- Email: [email protected]
P97. The pathophysiology of sudden unexpected death in epilepsy (SUDEP)
e150
Society Proceedings / Clinical Neurophysiology 126 (2015) e63–e170
reporter gene, the Bmal1 promoter-driven luciferase gene, using a lentiviral system. The luciferase activity showed a circadian rhythm of lumincescence expression. The individual period length over a time course of 5 days was detectable by measuring the bioluminescence every ten minutes in vitro. Previous studies had proven that the physiological period length of human circadian clock in vivo is directly proportional to period in human fibroblast. To test whether differences in the magnitude of oscillatory amplitude of the clock genes Bmal1, Per1 and Per2 might account for period and phase differences, we quantified the transcriptional gene expression of clock genes in dermal fibroblasts by a different method because the measurement of the bioluminescent oscillation of clock genes which is sensitive to the degree of viral infection is not suitable to quantify the transcriptional amplitude. Thus we measured RNA levels of clock genes by means of quantitative real-time PCR (qPCR) and complemented these data with the bioluminescence assay. Total RNA was extracted from fibroblast cell lines every 6 h over 72 h and totalRNA was reverse transcribed into cDNA followed by qPCR using the primer for the clock genes. Results: In fibroblasts from patients suffering from idiopathic hypersomnia clock gene expression exhibit a diminished amplitude of BMAL1 which was significantly reduced by 63% (P = 0.004) compared to healthy controls. The amplitude of PER1 was reduced by 45% (P = 0.048) compared to the control group so was the amplitude of PER2 reduced by 32% (P = 0.032). In the luciferase assay using the same fibroblast cell lines,an averaged period length of 24.6 h could be detected in dermal fibroblasts obtained from healthy volunteers. Conclusion: Due to the significantly diminished amplitude of clock gene expression in the group of idiopathic hypersomniacs, our data suggest a disturbed chronobiology as a heterogeneous aspect in a primary sleep disorder. The implementation of this combined strategy to measure the dynamics of clock gene expression permits a reliable assessment – in objective statistical terms – of both the period length and the absolute magnitude of oscillatory amplitude. The coupling of the circadian gene regulation with individual EEG-parameter following the principles of the two-process-model of sleep regulation can be a useful tool to quantify therapeutic agents and regimens modifying circadian disruption (e.g. period length, phase and amplitude of circadian rhythms) and to develop possible personalized therapeutic options. doi:10.1016/j.clinph.2015.04.246
sleep-stages were analysed. Moreover, the respiratory pattern peri-ictal (before and following generalized tonic–clonic and complex partial seizures) were analyzed, since this period has been identified as the crucial time window for SUDEP. doi:10.1016/j.clinph.2015.04.247
P197. High-frequency oscillations (HFO, >500 Hz) in the intraoperative somatosensory evoked potential (SEP)—S. Burnos, O. Schmid, K. Niklaus, J. Sarnthein (UniverstitätsSpital Zürich, Klinik für Neurochirurgie, Zürich, Switzerland) Objective: The somatosensory evoked potential (SEP) of the medianus nerve elicits a N20 component and a high-frequency oscillation (HFO, >500 Hz). Here we investigate the feasibility of intraoperative subdural HFO recordings and the temporal and spatial relationship between N20 and HFO. Methods: During neurosurgical interventions in 7 anesthetized patients, the medianus SEP was recorded (11 recordings, 52 channels) from subdural electrode strips to localize the central sulcus. Depending on surgical restrictions, the strips were placed directly on sensory cortex or motor cortex or both. Results: The SEP response consisted of the two distinct spectral components N20 (<250 Hz) and HFO (721 ± 70 Hz) in the time–frequency domain. The HFO maximum amplitude appeared at the same or an adjacent electrode contact as the N20 maximum in 10 of 11 recordings. HFO amplitude was proportional to N20 amplitude over patients. The N20 amplitude decayed with a larger spatial extent (exponential space constant 5.2 ± 4.0 cm) than the HFO amplitude (2.4 ± 1.9 cm, p < 0.05). The HFO peak (21.4 ± 1.8 ms) preceded the N20 (23.2 ± 1.4 ms, p < 0.05) by up to 8 ms. Conclusions: HFOs in response to medianus stimulation can be recorded under conditions of anesthesia. Since we recorded highly localized HFO bursts, the HFO bursts must be of cortical origin even if they precede the N20 component. doi:10.1016/j.clinph.2015.04.248
Neurophysiology
P97. The pathophysiology of sudden unexpected death in epilepsy (SUDEP)—S. Lauxmann, Y. Weber, H. Lerche, H. Koch (UKT, Tübingen, Germany)
P122. Alpha1/theta ratio from quantitative EEG (qEEG) as a reliable marker for mild cognitive impairment (MCI) in patients with Parkinson’s disease (PD)—H. Bousleiman a,b, M. Chaturvedi a, U. Gschwandtner a, F. Hatz a, C. Schindler b, R. Zimmermann a, P. Fuhr a (a Universitätsspital Basel, Basel, Switzerland, b Swiss Tropical and Public Health Institute, Basel, Switzerland)
Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death in people suffering from chronic refractory epilepsy. The underlying pathophysiological mechanisms that are critically involved in SUDEP are still not well understood. Cardiac arrhythmia, depressed autonomic function after seizure activity and also seizure-related respiratory failure have been discussed to be part of the final cascade leading to SUDEP. This final cascade is thought to be triggered by the seizure activity resulting in dramatically elevated levels of epinephrine, norepinephrine as well as other regulatory hormones and neurotransmitters. However, not all cases of SUDEP are directly linked to a seizure suggesting that SUDEP is not an unitary event and most likely caused by multiple factors. We therefore analysed the respiratory patterns, heartbeat and arousals of patients in the epilepsy video-eeg monitoring unit (EMU), before and after the withdrawal of antiepileptic (AED). The frequency, variability of the breathing and heartbeat in correlation with the
Objective: We investigated whether a combination of qEEG variables, in particular signal power in the alpha1 (8–10 Hz) and theta (4–8 Hz) bands, could represent a robust marker for MCI in patients with PD. Background: MCI is diagnosed based on the results of a large standardized set of cognitive tests. Certain qEEG parameters are associated with dementia. Previous studies demonstrated a relation between MCI in PD patients and alpha1 power (Bousleiman et al., 2014). Other studies introduced a ratio between alpha and theta powers and demonstrated its association with Alzheimer’s disease (Schmidt et al., 2013). Methods: High-resolution 256-channel EEG were recorded in 43 PD patients (MCI/non-MCI: 18/25 jage: 68.1 ± 7.9j female/male: 16/27). The data was pre-processed semi-automatically and global relative power in alpha1 and theta bands was calculated. Follow-up recordings at four weeks (4W) and six months (6 M) were
Society Proceedings / Clinical Neurophysiology 126 (2015) e63–e170
reporter gene, the Bmal1 promoter-driven luciferase gene, using a lentiviral system. The luciferase activity showed a circadian rhythm of lumincescence expression. The individual period length over a time course of 5 days was detectable by measuring the bioluminescence every ten minutes in vitro. Previous studies had proven that the physiological period length of human circadian clock in vivo is directly proportional to period in human fibroblast. To test whether differences in the magnitude of oscillatory amplitude of the clock genes Bmal1, Per1 and Per2 might account for period and phase differences, we quantified the transcriptional gene expression of clock genes in dermal fibroblasts by a different method because the measurement of the bioluminescent oscillation of clock genes which is sensitive to the degree of viral infection is not suitable to quantify the transcriptional amplitude. Thus we measured RNA levels of clock genes by means of quantitative real-time PCR (qPCR) and complemented these data with the bioluminescence assay. Total RNA was extracted from fibroblast cell lines every 6 h over 72 h and totalRNA was reverse transcribed into cDNA followed by qPCR using the primer for the clock genes. Results: In fibroblasts from patients suffering from idiopathic hypersomnia clock gene expression exhibit a diminished amplitude of BMAL1 which was significantly reduced by 63% (P = 0.004) compared to healthy controls. The amplitude of PER1 was reduced by 45% (P = 0.048) compared to the control group so was the amplitude of PER2 reduced by 32% (P = 0.032). In the luciferase assay using the same fibroblast cell lines,an averaged period length of 24.6 h could be detected in dermal fibroblasts obtained from healthy volunteers. Conclusion: Due to the significantly diminished amplitude of clock gene expression in the group of idiopathic hypersomniacs, our data suggest a disturbed chronobiology as a heterogeneous aspect in a primary sleep disorder. The implementation of this combined strategy to measure the dynamics of clock gene expression permits a reliable assessment – in objective statistical terms – of both the period length and the absolute magnitude of oscillatory amplitude. The coupling of the circadian gene regulation with individual EEG-parameter following the principles of the two-process-model of sleep regulation can be a useful tool to quantify therapeutic agents and regimens modifying circadian disruption (e.g. period length, phase and amplitude of circadian rhythms) and to develop possible personalized therapeutic options. doi:10.1016/j.clinph.2015.04.246
sleep-stages were analysed. Moreover, the respiratory pattern peri-ictal (before and following generalized tonic–clonic and complex partial seizures) were analyzed, since this period has been identified as the crucial time window for SUDEP. doi:10.1016/j.clinph.2015.04.247
P197. High-frequency oscillations (HFO, >500 Hz) in the intraoperative somatosensory evoked potential (SEP)—S. Burnos, O. Schmid, K. Niklaus, J. Sarnthein (UniverstitätsSpital Zürich, Klinik für Neurochirurgie, Zürich, Switzerland) Objective: The somatosensory evoked potential (SEP) of the medianus nerve elicits a N20 component and a high-frequency oscillation (HFO, >500 Hz). Here we investigate the feasibility of intraoperative subdural HFO recordings and the temporal and spatial relationship between N20 and HFO. Methods: During neurosurgical interventions in 7 anesthetized patients, the medianus SEP was recorded (11 recordings, 52 channels) from subdural electrode strips to localize the central sulcus. Depending on surgical restrictions, the strips were placed directly on sensory cortex or motor cortex or both. Results: The SEP response consisted of the two distinct spectral components N20 (<250 Hz) and HFO (721 ± 70 Hz) in the time–frequency domain. The HFO maximum amplitude appeared at the same or an adjacent electrode contact as the N20 maximum in 10 of 11 recordings. HFO amplitude was proportional to N20 amplitude over patients. The N20 amplitude decayed with a larger spatial extent (exponential space constant 5.2 ± 4.0 cm) than the HFO amplitude (2.4 ± 1.9 cm, p < 0.05). The HFO peak (21.4 ± 1.8 ms) preceded the N20 (23.2 ± 1.4 ms, p < 0.05) by up to 8 ms. Conclusions: HFOs in response to medianus stimulation can be recorded under conditions of anesthesia. Since we recorded highly localized HFO bursts, the HFO bursts must be of cortical origin even if they precede the N20 component. doi:10.1016/j.clinph.2015.04.248
Neurophysiology
P97. The pathophysiology of sudden unexpected death in epilepsy (SUDEP)—S. Lauxmann, Y. Weber, H. Lerche, H. Koch (UKT, Tübingen, Germany)
P122. Alpha1/theta ratio from quantitative EEG (qEEG) as a reliable marker for mild cognitive impairment (MCI) in patients with Parkinson’s disease (PD)—H. Bousleiman a,b, M. Chaturvedi a, U. Gschwandtner a, F. Hatz a, C. Schindler b, R. Zimmermann a, P. Fuhr a (a Universitätsspital Basel, Basel, Switzerland, b Swiss Tropical and Public Health Institute, Basel, Switzerland)
Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death in people suffering from chronic refractory epilepsy. The underlying pathophysiological mechanisms that are critically involved in SUDEP are still not well understood. Cardiac arrhythmia, depressed autonomic function after seizure activity and also seizure-related respiratory failure have been discussed to be part of the final cascade leading to SUDEP. This final cascade is thought to be triggered by the seizure activity resulting in dramatically elevated levels of epinephrine, norepinephrine as well as other regulatory hormones and neurotransmitters. However, not all cases of SUDEP are directly linked to a seizure suggesting that SUDEP is not an unitary event and most likely caused by multiple factors. We therefore analysed the respiratory patterns, heartbeat and arousals of patients in the epilepsy video-eeg monitoring unit (EMU), before and after the withdrawal of antiepileptic (AED). The frequency, variability of the breathing and heartbeat in correlation with the
Objective: We investigated whether a combination of qEEG variables, in particular signal power in the alpha1 (8–10 Hz) and theta (4–8 Hz) bands, could represent a robust marker for MCI in patients with PD. Background: MCI is diagnosed based on the results of a large standardized set of cognitive tests. Certain qEEG parameters are associated with dementia. Previous studies demonstrated a relation between MCI in PD patients and alpha1 power (Bousleiman et al., 2014). Other studies introduced a ratio between alpha and theta powers and demonstrated its association with Alzheimer’s disease (Schmidt et al., 2013). Methods: High-resolution 256-channel EEG were recorded in 43 PD patients (MCI/non-MCI: 18/25 jage: 68.1 ± 7.9j female/male: 16/27). The data was pre-processed semi-automatically and global relative power in alpha1 and theta bands was calculated. Follow-up recordings at four weeks (4W) and six months (6 M) were