Clinical Neuropsychology in Pediatric Epilepsy Neurosurgery

To mark International Epilepsy Day, psychology student Cristian Francisco Liebanas Vega writes about clinical neuropsychology in pediatric epilepsy neurosurgery. Specifically, he explains what epilepsy is, its types and causes, the stages of an epileptic seizure, and the epileptic syndromes associated with cognitive manifestations. Liebanas also emphasizes the importance of neuropsychological assessment and neurorehabilitation in patients with epilepsy

Definition and clinical considerations of epilepsy

Epilepsy, like other neurodevelopmental disorders, is not a single disease entity. Although its hallmark is recurrent seizures, in a significant proportion of children and adolescents it is associated with intellectual, cognitive, and behavioral problems.

Seizures, epilepsy, and epileptic syndromes

The common denominator of epilepsy is seizures. According to the International League Against Epilepsy (ILAE), a seizure is defined as “a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain”.

Types of epileptic seizures

There are two basic types of epileptic seizures:

1. Focal seizures

Localized excitability of cortical or subcortical origin that occurs within networks limited to one hemisphere, which may be more localized or more widely distributed.

Forms of presentation

In this type of seizure, awareness may be preserved or impaired, and different forms of presentation can be observed:

• Motor onset: possibly with motor automatisms. Different seizure types can be distinguished, such as:
  • Atonic seizures,
  • clonic,
  • hyperkinetic,
  • myoclonic,
  • tonic,
  • Non-motor onset (autonomic).

• They may present with autonomic manifestations such as sweating, temperature changes, excessive salivation, and so on.
• Sensory: tingling, feeling hot or cold, strong smells, visual disturbances, or pain.
• Cognitive: difficulty with language or a specific cognitive function (aphasia, apraxia, or neglect)
• Memory lapses, a feeling of déjà vu, repetitive thoughts, and hallucinations, among others.
• Emotional: intense reactions unrelated to the situation, fear, aggression, crying, sudden changes (laughing-crying), and so on.

2. Generalized seizures

Diffuse throughout the cortex. They originate at some point within bilaterally distributed neural networks and spread rapidly. These bilateral networks may include cortical and subcortical structures and may be asymmetric (Berg et al., 2017).

They can present as:

• Motor: tonic-clonic (tonic and clonic), myoclonic, myoclonic-tonic-clonic, myoclonic-atonic,
• Non-motor: (absence seizures): typical or atypical, myoclonic absence, or with eyelid myoclonia.

When a seizure lasts longer than 60 minutes and does not respond to medication, it is considered refractory status epilepticus. According to the ILAE (2017), this condition can have long-term consequences, including neuronal injury or death and alteration of neural networks, depending on the type and duration of the seizures.

Not all seizures are epileptic: many circumstances can cause acute non-epileptic seizures. Recognizing non-epileptic semiology is just as important as recognizing epileptic semiology, for example, non-epileptic paroxysmal disorders, defined as brain dysfunction caused by mechanisms other than those of epileptic seizures. These mechanisms can be:

• anoxic (breath-holding spells),
• sleep-related (night terrors),
• psychological (anxiety attacks),
• stereotyped movements,
• pathological muscle contractions,
• muscle spasms,
• etc.

Epilepsy is defined as a brain disorder characterized by an enduring predisposition to generate epileptic seizures, with neurobiological, cognitive, psychological, and social consequences.

Conceptually, epilepsy is present when the patient has had at least one unprovoked seizure and there is a high probability of another seizure. In 2014, the ILAE proposed an operational (practical) clinical definition of epilepsy, which is the one currently in use.

What is epilepsy? Circumstances that define epilepsy

1. At least two unprovoked (or reflex) seizures occurring more than 24 hours apart;
2. one unprovoked (or reflex) seizure and a probability of further seizures over the next 10 years similar to the general recurrence risk (at least 60%) after two unprovoked seizures;
3. diagnosis of an epilepsy syndrome.

Stages of an epileptic seizure

Each epileptic event usually has three stages that must be known and recognized: pre-seizure, seizure onset, and post-seizure.

1. Pre-seizure stage

This stage involves precipitating or facilitating factors, such as fever, overstimulation, or lack of sleep. It’s important to learn which stimuli trigger seizures in each patient in order to avoid or minimize them as much as possible.

Sometimes environmental stimuli trigger the seizure, such as exposure to certain light stimuli or sudden or unexpected sounds. In some more severe cases, such as developmental and epileptic encephalopathies, sensory stimulation can trigger a seizure. In encephalopathies with motor involvement, seizures sometimes appear when the patient tries to make a voluntary movement.

2. Seizure onset

The clinical manifestations typical of each seizure type appear. The most striking are usually generalized tonic-clonic seizures, but there are also more subtle ones, such as eyelid myoclonia.

3. Post-seizure stage

The post-seizure or postictal stage also has clinical manifestations, such as headaches, drowsiness, and muscle weakness.

An epileptic syndrome is defined as “a characteristic cluster of clinical and EEG features, often supported by specific etiological findings” (structural, genetic, metabolic, immune, and infectious).

It often has prognostic or treatment implications and frequently has age-dependent presentations, meaning that it generally begins at specific ages and, in some cases, may also remit at certain ages.

Many syndromes are strongly correlated with a variety of specific intellectual, psychiatric, and other comorbidities, whereas in other syndromes, the absence of such comorbidities is a characteristic feature.

Epileptic syndromes by age of onset

Epileptic syndromes have traditionally been grouped by age of onset. The ILAE describes separately:

1. Syndromes with onset in neonates and infants (up to 2 years of age);
2. syndromes with onset in childhood;
3. syndromes with onset at variable ages (that is, in both pediatric and adult patients).

When epilepsy occurs while the nervous system is still developing, the manifestations of neurological disease in childhood appear, corresponding to a neurodevelopmental disorder.

There are epidemiological, anatomical, logical, and pathophysiological reasons to consider epilepsy in children and adolescents a neurodevelopmental disorder. Above all, there are reasons related to neurodevelopment itself: the immature brain is hyperexcitable, and its properties change with maturation, determining the appearance of age-specific epileptic syndromes (Mas Salguero, 2020).

Causes of epilepsy

In 2017, the ILAE urged classifying epilepsy by cause and in the context of its comorbidities, such as neurodevelopmental disorders, with the aim of achieving optimal seizure control and improving quality of life. Although the causes of epilepsy in childhood and adolescence are very varied, three main groups can be distinguished:

1. Lesional epilepsy

Caused by any agent that permanently damages the brain: injuries related to prematurity, infections, malformations, trauma, hypoxia, and so on.

2. Genetic epilepsy

Most cases are caused by a de novo alteration (Dravet syndrome, for example), while others are clearly hereditary (benign familial neonatal seizures, for example),

Seizures that cause epileptogenic lesions. This is the case of acute inflammatory encephalopathies that cause status epilepticus, hemiconvulsion-hemiplegia syndrome (IHHS), or febrile infection-related epilepsy syndrome (FIRES), whose cause is unknown.

All of them disrupt normal brain function and create a state of high brain excitability that, through different mechanisms, facilitates the appearance of the different seizure types.

Clinical manifestations by seizure type

It is extremely important to know how to detect and recognize the semiology most common in the different seizure types. This helps build a clinical pattern of each patient’s epilepsy, which is very useful for planning the intervention or prevention program.

Sometimes the clinical manifestations are very subtle, which is why it’s recommended to ask family members for a detailed description of the episodes and to record them whenever possible. Different clinical manifestations can be observed depending on the location of the seizures.

Below are some of the clinical manifestations most often observed in pediatric patients.

1. Temporal focal seizures

Mesial temporal

Patients may present rising epigastric discomfort (described as a burning sensation in the pit of the stomach), increased or new drooling, belching, pallor, facial flushing, breath-holding, pupil dilation, fear, panic, and olfactory or gustatory hallucinations.

Neocortical temporal

The most common symptoms in childhood are automatisms (lip smacking, chewing or swallowing, facial grimaces, laughter more pronounced on one side of the face, etc.) and a blank stare with apparent temporary absence.

During the automatism, the patient is amnesic, although they may behave as if aware, albeit confused. The average duration is 1 to 2 minutes.

Feelings of fear and strangeness are also common clinical manifestations in childhood (Etchepareborda, 1999).

2. Frontal focal seizures

Dorsolateral area

• Discharges at the anterior end of the dorsolateral surface of the frontal lobe: cause generalized tonic-clonic seizures with rapid posterior spread, abnormal eye movements, and loss of consciousness, as the electrical activity spreads quickly to posterior areas.
• Discharges in the intermediate area of the dorsolateral surface: cause complex partial seizures.
• If the electrical discharge is located in the neuronal population immediately anterior to the Rolandic fissure, it causes seizures with motor symptoms that spread following the somatotopic representation of this brain area (starting in a finger and spreading through the whole limb, for example). These are known as Jacksonian seizures and occur without impaired consciousness.
• If the electrical discharge occurs in the so-called opercular region of the frontal lobe, it causes chewing and swallowing seizures, excessive salivation, dysarthria, and partial motor signs in the face, without loss of consciousness.

Medial area

• If the discharge appears in the supplementary motor area, there is usually turning of the head and eyes to the opposite side, accompanied by trunk rotation in the same direction, tonic posturing of the contralateral arm, and dysarthria (Palacios and Clavijo-Prado, 2016).
• When the electrical discharge affects the cingulate or pericallosal region, the manifestations are bimanual movements, bipedal movements, brief absences, unprovoked laughing or crying, terror or rage attacks, and autonomic signs (tachycardia, tachypnea, pupil dilation) (Etchepareborda, 1999).

Basal area

• When discharges appear in the basal or orbital area of the frontal lobe, there are gestural automatisms, tonic and clonic movements of all four limbs, olfactory hallucinations, autonomic signs (tachycardia, tachypnea, mydriasis), and sudden falls (Etchepareborda, 1999).

3. Absence seizures

They are a type of generalized epilepsy.

Typical absences involve a disconnection from the environment with abrupt onset and end and short duration. They are sometimes accompanied by motor manifestations, such as oral or eye movements.

Atypical absences involve a disconnection from the environment with a more gradual onset and end and a longer duration. Patients usually don’t remember the episode.

In some types of absence seizures, the patient seems aware and may even speak. Some absences occur when the patient engages in a particular activity, such as reading or writing (Alonso, 2020).

This type of seizure usually affects the patient’s cognitive performance, especially when it occurs very frequently: patients resume the task confused and without a goal, which affects their performance. Absences often go unnoticed by family and school and significantly affect learning. They are sometimes misdiagnosed, mainly as ADHD or as a learning disorder.

4. Infantile epileptic spasms

This is a rare type of seizure. If not treated in time, it can lead to stalled neurodevelopment and even regression.

They present as spasms characterized by head drops, raising and extension of the upper and lower limbs, back arching, bending forward at the waist, and raising of the knees when lying down. They can also be more subtle, such as slight head drops or subtle eye deviations.

It is important not to confuse them with infant colic, an exaggerated Moro reflex, or benign sleep myoclonus, among others (Alonso, 2020).

These are some of the clinical manifestations of epileptic seizures, but many others may occur that differ in form and frequency from those described. It is worth noting that in newborns and infants, seizures are sometimes more subtle or may be confused with non-epileptic paroxysmal events (described above), so epileptiform pathology should always be ruled out when in doubt.

Epileptic syndromes associated with cognitive manifestations

Below, we briefly describe some epileptic syndromes that present with encephalopathy.

1. West syndrome

An epileptic encephalopathy characterized by infantile spasms, hypsarrhythmia (an EEG pattern), and arrested neurodevelopment involving all areas. Patients’ neuropsychological patterns vary: some patients function with little impairment, while others are severely affected. Symptomatic cases, that is, those with a known cause, have a worse prognosis than cases with an unknown cause (West Syndrome Foundation, 2011).

2. Lennox-Gastaut syndrome

The clinical manifestations of this syndrome are tonic seizures predominantly during sleep, atonic seizures, atypical absences, and progressive neuropsychological decline. The later the seizures begin and the fewer the prior risk factors, the better the response to treatment and the prognosis for cognitive development.

They are usually refractory to treatment and require pharmacological polytherapy, which further worsens the cognitive symptoms (West Syndrome Foundation, 2011)

3. Dravet syndrome

It is a rare epileptic syndrome characterized by 3 progressive stages:

Epidemiology of epilepsy and physiology of the developing brain

The incidence of epilepsy by age follows a U-shaped curve (Image: Incidence of epilepsy), with peak values in the first ten years of life that then stabilize and rise again at older ages.

The incidence of childhood epilepsy is higher at younger ages. Not only does it interfere with brain growth by delaying the emergence of appropriate adaptive behaviors, but the likelihood of it appearing in the course of a neurodevelopmental disorder is much higher than in the general population, which is highly significant. Overlap between epileptic syndromes and neurodevelopmental disorders is very common.

Epileptic encephalopathies appear at early ages and are characterized by an electroencephalogram with abnormal, intractable electrical discharges associated with progressive neurological dysfunction and a considerable impact on neurodevelopment, leading to permanent deficits in motor skills, cognition, and social behavior typical of different neurodevelopmental disorders.

On the other hand, other conditions involving a neurodevelopmental disorder (such as Rett syndrome, fragile X syndrome, trisomy 21, or tuberous sclerosis complex, among many others) carry a high risk of epilepsy, which in turn worsens the prognosis of the underlying condition.

It is no coincidence that more people develop epilepsy at the extremes of life. It is most likely closely related to brain development processes in childhood and degeneration in old age (formation of connections during growth versus their loss in old age).

However, although the synaptic mechanisms that are disrupted are the same at both ends of life, the results are not the same.

Epilepsy in childhood is more frequent, with more varied types and syndromes, and its pathophysiological mechanisms are closely linked to brain growth.

The stage of neurodevelopment shapes brain anatomy and physiology and, therefore, the characteristics of seizures.

So if we look at the incidence of the different seizure types (Figure 4.1. Incidence of epilepsy), we see that myoclonic seizures are the most common in newborns, when the primary motor and sensory areas are barely myelinated and epileptic discharges cannot spread. Although much less common, focal seizures are also seen at this age.

However, there are no hemibody or generalized seizures, which can only appear as intracortical connections form and myelination progresses.

Following a posterior-to-anterior gradient, connections are activated successively in these regions:

• Perisylvian: from birth,
• parieto-occipital: between 3 and 7 months of age,
• frontal premotor: from 12 months to the first decade of life.

At the same time, myelination follows a caudal-to-rostral gradient.

All of this contributes to the semiology of seizures in newborns and infants, which is determined by these anatomical and functional characteristics, as well as by hemispheric specialization and the progressive maturation of long pathways.

To grow, build circuits, and modify them, the neurons of the child’s nervous system need to be easily excitable, with facilitating (excitatory) synapses rather than ones that hinder this development (inhibitory).

We have seen that in the first two years of life, the predominant neurodevelopmental phenomenon is synaptogenesis. It happens at a dizzying speed (about 1,000 new synapses form per second), with synapses firing continuously to get started and synchronize with one another.

On the one hand, neurotransmission in immature neurons is mainly excitatory: the GABA receptor promotes chloride entry into the cell, and there is an abundance of glutamate receptors, both of which favor the passage of the electrical signal and increase neuronal excitability.

On the other hand, developing neural circuits have higher intrinsic resistance (which favors the transmission of action potentials) and emit periodic discharges that help synchronize new networks, with discontinuous activity that increases with maturation. This whole excitatory environment promotes growth and learning but also favors the development of epileptic mechanisms.

Protective factors against hyperexcitability

Intrinsic protective factors against hyperexcitability

Since epilepsy only occurs in 1–2% of children under two, the brain has intrinsic protective factors against this hyperexcitability:

• A high concentration of neurotrophic factors, which are neuroprotective,
• glutamate reuptake transporters in astrocytes,
• immature cytotoxic cascades that protect against glutamate toxicity,
• a lower concentration of pro-inflammatory cytokines.

Extrinsic protective factors against hyperexcitability

Other extrinsic factors also act as protectors:

• Maternal oxytocin released during birth causes chloride to leave the fetal neuron, favoring a more inhibitory action of GABA,
• the newborn’s lipid-rich diet promotes the formation of ketone bodies, which have a protective effect on the brain.

From the second year of life, synapse formation slows down and brain myelination is more advanced, which contributes to the decline in epilepsy incidence from this age.

Early-onset epilepsy occurs when damaging mechanisms specific to childhood (genetic defects, neuronal migration defects, inflammatory, infectious, or traumatic agents, and tumors) act on this natural hyperexcitability of the developing brain. They can act at the presynaptic or postsynaptic level, on glia, or on cell adhesion molecules. They also interact with one another, making their study much more complex.

Alterations in synaptic proteins cause neural circuit dysfunction and are involved in the etiological and damaging mechanisms of both childhood epileptic syndromes and conditions related to autism or intellectual disability.

Genetic studies of childhood epilepsies

Indeed, genetic studies of childhood epilepsies have led to the identification of genes whose alteration and loss of function cause adverse effects on neurodevelopment, with or without epilepsy.

This is the case of the SCN2A gene, which encodes the alpha-2 subunit of the sodium channel. Its mutations can cause disorders of varying severity, including:

• benign familial infantile seizures (which disappear by age two without long-term consequences),
• an infantile epileptic encephalopathy (with hard-to-control seizures before the first year of life, followed by neurodevelopmental delay),
• or autism spectrum disorder, in which only 30% of those affected will develop epilepsy, in this case after 12 months of age.

These cases of epilepsy that share a genetic origin with neurodevelopmental disorders have led to changes in the ILAE classification of epilepsies, which replaced the term “epileptic encephalopathy” (2010) with “developmental and epileptic encephalopathy” (2017).

This is another step toward recognizing that epilepsy in children and adolescents should be considered, without reservation, a neurodevelopmental disorder, and more and more research supports this premise.

Neuropsychological assessment and the importance of the clinical neuropsychologist in pediatric epilepsy

Today, not only the neuropsychological assessment of patients with epilepsy but also the role of the neuropsychologist in epilepsy teams and units has become very important, in diagnosis, surgical intervention, and rehabilitation.

In the pediatric population, neuropsychological assessment and follow-up provide essential information for managing and guiding children with epilepsy, since the effect of this disease on a developing brain can lead to the establishment of extensive dysfunctional networks (Fournier, 2019).

The goals of neuropsychological assessment can be understood from a diagnostic perspective, since cognitive or behavioral changes can provide important data for localizing and lateralizing seizures, which is very useful in epilepsy surgery. It also helps to understand the epileptic syndrome as a whole, allowing better treatment decisions, both pharmacological and non-pharmacological.

Goals of a neuropsychological study in pediatric epilepsy

According to Chelune (2010), the main goals of a neuropsychological study are:

1. Establishing a baseline neuropsychological profile to identify any risk of developmental, cognitive, academic, or psychopathological problems from the first seizure.
2. Helping detect neurological disorders, which often go unnoticed in the pediatric population and are confused with normal developmental delays.
3. Monitoring cognitive and behavioral changes over the course of the disease.  
4. Diagnosing psychopathological disorders and assessing their impact on both cognition and adaptive functioning.
5. Helping make decisions about planning treatment and educational measures.
6. Recording and documenting possible adverse side effects, both cognitive and behavioral, of antiepileptic drug treatment.  

The ILAE advises that neuropsychological assessment should be included in the routine care of patients with epilepsy (Wilson et al., 2015). The clinical neuropsychologist’s role must therefore be active and go far beyond administering cognitive tests and analyzing them statistically; it requires extensive training and years of experience in both clinical and developmental neuropsychology.

Analyzing cognitive semiology is crucial in these studies to analyze and synthesize the information provided by the tests administered together with the information gathered from the patient’s medical history and examination.

Examinations of young children with significant neurodevelopmental impairments often make it difficult to use structured protocols, so professionals need to be able to adapt cognitive tests and tasks to obtain the cognitive profile that allows the goals mentioned above to be met.

Neuropsychological assessment protocols

Given the characteristics of epilepsy in the pediatric population and its developmental implications, it is very difficult to establish standard protocols, unlike adult patients, for whom several protocols approved by the national and international scientific community guide these assessments.

It is important to understand that we cannot assess cognitive functions or circuits that are still developing or have not yet emerged. Likewise, in the pediatric population more factors can affect the assessment process and interfere with the patient’s performance, so the main recommendations for pediatric protocols are flexibility, letting the patient get used to the evaluator before starting, and not treating time as a decisive factor.

Using cognitive screening protocols alone is not recommended. Protocols must be broad enough to cover the different cognitive processes and domains so we can understand the patient’s neuropsychological functioning profile. Keep in mind that functions such as memory cannot be reliably assessed in children under 5.

When assessing executive functions and certain subcortical processes, we must know that the available tests are very sensitive but not very specific, since they are frequently affected by antiepileptic drugs. Their sedative effect lowers processing speed and sustained attention systems, so many tests that depend on information processing will be affected secondarily, preventing us from obtaining objective quantitative data.

This is when cognitive semiology and qualitative analysis become more relevant for the conclusions.

Clinical neuropsychology in pediatric epilepsy neurosurgery

Epilepsy neurosurgery in pediatric patients is often not considered one of the main lines of action. However, it should not be viewed as a last resort for drug-resistant epilepsies.

Given the importance of a developing brain, the main goal of the entire specialized epilepsy surgery team must be, above all, not to worsen the neurodevelopmental prognosis. Neuropsychology’s contribution is crucial for this. The neuropsychologist plays an active role mainly in assessing and selecting candidates and during the procedure, but above all in the post-surgical process, when the neuropsychologist becomes a guide for the family as well as for the medical and rehabilitation teams.

Thanks to advances in structural and functional neuroimaging techniques, early detection of candidates with lesions or structural abnormalities causing refractory epilepsy has improved (Berg et al., 2017).

Main goals of a neuropsychological assessment in epilepsy

The main goals of a neuropsychological assessment, which is now part of epilepsy surgery unit protocols according to the ILAE (Jayakar et al., 2014), are to:

1. Establish a baseline to quantify the impact of surgery and its outcomes,
2. characterize cognitive strengths and deficits, not always detected previously,
3. contribute to the localization or lateralization of function,
4. report the risk of deficits after surgery,
5. provide information on children’s educational needs and plan their rehabilitation,

The standard pre-surgical protocol includes:

• A high-definition structural neuroimaging study (3 Tesla MRI),
• a neurophysiological study with video-electroencephalography monitoring (video EEG),
• a complete neuropsychological study.

To achieve good post-surgical outcomes (complete resection of the lesion with minimal functional sequelae), it is essential to locate the lesion in the epileptogenic zone as precisely as possible.

It is therefore essential to distinguish between the symptomatogenic zone, the area of cortex activated by an epileptogenic discharge that produces ictal symptoms, and the irritative zone, the cortex that generates the interictal discharges that EEG and MRI aim to locate.

These discharges generally do not produce symptoms, as very intense afterdischarges are needed for that; most symptoms result from propagation. Only sometimes, if the seizure originates in an eloquent area, does it produce clinical manifestations (Rosenow and Lüders, 2001).

Complete resection of the lesion is not always necessary for a good clinical outcome, and sometimes seizures persist despite complete resection (López and Pomposo-Gaztelu, 2001). This is mainly because structural studies only show an outline of the lesion, “the tip of the iceberg”, which is why many final decisions about whether to perform a complete resection are made during the procedure, when direct information about the lesion is available. That’s why the neuropsychologist is needed in the operating room, even when the patient is not always awakened.

This role is even more important in pediatrics, as the neuropsychologist builds a direct relationship with the child and a bond of trust with the family.

Brain plasticity

The potential for brain plasticity in childhood is critical for planning an intervention, not only because of the ability of cognitive functions to reorganize but also because chronic seizures disrupt neurodevelopment, causing greater cognitive delays.

The neurocognitive development of children who undergo surgery therefore depends on many factors:

• etiology of the lesion,
• age at seizure onset,
• age at the time of surgery,
• type of surgery and complications,
• pharmacological treatments,
• context before surgery,
• access to prior neurorehabilitation interventions,
• etc.

However, it is clear that if complete control or a significant reduction in seizures can be achieved, with antiepileptic drugs withdrawn or reduced, patients’ cognitive development will progress significantly.

Most of the available information comes from single cases and experiences or short series. It is necessary to document these patients’ neuropsychological progress to better analyze the risks and benefits of early radical interventions (Fournier, 2019).

Specific protocols will be similar to those described above, with case-by-case nuances; certain functions such as language, memory, or visuospatial function can be explored in more depth.

They may also include psychopathological rating scales to rule out or confirm mood or personality disorders.

Patient follow-up

What varies most significantly is patient follow-up. In a surgical protocol, it is important to assess the child’s level of consciousness and basic functions on waking from surgery and in the following days before discharge, and to carry out a complete post-surgical neuropsychological assessment at 6 months. The main goal is to set the guidelines for the rehabilitation program and the educational support needed in each case.

In some cases, depending on the patient’s age (generally 7–8 years) and the type of lesion and its relationship with eloquent areas, an intraoperative assessment with intraoperative brain mapping may be considered. In these specific cases, training in the assessment and control of the patient with the referring neuropsychologist should be part of the standard protocol.

However, the usual aim is to avoid subjecting a pediatric patient to these protocols, first analyzing the case with complementary studies such as functional MRI or the Wada test.

When no conclusive data are obtained or the risk to the eloquent area is very high (especially for language and memory), intraoperative brain mapping is necessary. For this, it is advisable, as far as possible (since it depends on each hospital’s resources), to carry out a neuropsychological assessment protocol in the months before surgery in order to:

• assess the patient fully and longitudinally,
• build a relationship of trust with the child and family,
• carry out simulated training with the tests that will be used during brain mapping.

In this period before surgery, it is also advisable to develop a neuropsychological rehabilitation and stimulation program, which not only improves the results of the pre-surgical study but also improves results in the operating room and helps prevent anxiety attacks that could even lead to post-traumatic stress disorder.

Cognitive neurorehabilitation in epilepsy

Factors to consider in patients with epilepsy when designing a neurorehabilitation program

The neuropsychological profile of patients with epilepsy varies depending on several factors. The main ones to consider in a neurorehabilitation program are:

1. Age at seizure onset

As mentioned above, age is a decisive factor in the pathophysiology of the different seizure types and epileptic syndromes, since the structural and functional changes the brain undergoes from birth to adolescence shape the clinical and neurophysiological expression of epilepsies.

The timing of symptom onset and the prior maturation of brain functions determine the impact on neurodevelopment.

Early seizure onset increases the risk of cognitive decline. Several studies suggest that the most critical period, with the greatest impact on neurodevelopment, is from 0 to 5 years (Mauri et al., 2001).

2. Seizure types

Generalized seizures usually involve greater cognitive impairment than focal seizures.

• Generalized seizures affect deep structures: subcortical areas, the thalamus, and the brainstem reticular activating system, which are involved in controlling complex brain functions.
• Focal epilepsies are usually associated with specific neuropsychological deficits depending on the location of the seizures (Mulas et al., 2006).

3. Seizure frequency

A higher frequency of epileptic seizures compromises underlying cognitive functioning to a greater extent.

Etiology of the epilepsy or epileptic syndrome

Epileptic encephalopathy (such as West syndrome or Lennox-Gastaut syndrome) has the worst prognosis, as it involves progressive deterioration of brain function, including evolving neuropsychological impairment, probably secondary to abnormal, excessive, and diffuse electrical activity (Nieto, 2011).

4. Pharmacological treatment

Antiepileptic drugs can have a positive influence on patients’ cognition and emotions by controlling seizures. However, because they also act on neural circuits that regulate cognition, they can cause undesirable neuropsychological effects.

Although newer antiepileptic drugs have a smaller effect on cognition, daily practice with these patients still shows a relationship between drug effects and cognitive performance. The problems observed usually involve specific cognitive deficits rather than generalized cognitive dysfunction.

Monotherapy

Drug blood levels may be abnormally high or doses may be increased too quickly (Álvarez-Carriles et al., 2011). Two drugs with mild cognitive effects can potentiate each other or cause tolerability problems, leading to cognitive dysfunction (Moog, 2009).

Most of these drugs reduce membrane excitability, increase postsynaptic inhibition, or generally alter the synchronization of neural networks. As a result, reduced neuronal excitability causes a significant decrease in processing speed and in the systems of control and sustained attention. In developing brains, these negative side effects can be as disabling as the seizures themselves, or more so.

General side effects of antiepileptic drugs

Although there are major individual differences in treatment response, some general side effects of the different antiepileptic drugs can be identified, such as:

• attention and inhibition problems, worsened by the drowsiness some antiepileptic drugs cause or the insomnia others cause;
• slowed processing speed;
• irritability,
• motor restlessness;
• emotional dysregulation;
• impaired working memory
• effects on the visual field,
• among others (Campos-Castelló and Campos-Soler, 2004).

The greatest decline is usually seen in patients with drug-resistant seizures, especially when onset was early, not only because they usually have had the disease longer but also because they have tried many treatments.

Patients’ drug doses and titration schedules must be taken into account, as there is a relationship between increased doses and increased cognitive symptoms.

5. Brain plasticity

Brain plasticity and functional reorganization in pediatric epilepsy patients provide interesting and very useful data for understanding that functions such as language or memory are flexible and modifiable, especially during development.

The chronic nature of the disease caused by an epileptogenic zone is associated with the recruitment of homologous areas in the contralateral hemisphere or interhemispheric regions that are not considered eloquent. During rehabilitation programs, this allows us to use techniques to optimize or compensate for functional impairments. Slowly progressive impairments can shift functions such as language from the hemisphere classically considered dominant (left) to the right, or redirect language networks during development to non-traditional areas within the same hemisphere (Brazdil et al., 2005). Even so, we must always consider functional reorganization a unique, individual, and very complex process that requires intervention and follow-up by professionals specialized in neuropsychological rehabilitation.

These are some of the factors that differ in each patient and influence the neuropsychological profile. However, in epileptic conditions, some cognitive functions are usually affected to a greater or lesser extent in most cases.

It is common to find impairments with subcortical features, either primarily, caused by abnormal paroxysmal activity, or secondarily, as a result of drug treatment, or a combination of both, which is the most common situation.

That is, there is a primary subcortical impairment (sustained attention, working memory, processing speed, category retrieval) that is accentuated and significantly worsened by certain drugs.

Clinical and neuropsychological manifestations observed in patients with epilepsy

The clinical and neuropsychological manifestations observed in patients with epilepsy mainly affect attention, memory, language, processing speed, inhibition, and working memory.

In developmental and epileptic encephalopathies, there is greater overall impairment of both cognitive and motor processes, so most patients will need interdisciplinary teams across the different intervention settings.

The symptoms of patients with epilepsy are usually the same as or similar to those of many neurodevelopmental disorders. That’s why, when intervening and setting goals to stimulate cognitive deficits or impairments, strategies used in other clinical conditions can be applied, such as cognitive stimulation, optimizing other cognitive processes, or compensating for the lost function.

The most important thing to keep in mind when working with a child with epilepsy is the semiology of the seizures and their course, as they will determine the cognitive profile and its progression.

Epilepsy occurs in other conditions

We must not forget that epilepsy occurs in other conditions, such as cerebral palsy, genetic syndromes, and autism, worsening their clinical manifestations and sometimes causing neuropsychological regression.

It should be noted that any type of recurrent seizure affects cognitive functioning, including those labeled as benign childhood seizures. Most patients with benign childhood seizures don’t show symptoms when the seizures begin, but in the long term subtle signs of brain dysfunction start to appear (mainly related to sustained attention, working memory, and inhibitory control processes). It is therefore important to carry out assessments in these cases.

Requirements for a neuropsychological rehabilitation program for epilepsy

Every neuropsychological rehabilitation program for epilepsy must meet the following requirements:

• Be based on reference theoretical models;
• adopt an interdisciplinary, multifaceted perspective across the child’s different settings (therapies, school, family, etc.);
• it is essential to set priorities;
• it is important to start the intervention early;
• provide sufficient treatment time (depending on the case);
• preserved skills are the foundation of treatment;
• it is very important to consider emotional and motivational variables;
• have good family support.

The importance of neurorehabilitation in patients with epilepsy

In light of all the above, neurorehabilitation is important not only for cognitive stimulation and rehabilitation but also for gradually building the patient’s cognitive profile and seizure pattern.

Neuropsychological treatment allows continuous clinical monitoring of the patient’s progress, enabling the neuropsychologist to understand the semiology of each patient with epilepsy and to identify different clinical manifestations or changes in seizure patterns, which may be due to many factors (changes in drug treatment, the patient’s emotional state, overstimulation, etc.).

Following the patient in neurorehabilitation sessions allows the neuropsychologist to observe whether there is progressive cognitive decline, and therefore document disease progression, as well as objectively identify any impact of medication on cognitive functions.

This last point is important: if we are in contact with the medical team, the neuropsychologist’s observations can contribute to choosing the most effective drug doses with fewer adverse cognitive effects for the patient.

Finally, we want to stress that all programs (both computer-based and paper-and-pencil) are tools for working on the affected processes. They don’t rehabilitate simply by being applied: a program’s success depends on our goal and the procedure used.

Cognitive processes cannot be understood as independent entities, especially in a network disorder like epilepsy. The human cognitive system is based on the interaction of different neuropsychological processes that influence one another in both development and recovery, so we should rule out rehabilitating specific functions in isolation.

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“This article has been translated. Link to the original article in Spanish:”
Neuropsicología clínica en la neurocirugía de la epilepsia pediátrica