Arq Neuropsiquiatr 81(9): 835-843.
32. Wilson BA (1997) Cognitive rehabilitation: How it is and how it might be. J Int Neuropsychol Soc 3: 487-496.
33. Roberts JL, Anderson ND, Guild E, Cyr AA, Jones RS, et al. (2018) The benefits of errorless learning for people with amnestic mild cognitive impairment. Neuropsychological Rehabilitation 28(6): 984-996.
34. Beghi E, Borroni S, Canonico PL, Croce D, Kruger P, et al. (2019) Il Libro Bianco Dell'Epilessia in Italia. UCB Pharma SpA, pp. 1-114.
35. (2023) Epilepsy is a social pathology. The proposals of the lice. Daily Health.
36. Chung YT, Hsieh IC, Lai MC, Huang CW (2014) The potential role of neurocognitive rehabilitation in Epilepsy. Int J Neurorehabilitation 1(3): 1-4.