NEUROPSYCHOLOGICAL ASPECTS OF FOCAL EPILEPSIES IN CHIDREN AND POSTOPERATIVE OUTCOME

ABSTRACT: 

Neuropsychological deficits in terms of specific learning disabilities are frequently a concomitant of symptomatic focal epilepsies in childhood. The likelihood for developing such disabilities is dependent on the epileptic syndrom. Neither in TLE nor in FLE or other extratemoral epileptic syndromes a typical pattern of disabilites is sufficiently confirmed by empirical data. Nevertheless the deficits in TLE are better described than in FLE and extratemporal epilepsies. Apart from language related disabilities and verbal memory dysfunctions other specific learning disabilities are significantly fewer strongly related to an hemisshere. The lateralized or localized lesion or the epileptogenic area called “functional deficit zone (28) is very likely not the sole substrate of neuropsychological deficits particularly of circumscribed type. Etiologically we have to assume a complex network, that is influenced to a higher or lower extent by pre-, peri- or interictual epileptic activity. It is evident that neuropsychological findings have less importance for lateralisation and localisation of functions. The thesis has to be underlined: „Much less is known about the degree to which psychologic functions are lateralized or localized in children between the age of 6 and 12 and of normal intelligence than is known about adults” (32).

By the way specific learning disabilities were observed in children without any neurological deficit. These children get the lable “underachievers”.

Introduction

The frequency of focal epilepsies in adulthood is nearly 60 per cent. Even in childhood we can observe higher rates, which is referred to the increased exitatory electrical activity or processes in that stage of development. Higher exitatory activity in the developing brain determines the threshold for seizures and as well the clinical manifestation (13). Regarding the etiology there are idiopathic, cryptogenic syndromes. Up to now that differentiation has determined each form of classification (5). Recently other classication systems were proposed, that stresses the lokalisation of the underlying brain lesions or the epileptic focus (39). According to these propositions one can differentiate between temporal, frontal, parietal and occipital epilepsies(25). Most focal epilepsies, i.e. 70-80% have its origin in the temporal lobe especially in the mesial region (70%). 20 % have a frontal and 5 % a parietal or occipital origin. Epilepsies with frontal origin constitute the largest group of extratemporal epilepsies (19). It has to be emphasized, that often the demarcation of the lesion is not congruent with the demarcation of the brain lobe, that means that in many cases the location of the lesion overlaps several brain lobes (20). The brain lesion, caused by a tumor, a dysplasia, a malformation etc. is in symptomatic epilepsies and without much doubt in cryptogenic epilepsies, too, the most important risk-factor for the development of neuropsychological functions (8). It is assumed that in idiopathic epilepsies heriditary maturation disorders are the most prominent risk-factor. More and more the pre-, peri and postictual epileptic activity and its concommitant electrophysiological and biochemical disturbances that often remain transient, is regarded as a risk-factor (7). Recent investigations have shown that epileptic activity especially in the long run determines the development and stability of neuropsychological and behavior functions (24). At least one third of focal epilepsies are drug resistent. Often seizure control can only be reached at the price of side effects.

Without doubt such side-effects of the antiepileptic treatment are a further risk-factor for neuropsychological functions and behavior regulation. The presented risk-factors do not operate in a single way but they do interact dynamically in a network (27).

2. Syndrome-related global neuropsychological findings:

That network determines not only the clinical features of the epilepsy but also the neuropsychological and in the long run psychosocial concomitants. For a long time descriptons of neuropsychological findings in childhood epilepsy have been little differentiated because epilepsy was considered, and has partly been until now, in a global and uniform manner(7).

Inrecentyears more careful investigations demonstrate, that neuropsychological deficits are syndrome-related (31). The emphasis placed on epileptic syndromes is justified by the inadequacies of the traditional approach to neuropsychological research in epilepsy which is first of all based on seizure types (7).

As a rule symptomatic epilepsies show the highest frequencies of global cognitive disturbances, that means IQ-scores below average. In comparision to patients with idiopathic or crytogenic syndromes a significant smaller part of these patients display IQ scores in the normal range (fig. 1).

It is evident, that focal epilepsies have to be well described in order to avoid simplifications, which prevent scientific progress and facilitate prejudices (7, 21). From a methodological point of view it is urgently neccessary to acknowledge that any study on cognitive function in a group of children with epilepsy is meaningless without further definition and differentiation (7).

3. Syndrome-related circumscribed neuropsychological findings

The high rates of global cognitive deficits, that can be observed in focal epilepsies have the major consequences of the riskfactors. The cause of academic underachievement (28) and also behavioral problems is often specific learning and developmental disabilities, also called neuropsychological deficits (1, 11). Such deficits, for example in idiopathic focal syndromes, cannot be discovered if only the overall IQ is assessed. That lacking is an important reason why the lable “benign”, which relates to the prognosis of seizure control, has been uncritically extended until now to the development of cognitive functions at a large extent.

The frequency of such disabilities in different epileptic syndromes is unknown to a higher or lower extent. Nevertheless some years ago an investigation with patients, whose epilepsy entered remission, demonstrated a syndrom-related distribution (fig. 2).

The smallest incidences were found in idiopathic syndromes. The occurrence of such disabilities in idiopathic syndromes was for a long time a matter of extensive discussion. Meanwhile these findings are scientifically widely accepted. In IGE syndromes (of early childhood) nearly the same incidences could be proved. Figure 2 (28) stresses three special risk group, to which belong symptomatic epilepsies, IGE and the undifferentiated syndromes. The syndromes do not vary in the type but in the proportion of learning disabilities. That means each type can be found in each syndrome (33, 36). Without doubt the major risk in the symptomatic group is the underlying brain lesion. Sort, size and location of a lesion play an important role what specific type of learning disablity develops. That the learning disabilities can be aggravated by continuing epileptic activity is assumed but a definitive evidence is lacking. More incidences of specific learning disabilities in patients, whose epilepsy enters remission support that assumption (27). Up to today there has been a controversy if the disabilities, one can say circumscribed neuropsychological deficits, have a close relation to the localisation of an epileptic focus. The most impressive data for such location-related disabilities exist for language deficits and left hemisheric foci (27, 33). Other disabilites can be found in relation to right or left foci and also without any focus having proved (27, 33). It is not surprising that knowledge in these topic is limited.

3.1 Neuropsychological findings in TLE

In childhood and adulthood the TLE syndrome marks the largest one of focal epilepsies. It is assumed, that the left temporal lobe is very intensively involved in the language functions. But also non-verbal functions need the support of the temporal region, especially non-verbal memory functions (21). Within the temporal lobe the importance of the mesial structures, i.e. the structures of the hipocampus region cannot be undervalued (21). The pattern of neuropsychological deficits in children with TLE  seem to differ from that in adults (30)

In adults more frequent impairments of verbal memory functions are associated with left TLE and and deficits in non-verbal functions with right TLE (16). Such material specific memory deficits have more rarely been reported in investigations with children. Until now very controversial data have been reported. Taken these data in account, it becomes evident that the relationship of the right temporal lobe to non-verbal memory functions is no simple analogy to the relationship of the left temporal lobe to verbal memory functions. It can be assumed, that left sided lesions have more comprehensive impacts. Functions of the right temporal lobe could be disturbed in terms of a selective crowding effect. By the way one has to underline that memory functions (15, 32) particularly in childhood are influenced by a lot of factors like level of attention or mental speed (29).

The reason for the scientific controversy are not only methodological differences in the study design, in the assessment instruments or in the classification of syndromes. The major reason seems to be different maturation and organisation processes in the left and right temporal region that do develop when a lesion exists. A lesion may weaken the association of the material-specific memory function of left and right temporal lobe particularly in childhood.

It can be assumed that the processes just discussed also do influence the laterality of language functions (38). That means that the shift of language functions may trouble memory functions, too (4, 22). Otherwise language functions in childhood seem to have similar patterns of laterality as in adults (12, 28). Investigations assuming that other neuropsychological functions and corresponding deficits, i.e. spelling and reading, can be lateralized (35) to the left temporal region could not approved (36, 3).

Many controversial findings regarding the localisation and laterlisation do support the concept of bilateral functional disturbances and reorganisation of neuropsychological functions in children especially in those with early onset. In contrast focal lesions in adulthood cause more specific functional disturbances depending on the localisation and lateralisation of the lesion’s focus.

Nevertheless the findings on specific neuropsychological impairments in children with TLE remain contradictory. It is more likely to find a focus (21) of neuropsychological deficits than a special pattern. (27).

3.2 Neuropsychological findings in FLE

For a long time focal epilepsies of extratemporal origin has not been a matter of intensive scientific interest (16). Not until in the last decade has FLE attracted intensive scientific attention (17,18). The reason why scientific attention was lacking is surprising, because the frontal brain areas, particularly the prefrontal regions are very intensivly involved in evolving many behavior and neuropsychological functions. Mostly accepted is the concept of frontal lobe functions in terms of so-called executive functions (18). That means abilities like planning, decision making, goal selection and monitoring of action in order to plan and organize behavior. Additionally also working memory and attentional functions are strongly associated with the prefrontal region. Patients with prefrontal lesions have difficulties holding and shifting attention (6). In contast interest in the development of frontal lobe functions in children is comparatively new. Nevertheless a lot of papers were published, which seem to confirm findings achieved by investigations in adults with frontal lesions. Sophisticated empirical investigations are still lacking. It is not overstated that most of our knowledge about neuropsychological consequences of FLE in children is based on a few single case reports. (21).

One reason for the lacking of group studies is the difficulty to find a unitary conceptualisation of frontal lobe functions. The other reason is the divergent inconsistent assessment instruments particularly in childhood (10). Mostly used or applied instruments are only adaptations of tests, which are developed and standardized for adults. Most named tests, that are used are the WCST, the verbal and design fluency test, the CVLT, a GO/NO task and the TOL, and the Stroop-Test (34). Also tests that have been known for a long time measuring non-verbal intelligence like the SPM are used (34).

A special methodological problem is the fact that some tests are validated by tests, whose validity is not proved sufficiently, for example the WCST (10). Until now there have been rare studies, that have proved the validity and reliability of the applied tests. That is not surprising because it is a very difficult task particularely in childhood. In these stages of age frontal lobe functions i.e. executive functions have a developmental dynamics, that means for example different functions reach their highest functional level at different times in relation to maturation of basic brain processes like myelination and synaptic networks. For this reason the selection of tests is often guided much more by clinical experience than empirical know-how (17).

A recent study (18) could demonstrate that only children with FLE in contrast to children with TLE and IGE have difficulties with tasks requiring attention, mental flexibility planning, response inhibition, verbal search and visual-spatial abilities and speed of execution (2). All three groups under investigation show significant memory deficits in contrast to the control group. Visual working memory functions were not significantly impaired in the FLE group. Also the WCST, a widely used test to assess concept formation and mental flexibility failed to discriminate the groups. To sum up children with FLE do demonstrate similar behavior and neuropsycholgical patterns reported commonly in adults (18, 6). The question remains if the findings indicate similar deficits or age related special developmental features (18).

We need better assessment instruments to discriminate between the subgroups of symptomatic epilepsies particularly in childhood. At this point of time we have to acceptthat lesions are easier to localize than neuropsychological functions. The association between the lesion and the function is less closely connected than we have expected it (23).

3.3 Stability and dynamics of neuropsychological findings in terms of special learning disabilities after epilepsy-surgery

Learning disabilities are as a rule in the course of the disease very stable. Developed at the start, it cannot be influenced by antiepileptic treatment or psychological interventions (28). The distribution in figure 2 is interesting because all children entered remission at least three years ago, when the neuropsychological assessment was carried out. That is why the neuropsychological findings in this figure show more residual or chronical deficits than seizure-related ictual dysfunctions (7). The importance of pre-, peri-or postictual disturbances can be underlined by the fact that seizure relapse facilitates the development of disabilities. Only recently the risk potential of ictual processes has attracted more scientific attention ( 7, 38)

In that regard neuropsychological findings after surgical interventions, which also have become a standard in childhood in the last years are very important (9). The outcome of epilepsy surgery in childhood is similar benificial in terms of seizure free patients and quality of life (16, 9).

The neuropsychological findings in post-surgical assessments are reported to be benificial as well (18). But the pattern of neuropsychological findings in memory functions are not consistent particularly in terms of material specific dysfunctions (14, 26). Gains in the postsurgical assessment are often related to a lower presurgical neuropsychological level. Moreover from a statistical point of view (regression to the mean) it can be expected that losses are related to higer functional level.

Our own investigations carried out at least two years after surgery display the following outcome concerning the rates of disabilities (fig. 3, 4). A change in a psychometric test was considered as significant, if in comparison to the presurgical finding a difference of 1 SD could be assessed, (presurgical T-scores 30 and postsurgical T-score 40). We could investigate 16 patients (IQ < 70) with LTLE, 18 with RTLE, 12 patients with FLE and 12 with PLE . The average age was 13,8 when patients underwent the surgery. The neuropsychological evaluation comprehend language and memory, visuoconstructive, executive, attentional functions. Also special learning disabilites in spelling, reading and arithmetic were psychometrically assessed.

In the presurgical evaluation we could find 68 % of patients with LD (Fig. 3), which is comparable to the proportion in symptomatic epilepsies (fig. 2). In the postsurgical evaluation the frequency is only 54 %. In general that difference is an indication for a successful outcome. The gains do regard visoconstructive, attentional and executive functions. In the TLE group the neuropsychological pattern remains stable in terms of language and memory functions. Only two patients do display losses in non-verbal memory functions. It can be assumed that those functions which are more strongly associated with circumscribed brain areas, that means language and memory functions, have a tendency to remain stable. Functions that are not so closely associated with brain areas experience more frequently gains after surgery. That thesis is not widely accepted. Up to now it has not been obvious, what ressources of plasticity especially in childhood are stimulated by epilepsy surgery. It could be that only those resources become efficient, which are disturbed by ictual epileptic activity. Moreover irrespective of the placticity concept it is likely that the risk factors mentioned above lose their potency so that first of all attentional function, the mental speed and other so-called frontal functions (23).

Literature

1. Aldenkamp, A.; Weber, B.; Overweg-Plandsoen, W.; Reijs, R.; van Mil, S. (2005) Educational underachievement in Children with Epilepsy: A Model to predict the Effects of Epilepsy on Educational Achievement, J. Child Neurol., 20, 3, 175-180. Brickenkamp, R.; Brahler, E., Holling, H. (2002) Handbuch psychologischer und padagogischer Tests, 2 Bde., Gottingen, Hogrefe.
2. Camfield, P.; Gate, R,; Rosen, G.; Camfield, C; Fergueson, A.; McDonald, G. (1984). Comparision of Cognitive Ability, Personality Profile, and School Success in Epileptic Children with Pure Right versus Left Temporal Lobe EEG Foci. Ann. Neurol., 15, 122-126.
3. Cohen, M. (1992). AuditoryA/erbal and Visual/ spatial Memory in Children with Complex Partial Epilepsy of Temporal Lobe Origin, Brain and Cognition, 20, 2, 315-326. Commission on Classification and Terminology of The International League against Epilepsy. Proposal for Revised Classification of Epilepsies and Epileptic Syndromes. Epilepsia 1989;30:389-399.
4. Culhane-Shelburne, k.; Chapieski, L.; Hiscock, M,; Glaze, d. (2002) Executive Functions in Children with Frontal and Temporal Lobe Epilepsy, J. intern. Neuropsychol. Soc, 8, 623-632.
5. Deonna & Roulet-Perez, (2006) Cognitive and Behavioral Disorders of Epileptic Origin in Children, London, Cambridge University.
6. Diener,       W.;       Mayer,       H.       (1996) Epilepsiesyndrome     des     Kindes-     und Jugendalters, Zuckschwerdt, Munchen.
7. Duchowny,   M.;   Harvey,  A.;   Sperling,   M; Williamson. P. (1997) Indications and Criteria for Surgical Intervention. In Engel, J.; Pedley, T.(eds.), Epilepsy: A Comprehensive Texbook, Lipincott-Raven, Philadelphia, 1677-1686.
8. Dugbartey, A.; Rosenbaum, J.; Sanchez, P.; Townes, B. (1999). Neuropsychological Assessment of Executive Functions, Seminars in Clinical Neuropsychiatry, 4, 1, 5-12.
9. Esser,    G.(1996).    Umschriebene    Entwick-lungsstorungen.   In:   Petermann,   F.   (Hrsg.) Lehrbuch  der  klinischen   Kinderpsychologie, Hogrefe, Gottingen, 267-285. Fedio, P.; Mirsky,, A. (1969) Selective Intellectual Deficits in Children with Tempora Lobe or Centrecephalic Epilepsy, Neuropsychologia, 7, 287-300.
10. Freeman, J. (1995). A clinical’s Look at the Developmental Neurobiology of Epilepsy. In P. Schwartzkroin; S. Moshe; J. Noebels; J. Swan (eds.). Brain Development and Epilepsy, N.Y.:Oxford University Press.
11. Gleissner, U.; Sassen; R., Lendt, M; Clusmann, H.; Elger, C; Helmstaeter C. (2002) Pre-and Postoperative Verbal Memory in Paediatric Patients with Temporal Lobe Epilepsy, Epilepsy Res., 51, 3, 287-296. Gotman-Jones, M.; Smith, ML.; Zatorre, R.J. (1993). In: Engel, J.(Jr.) Surgical Treatment of the Epilepsies, Raven, N.Y. 245-261.
12. Helmstadter.C; Lendt, M. (2001) Neuropsychological Outcome of Temporal and Extratemporal lobe Resections in Children. In: Jambaque I.; Lassonde, I.; Dulac, O.; (eds.) Neuropsychology of Childhood Epilepsy, Kluwer Academic / Plenum Publishers, N.Y., 215-227.
13. Hernandez, M., Sauerwein, H.; de Guise, E.; Lortie, A.; Jambaque, I; Dulac, O.; Lassonde, M.(2001) Neuropsychology of Frontal Lobe Epilepsy in Children. In: Jambaque I.; Lassonde, I.; Dulac, O.; (eds.)
14. Neuropsychology   of   Childhood   Epilepsy, Kluwer Academic / Plenum Publishers, N.Y., 103-111.
15. Hernandez, M., Sauerwein, H.; Jambaque, I.; de Guise, E.; Lussier, F.; Lortie, A.; I;Dulac, O.; Lassonde, M. (2002) Deficits in Executive Functions and Motor Coordination inChildren with Frontal Lobe, Neuropsychologia, 40, 384-400.
16. Hosking, P. (2003) Surgery for Frontal Lobe, Sezure, 12, 160-166.
17. Hufnagel,   A.(2000)   Epilepsien   und   ihre Therapie, Uni-Med, Bremen.
18. Jambaque,    I;    (2001)   Neuro-psychology of Temporal Lobe Epilepsy in Children. In: Jambaque I.;
19. Lassonde,      I.;       Dulac,      O.;      (eds.) Neuropsychology   of   Childhood   Epilepsy,Kluwer Academic / Plenum Publishers, N.Y, 97-102.
20. Jambaque, I.;  Dellatolas, G.; Dulac, O.; Ponsot, G.; Signoret, JL. (1993). Verbal andVisual Memory Impairment in Children with Epilepsy, Neuropsychologia, 31, 12, 1321- 1337.
21. Johnston, M. (2004) Clinical Disorders of Brain Plasticity, Brain and Development, 26, 73-80.
22. Jokeit & Ebner, Effects of Chronic Epilepsy on Intellectual Functions (2002), Progress in Brain Resarch, 135,455-563.
23. Loddenkemper, T, Kellinghaus, C, Wyilie, E, et al. A proposal for a Five-DimensionalPatient-Oriented    Epilepsy    Classification. Epileptic Disord, in press.
24. Mabott, D.; Smith, M. (2003) Memory in Children   with   Temporal  or ExtratemporalExcions, Neuropsychologia, 41, 995-1007.
25. Mayer,   H.;   Diener,  W.,  Kruse,  R.(1995). Teilleistungsstorungen bei unter-schiedlichenepileptischen   Syndromen.   In:   Rating,   D. (Hrsg.), Aktuelle Neuropadiatrie, Ciba-Geigy Verlag, Wehr, 212-220.
26. Mayer,   H.   (1999)   Teilleistungsstorungen: AnmerkungenzueinemneuropsychologischenKonzept, Epilep-sieblatter, 12, 21-31.
27. Mayer, H. (2003) Epilepsie und ihr Einfluss aufdas Gedachtnis bei Kindern, Zeitschrift fur Epileptologie, 16, 1, 104-107.
28. Mayer,   H.;   Diener,   W.   (1997).   Cognitve functions
29. Nolan, M.; Redoblado, M.; Lah, S.; Sabaz, M.; Lawson, J.; Cunningham, A.; Bleasel,A.;  Bye, A.  (2004)  Memory Function in Childhood Epilepsy Syndromes, J. Paediatr. Child Health, 40, 20-27.
30. Nolan, M.; Redoblado, M.; Lah, S.; Sabaz, M.; Lawson, J.; Cunningham.A.; Bleasel, A.; Bye, A. (2003), Intelligence in Childhood Epilepsy Syndromes, Epilepsy Res.,53, 1-2, 139-150.
31. Oxbury,    S.    (1997).    Neuropsychological Evaluation in Children. In: Engel, J.;Pedley, T.,   Epilepsy:   A   Comprehensive   Texbook Lippincott-Raven   Publishers,   Philadelphia, 989-999.
32. Seidenberg, M. (1989). Neuropsychological Functioning of Children with Epilepsy.   In: Hermann,    B.P.;    Seidenberg,    M.    (eds.) Childhood   Epilepsies:   Neuropsychological, Psychosocial and Intervention Aspects, John Wiley & Sons, Chichester, 71-81.
33. Spreen, O. & Strauss, E. (1998) A Compendium of Neuropsychological Tests: Administration, Norms, and Commentary, University Press, Oxford. Stores, G. (1978). School Children with Epilepsy at Risk for Learning and Behavior Problems, Dev Med. Child Neurology, 20, 502-508.
34. Stores, G.; Hart, J. (1976). Reading Skills of Children with Generalized or Focal Epilepsy Attending Ordinary School, Dev. Med. Child Neurol., 18,704-716.
35. Vingerhoets, G. (2006) Cognitive Effects of Seizures, Seizure, 15, 221-226. van Rijckevorsel, R. (2006) Cognitive Problems Related to Epilepsy Syndromes, especially Malignant Epilepsies, Seizure, 15, 227-234
36. Walter-Frankel, S. (2004) Gedacht-nisdiagnostik bei Kindern mit fokaler Epilepsie. Der Beitrag des VLMT und RVDLT zur Fokuslokalisierung, Diplomarbeit, Universitat Freiburg.