Epilepsy is a common neurological disorder estimated to occur in 0.5–1% of the population in industrialized countries [16, 23]. The lifetime risk of epilepsy is several times higher still for people with intellectual disability and is largely dependent on the severity of impairment [5, 9, 24]. The proportion of treatment-resistant, difficult-to-treat patients is also higher in people with intellectual disability than in the rest of the population, reaching about 40–50% in cases of severe intellectual disability [5]. In the past, despite the often difficult and inadequately effective drug treatment, people with intellectual disability were often considered across the board to be unsuitable for epilepsy surgery based on the assumption—and rightly so—of a mostly large-scale, diffuse and usually multilobar epileptogenic network [8, 32]. Particularly patients with genetic epileptic encephalopathy (mostly channelopathies) are usually not candidates for epilepsy surgery. However, with epilepsy centers gaining ever greater experience in surgical activities, the spectrum of diagnostic and surgical possibilities, and thus the spectrum of surgically treated patient groups, has become increasingly broader. People with epilepsy and mental retardation have also benefited from this development. In addition, the goal of making it easier for disadvantaged patient groups to access complex and high-quality diagnostics and therapy has become established. However, this trend has not yet translated into the availability and quality of scientific data on this topic. There is little consideration in the literature of the specifics involved in the preparation, performance, and prognosis of epilepsy surgery for people with intellectual disabilities.

Prerequisites for epilepsy surgery in people with intellectual disabilities

Epilepsy surgery is the surgical manipulation of an epileptogenic zone or network with the aim of stop** the generation of epileptic seizures or reducing their frequency and severity [25]. The minimum prerequisite for starting diagnostic preparation for resective or disconnection epilepsy surgery is usually proof of treatment refractoriness based on the relevant 2010 International League Against Epilepsy (ILAE) definition [18], i.e., proof that at least two appropriate antiseizure medications (ASMs) have been used at adequate doses for an appropriate time without achieving seizure freedom. This requirement must also be met for persons with intellectual disabilities. Exceptions may be made for circumscribed, clearly epileptogenic lesions; however, an initial attempt at pharmacotherapy should be made also in these cases.

While resective epilepsy surgery is used exclusively for focal epilepsy [21], disconnection procedures can also be used for multilobar or diffuse epileptogenicity, but usually do not lead to complete seizure freedom. In all cases, however, it must be demonstrated that epileptic seizures are indeed present or prominent. Non-epileptic seizures are diagnosed in up to 20% of patients referred to specialized centers for presurgical diagnosis due to refractory epilepsy [3]. Owing to the cognitive impairment as well as the comorbidities that are often present, in particular movement disorders such as spasticity or dyskinesia, the differential diagnosis of epileptic seizures poses special challenges.

A particular problem is the frequently limited compliance with diagnostic procedures due to the cognitive disorders and concomitant psychiatric disorders, as well as the often limited or suspended capacity to consent. While simple diagnostic measures may be feasible with the help of psychological, educational, and pharmacological aids, epilepsy surgery, even in adults with more than mild cognitive impairment, usually requires the approval of the responsible guardianship court. The court’s decision is made only after an independent expert opinion is available, making preparation time longer than in other cases.

Specifics of presurgical diagnostics for people with intellectual disabilities

Almost all presurgical diagnostic protocols include the performance of video electroencephalography (EEG) monitoring to document seizures, in addition to detailed documentation of the history and clinical examination [11]. Even in simple cases such as mesial temporal lobe epilepsy with hippocampal sclerosis, this is considered necessary to confirm the diagnosis of epilepsy as well as the location of the epileptogenic zone [2, 10]. This requires the patient to have at least a minimum tolerance for inconvenience and restriction, especially when the risk of seizure-related injuries and falls needs to be reduced due to the often necessary reduction in ASM. Here, in addition to the use of simple educational and psychological measures, sometimes drug sedation and/or someone to keep a bedside vigil are required. The associated health risks to patients must be considered when weighing up the benefits and risks of epilepsy surgery.

Structural magnetic resonance imaging (MRI) is one of the most important investigative methods of presurgical epilepsy diagnosis to determine the epileptogenic zone and evaluate the surgical strategy in order to minimize risks; it can also provide clues on the etiology of possible lesions by sequentially viewing examinations from different time points [2, 10]. Patients with moderate and severe mental retardation and/or behavioral disorders have limited ability to tolerate the long scan times of established epilepsy surgery MRI protocols, such as the “essential six” with a scan duration of more than 30 min [31]. Here, it may be reasonable to cut back and limit scanning to the most important sequences. However, if necessary, cooperation must be sought with anesthesia in order to perform MRI under analgosedation.

Preoperative assessment of neuropsychological function serves not only to determine focal localization but also to assess the risk of postoperative deficits [25] and is therefore also one of the necessary tests included in almost all protocols [11]. However, the commonly used testing procedures require a minimum level of basic cognitive function to contribute to the localization hypothesis. Therefore, especially in patients with severe mental retardation, one has to limit oneself to the assessment of basal cognitive functions or completely abandon neuropsychological testing procedures. As a substitute, interviews with relatives usually enable an estimation of the intelligence level even in those patients who are not amenable to a formal neuropsychological examination. This also applies to the investigation of language lateralization by functional MRI examinations or the Wada test, where basic cognitive function and compliance limit feasibility.

Innovative procedures such as high-resolution EEG or magnetoencephalography (MEG) are also subject to limitations due to reduced compliance and behavioral disturbances when used for patients with intellectual disabilities.

Overall, the use of standardized examination protocols in patients with intellectual disability will vary widely. Depending on the cognitive disorders as well as physical and psychological comorbidity (especially due to behavioral disorders), decisions about epilepsy surgery often need to be made with a lower degree of diagnostic certainty and on the basis of reduced and less valid information. However, this problem is not a reason to deny people with epilepsy and mental retardation the highly effective treatment procedure of epilepsy surgery.

Postoperative outcome

A relevant factor in the consideration for or against the performance of epilepsy surgery is the assessment of the likelihood of seizure freedom and the risks or possible consequences of an intervention. Additionally, the question arises as to whether these are comparable to the likelihoods and risks in people with normal intelligence. The data on outcome after epilepsy surgery in people with mental retardation is also heterogeneous since the inclusion criteria of the available studies were quite different, with children, adults, or mixed cohorts being included. Studies including children with intellectual disability or developmental disability were also taken into consideration in this review.

Especially in case series on resective surgery of focal epilepsies, people with intelligence impairment represent only a small subgroup. However, a proportion of patients with epilepsy and intellectual disability—reported in older studies to be 9–32%—have focal epilepsy, meaning that presurgical diagnosis is indicated in the case of refractoriness [12, 28]. Some studies in children and/or adults showed an association between low intelligence quotient (IQ) and a lower chance of postoperative seizure freedom [4, 7, 19, 30]. However, this has not been consistently confirmed. One study found no difference in the achievement of postoperative seizure freedom when comparing children with normal IQ and with subaverage intelligence [12]. The available data also indicate that negative neuropsychological consequences of surgery or an increase in behavioral problems are not clustered in this patient group [12, 30]. In individual studies, postoperative seizure freedom was associated with better postoperative IQ test scores [4, 12, 22].

There are few studies comparing drug therapy with surgery in individuals with impaired intelligence. An observational study in children with epileptic encephalopathy demonstrated significantly longer seizure-free survival after resective epilepsy surgery compared to drug therapy or palliative surgical procedures (in this case, callosotomy or vagus nerve stimulation [VNS]; [22]). For example, a recent review of the various drug and surgical treatment procedures in patients with Lennox–Gastaut syndrome is provided in the articles by Samanta and Thirunavu et al. [26, 29].

Epilepsy surgery: procedures more frequently used in intellectual disability

In addition to the usual procedures of resective epilepsy surgery, some surgical procedures are used more frequently (although of course not exclusively) in people with impaired intelligence, such as hemispherectomy, callosotomy, and implantation of a vagus nerve stimulator. The latter is discussed in the article by Fauser and Rada in this issue.

Hemispherectomy

In hemispherectomy, the connections to the contralateral hemisphere in the white matter are severed (in contrast to resection of entire brain lobes, which was common in the past). Indications include acquired, usually unilateral lesions (e.g., perinatal infarcts), malformations of cortical development, or progressive diseases (e.g., Rasmussen’s encephalitis), all of which usually lead to refractory epilepsy in childhood [15]. Hemispherotomy is thus used more frequently in children than in adult patients. An additional reason for less frequent use in adults may be the procedure’s higher risk of adverse motor, sensory, or cognitive sequelae in older patients.

In suitable patients, hemispherotomy in childhood leads to seizure freedom in just over 70% [14], and a larger cohort study of adult patients also showed similar results [20]. Evidence suggests that people with a higher degree of intelligence impairment have a lower chance of postoperative seizure freedom after hemispherectomy [1]. Neuropsychological outcome after hemispherectomy was mostly unchanged from preoperative findings in adults [20]. If seizure freedom is achieved, there may be a higher chance for stabilization of cognitive development or even improvement [1]. Significant deterioration of cognitive function is rarely reported [1]. Most patients—for example, 60% in a cohort of adult patients—do not experience motor deterioration, especially with higher-grade preoperative paresis or lack of hand grasp function [17, 20]. An increase in contralateral hemiparesis or loss of grip function is found primarily in patients with preoperative low-grade paresis and in patients with postneonatal lesions, but the ability to walk was almost always preserved even in adults [20, 27]. Lesser loss of grasp function may be associated with very early damage, evidence of ipsilateral corticospinal tracts in the brainstem [17].

Callosotomy

Cleavage of the corpus callosum is considered a palliative procedure used for patients in whom resective surgery is not possible. Indications mainly include severe epilepsy with drop attacks or epileptic spasms. A meta-analysis of available studies through 2018 showed seizure freedom from drop attacks in 55% and complete seizure freedom in 19% of patients [6]. Other seizures, such as bilateral tonic–clonic seizures, or absences respond less well than drop attacks but are still often relevant to the intervention [13]. Since drop attacks are common in epileptic encephalopathies, such as Lennox–Gastaut syndrome, callosotomy is more frequently considered in patients with intellectual disability. A meta-analysis (indirectly) comparing callosotomy and VNS in children with Lennox–Gastaut syndrome (and almost always also impaired intelligence) showed a better efficacy for callosotomy on seizure frequency, but also a higher rate of complications [29].

Most studies showed either no change in cognition or improvement; worsening was occasionally reported [29]. Complications such as (often transient) neurological deficits, e.g., speech deterioration, paresis, or incontinence have been reported in 8–12% [6, 13]. Persistent disconnection syndromes, such as an alien limb phenomenon or tactile anomia, are less common and often not relevant in daily life [13].

Practical conclusion

  • Mental retardation should not be an impediment to presurgical diagnosis or resective epilepsy surgery in focal epilepsy.

  • In special clinical situations, the indication for surgical procedures such as vagus nerve stimulation, hemispherectomy, and callosotomy should also be evaluated.

Data Availability.

No original data were used for this manuscript.