TEMPORAL LOBE EPILEPSY AND SLEEP: FOCUS ON INTERICTAL SPIKES AND MEMORY CONSOLIDATION

Transcription

1 Ph.D thesis TEMPORAL LOBE EPILEPSY AND SLEEP: FOCUS ON INTERICTAL SPIKES AND MEMORY CONSOLIDATION Zsófia Clemens National Institute of Psychiatry and Neurology Semmelweis University Budapest János Szentágothai (Neuroscience) PhD School Program director: Prof. Dr. Zoltán Nagy Consultant professor: Prof. Dr. Péter Halász 2005.

2 Introduction Epilepsy, sleep and memory processes are interrelated through several anatomical and functional factors. Sleep might exert an influence on both ictal and interictal events; in turn epileptic seizures and interictal spikes might alter the structure of sleep (Méndez, 2001). Clinical data suggested that understanding complex interrelationship between sleep and epilepsy needs a syndrome-oriented approach (Ferillo, 2000). In general, in temporal lobe epilepsy (TLE) patients, interictal spikes are activated mostly during deep NREM stages (Sammaritano, 1991). However, data derived from intracranial recordings have given rises to much controversy in this regard (Kajtor, 1957; Rossi, 1984). Further questions are raised by the case of those TLE patients exhibiting scalp spiking rate maxima during vigilance states other than deep NREM. Neuropsychological assesement in epileptic patients, besides constituting an important part of the presurgical evaluation, might also offer a unique possibility to get an insight into human memory processes. In our third study we focused on memory consolidation in patients with different epilepsy syndromes. Aims The aim of the first study was to assess distribution of temporal lobe spikes across different states of sleep and wakefulness in simultaneous scalp and foramen ovale electrodes (FoE). The second study was aimed to investigate the possible influencing role of different clinical factors on spiking during sleep and wakefulness in TLE. In the third study we investigated memory consolidation during sleep in patients with different epilepsy syndromes and normal controls. Based on previous data, we suggested that TLE interferes with memory consolidation, while in an epilepsy syndrome without temporal involvement (idiopathic generalised epilepsy, IGE) consolidation might be spared. Another purpose was to examine whether interictal spike activity in TLE impair memory consolidation. Methods 1. study 2

3 The study included 9 patients with mesial TLE. As part of their presurgical evaluation, patients underwent long-term video-eeg monitoring with combined scalp and FoEs. In addition to traditional sleep scoring, waking was subdivided into eyes-opened and eyes closed states and REM sleep was divided into phasic and tonic states. Spike counts were carried out visually for scalp and FoEs and spiking rates were determined for each state. A ratio between scalp and FoE was also calculated for each state. Because of uncertain distribution of spike rates the hypothesis of statistical difference between spiking rates across different states was tested by means of sign-test. 2. study The study included 38 TLE patients who underwent presurgical evaluation including longterm EEG. In addition to traditional sleep scoring, waking was subdivided into eyes-opened and eyes-closed states. Spike count was carried out visually. The following spike measures were investigated: spike rates for each state, mean spike rate, spiking stability across states (mean/sd) and relative spike density (spiking rate in a state/ mean spiking rate) for each state. These measures were investigated according to clinical variables, such as age, age at epilepsy onset, duration of epilepsy and seizure frequency. High-resolution MRI data and the presence of secondarily generalised tonic-clonic seizures were also investigated. For the analysis between continuous spike measures and clinical variables, a Pearson Product- Moment Correlation-test was carried out. For categorical variables, one-way MANOVA was used. Since the variables, age at onset and epilepsy duration showed a high correlation with each other, mutual partial correlations were introduced for these variables if a correlation with a spike measure was found to be significant. 3. study Left temporal lobe epilepsy (LTLE), right temporal lobe epilepsy (RTLE), IGE patients and a matching normal control group were investigated. These groups comprised 13, 14, 8 and 12 persons, respectively. Testing for overnight verbal and visual memory retention was carried out in course of their long-term EEG monitoring procedure. Patients included did not experienced epileptic seizures during the night studied for memory consolidation. Statistical analysis of comparison between groups relied on t-test and ANOVA (with factors: groups and evening/morning) and planned comparison. To test whether epileptic spikes occurring during the retention interval impair memory consolidation in TLE patients, overnight verbal and visual memory retention were correlated with the number of spikes. 3

4 Results 1. study Scalp spiking showed a significant increase during NREM3,4, while FoE spiking increased during NREM2. The scalp/foe ratio significantly increased during NREM3,4. A significant difference in spiking rate was also found between phasic and tonic REM states as well as between waking with eyes opened and closed in FoE recordings. 2. study Spiking rates during most states and spiking stability showed a significant positive correlation with epilepsy duration. Relative spike density during NREM3,4 significantly correlated with age at epilepsy onset. Spiking rates and relative spike densities during REM were significantly higher if a patient had secondarily generalised tonic-clonic seizures, while relative spiking rates during WEC were higher in the presence of hippocampal sclerosis. 3. study We found that both IGE and LTLE patients showed weaker verbal memories on evening (short-term) trials when compared with controls, but LTLE and RTLE patients did not significantly differ from each other. Sleep resulted in further impairment of verbal memories in the LTLE group, whereas all other groups improved their verbal memory during sleep (Fig. 1). In the visual test, despite normal retention on short-term trials, both LTLE and RTLE patients consolidation was impaired during sleep. The total number of spikes during retention interval did not correlate with verbal or visual memory retention in TLE patients. 4

5 Fig.1 Verbal recall score means for the groups in the evening (short-term) and in the morning (long-term) testing sessions. Standard deviations are indicated in parentheses. Asterisk indicates the significant interaction effect (delay x group) revealed by planned comparisons between LTLE and control groups. Discussion 1. study Our data provides evidence for a discrepancy in spike distribution across different states of sleep and waking monitored by scalp and FoE recordings. We suggest that these discrepancies may reflect differences in archicortical and neocortical spike synchronisation. 2. study 5

6 Our data provide evidence that different aspects of spiking during sleep and wakefulness are affected by different clinical factors, consequently individual spiking profiles imply clinical information on the TLE patient being studied. 3. study We suggested that short-term verbal memory impairment found in IGE patients might reflect frontal dysfunction characterising these patients, while impairment of verbal memory consolidation in LTLE patients and long-term visual memory in both TLE groups might be attributed to the crucial role of the temporal lobes in long-term consolidation. Spiking in TLE patients does not seem to deteriorate memory consolidation. As to the clinical relevance of our data, we suggest that measuring verbal memory consolidation during sleep might serve as a new lateralising method in neuropsychological evaluation of TLE patients. Summary 1. Mesiotemporal and scalp spiking are discrepant regarding sleep-related changes in spiking rates. In most patients spiking rates are maximal during light NREM states, while scalp spiking peaks during NREM3,4. 2. Spiking rates during most states and spiking stability positively correlated with the duration of epilepsy. 3. Relative spike density during NREM3,4 positively correlated with age at epilepsy onset. 4. REM spiking rates and REM spiking density was higher if a patient had secondarily generalised tonic-clonic seizures, and relative WEC spiking density was higher in the presence of hippocampal sclerosis. 5. IGE patients are impaired on short-term verbal memory, LTLE patients on overnight verbal retention and both TLE groups are impaired on overnight visual retention. 6

7 Acknowledgements I would like to thank Dr. Péter Halász, my consultant professor for introducing me to research fields related to sleep and epilepsy and for his professional guidance. I thank Dr. József Janszky for sharing enthusiasm toward epileptic spikes. I am also grateful to Dr. György Rásonyi, Dr. Anna Szűcs, Dr. András Holló, Dr. Anna Kelemen and Dr. Gábor Barcs for their clinical contribution. I also thank Gábor Szabó for his indispensable technical support. I am also grateful to Dr. Béla Clemens for helpful advices. Finally, I would like to thank to Zita Csepella, Etelka Kakukk, András Filep, Anikó Papp, Zoltán György, assistants of the EEG laboratory for their cooperation and patience. References Ferillo F, Beelke M, Nobili L. Sleep EEG synchronisation mechanisms and activation of interictal epileptic spikes. Clin Neurophysiol 2000;111:S65-S73. Kajtor F, Hullay J, Farago L, Haberland K. Effect of barbiturate sleep on the electrical activity of the hippocampus of patients with temporal lobe epilepsy. EEG Clin Neurophysiol 1957;9: Méndez M, Radtke RA. Interactions between sleep and epilepsy. J Clin Neurophysiol 2001;18: Rechtschaffen A, Kales A. A manual of standarized terminology, techniques and scoring system for sleep stages of human subjects Los Angeles: UCLA, Brain Information Service. Rossi GF, Colicchio G, Pola P. Interictal epileptic activity during sleep: a stereo-eeg study in patients with partial epilepsy. Electroencephalogr Clin Neurophysiol 1984;58: Sammaritano M, Gigli GL, Gotman J. Interictal spiking during wakefulness and sleep and the localisation of foci in temporal lobe epilepsy. Neurology 1991;41:

8 Publications 1. Publications related to the present work Z. Clemens, J. Janszky, A. Szűcs, M. Békésy, B. Clemens, P. Halász. Interictal epileptic spiking during sleep and wakefulness in mesial temporal lobe epilepsy: a comparative study of scalp and foramen ovale electrodes Epilepsia; 44: Z. Clemens, J. Janszky, B. Clemens, A. Szűcs, P. Halász. Factors affecting spiking related to sleep and wake states in temporal lobe epilepsy (TLE) Seizure 14: Citable abstract related to the present work Z. Clemens, B. Clemens B, J. Janszky, A. Szűcs, G. Rásonyi, P. Halász. Memory consolidation during sleep in epilepsy patients Epilepsia 44: Suppl Other publications related to epilepsy and sleep research A. Szűcs, J. Janszky, P. Barsi, E. Erdei, Z. Clemens, G. Migléczi, R. Bódizs, P. Halász. Sleep-related painful erection is associated with neurovascular compression of basal forebrain J. Neurology; 249: J. Janszky, G. Rásonyi, Z. Clemens, R. Schulz, M. Hoppe, P. Barsi, A. Fogarasi, P. Halász, A. Ebner. Clinical differences in patients with unilateral hippocampal sclerosis and unitemporal or bitemporal epileptiform discharges Seizure; 12: P. Halász, J. Janszky, G. Rásonyi, G. Barcs, A. Szűcs, A. Holló, A. Kelemen, Z. Clemens, Z. Csepella. Postoperative interictal spikes during sleep contralateral to the operated side is associated with unfavourable surgical outcome in patients with preoperative bitemporal spikes Seizure; 13: Z. Clemens, D. Fabó, P. Halász. Overnight verbal memory retention correlates with the number of sleep spindles Neuroscience (in press) 8