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INVITED REVIEW |
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| Year : 2008 | Volume
: 3
| Issue : 1 | Page : 30-34 |
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Cognitive development and pediatric epilepsy surgery
Santhosh George Thomas1, Roy Thomas Daniel1, Paul Swamidhas Sudhakar Russell2
1 Department of Neurological Sciences, Christian Medical College, Vellore, India
2 Child and Adolescent Psychiatry Unit, Christian Medical College, Vellore, India
Correspondence Address:
Roy Thomas Daniel
Department of Neurological Sciences, Christian Medical College, Vellore, Tamil Nadu
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/1817-1745.40587
 Abstract | | |
Children with intractable epilepsy are at considerable risk for cognitive impairment, school failure, behaviour and mental health problems and overall compromised quality of life. It influences the development of cognitive functions during the period of brain plasticity. Fifty percent of patients with intractable epilepsy have surgically remediable epilepsy syndromes. Epilepsy surgery can lead to seizure freedom following which development of functions in the residual brain occur which leads to cognitive improvement. Social aspects, side effects of antiepileptics, seizure perception and the overall level of quality of life are found to improve after surgery. The nature of the underlying brain disorder giving rise to the seizures appears to affect outcome. Follow up period is essential to determine effects of cognition after epilepsy surgery. It should be long enough for reconfiguration of the individual, family functioning and for restitution at the level of brain plasticity to occur.
Keywords: Cognitive decline, cognitive outcome, epilepsy surgery, intractable epilepsy, rehabilitation
How to cite this article:
Thomas SG, Daniel RT, Russell PS. Cognitive development and pediatric epilepsy surgery. J Pediatr Neurosci 2008;3:30-4 |
| Introduction | |  |
The word 'epilepsy' is derived from the Greek word meaning 'to seize upon' or 'a taking hold of'. [1] 'Epileptic Seizure' is defined as a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous activity of the brain. "Epilepsy" is defined as a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. An epileptic seizure is a transient occurrence of signs and/or symptoms due to an abnormal excessive or synchronous neural activity of the brain. [2] "Hemispheric epilepsy' refers to epileptiform activity in all four lobes of one hemisphere and when it involves more than two lobes of the brain, it is termed 'subhemispheric epilepsy'. Epilepsy is controlled in about 70% to 80% of epilepsy patients with antiepileptic drug (AED) therapy and 20 % to 25% of patients who develop epilepsy will continue to have chronic seizures despite optimal AED therapy. There cannot be a single definition for 'intractable' epilepsy that can suit all situations. Definitions of intractability are individualized to the patient. However, the commonest definition for intractable epilepsy is when seizures continue despite maximally tolerated doses of more than two AEDs, occurrence of an average of one seizure per month for 18 months with no more than a 3-month seizure free period during these 18 months. Of patients deemed to be intractable, approximately 50% are estimated to have surgically remediable epilepsy. [3]
| Effect of Intractable Epilepsy on Children | | |
The management of children with intractable epilepsy is a major problem in pediatric neurology which requires frequent outpatient visits and multiple ward admissions. Occasionally the children may require intensive care because of status epilepticus and /or may require long-term periods of hospitalization. Children with refractory epilepsy are at considerable risk for cognitive impairment, [4],[5],[6],[7] as well as school failure, [8] behaviour and mental health problems [9],[10],[11],[12] and overall compromised quality of life. [13] Other co morbid factors discussed in literature are numerous and comprise of the following: presence of seizures, [7] seizure related variables such as age of onset, frequency and/or severity, duration, underlying pathology, [13] AEDs [7],[8],[9],[12] and various psycho-social factors [11] often called as the 'burden of epilepsy' [13]
| Effect of Intractable Epilepsy on Cognition | | |
The nature and severity of cognitive symptomatology following seizures are probably related to the age of onset of seizures. Neuronal disruption sustained earlier in life has a more impairing effect on problem solving and psychometric abilities, than does brain damage that occurs after a longer period of normal growth and development. [12] Thus the cognitive impairment in these children can be extrapolated as either because of a failure to develop normal cognition or loss of cognitive skills after they had developed normally for a while respectively. The cognitive symptoms following seizures are either transient or chronic and static or progressive in nature.
Currently, a contemporary numerical taxonomy based on the nature, pattern and severity of evident cognitive complications classifies the cognitive impairment among children with seizures as those with minimal impairment, predominantly memory Impairment and generalized Impairment (impairment to memory, cognitive speed and execution). [14]
Minimally Impaired consist of approximately half (47%) of the epilepsy subjects. They exhibited the most intact cognition of the three groups. Their performance across several cognitive domains, including language, immediate and delayed memory, executive function and psychomotor speed domains is impaired but is mild. Predominantly Memory Impaired consists of 27% and exhibit marked impairments in immediate and delayed memory as well as significantly poorer performance in other cognitive domains. Thus, memory is the most striking cognitive abnormality and occurrs in the context of a mild, generalized depression of overall cognitive performance. Generalized Impairment consisted of 29% of the temporal lobe epilepsy subjects. They demonstrate the poorest cognition across all domains compared and significantly poorer performance across all cognitive domains when compared with the other two groups. The most striking impairments in this group are in the areas of executive function and cognitive/psychomotor speed. This taxonomy is useful in planning the cognitive rehabilitation that is necessary after the surgical procedures to control intractable seizures.
| Risk Factors for Intractable Epilepsy Related Cognitive Decline | | |
Age
Huttenlocher et al , found that the majority (61%) of children with uncontrollable seizures were mentally retarded and that most of these children (73%) had their first seizure before 2 years of age. These results suggest that young age of seizure onset is a risk factor for mental retardation. [15] The number of children experiencing difficulties in school because of learning disabilities or behavioural problems is greater in children with seizures than in the normal population. [7],[16] The plasticity of the brain and the nociferous effects of frequent uncontrolled seizures, antiepileptic medications (at high doses) on the developing brain; social stigma of the disease and the lost time at school makes treatment of this condition a priority. [17]
Recurrence and frequency of seizures
The pathophysiologic changes that accompany prolonged seizures have been investigated extensively and reviewed. [6],[18],[19] Some neurons are highly vulnerable to damage by continuing seizures like those in the hippocampus (CA1 and CA3 areas), amygdala, entorrhinal, piriform and neocortex, septum and thalamus. [18] Several animal experiments have been done with regard to effects of recurrent seizures. Holmes and Swann proposed that recurring seizures during early development result in decreased ability of neuronal circuits to learn and store memories. Recurrent seizures thus cause reduced synaptic plasticity, leading to long term cognitive defects. [16],[20] Bailet and Turk assessed the neurocognitive and behavioural performance in children with idiopathic epilepsy, which showed poor performance in cognitive and academic tests. [7] Recent efforts are to find correlation of specific deficits with the seizure variables that may have caused them. The variables that could result in decrease in cognitive capacity in patients with epilepsy include the underlying pathology resulting in the seizures and the seizures themselves - age of onset, frequency, duration of the disorder, type of seizure and the anticonvulsant drugs. [4],[21],[22],[23] Individuals with recurrent seizures have been studied in groups to find out the correlates of poor intellectual function. When inter-group analyses were performed, strong correlates of impaired neuropsychological abilities were a long seizure history, high seizure frequency and early age of onset. [24] Onset of intractable epilepsy within the first 24 months of life was a significant risk factor for mental retardation, especially if seizures occurred daily. It has been proved that when children with well controlled epilepsy are given a battery of tests including IQ tests, the age of onset is a major correlate of poor performance. [12],[25] When patients with perinatal brain injuries and hemiparesis were grouped together according to the presence of seizures and compared with controls, the presence of seizures were correlated with lower scores, regardless of degree of injury as seen on brain imaging. [26] Airaksinen et al , report that the probability of developing epilepsy increases fivefold in severely mentally retarded children compared with mildly retarded children. [9]
Hermann et al , [27] have found that that childhood onset epilepsy patients performed significantly worse across all cognitive domains compared with controls, including intelligence, language, visuo-perception, memory and executive function. Cognitive compromise was widespread and consistent with the generalised nature of volumetric abnormalities. The presence of recurrent seizures in the developing brain appeared to be associated with an adverse effect on both brain function and structure. Cross [28] pointed out that early onset seizures are associated with poor cognitive outcome and that early surgical intervention, either lobar, multilobar or a hemispherotomy may be associated with improved outcome.
Interictal discharges
As early as 1939, Schwab [29] showed that subclinical epileptiform discharges may be associated with subtle decrements in cognitive function. This finding has been confirmed and given the name Transitory Cognitive Impairment (TCI) by Aarts et al . [21] TCI is found in approximately 50% of the patients who show frequent subclinical interictal discharges on EEG. The finding of TCI establishes that epileptiform activity may impair cognitive function even if unaccompanied by overt seizure activity. Epileptic EEG paroxysms such as those related to a single spike and electrical status epilepticus during slow-wave sleep (ESES) can produce transitory cognitive impairment, with neuroanatomical specificity between the site of the epileptic focus and the impaired cognitive tasks. It has been reported that a local increase of slow-wave activity (SWA) during sleep after learning is associated with improved performance of the learned task after sleep. ESES interferes with the local SWA and impairs the the local plastic changes associated with learning and other cognitive functions. The duration of ESES and the localization of interictal foci determine the degree and type of cognitive dysfunction. [30] When frequent epileptiform EEG discharges persist over years, they result in effects on stable aspects of cognitive function such as educational achievement and intelligence. The clinical significance is that early detection and treatment of these EEG discharges may prevent a negative impact on cognitive and educational development.
Antiepileptic drugs
Drug treatment has been the principal therapy for epileptic seizures since the introduction of bromide in 1857. At present about 80% of patients with epilepsy have good seizure control on AEDs. These results are usually achieved without serious adverse effects on cognition, particularly if the seizures are controlled with one drug and blood serum levels are within the recommended range. [31] The main cause of cognitive impairment in epilepsy is still under research, but three factors clearly are involved: etiology, the seizures and the "central" side effects of drug treatment. [5] Although the severity of cognitive side effects is generally considered to be mild to moderate for most AEDs, all commonly used AEDs have some impact on cognitive function. Most antiepileptic drugs, with the exception of the benzodiazepines (which themselves adversely affect cognition) and lamotrigine, do not suppress inter-ictal discharges. Well-designed clinical trials of the effects of antiepileptic drugs are difficult to perform. An ideal drug should control both the seizures and inter-ictal discharges. This can actually improve the cognitive function provided the drugs themselves do not have a cognitive penalty. The effects may increase with prolonged therapy, which contributes to the impact on daily life functioning in refractory epilepsies. [5],[32] The risk of AED cognitive side effects is increased with polypharmacy and at higher dosages and higher AED blood levels and slow titration during drug initiation could reduce these effects. [33]
Assessment of cognition in children with Intractable Epilepsy
Cognitive outcome of epilepsy surgery
The outcome of epilepsy surgery has been found to be excellent in most reported series. [3] At follow-up, on average about 5 years after surgery, intelligence, language, visual-motor and adaptive/developmental skills for most children were impaired, but not worse than before surgery. This has been seen especially in patients with Rasmussen's encephalitis because they indicate a halt in the cognitive decline. The nature of the underlying brain disorder giving rise to the seizures appears to affect outcome far more than the procedure itself. Patients with congenital disorders like infantile hemiplegia perform better on tests of gross and fine motor skills. The apparent lack of worsening of motor deficits in this group could be related to their early age at onset (with greater age-related plasticity). [34] Children with large unilateral dysplasias such as hemimegalencephaly usually have the least favorable outcome. [35],[36] This could be due to organic impairment of both hemispheres as well as cumulative developmental delay from the very early onset severe seizure disorder.
Another important factor that would determine the outcome would be the shorter duration of epilepsy as reported by Freitag et al , who showed a trend towards a post operative increase in developmental quotient in such patients. [13] The side of the lesion could also have a bearing on cognitive outcome. Patients with left sided lesions in Rasmussen's encephalitis have been seen to display lower academic and communication skills than did those with right sided lesions. The particular impairment of language functioning in left hemispherectomy patients is consistent with models of brain lateralization. The lack of obvious lateralization in infantile hemiplegia could reflect a greater brain plasticity at the very early age at seizure. Early intervention to develop gross and fine motor skills should be an important part of post surgical treatment. [34]
Positive effects on quality of life during the first year after surgical intervention were suggested by reduced internalizing symptoms and increased social interaction. [37] Social aspects, drug side effects, seizure perception and the overall level of quality of life is found to improve after surgery. [38] Several studies indicate that quality of life measures parallelled the improvements in seizures control. [39] Adult patients have shown to maintain stable levels of performance after drug treatment as well as following epilepsy surgery. [31] Follow up period is crucial to determine effects of cognition after epilepsy surgery. Smith, Elliot et al , report little discernable change in cognitive function one year after pediatric epilepsy surgery. [11] It should be long enough for reconfiguration of the individual, family functioning and for restitution at the level of brain plasticity to occur.
Cognitive rehabilitation in children after epilepsy surgery
Factors common to chronic illnesses such as medication regimen, frequent hospitalization, disruption of family and school life and limitation of activities (Hamlett, Pellegrini, and Katz, 1992; Kazak, Segal-Andrews, and Johnson, 1995) in addition to epilepsy itself may impede normal cognitive processes in children with epilepsy. [40] The high overlap between intractable seizure and intellectual disability makes it essential to differentiate groups of children with failure to develop age appropriate cognitive skills along with intractable seizures from children with intractable seizures who have regressed cognitively in the absence of an intellectual disability. In the former group of children with failure to develop skills, a habilitative approach may be useful and in the latter group with regression focused rehabilitation based on the cognitive impairment profile recently described may be useful. [14] This hypothesis however needs to be tested with controlled studies. Irrespective of habilitation-rehabilitation approach, a multimodal-multidisciplinary approach may be the most beneficial in building the cognitive skills of these children. [39]
| Conclusion | | |
Seizures that are not controlled in children adversely influence the development of cognitive functions during the period of brain plasticity. In our experience, over 80% of children with focal, sub hemispheric and hemispheric epilepsy syndromes achieve an excellent seizure outcome following surgery. Following seizure freedom, development of functions in the residual brain occur and, this in turn leads to a "catch up" of cognitive functions. Early diagnosis of intractability and investigations directed towards the identification of surgically remediable epilepsy syndromes prior to the cessation of neural plasticity should be the cornerstone of management of pediatric epilepsy.
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