Brain Advance Access originally published online on June 23, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Brain, Vol. 126, No. 9, 2043-2051,
September 2003
© 2003 Guarantors of Brain
doi: 10.1093/brain/awg193
Epileptic activity influences the speech organization in medial temporal lobe epilepsy
1 Epilepsy Center Bethel, Bielefeld, Germany and 2 Epilepsy Center, National Institute of Psychiatry and Neurology, Budapest, Hungary
Correspondence to: Dr J. Janszky, Epilepsie-Zentrum Bethel, Mara Krankenhaus, Maraweg 21, D-33617 Bielefeld, Germany E-mail: janszky{at}index.hu
Received February 27, 2003. Revised April 11, 2003. Accepted April 16, 2003.
 |
Summary |
|---|
 Top Summary IntroductionMethodsResultsDiscussionReferences |
|---|
Factors influencing atypical speech lateralization have theoretical importance in understanding the organization and reorganization of higher cognitive functions, as well as having practical implications, especially in brain surgery and neurorehabilitation. Atypical (right-sided or bilateral) language representation is more frequent in focal epilepsy than in healthy people. This difference is thought to be related to early childhood brain injuries localized in the neighbourhood of speech centres. The effect of epileptic activity on speech lateralization has not been investigated, although much data suggest that epileptic activity may interfere with higher brain functions. It can only be evaluated in a homogeneous human population with epilepsy having the same lesion type in the same localization. For these reasons, we investigated 184 patients with medial temporal lobe epilepsy (MTLE) due to unilateral hippocampal sclerosis (HS), but without other epileptogenic lesions. All patients underwent comprehensive presurgical evaluation. In MTLE, the influence of age at the time of brain damage, i.e. the initial precipitating injury (IPI), could be evaluated separately from the other timing factors. Of 100 patients in whom a Wada test was performed, left-sided speech occurred in 76% of the left-sided and in 100% of the right-sided MTLE patients (P < 0.05). For further evaluation, we included only the 83 left-sided MTLE patients. The mean age at seizure onset was 10.1 ± 7.8 years (range 1–37 years); the mean age at evaluation was 35.7 ± 9.8 years. Based on the Wada test, left-sided speech was present in 63 patients, while in 20 (24%) patients the Wada test revealed atypical speech dominance. We found that atypical speech representation in left MTLE was associated with higher spiking frequency (P < 0.05) and with sensory auras representing an ictal involvement of the lateral temporal structures (P < 0.01). Psychic auras suggesting limbic seizure spread showed a significant association with left-sided speech dominance in left MTLE (P < 0.05). Neither age at epilepsy onset, nor age at IPI was associated with atypical speech in left MTLE. Conclusively, we found that in patients with focal epilepsy, not only the known factors, i.e. the age at which the brain injury occurred and its localization, but also the epileptic activity itself, i.e. interictal discharges and seizure spread, may influence speech reorganization. Our findings also suggest that not only structural elements but also functional factors have an effect on the language organization of the brain.
Keywords: language reorganization; mesial temporal lobe epilepsy; interictal epileptiform discharges; seizure spread
Abbreviations: fMRI= functional MRI; HS = hippocampal sclerosis; IEDs = interictal epileptiform discharges; IPI = initial precipitating injury; MTLE = medial temporal lobe epilepsy
|
Introduction |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Factors influencing typical and atypical speech lateralization have received a great deal of attention because they have theoretical importance in understanding the organization and reorganization of higher cognitive functions, as well as practical implications, especially in brain surgery and neurorehabilitation. In patients with epilepsy, speech lateralization is more frequently atypical in comparison with healthy people (Springer et al., 1999
). This is not surprising because in many patients the cause of focal epilepsy is a morphological abnormality which frequently is developmental or acquired in early childhood at an age when neuronal plasticity allows speech reorganization (Hecaen, 1976; Rasmussen and Milner, 1977; Springer et al., 1999). Such a brain abnormality may interfere with the normal neuroanatomical organization of cognitive functions resulting in reorganization, even if this abnormality is far from the speech centres or does not affect the cortex at all (Staudt et al., 2001).
The presurgical evaluation prior to epilepsy surgery is comprised of a careful delineation of the epileptogenic lesion and the seizure onset zone. Moreover, it encompasses a comprehensive neuropsychological assessment including a Wada test, by which speech dominance can be determined (Ebner, 2001; Rosenow and Lüders, 2001). In the past years, many studies investigated speech lateralization in epilepsy patients (Rasmussen and Milner, 1977; Rausch and Walsh, 1984; Woods et al., 1988; Rey et al., 1988; Duchowny et al., 1996; Helmstaedter et al., 1997; Springer et al., 1999; Brazdil et al., 2002). These studies provide evidence that early injuries and lesions residing in the speech centres induce atypical speech lateralization, which is often associated with left-handedness. In pre-school children, injury affecting the left hemisphere results in an interhemispheric reconstitution of language functions to the right hemisphere (Hecaen, 1976; Rasmussen and Milner, 1977). After age 5 years when language becomes gradually lateralized (Kimura, 1967), contralateral language reorganization after brain injury occurs less frequently (Springer et al., 1999). The drawbacks of all these studies is that they included a mixed population of epileptic patients and not a circumscribed epilepsy syndrome. Consequently, in such populations, the different types of disturbances cannot be investigated adequately and separated from each other, i.e. the influence of age, localization, lateralization of the lesion and the epileptic activity itself.
Although some memory disturbances caused by epilepsy can be modelled experimentally in animals (Kotloski et al., 2002), it is impossible to investigate speech in experimental models, as language is a unique human ability, the main basis for communication, human thinking and self-consciousness (Serafetinides et al., 1965; Popper and Eccles, 1977; Ebner et al., 1995). In this study, we investigated patients with medial temporal lobe epilepsy (MTLE) who exclusively had hippocampal sclerosis (HS), but no other epileptogenic lesion. In MTLE with HS, the seizure onset region is localized to the mesiotemporal structures (Williamson et al., 1993); thus, it is a unique, homogeneous epilepsy syndrome (Engel et al., 1998). Moreover, it is the most frequent chronic focal epilepsy. Human and experimental data suggest that the cause of HS is thought to be due to an initial precipitating injury (IPI) occurring in early childhood or infancy, which induces functional and structural damage to the hippocampus gradually evolving to HS (Maher et al., 1995; Mathern et al., 1995, 2002; Toth et al., 1998; Chen et al., 1999; Dube et al., 2000; Schulz and Ebner, 2001). The factors that influence speech reorganization can be investigated in MTLE since these patients have the same pathology in the same location, and this pathology is located distantly from the eloquent speech areas. The influence of the timing of the brain damage (i.e. IPI) can also be evaluated separately from the other timing factors, e.g. onset of non-febrile seizures. In addition, the influence of epileptic activity can be investigated independently from the lesional factors.
The present study addressed whether timing factors, gender, lateralization or the epileptic activity are responsible for the evolution of atypical speech. The novelty of our study has been that by evaluating a homogeneous epilepsy population, we were able to investigate the effect of epileptic activity on speech organization separately from the lesion effects. To our knowledge, except for the epilepsy onset, no other study has investigated the epileptic factors in speech organization.
|
Methods |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Patients
In this retrospective study, we included 184 adult patients (85 men and 99 women, aged 19–59; mean: 35.2 years) who consecutively underwent presurgical evaluation at our centre from 1994 to 2002 and had intractable MTLE associated with HS. There were 102 patients with left-sided and 82 patients with right-sided MTLE. One hundred and twenty-five patients had epilepsy surgery with >1-year follow-up; 74% of them became seizure free postoperatively.
Our further inclusion criteria were: (i) complex partial seizures proved by ictal video-EEG which are characteristic of MTLE; (ii) definitive interictal epileptiform discharges (IEDs, spikes or sharp waves) above one or both temporal regions; patients with extratemporal or generalized IEDs were excluded; and (iii) unilateral hippocampal sclerosis detected by high-resolution MRI. We defined HS if both hippocampal atrophy and increased T2 signal intensity in hippocampus were present on MRI. Patients with bilateral HS or any other abnormalities other than HS (e.g. dual pathology) were excluded. The examinations were made exclusively on 1.5 or 1.0 T Siemens Magnetom MR machines. Sagittal T1, axial T2 as well as coronal T1, T2 and proton density or FLAIR (fluid attenuated inversion recovery) sequences perpendicular to the long axis of the hippocampus were made, which gave adequate delineation of the temporal lobes.
Clinical history
The data regarding the age at the first unprovoked seizure, usual seizure frequency, presence of generalized tonic–clonic seizures, presence and type of aura, and the timing of the IPI thought to be the original cause for HS were derived from medical records. At admission to the presurgical unit, all patients and (if available) their parents were asked about the history of the IPI and other epilepsy risk factors.
Clinical examinations
All patients underwent an internal, neurological, psychiatric and neuropsychological examination at admission to our in-patient department. For evaluation of handedness, the Edinburgh Inventory was used.
Non-invasive continuous video-EEG monitoring
All patients underwent continuous video-EEG monitoring lasting 3–7 days as a part of their presurgical evaluation. EEG recordings with 32–64 channels were used; electrodes were placed according to the 10–10 system. In most cases, sphenoidal electrodes were also used. Interictal EEG samples were automatically recorded and stored by computer. In this study, the first 2 min of each hour stored automatically by the computer were evaluated. The location and frequency of IEDs as well as the EEG seizure localization were analysed.
Wada test procedure
The Wada test was necessary for presurgical evaluation of memory and language functions in 100 patients, 17 of whom had right-sided MTLE. Our Wada test procedure has been described elsewhere (Jokeit et al., 1997). Immediately after the injection of amobarbital into the arteria carotis interna, the patient was asked to perform simple verbal tasks and non-verbal actions followed by naming objects, pictures, numbers and colours, as well as reading words and sentences in order to test speech functions of the investigated hemisphere. Speech lateralization was based on semi-quantitative evaluation of a patient’s performance in expressive and receptive language tasks during the Wada test. Initial speech arrest and, later on, word-finding problems, paraphasias, global aphasia, fluent aphasia and non-fluent aphasia describe frequent disturbances of language. Up to 5 points were given for complex language tasks depending on the severity of the language disturbance: 0 = no reaction; 1 = not understandable; recurring utterances; 2 = spontaneous and incorrect repetition; neologisms, paraphasias; 3 = spontaneous incorrect and correct repetition; 4 = correct self-correction; 5 = unimpaired. Simple tasks such as ‘Show me your tongue’ were credited with 1 point because they merely test speech reception. The maximum number of points amounted to 104, reflecting complete unimpaired speech production of the investigated hemisphere.
Investigated variables and statistical methods
The following timing factors were chosen: age at the Wada test, duration and onset of epilepsy, age at the IPI. We also investigated the lateralization and localization of the epileptic activity characterized by the following variables: seizure frequency, presence of secondarily generalized seizures, spike frequency, presence of interictal and ictal bilateral epileptic activity, as well as different aura types. The latter were chosen because they suggest a limbic, temporolateral or other seizure propagation. All variables were chosen according to whether they were previously reported in influencing speech lateralization or because it was reasonable to assume that they may have an effect on this process.
For the multivariate analysis of variables which were supposed to be associated with atypical speech representation, a stepwise logistic regression was performed. For bivariate analysis, Mann–Whitney U test was used for continuous and Fisher’s exact test for categorical variables. Two-tailed error probabilities smaller than P < 0.05 were considered to be significant.
|
Results |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Of 100 patients in whom the Wada test was performed, left-sided speech occurred in 75.9% of the left-sided and in 100% of the right-sided MTLE patients (P < 0.05). Thus, no patients with right-sided TLE had atypical speech lateralization. Atypical speech lateralization was correlated with left-handedness: 10 of 20 patients (50%) with atypical speech were left-handed, while of 80 patients with left-sided speech, left-handedness was present in seven cases (9%, P < 0.0001).
For the Wada test, there was a strong bias for the left-sided patients (see Methods). This bias was because in the presurgical evaluation of MTLE, the main indication for the Wada test is memory testing and not the investigation of speech lateralization. Left-sided MTLE patients are known to have a much higher risk for disabling postoperative memory loss than right-sided MTLE patients (Jokeit et al., 1997; Gleissner et al., 1998; Rausch et al., 1998). Due to this bias, for the further evaluation, we included only those 83 patients in whom an amobarbital (Wada) test was performed, and those who had a left-sided MTLE in order to identify factors responsible for atypical speech lateralization.
Of 83 left-sided MTLE patients having taken the Wada test, there were 36 men and 47 women. The mean age at seizure onset was 10.1 ± 7.8 (range 1–37) years, the mean age was 35.6 ± 9.8 (range 19–59) years. Ten patients had a family history of epilepsy. An IPI which may lead to HS was present in 51 patients (61%): febrile seizures in 34; cerebral infections in 11; significant cerebral trauma in six; and perinatal asphyxia in two patients. All IPIs occurred before age 7 years. There were 67 right-handed and 16 non-right-handed (ambidextrous or left-handed) patients. Based on the Wada test, left-sided speech was present in 63 patients, while in 20 patients the Wada test revealed atypical (right-sided or bilateral) speech dominance. None of the patients had a neurological deficit. Of 83 patients, 62 patients had epilepsy surgery with >1-year follow-up; 73% of them became seizure free postoperatively (category I according to Engel).
We compared patients with left-sided versus atypical speech according to general data, clinical history, interictal and ictal epileptic activity. A stepwise forward logistic regression was performed except for age at IPI and spike frequency.
Table 1 shows the general data and the clinical history of patients with or without left-sided speech. No variables showed significant differences in the two groups. Because all IPIs occurred before age 7 years and only five of them appeared after age 3 years, we did not categorize the age at IPI according to pre-school age because in all but one patient the IPI occurred before pre-school age. Inclusion of categories of ages at the IPI in the logistic regression model would have reduced the number of patients to 51 because IPIs were present in only 61% of the cases. Of patients in whom a history of IPI was evident, 38 had left-sided speech, while 13 had atypical speech. Patients with left-sided speech had an IPI at the mean age of 20 ± 18.7 months, while those who had atypical speech had an IPI at the mean age of 13 ± 9.6 months, but this difference was not significant according to the Mann–Whitney test. We also performed a Fisher’s exact test to determine whether age at IPI before 1 year was associated more often with atypical speech. In patients in whom an IPI occurred before age 1 years, atypical speech occurred in 31%, while left-sided speech was present in 69% of the patients. Conversely, in patients in whom an IPI occurred after age 1 years, atypical speech was present in 21%, while left-sided speech was present in 79% of patients; the difference between the two groups was not statistically significant.
|
Table 2 presents the laterality of interictal and ictal epileptic activity and aura characteristics of patients. Investigating the severity of interictal epileptiform activity, we examined only patients with unitemporal spikes because patients with bilateral epileptiform activity and with frequent spikes might have an antagonistic effect on speech lateralization if we suppose that epileptic activity may really influence speech lateralization. We found an association between the frequency of interictal activity in unilateral MTLE and atypical speech representation (P < 0.05, Mann–Whitney test). Patients with left-sided speech had a median spike frequency of 15.5 IEDs/h (25–75%, range: 2.25–80.5 IEDs/h), while patients with atypical speech had a median spike frequency of 48 IEDs/h (25–75%, range: 23.5–64 IEDs/h).
|
The presence of sensory auras (auditory, vertigous, somatosensory) suggesting a temporo-latero-posterior ictal spread was also associated with atypical speech, while psychic auras indicating a medial (temporo-limbic) seizure spread were significantly associated with typical speech lateralization (see Table 2).
|
Discussion |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
The main findings of our study are: (i) atypical speech dominance was only present in left-sided MTLE; (ii) 24% of patients with left MTLE had an atypical pattern of speech dominance; (iii) atypical speech representation in left MTLE was associated with higher spiking frequency and with sensory auras representing an ictal involvement of the posterio-lateral temporal structures (Ebner, 1994
; Wunderlich et al., 2000); (iv) psychic auras suggesting a limbic seizure spread showed a significant association with left-sided speech dominance in left MTLE; and (v) neither age at IPI, age at epilepsy onset nor gender was associated with atypical speech representation in left MTLE. One of the major limitations of this study was that it was retrospective, thus, we could investigate epileptic variables, e.g. the severity of the interictal activity and the seizure spread as a variable at the time of Wada test, and not longitudinally or before the speech organization/reorganization evolved.
Plasticity of language lateralization
Both the executive speech region (Broca’s area) (Foundas et al., 1996) and perceptive secondary auditory centres (planum temporale) (Geschwind and Levitsky, 1968) show a morphological asymmetry in comparison with the contralateral homologous brain regions in favour of the left side. This asymmetry is already present in the last gestational trimester (Wada et al., 1975) and shows no change with increasing age, suggesting that the left–right functional differentiation follows a structural asymmetry that is already ‘pre-set’ (Geschwind and Levitsky, 1968). Human non-speech sounds, e.g. baby babbling (Holowka and Petitto, 2002) or non-verbal vocalizations in frontal lobe seizures (Janszky et al., 2000), may also be related to the left hemisphere, suggesting that not only speech, but vocalization at a subverbal level independent of age is also a product of the left hemisphere in humans. Moreover, the lateralization of sound production is not a human-specific phenomenon; subhuman vertebrates appear to have left hemisphere dominance of vocal productions (Walker, 1980). Others suggest that the left–right functional asymmetry is already present in the pre-language age in babies, i.e. the left hemisphere is specialized in the temporal modality of a given stimulus, while the right hemisphere is specialized in the spatial modality, which difference is the functional basis as to why language becomes confined to the left hemisphere (Witelson, 1987). Indeed, Dehaene-Lambertz et al. (2002) found that precursors of adult cortical language areas are already active in infants well before the onset of speech production. They investigated 3-month-old infants by using functional MRI (fMRI) activated by speech perception. They found that the left-lateralized brain regions similar to those of adults, including the superior temporal and angular gyri, were already active in infants during speech perception.
Despite this strong left-sided predispostion of the brain morphology and function, Chiron et al. (1997) suggested that the right hemisphere until age 3 years is still the dominant hemisphere considering the Broca and Broca-homologous areas, sensorimotor cortex and the temporoposterior regions. After age 3 years, a shift towards the left hemispheric dominance begins (Rasmussen and Milner, 1977; Marcotte and Morere, 1990) and may be completed at age 4–8 years (Hecaen, 1976; Rasmussen and Milner, 1977; Ameli, 1980; Vargha-Kadem et al., 1997; Balsamo et al., 2002). However, Gaillard et al. (2000) found that even children aged 8–12 years showed significantly more right hemispheric participation in speech production than adults. A recent fMRI study found that although there is a negative correlation between age at brain injury and speech reorganization, there is no cut-off point after which contralateral speech reorganization does not occur in epilepsy patients (Springer et al., 1999). Moreover, even in adult patients suffering from aphasia, Wada tests suggested that improvement of aphasia was paralleled by the participation of the right hemisphere in speech production, indicating some kind of contralateral speech reorganization in adulthood (Czopf, 1972).
Effects of gender, lateralization and age at brain injury on speech representation
There are contradictory data as to whether speech lateralization is related to gender. Some studies found that women had less frequent or weaker lateralized speech (McGlone, 1977; Helmstaedter et al., 1997; Kansaku et al., 2000), whereas others found no sex difference in speech lateralization (Kertész and Sheppard, 1981) either in healthy subjects (Frost et al., 1999; Knecht et al., 2000) or in epilepsy patients (Springer et al., 1999). We also found no difference in gender for speech lateralization.
Although most studies found that left-sided lesions may cause contralateral speech reorganization (Rasmussen and Milner, 1977; Rausch and Walsh, 1984; Rey et al., 1988; Woods et al., 1988; Helmstaedter et al., 1997), a recent fMRI study did not find such a correlation (Springer et al., 1999). However, this study did not include left-handed patients, and the number of patients was relatively small. In our study, we found that atypical speech dominance was present in only left-sided MTLE, whereas atypical speech did not occur in right-sided MTLE, which confirms a recent study investigating temporal lobe epilepsy (Brazdil et al., 2002).
It may be questioned by which mechanism a lesion localized to the mesiotemporal region can influence the speech lateralization when this lesion is rather far from the eloquent speech centres and no morphological abnormalities in the speech centres were visualized by high-resolution MRI. Even left periventricular white matter lesions acquired perinatally may be associated with atypical speech lateralization (Staudt et al., 2001), thus it is possible that an IPI leading to hippocampal damage is able to cause a left–right shift of the language organization. Surprisingly, in our study, neither the age at the presumed brain injury, i.e. the IPI, nor the age at epilepsy onset was correlated with atypical speech representation in left MTLE. These findings may be a result of a bias for the age at IPI and development of HS in early childhood (Sagar and Oxbury, 1987; Schulz and Ebner, 2001). Indeed, in our study, most IPIs occur before age 3 years, and only one patient had an IPI after pre-school age, i.e. almost all known IPIs of our patients occurred at an age when the brain plasticity certainly allows a left–right shift of speech centres. Thus, the age effect of brain injury is not pronounced in MTLE because all brain injuries occurred at the age of maximal brain plasticity. The question is why all the patients did not have a right–left speech shift due to the early brain injury; in other words, which factors induce or do not induce speech reorganization after an early brain injury affecting the left side.
Effects of seizures and interictal epileptiform activity on speech lateralization
Similarly to Springer et al. (1999), we did not find a cut-off age at seizure onset after which no atypical speech can occur. Moreover, the participation and the reorganization capacity of the right hemisphere for speech functions is present to some degree even in adolescence or adulthood (Czopf, 1972; Gaillard et al., 2000). Thus it is reasonable to assume that not only the timing of the first seizures, but other epileptogenic factors as well may participate in speech reorganization in epilepsy.
Previous studies investigating the speech reorganization in epilepsy did not consider the ictal or interictal epileptological data. In this study, we hypothesized that not only the lateralization and localization of the injury and age, but also the functional disturbance caused by epileptic activity may also play a role in the organization of speech in epilepsy. This could be answered in our study because (i) all patients had left-sided brain injury and epilepsy; (ii) all patients had the same pathology in the same localization; (iii) no patient had a lesion in the brain regions responsible for the speech production; and (iv) the age at the brain injury (IPI) was not correlated with atypical language because most patients probably had an early brain injury.
Experimentally evoked repeated seizures induce a long-term spatial memory deficit in rats (Kotloski et al., 2002). Few data concerning human epilepsy suggest that temporal lobe seizures had short-term and probably also long-term effects on human memory functions (Jokeit et al., 2001). Not only the memory, but even speech lateralization may be directly influenced by temporal lobe seizures. Jayakar et al. (2002) reported a case of a 14-year-old child in whom, after a cluster of left temporal lobe seizures, the language-activated fMRI using four different tasks suggested a right temporal receptive speech centre. Two weeks later, when the patient had their usual seizure frequency, the fMRI using the same tasks was repeated and revealed a left temporal receptive speech centre. Dominant temporal lobe seizures cause ictal and post-ictal speech disturbances in 75% of patients (Gabr et al., 1989), suggesting that they can disturb speech production, at least transiently. PET studies suggest that seizures cause not only transient, but also sustained functional disturbance (Savic et al., 1997; Schlaug et al., 1997). Consequently, it is reasonable to assume that frequent ictal involvement of lateral temporal structures may occasionally result in long-term functional speech disturbance which may induce a more prominent participation of the contralateral structures in speech production, finally resulting in a reorganization of speech.
In MTLE patients, the seizures originating in mesiotemporal regions can spread to the ipsilateral (lateral) temporal neocortex and to the limbic structures without involving the lateral temporal regions, or they may show an initial frontal, mainly fronto-orbital spread (Lieb et al., 1991; Gloor et al., 1993), without involving the frontal speech centres.
We found that seizure spread had an influence on the speech organization in epilepsy. Namely, sensory auras typically representing a temporo-posterior seizure involvement (Ebner, 1994; Wunderlich et al., 2000) were associated with atypical speech in left MTLE, indicating that seizures may cause a long-term functional disturbance in the left auditory/speech receptive region and may induce contralateral speech reorganization. On the other hand, seizure spread probably not involving the lateral neocortical regions (complex partial seizures with psychic auras) was associated with left-sided speech.
Not only the seizures, but also the interictal epileptiform activity may disturb higher cognitive functions, potentially leading to functional reorganization. Frequent interictal epileptiform discharges may result in transient cognitive impairment, while such impairment is absent in those periods when no interictal epileptiform activity occurs, e.g. during neuropsychological testing (Aarts et al., 1984). Moreover, an impairment of spatial task performance was demonstrated during right-sided interictal discharges, while during left-sided paroxysm, the verbal cognitive performance was disturbed (Aarts et al., 1984). This suggests that the cognitive impairment caused by interictal spikes is not non-specific, but reflects the functional disturbance in the area where the spikes originate or to which they are propagated. Consequently, we can assume that frequent interictal activity propagating to the speech centres may also cause speech disturbances.
Spikes in MTLE are generated in the mesiotemporal structures. Conversely, 10–50% of them propagate to the lateral temporal neocortex (Niedermeyer and Rocca, 1972; Alarcon et al., 1994; Clemens et al., 2003). Since we did not use intracranial electrodes in this study, the spike frequency was related to the degree of the interictal epileptic involvement of the temporal neocortex. In this study, we found that the higher spike frequency was associated with atypical speech. Thus, our findings may indicate that even the interictal epileptic activity may interfere with the functions of the temporal speech receptive areas.
Our study was retrospective; thus, we do not know when the transfer of speech occurred. Therefore, it is also not completely clear whether it was progressive during the course of the epilepsy due to the interictal and ictal epileptic activity, as we suppose considering our results, or earlier, as a mere consequence of the IPI that caused the epilepsy and determined by the extent of brain damage caused by the IPI, independent of the age of its occurrence. Our data could stimulate prospective and longitudinal studies in children and adolescents, using non-invasive methods for determination of speech dominance (for instance fMRI or fTCD), prospectively, from early in the course of MTLE.
Conclusion
We found that in patients with focal epilepsy, not only the known factors, i.e. the age at and the localization of the brain injury, but also the epileptic activity itself, interictal and ictal activity, could be responsible for speech reorganization. Our findings also suggest that the question of whether an early prevention of the development of epilepsy after a known IPI should be reconsidered. Because in patients with left-sided brain injury, even if the speech centres had shifted to the right hemisphere ‘escaping’ from the seriously damaged functions, poor verbal cognitive performance was found (Helmstaedter et al., 1997), this suggests that the speech reorganization (i.e. the replacement of language functions from the predetermined regions) does not mean a complete restitution of speech functions. Our findings also suggest that not only structural elements but also the functional factors may have an effect on the language organization of the brain.
|
Acknowledgements |
|---|
We wish to thank Terri Shore Ebner who carefully reviewed the manuscript as a native English speaker. This work was supported by a grant from the Deutsche Forschungs gemeinschaft (DFG-Eb 111/2-2 to A.E.) and Humboldt Stiftung (to J.J.).
|
References |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Aarts JH, Binnie CD, Smit AM, Wilkins AJ. Selective cognitive impairment during focal and generalized epileptiform EEG activity. Brain 1984; 107: 293–308.
Alarcon G, Guy CN, Binnie CD, Walker SR, Elwes RD, Polkey CE. Intracerebral propagation of interictal activity in partial epilepsy: implications for source localisation. J Neurol Neurosurg Psychiatry 1994; 57: 435–49.[Abstract]
Ameli NO. Hemispherectomy for the treatment of epilepsy and behavior disturbance. Can J Neurol Sci 1980; 7: 33–8.[ISI][Medline]
Balsamo LM, Xu B, Grandin CB, Petrella JR, Braniecki SH, Elliott TK, et al. A functional magnetic resonance imaging study of left hemisphere language dominance in children. Arch Neurol 2002; 59: 1168–74.
Brazdil M, Zakopcan J, Kuba R, Fanfrdlova Z, Rektor I. Atypical language in left temporal epilepsy as a result of reorganization of language functions [abstract]. Epilepsia 2002; 43 Suppl 8: 49.
Chen K, Baram TZ, Soltesz I. Febrile seizures in the developing brain result in persistent modification of neuronal excitability in limbic circuits. Nat Med 1999; 5: 888–94.[CrossRef][ISI][Medline]
Chiron C, Jambaque I, Nabbout R, Lounes R, Syrota A, Dulac O. The right brain hemisphere is dominant in human infants. Brain 1997; 120: 1057–65.
Clemens Z, Janszky J, Szücs A, Bekesy M, Clemens B, Halasz P. Interictal epileptic spiking during sleep and wakefulness in mesial temporal lobe epilepsy: a comparative study of scalp and foramen ovale electrodes. Epilepsia 2003; 44: 186–92.[CrossRef][ISI][Medline]
Czopf J. Über die Rolle der nicht dominanten Hemisphäre in der Restitution der Sprache der Aphasischen. Arch Psychiatr Nervenkr 1972; 216: 162–71.[CrossRef][ISI][Medline]
Dehaene-Lambertz G, Dehaene S, Hertz-Pannier L. Functional neuroimaging of speech perception in infants. Science 2002; 298: 2013–5.
Dube C, Chen K, Eghbal-Ahmadi M, Brunson K, Soltesz I, Baram TZ. Prolonged febrile seizures in the immature rat model enhance hippocampal excitability long term. Ann Neurol 2000; 47: 336–44.[CrossRef][ISI][Medline]
Duchowny M, Jayakar P, Harvey AS, Resnick T, Alvarez L, Dean P, et al. Language cortex representation: effects of developmental versus acquired pathology. Ann Neurol 1996; 40: 31–8.[CrossRef][ISI][Medline]
Ebner A. Lateral (neocortical) temporal lobe epilepsy. In: Wolf P, editor. Epileptic seizures and syndromes. London: John Libbey; 1994. p. 375–82.
Ebner A. Preoperative evaluation in epilepsy surgery: some principal considerations. In: Lüders HO, Comair YG, editors. Epilepsy surgery. 2nd edn. Philadelphia: Lippincott-Williams & Wilkins; 2001. p. 177–83.
Ebner A, Dinner DS, Noachtar S, Lüders H. Automatisms with preserved responsiveness: a lateralizing sign in psychomotor seizures. Neurology 1995; 45: 61–4.
Engel J Jr, Cascino GD, Shields WD. Surgically remediable syndromes. In: Engel JJr, Pedley TA, editors. Epilepsy: a comprehensive textbook. Philadelphia: Lippincott-Raven; 1998. p. 1687–96.
Foundas AL, Leonard CM, Gilmore RL, Fennell EB, Heilman KM. Pars triangularis asymmetry and language dominance. Proc Natl Acad Sci USA 1996; 93: 719–22.
Frost JA, Binder JR, Springer JA, Hammeke TA, Bellgowan PS, Rao SM, et al. Language processing is strongly left lateralized in both sexes. Brain 1999; 122: 199–208.
Gabr M, Lüders H, Dinner D, Morris H, Wyllie E. Speech manifestations in lateralization of temporal lobe seizures. Ann Neurol 1989; 25: 82–7.[CrossRef][ISI][Medline]
Gaillard WD, Hertz-Pannier L, Mott SH, Barnett AS, LeBihan D, Theodore W. Functional anatomy of cognitive development: fMRI of verbal fluency in children and adults. Neurology 2000; 54: 180–5.
Geschwind N, Levitsky W. Human brain: left–right asymmetries in temporal speech region. Science 1968; 161: 186–9.
Gleissner U, Helmstaedter C, Elger CE. Right hippocampal contribution to visual memory: a presurgical and postsurgical study in patients with temporal lobe epilepsy. J Neurol Neurosurg Psychiatry 1998; 65: 665–9.
Gloor P, Salanova V, Olivier A, Quesney LF. The human dorsal commissure. An anatomically identifiable and functional pathway. Brain 1993; 116: 1249–73.
Hecaen H. Acquired aphasia in children and the ontogenesis of hemispheric functional specialization. Brain Lang 1976; 3: 114–34.[CrossRef][ISI][Medline]
Helmstaedter C, Kurthen M, Linke DB, Elger CE. Patterns of language dominance in focal left and right hemisphere epilepsies: relation to MRI findings, EEG, sex, and age at onset of epilepsy. Brain Cogn 1997; 33: 135–50.[CrossRef][ISI][Medline]
Holowka S, Petitto LA. Left hemisphere cerebral specialization for babies while babbling. Science 2002; 297: 1515.
Janszky J, Fogarasi A, Jokeit H, Ebner A. Are ictal vocalisations related to the lateralisation of frontal lobe epilepsy? J Neurol Neurosurg Psychiatry 2000; 69: 244–7.
Jayakar P, Bernal B, Medina S, Altman N. False lateralization of language cortex on functional MRI after a cluster of focal seizures. Neurology 2002; 58: 490–2.
Jokeit H, Ebner A, Holthausen H, Markowitsch HJ, Moch A, Pannek H, et al. Individual prediction of change in delayed recall of prose passages after left-sided anterior temporal lobectomy. Neurology 1997; 49: 481–7.
Jokeit H, Daamen M, Zang H, Janszky J, Ebner A. Seizures accelerate forgetting in patients with left-sided temporal lobe epilepsy. Neurology 2001; 57: 125–6.
Kansaku K, Yamaura A, Kitazawa S. Sex differences in lateralization revealed in the posterior language areas. Cereb Cortex 2000; 10: 866–72.
Kertész A, Sheppard A. The epidemiology of aphasic and cognitive impairment in stroke: age, sex, aphasia type and laterality differences. Brain 1981; 104: 117–28.
Kimura D. Functional asymmetry of the brain in dichotic listening. Cortex 1967; 3: 163–78.
Knecht S, Deppe M, Dräger B, Bobe L, Lohmann H, Ringelstein E, et al. Language lateralization in healthy right-handers. Brain 2000; 123: 74–81.
Kotloski R, Lynch M, Lauersdorf S, Sutula T. Repeated brief seizures induce progressive hippocampal neuron loss and memory deficits. Prog Brain Res 2002; 135: 95–110.[Medline]
Lieb JP, Dasheiff RM, Engel J Jr. Role of the frontal lobes in the propagation of mesial temporal lobe seizures. Epilepsia 1991; 32: 822–37.[ISI][Medline]
Maher J, McLachlan RS. Febrile convulsions. Is seizure duration the most important predictor of temporal lobe epilepsy? Brain 1995; 118: 1521–8.
Marcotte AC, Morere DA. Speech lateralization in deaf populations: evidence for a developmental critical period. Brain Lang 1990; 39: 134–52.[CrossRef][ISI][Medline]
Mathern GW, Babb TL, Vickrey BG, Melendez M, Pretorius JK. The clinical-pathogenic mechanisms of hippocampal neuron loss and surgical outcomes in temporal lobe epilepsy. Brain 1995; 118: 105–18.
Mathern GW, Adelson PD, Cahan LD, Leite JP. Hippocampal neuron damage in human epilepsy: Meyer’s hypothesis revisited. Prog Brain Res 2002; 135: 237–51.[Medline]
McGlone J. Sex differences in the cerebral organization of verbal functions in patients with unilateral brain lesions. Brain 1977; 100: 775–93.
Niedermeyer E, Rocca U. The diagnostic significance of sleep electroencephalograms in temporal lobe epilepsy. A comparison of scalp and depth tracings. Eur Neurol 1972; 7: 119–29.[ISI][Medline]
Popper KR, Eccles JC. The self and its brain. New York: Springer International; 1977. p. 304–5, 450–6.
Rasmussen T, Milner B. The role of early left-brain injury in determining lateralization of cerebral speech functions. Ann NY Acad Sci 1977; 299: 355–69.[Medline]
Rausch R, Walsh GO. Right-hemisphere language dominance in right-handed epileptic patients. Arch Neurol 1984; 41: 1077–80.[Abstract]
Rausch R, Le MT, Langfitt JT. Neuropsychological evaluation—adults. In: Engel J Jr, Pedley TA, editors. Epilepsy: a comprehensive textbook. Philadelphia: Lippincott-Raven; 1998. p. 977–86.
Rey M, Dellatolas GJ, Bancaud J, Talairach J. Hemispheric lateralization of motor and speech functions after early brain lesion: study of 73 epileptic patients with intracarotid amytal test. Neuropsychologia 1988; 26: 167–72.[CrossRef][ISI][Medline]
Rosenow F, Lüders HO. Presurgical evaluation of epilepsy. Brain 2001; 124: 1683–700.
Sagar HJ, Oxbury JM. Hippocampal neuron loss in temporal lobe epilepsy: correlation with early childhood convulsions. Ann Neurol 1987; 22: 334–40.[CrossRef][ISI][Medline]
Savic I, Altshuler L, Baxter L, Engel J Jr. Pattern of interictal hypometabolism in PET scans with fludeoxyglucose F 18 reflects prior seizure types in patients with mesial temporal lobe seizures. Arch Neurol 1997; 54: 129–36.[Abstract]
Schlaug G, Antke C, Holthausen H, Arnold S, Ebner A, Tuxhorn I, et al. Ictal motor signs and interictal regional cerebral hypometabolism. Neurology 1997; 49: 341–50.
Schulz R, Ebner A. Prolonged febrile convulsions and mesial temporal lobe epilepsy in an identical twin. Neurology 2001; 57: 318–20.
Serafetinides EA, Hoare RD, Driver MV. Intracarotid sodium amylobarbitone and cerebral dominance for speech and consciousness. Brain 1965; 88: 107–30.
Springer JA, Binder JR, Hammeke TA, Swanson SJ, Frost JA, Bellgowan PSW, et al. Language dominance in neurologically normal and epilepsy patients. Brain 1999; 122: 2033–46.
Staudt M, Grodd W, Niemann G, Wildgruber D, Erb M, Krägeloh-Mann I. Early left periventricular brain lesions induce right hemispheric organization of speech. Neurology 2001; 57: 122–5.
Toth Z, Yan X, Haftoglou S, Ribak CE, Baram TZ. Seizure-induced neuronal injury: vulnerability to febrile seizures in an immature rat model. J Neurosci 1998; 18: 4285–94.
Vargha-Khadem F, Carr LJ, Isaacs E, Brett E, Adams C, Mishkin M. Onset of speech after left hemispherectomy in a nine-year-old boy. Brain 1997; 120: 159–82.
Wada JA, Clarke RJ, Hamm AE. Cerebral hemispheric asymmetry in humans. Arch Neurol 1975; 32: 239–46.[Abstract]
Walker SF. Lateralization of functions in the vertebrate brain: a review. Br J Psychol 1980; 71: 329–67.[ISI][Medline]
Williamson PD, French JA, Thadani VM, Kim JH, Novelly RA, Spencer SS, et al. Characteristics of medial temporal lobe epilepsy: II. Interictal and ictal scalp electroencephalography, neuropsychological testing, neuroimaging, surgical results, and pathology. Ann Neurol 1993; 34: 781–7.[CrossRef][ISI][Medline]
Witelson SF. Neurobiological aspects of language in children. Child Dev 1987; 58: 653–88.[CrossRef][ISI][Medline]
Woods RP, Dodrill CB, Ojemann GA. Brain injury, handedness, and speech lateralization in a series of amobarbital studies. Ann Neurol 1988; 23: 510–8.[CrossRef][ISI][Medline]
Wunderlich G, Schuller MF, Ebner A, Holthausen H, Tuxhorn I, Witte OW, et al. Temporal lobe epilepsy with sensory aura: interictal glucose hypometabolism. Epilepsy Res 2000; 38: 139–49.[CrossRef][ISI][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. J. Hamberger, W. T. Seidel, R. R. Goodman, A. Williams, K. Perrine, O. Devinsky, and G. M. McKhann II Evidence for cortical reorganization of language in patients with hippocampal sclerosis Brain, November 1, 2007; 130(11): 2942 - 2950. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. D. Gaillard, M. M. Berl, E. N. Moore, E. K. Ritzl, L. R. Rosenberger, S. L. Weinstein, J. A. Conry, P. L. Pearl, F. F. Ritter, S. Sato, et al. Atypical language in lesional and nonlesional complex partial epilepsy Neurology, October 30, 2007; 69(18): 1761 - 1771. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sveller, R. S. Briellmann, M. M. Saling, L. Lillywhite, D. F. Abbott, R.A.J. Masterton, and G. D. Jackson Relationship between language lateralization and handedness in left-hemispheric partial epilepsy Neurology, November 28, 2006; 67(10): 1813 - 1817. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. T. Crinion, E. A. Warburton, M. A. Lambon-Ralph, D. Howard, and R. J.S. Wise Listening to Narrative Speech after Aphasic Stroke: the Role of the Left Anterior Temporal Lobe Cereb Cortex, August 1, 2006; 16(8): 1116 - 1125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Jefferies and M. A. Lambon Ralph Semantic impairment in stroke aphasia versus semantic dementia: a case-series comparison Brain, August 1, 2006; 129(8): 2132 - 2147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Spitsyna, J. E. Warren, S. K. Scott, F. E. Turkheimer, and R. J. S. Wise Converging language streams in the human temporal lobe. J. Neurosci., July 12, 2006; 26(28): 7328 - 7336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. L. Voets, J. E. Adcock, D. E. Flitney, T. E. J. Behrens, Y. Hart, R. Stacey, K. Carpenter, and P. M. Matthews Distinct right frontal lobe activation in language processing following left hemisphere injury Brain, March 1, 2006; 129(3): 754 - 766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Weber, J. Wellmer, M. Reuber, F. Mormann, S. Weis, H. Urbach, J. Ruhlmann, C. E. Elger, and G. Fernandez Left hippocampal pathology is associated with atypical language lateralization in patients with focal epilepsy Brain, February 1, 2006; 129(2): 346 - 351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Noppeney, C. J. Price, J. S. Duncan, and M. J. Koepp Reading skills after left anterior temporal lobe resection: an fMRI study Brain, June 1, 2005; 128(6): 1377 - 1385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Janszky, I. Ollech, H. Jokeit, K. Kontopoulou, M. Mertens, B. Pohlmann-Eden, A. Ebner, and F. G. Woermann Epileptic activity influences the lateralization of mesiotemporal fMRI activity Neurology, November 23, 2004; 63(10): 1813 - 1817. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Helmstaedter, T. Brosch, M. Kurthen, and C. E. Elger The impact of sex and language dominance on material-specific memory before and after left temporal lobe surgery Brain, July 1, 2004; 127(7): 1518 - 1525. [Abstract] [Full Text] [PDF] |