Development of cognitive performance in children before and after surgical treatment of pharmacoresistant temporal lobe epilepsy

Summary

This case study focuses on the long-term cognitive sequelae of temporal lobe epilepsy (TLE) in childhood and their influence by surgical treatment. The study follows four pediatric patients with TLE who underwent successful resectional epilepsy surgery at the Motol Epilepsy Center. While the standard measure of success of epilepsy surgery is postoperative seizure cessation, reduced medication, and improved quality of life, our study also underscores the importance of monitoring the overall neuropsychological profile and providing additional clinical-psychological care. Monitoring of intelligence performance alone is insufficient to fully understand cognitive development after epilepsy surgery. In the cases reported, we documented a gradual consolidation of cognitive functions over time. Comprehensive care, interdisciplinary collaboration, and early indication for epilepsy surgery are crucial to achieve an overall favorable outcome. Early referral of pharmacoresistant patients to specialized centers and prompt effective treatment of epileptic seizures are essential to prevent long-term negative consequences of untreated epilepsy, including cognitive difficulties and psychosocial problems. Simultaneously, further research into the neuropsychology of TLE in children and the development of more effective treatment and support strategies for these patients and their families are essential.

Keywords:

epilepsy surgery – Intelligence – temporal lobe epilepsy – longitudinal perspective – cognition in children – cognitive development

This is an unauthorised machine translation into English made using the DeepL Translate Pro translator. The editors do not guarantee that the content of the article corresponds fully to the original language version.

 

Introduction

Temporal lobe epilepsy (TLE) is one of the most common forms of focal epilepsy in children [1]. Despite extensive research on the etiology, treatment, and clinical manifestations, the impact of TLE on cognitive development in the pediatric population remains an important area of investigation. While the seizure semiology and electroclinical features of TLE have been thoroughly investigated, the long-term cognitive impact and the potential for surgical treatment to influence it remain largely unclear. Children with TLE often have cognitive impairment (selective or global) in memory, attention, language functions, executive functions, visuospatial or motor functions. The development of cognitive function in children with TLE (including long-term) is far less well studied than the cognitive profile in adults [2-4].

Patients who are not seizure-free after the first anti-seizure medication (ASM) are very unlikely to be seizure-free in the long term even with additional ASM [5]. Outside of the chosen anti-seizure treatment, an important (and often the only effective) treatment modality for pharmacoresistant epilepsy is surgery (epileptocurrent surgery). Resectional epilepto-surgery in children with TLE is chosen taking into account the presumed aetiology of the disease, the abnormalities found on imaging and electrophysiological examinations, and the presumed location of epileptogenic tissue (the so-called epileptogenic zone); in any case, it is necessary to approach each case individually. These factors, including age of onset, duration, frequency and type of seizures, may cause differences in the results [6].

A successful outcome of epilepsy surgery is considered to be a reduction in the severity or frequency of seizures (ideally their complete compensation) and the possibility of subsequent reduction or withdrawal of treatment [7]. Increasingly, however, improvement in the quality of life of the patient and family is cited as the most important parameter for assessing the outcome of epilepsy surgery [8-11]. This is related not only to postoperative reduction or complete absence of seizures, but also to improved cognitive performance and improvement or prevention of other negative consequences of long-term uncompensated epilepsy, such as psychiatric comorbidities [12-15] or social stigma [16-18].

Although long-term failure to compensate for seizures can lead to the development of mental health problems, behavioural disorders or cognitive deficits, psychosocial and neuropsychological effects are often reported on the basis of intelligence test results, which are not a valid measure of neurological disease and from which cognitive function cannot be adequately inferred [19].

Due to the gradual development of paediatric neuropsychology, including the development of neuropsychological measures in the Czech Republic, we do not have a sufficiently robust dataset to follow the detailed cognitive development of patients with TLE 5 years or more after surgery. In this article, we present four patients with focal epilepsy with a temporal lobe source who were followed for a long time by a pediatric neurologist and a pediatric neuropsychologist. All of them underwent comprehensive preoperative diagnostics at the Department of Child Neurology, 2nd Faculty of Medicine, University of Charles University and Motol University Hospital, where they were examined neuropsychologically before surgery, 1 year after surgery, 2 years after surgery and 5 years or more after surgery. In cases 1 and 2 we describe patients with focal cortical dysplasia (FCD), in cases 3 and 4 it was temporal lobe epilepsy due to benign brain tumours.

 

Case 1 -⁠ girl after left anteromesial temporal resection for focal cortical dysplasia type 2A

Initial manifestations

A 29-year-old female patient with no family or personal history of risk, who had her first seizure in the 5th month of life. According to the description, it was a tonic seizure (upper limb extension [HKK], screaming, duration up to 1 min), the same or similar seizures subsequently occurred with daily frequency. The EEG showed unspecified epileptiform findings with probable generalization. MRI was normal. Valproate (VPA) and subsequently adrenocorticotropic hormone (ACTH) treatment was started, the conditions resolved and the patient was fully compensated. Her treatment was discontinued at the age of 3 years. Her psychomotor development was normal (sitting up at 6 months, crawling at 9 months, independent walking at 12 months, using short sentences at 24 months, maintaining hygiene, starting kindergarten at 3 years, no difficulties in adaptation).

 

Further course

The seizures returned at the age of 5 years and were typical for TLE -⁠ at night she woke up from sleep, she had perioral cyanosis, she did not respond to address. EEG and CT were normal, the frequency of these seizures was uncertain, they were not recognized as epileptic, and she was left untreated. At 9 years of age, apparent nocturnal seizures with vocalization, absent gaze, impaired consciousness, oroalimentary automatisms, head and eyeball curling to the right, dystonic posturing of the left HK and automatisms of the right HK, with a frequency of 1-2 times per week, were already present. EEG showed focal epileptiform activity temporally (T) on the left, and brain MRI was again normal. At age 13, there was again an increase in seizure frequency to every 2-3 days with a maximum of two per night. The ASMs used were VPA, lamotrigine (LTG), topiramate (TPM), levetiracetam (LEV), carbamazepine (CBZ), lacosamide (LCM) and zonisamide (ZNS). At 11 years, shortly after the TPM was started, significant weight loss occurred, for this reason it was discontinued, subsequently with no further comorbidities, neither the parents nor the girl reported subjective complaints of cognition.

 

Preoperative diagnostics

At the age of 18, the patient was comprehensively examined by us. In summary: neurological findings were normal, left-sided, seizure semiology was characteristic of left-sided mesotemporal onset (confirmed on video EEG). The hypothesis of left-sided mesotemporal localization of the epileptogenic zone is supported by the findings on high-resolution brain MRI (demonstration of left temporal lobe FCD, especially mesially in the amygdala) and other imaging examinations (FDG-PET [fluorodeoxyglucose positron emission tomography], ictal SPECT -⁠ SISCOM [Subtraction Ictal SPECT Co-registered to MRI].

 

Neuropsychological examination before surgery

The neuropsychological examination before surgery showed a multidomain amnestic mild cognitive impairment, dominated by impairment of mnestic functions (in short-term verbal memory and delayed equipment, without significant effect of recognition, narrative memory was impaired in immediate and delayed equipment), language functions in naming and comprehension and motor functions in fine motor and oromotor skills. Slight impairments were also evident in attentional focus and executive functions in attentional flexibility. Intellectual performance was in the moderate subaverage range.

 

Epilepsy surgery

The patient underwent an anteromesial temporal resection, i.e. including removal of the hippocampus, at 18.2 years (17.5 years after diagnosis). The operation was evaluated as complete after the procedure, it was performed without significant complications, with no observed fatal or motor deficits, and the girl was also free of difficulties and seizures in the subsequent course (EEG normal). Histology showed FCD type 2A. She was subsequently seizure-free for a long time after surgery.

 

Cognitive performance 1 year after surgery

Intelligence performance was unchanged, still in the range of slightly below average. Impairment of mnestic functions, especially in immediate equipment, was predominant; remote equipment was also impaired. Narrative verbal memory, however, was already in the average range. Improvement occurred in attentional-executive functions, which were currently in the band of average. Visual-constructive functions were slightly impaired.

 

Long-term follow-up after surgery (9 years after surgery)

The girl is seizure free and is completely off ASM. Intellectual performance is still in the moderate subaverage range. The cognitive profile is dominated by scores ranging from mildly below average to average. There has been a slight improvement in mnestic functions, which are currently slightly impaired. Improvements also occurred in semantic and non-verbal memory, language functions in the area of naming and visual-constructive functions, which are currently in the average range. Attention-executive functions are also currently in the average range. No anxiety-depressive symptomatology emerges from the self-assessment or interview.

 

Case 2 -⁠ boy after resection of focal cortical dysplasia type 2B temporo-occipitally on the left

Initial manifestations

Currently a 17-year-old boy with no family or personal history of epilepsy who developed epilepsy at 15 months of age. He presented with uniform seizures with an initial visual aura (later he was able to describe subjectively as "eye rolling"), objectively observed mydriasis with general areactivity, no other obvious manifestations (no convulsions, automatisms, autonomic changes), postictally no fatal disorder. MRI initially evaluated as nonlesional, EEG with normal findings. VPA was administered, with no long-term effect. Psychomotor development was within the broader normal range (independent walking at 14 months, first word at 12 months, short sentences at 4 years of age, started kindergarten at 5 years, adaptation good).

 

Further course of the disease

Furthermore, seizures of the same character were observed, always shortly after waking, with irregular frequency. The course was clearly pharmacoresistant (he was taking VPA, TPM, LEV, CBZ and ZNS, each of the drugs was effective for about one month, then no further effect). He was doing moderately well at school, and his parents did not report any psychiatric difficulties or cognitive deterioration.

 

Preoperative diagnostics

The boy was admitted at the age of 9 years for a comprehensive examination, neurological findings were normal, right-handed. EEG repeatedly showed an abnormality dorsal to T left with incomplete generalization. MRI of the brain showed atypical gyrification at the temporo-occipital border on the left with focal cortical enhancement, subcortical bordering white matter signal alteration with transmantle signal change directed towards the occipital corner of the left lateral ventricle. Consistent with these findings, FDG-PET and ictal SPECT (SISCOM) were performed.

 

Neuropsychological examination before surgery

Actual intellectual performance was in the lower average range, with no significant partial disparities. Attention, however, was markedly fatigued, and attentional tenacity fell into the below-average band with load. Mnestic performance was in the good-average band, modally without disparities. More striking then was performance in naming and speech comprehension, which was performance deficient. Perceptual test performance was in the below average range, fine motor skills with tremor, and performance in the borderline deficit range. In summary, test and clinical deficits were present in the speech domain, and attentional stamina, fine motor skills and visual-spatial perception were borderline deficient, with intellectual performance at the lower end of average.

 

Epilepsy surgery

A single resection of the dysplastic cortex temporo-occipitally on the left side was performed at the age of 9 years (7.5 years from the diagnosis of epilepsy), without complications. The postoperative course was also without complications, and the procedure was assessed as complete. No epileptic seizures have been observed since then. Histology confirmed FCD type 2B. ASM was discontinued at 11 years of age (2 years after surgery). EEG in wake and sleep was free of epileptoform activity.

 

Neuropsychological examination 1 year after surgery

The boy was completely without difficulties, generally more lively, more involved in the team, more attentive at school, and his learning process improved. Actual intellectual capacity was in the average range, verbally more confident, non-verbal slightly below the range on account of reduced visual-perceptual skills and fine-motor coordination, which were performance deficient. Attentional functions were slightly impaired. In language functions, impairments in naming continued to dominate, but there was significant improvement in comprehension. The neuropsychological profile was characterized by mild impairments in verbal-mesthetic functions and visual-perceptual skills, with the most striking impairments in fine-motor and graphomotor coordination. Compared to the previous examination, consolidation of the initially problematic areas (attention and speech understanding) could be considered, but the localization-related impairment in the form of borderline deficits in visual-spatial perception persisted.

 

Neuropsychological examination 2 years after surgery

The results were consistent with the previous examination.

 

Long-term follow-up of cognitive development (6 years after surgery)

The boy is also free of neurological problems and anti-seizure medication. Intellectual performance is in the lower average range, performance is unchanged throughout. However, significant improvement is seen in verbal-mnestic function and visual-constructive function. Impairment in language functions persists in the area of naming. Other cognitive functions are unchanged.

 

Case 3 -⁠ a girl after resection of a benign tumour mesotemporally on the left

Initial manifestations

Currently a 22 year old girl with no family or personal history. Parents retrospectively cannot rule out brief (second) preoccupations in infancy -⁠ not sure, no other symptoms present at the time, preoccupations resolved, association with epilepsy was questionable. At 6 years of age, the mother noticed conditions where the girl would suddenly stop in activity, blush, with no complete loss of contact; when asked what was wrong, she replied that her tummy hurt. Frequency sporadic at first, about 1-2 times a month, gradually about once a week. She was first examined at her place of residence at the age of 7 years for abdominal pain. EEG revealed very frequent epileptiform activity localized frontotemporally (FT) on the left. Initial brain MRI was evaluated without pathology. CBZ therapy was initiated. This was with effect, the seizures stopped, the control EEG was normal, the diagnosis of epilepsy began to be questioned, moreover, on CBZ therapy the girl was significantly more tired. Based on this, CBZ was phased out after 1 year.

 

Further course of the disease

She was free of seizures and other difficulties until she was 9 years and 4 months old. Recurrence of epilepsy occurred at 9 years and 5 months, with seizures with the same semiology as the previous one. Initially, the frequency was about once every 3 weeks, but gradually became daily. CBZ was re-introduced with only partial effect, the frequency of seizures was 2-3× weekly. Repeated MRI of the brain with the conclusion: tumoral lesion intraaxially temporomedially on the left. Ganglioglioma or another form of benign tumour was considered in the differential diagnosis. EEG with left FT slowing with contralateral propagation. Up to this time she was taking CBZ, LEV and VPA. However, she still complained of abdominal pain, which was a long-standing problem that started before the diagnosis of epilepsy and was not epileptic in nature according to her history and video EEG. At the same time, the mother observed mood changes in the girl, increasing anxiety. She was managing at school, but at times, according to her mother, she had a "lapse" in her learning, for example, when she did not remember part of her homework.

 

Preoperative diagnostics

The girl was admitted at almost 10 years for a comprehensive examination. At that time, she had occasional seizures (about once a week). Topical neurological findings were normal, the girl was right-handed. VideoEEG showed seizures preceded by 5-10 with nonspecific aura. Anxiety, fear, vegetative changes (flushed, no mydriasis) followed. No automatisms, no falls, no convulsions. Duration up to 30 s, after seizure she understood and was also free of expressive fatal disturbance. Apart from this, there were irregularly separate auras -⁠ about once a day. An MRI was performed with the following conclusion: suspicious for glioneural expansion in the medial temporal lobe on the left and gyrus parahippocampalis on the left, with no clear signal alteration or hippocampal infiltration. FDG-PET of the brain, functional MRI (fMR) and diffusion tensor imaging (DTI) supported the hypothesis of a left-sided mesotemporal localization of the epileptogenic zone, but also did not demonstrate unequivocal hippocampal involvement.

 

Neuropsychological examination before the procedure

The girl's actual intellectual performance was in the good average range, erratic in favour of the verbal component (slightly above average), and rather more average in the non-verbal range. Mnestic functions were without deficits, but there was a striking reduction in visual long-term memory, with performance bordering on deficit (suspected to be due to attention deficit disorder). In verbal episodic memory, there was impaired first-attempt imbibition, but an upward learning curve, with good quality output even in remote equipment. Auditory working memory was without alteration. The cognitive profile showed a slightly reduced psychomotor tempo, indicating difficulties in concentration of attention, which was sustained, with a tendency to be more easily distracted.

 

Epilepsy surgery

At 10.1 years of age, a single individual resection of a benign tumor mesotemporally on the left was performed, resecting the tumor in the temporal pole, amygdala and anterior part of g. parahippocampalis, sparing the hippocampus. The operation was performed without complications. Postoperatively, she was seizure-free. MRI showed complete removal of the lesion and intact hippocampus. Postoperative EEG was free of epileptoform activity. Histology showed ganglioglioma grade I. At the age of 14 years, the girl manifested polymorphic difficulties, different in nature from preoperative. Examination by a paediatric neurologist, a paediatric clinical psychologist and a paedopsychiatrist established the non-epileptic nature of the difficulties with the conclusion of an anxiety-depressive disorder; pharmacotherapy and psychotherapy at the place of residence were indicated. ASM was discontinued at 14 years of age, but LCM was reinstated at 17 years of age due to recurrence of aura-like seizures that persisted at sporadic frequency (1-2 times per year).

 

Neuropsychological examination 1 year after surgery

Actual intellectual and memory performance was in the upper average to slightly above average range, with a minor notability in verbal instinct. There was a marked positive shift towards levelling out some of the irregularities when compared with the previous examination, with the persistent difficulties being only a minor sign of ongoing illness, but still with an eventual negative impact on school performance.

 

Neuropsychological examination 2 years after surgery

Polymorphic difficulties, including the reported form of mnestic disorder, were psychogenic in nature, superimposed on partial neuropsychological impairment in the form of negative fluctuations in the ability to consolidate and delayed equipping of verbally stimulus material in otherwise cognitively/intellectually average performance. The girl's personality composition toward lower emotional stability and resilience to stress, i.e., an anamnestic history of prolonged exposure to painful conditions and interpersonal strain in peer environments, underlay the activation of dysfunctional adaptive mechanisms.

 

Long-term follow-up of cognitive performance (10 years after surgery)

Current intelligence performance is consistent with the screening average. Cognitive picture shows impairment in overall memory capacity and learning process (for verbal and non-verbal material). Remote equipment is within the average range. Cue memory performance improves. Fatal functions are average in naming. The remaining cognitive domains appear rather spared (executive functions, visual-spatial functions and working memory). Psychomotor tempo is normal. Self-assessment shows moderate anxiety-depressive symptomatology.

 

Case 4 -⁠ girl after right-sided anteromesial temporal resection for benign tumour associated with cortical dysplasia

Initial manifestations

Currently, a 21-year-old girl with no clear family or personal history. Seizures appeared in the girl at the age of 4 years, but for a long time they were not recognized as epilepsy (due to psychosocial burden -⁠ death of both parents evaluated as a predisposition to psychogenic non-epileptic seizures, although she reported the conditions before the death of her parents). These were semiologically uniform focal seizures with an atypical complex aura (visual pseudohallucinations of figures threatening the patient and her surroundings). The seizure subsequently continued with gestural and oroalimentary automatisms, vocalizations, non-constant suggestion of left HK dystonia and postictal rubbing of the nose with the right HK -⁠ all without disturbance of consciousness and subsequent fatal or mnestic disturbance. Diagnosis of epilepsy was made at 10 years of age of the girl (prior inference of fantasy experiences). EEG at 10 years of age of the girl with findings of epileptoform activity, MRI initially described as normal. CBZ and LEV were administered but without effect. The patient had a completely normal psychomotor development (walking and first words at 12 months, started kindergarten at 3 years, adaptation good).

 

Further course of the disease

Initially, the states lasted many minutes to an hour, but later they were much shorter (up to 2 min, up to 30 s from 11 years of age). During large seizures she often fell down, waved her HKK, had absent facial expression, tonic posture of both lower limbs (LBP) was possible, and after resolution she was drowsy, confused. Oroalimentary automatisms were sometimes observed at the onset of the seizure. The frequency was stationary 1-3 per month, often with cumulations of 1-14 seizures. Signs of hyperactivity, emotional lability, difficulty concentrating at school, negativity were observed. Of the medications tried LEV, CBZ.

 

Preoperative diagnostics

The girl was admitted to the clinic at the age of 11. Neurological findings were normal, only slightly slower psychomotor pace, right side. EEG localized the epileptogenic zone to the right anterotemporally. MRI of the brain revealed a complex structural abnormality mesotemporally on the right as the cause of the disease; we considered a combination of cortical dysplasia of the temporal pole with a glioneural tumor of ganglioglioma character or a dysembryoplastic neuroepithelial tumor. The FDG-PET result supported the suspicion of mesotemporal localization of the epileptogenic zone.

 

Neuropsychological examination before surgery

Actual intelligence performance was in the below average range. Mnestic functions were in the average range in both immediate and delayed equipment for verbal material, and nonverbal memory was impaired, including memory for faces. Attentional, executive, and visual-constructive functions were also impaired. Fatal functions were preserved in the area of comprehension.

 

Epilepsy surgery

At the age of less than 12 years (8 years from the onset of epilepsy), a right-sided anteromesial temporal resection including the hippocampus was performed. Histology confirmed ganglioglioma, grade 1, and cortical dysplasia type 3B in the adjacent neocortex (according to the International League Against Epilepsy [ILAE]). The surgery was uneventful. The girl had no postoperative neurological deficit and was seizure-free. Postoperative MRI showed complete removal of the lesion and the EEG was free of epileptoform activity. ASM was discontinued at the age of 15 years.

 

Neuropsychology 1 year after surgery

There was a significant improvement in mnestic non-verbal functions, but memory for faces was still impaired. Intellectual performance was unchanged. Attentional functions were slightly impaired. Performance on tests of visual-constructive functions was in the lower average range. Fatal functions were impaired in the naming domain. Comprehension was preserved. On the other hand, behavioral difficulties and family conflicts progressed, and she was hospitalized in a psychiatric hospital for a long time. She saw a paedopsychiatrist regularly and was medicated with risperidone and sertraline. However, risperidone was gradually reduced.

 

Long-term follow-up of cognitive development (6 years after surgery)

The girl is no longer on psychiatric medication, lives a normal life, goes to work. Intellectual performance is still in the below average range. Mnestic function is in the average range, but impairment persists in memory for faces. Improvements have occurred in attention, executive (in inhibition and flexibility, ability to initiate, maintain and terminate action), language and visual-constructive functions, which are currently in the average range. Comprehension is in the average range.

 

Discussion

In this case study, we focused on the long-term cognitive performance outcomes of pediatric patients with focal pharmacoresistant epilepsy who underwent single resection epilepsy surgery in the temporal lobe. The aim was to illustrate the dynamics of cognitive development in these patients. Children with focal and pharmacoresistant epilepsy have up to 80% risk of developing cognitive impairment. Cognitive impairment may manifest in one or more cognitive domains and its severity depends on a number of factors, including the age of the patient at the time of epilepsy onset, the cause of the disease, the extent and location of the epileptogenic zone, the duration of the disease and the possibility of its compensation [20].

In paediatric patients with focal pharmacoresistant epilepsy, epilepsy surgery is the only causal treatment method that can dramatically affect not only seizure frequency and quality of life, but also the amount of medication used, cognitive performance, modify behavioural and emotional difficulties, improve the overall quality of life of the patient and family, and can contribute to the reintegration of the individual into society [16,21,22]. Dwivedi et al [9], in a unique randomized trial focusing on pediatric resectional epilepsy surgery, demonstrated that 77% of operated children were seizure-free 1 year after surgery. They then demonstrated an increase in quality of life and a reduction in behavioral-emotional difficulties in these patients. In contrast, in the group of non-operated patients, only 7% of the cases were compensated on medication and the quality of life scores were significantly worse than in the operated group.

An important aspect that affects long-term outcomes and the overall course of the disease is the early indication for epilepsy surgery. Early intervention may contribute to an earlier reduction in the number of seizures, increase the chances of complete remission of seizures, and ultimately stop the further deteriation process. Current experience shows that patients who undergo epilepsy surgery at an early stage of the disease show better social adaptation after surgery, including a lower risk of psychiatric comorbidities [16]. In the longer term, this leads to a greater chance of consolidation of affected cognitive functions and minimization of the negative impact of epilepsy on the life of the child and family [23,24]. However, to date, the prevailing work has performed retrospective analyses on small cohorts and has yielded rather inconsistent results (also mainly due to the limited scope of cognition assessment using intelligence tests and psychometric complexity). From the results of the meta-analyses, 70% of children's IQ does not change significantly after exercise. Initial studies suggest some improvement in intelligence scores after more than five years [25-28]. This ambiguity is particularly evident in the context of long-term uncompensated epilepsy [29,30].

The case reports presented here highlight the importance of a comprehensive clinical-neuropsychological examination during the care of pediatric patients with TLE, including their follow-up after surgery. A detailed assessment of the profile of mnestic functions, attentional and executive functions, language development (in receptive and expressive areas), visual-constructive, visual-spatial and motor functions (in fine motor and coordination, graphomotor, oromotor), as well as social cognition and emotional-behavioural profile is crucial. In contrast, mapping intelligence performance is less effective for tracking over time. However, it is essential to monitor it when it is necessary to predict the child's functioning in the educational process. Due to the heterogeneity of the disease, it is difficult to define a characteristic cognitive profile. In the literature, due to the localization, mnestic or language deficits are often emphasized, but from clinical practice and the cases reported here, the cognitive profile is characterized by different types of deficits [16,25,28]. In the patients reported by us, a gradual consolidation of cognitive functions can be considered, with possible residual impairment in the most affected cognitive function. In cases 3 and 4, monitoring of the patients' emotional and behavioral status and further targeted management at the place of residence (psychotherapeutic and psychiatric care) proved to be important.

On the basis of the above mentioned theoretical findings, our clinical experience and the cases reported here, we are convinced that early indication of epilepsy surgery is crucial for favourable outcomes, including cognitive outcomes. However, it should be emphasized that this area requires further research. More prospective studies in larger patient samples are needed to better understand the dynamics of these processes and their impact on cognitive outcomes in patients with epilepsy. Such research could lead to the development of more effective treatment strategies and improve the quality of life of patients with this disease. However, comprehensive care and multidisciplinary collaboration are also needed to achieve a favourable outcome. Collaboration between outpatient neurologists is crucial, as they are usually the first to come into contact with the patient and can thus be the first to suspect focal and pharmacoresistant epilepsy and refer the patient to an epilepsy centre at an early stage. From the case reports we have reported, it is a sad fact that the initial brain MRI performed outside the epilepsy centre can often have a misleading (false negative) result and can complicate the diagnostic process. A correct assessment of the clinical picture of the disease and EEG findings is therefore essential. Comprehensive diagnostics in an epilepsy centre includes detailed electrophysiological, neuroimaging and genetic investigations; neuropsychological testing is a standard part of this. Physiotherapists, clinical speech therapists or social workers may also be included in more targeted care. The outcome of this broad interdisciplinary collaboration is early and effective management of the disease to prevent the often catastrophic consequences of long-term uncompensated epilepsy, among which cognitive deterioration and severe psychosocial consequences such as reduced quality of life for the child and the family, mental illness, reduced socioeconomic status of the family, or, for example, unsatisfactory social inclusion of the individual [16] are at the forefront.

 

Conclusion

This case study demonstrated that epilepsy surgery is an effective causal treatment modality for selected pediatric patients with focal pharmacoresistant TLE. It contributes significantly in reducing seizure frequency, improving quality of life and allowing a reduction in the amount of medication used. In addition, in the long term, it leads to a gradual consolidation of cognitive functions and can improve behavioural and emotional difficulties, thus increasing the potential for reintegration of the individual into society. Interdisciplinary collaboration, early indication for epilepsy surgery, and a comprehensive approach to the patient are key factors influencing long-term outcomes (including minimizing the negative impact on the lives of patients and their families). In terms of neuropsychological approach, monitoring of the complete cognitive profile, not just intelligence performance, is essential. However, further prospective studies in larger patient samples are needed to better understand the dynamics of these processes and the development of cognitive function. This study represents an important step towards a better understanding of the impact of epilepsy surgery on cognitive development in pediatric patients with focal pharmacoresistant epilepsy. Further research is needed to develop more effective treatment, rehabilitation and support strategies for families and patients.

 

Ethical aspects

The work was carried out in accordance with the Helsinki Declaration of 1975 and its revisions in 2004 and 2008. The study was approved by the Ethics Committee of Motol University Hospital in Prague, Czech Republic, reference number EK-1195/19 (date of approval 17 October 2019). Each study participant signed an informed consent form.

 

Grant support

Supported by the Grant Agency of Charles University (GAUK), project number 666320; and the Ministry of Health of the Czech Republic, project number 00064203 FN Motol, also within the project of the 2nd Faculty of Medicine of Charles University, project number TL03000328, which was co-financed with the state support of the Technology Agency of the Czech Republic within the ÉTA Programme.

 

Conflict of interest

The authors declare that they have no conflict of interest in relation to the subject of the study.