- Email: [email protected]
P219 Cortical excitability in Dystrophia Myotonica type 1
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Abstracts / Clinical Neurophysiology 128 (2017) e178–e303
stimulation (rTMS) over the left DLPFC in treating patients with primary chronic daily headaches (chronic tension type headache and chronic migraine). Methods: Twenty-seven patients participated in the study, divided into two groups: a study group (sixteen patients) and a control group (eleven patients). Treatment consisted of twelve high frequency (5 Hz) real rTMS sessions, delivered over the left DLPFC, every other day excluding weekends, whereas sham rTMS was used for the control group. Measures of attack frequency, headache intensity and headache index were recorded before and after treatment. Results: Patients of the study group, after real rTMS stimulation, showed a high statistically significant reduction of the measured headache parameters compared to the control group (Pvalue < 0.001) and the percentage of improvement was 94.5%. No significant reduction of headache parameters, after sham rTMS stimulation, was observed in the control group (P-value > 0.05) and percentage of improvement was 7.9%. Discussion: Results came in agreement with most of other studies done in this field. Conclusion: High-frequency rTMS is effective in reducing chronic tension headache and chronic migraine. Significance: This finding runs with the approval of the suggested role of DLPFC in pain control. This might open opinions for new treatment strategies in tension type headache and migraine prevention. Keywords: Repetitive transcranial magnetic stimulation (rTMS), Chronic tension type headache (CTTH), Chronic migraine (CM) doi:10.1016/j.clinph.2017.07.224
P217 Serum metabolic profile of creatine correlates with repeated motor evoked potentials: A study on TMS-induced repetition suppression—Elisa Kallioniemi 1, Olli Kärkkäinen 2, Sara Määttä 1, Mervi Könönen 1, Petri Kivimäki 3, Outi Kaarre 4, Virve Kekkonen 4, Eila Laukkanen 4, Tommi Tolmunen 4 (1 Kuopio University Hospital, Department of Clinical Neurophysiology, Kuopio, Finland, 2 University of Eastern Finland, School of Pharmacy, Kuopio, Finland, 3 University of Eastern Finland, School of Medicine, Kuopio, Finland, 4 Kuopio University Hospital, Department of Adolescent Psychiatry, Kuopio, Finland) Objectives: The motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) mainly reflect the electrophysiological characteristics of the motor system. Although the MEP amplitude is a peripheral response, it can be applied to study several neural phenomena, such as repetition suppression (RS). In RS, a train of TMS pulses is repeated and the induced MEP amplitudes suppress after the first MEP. RS is suggested to be a general response of the brain to repeated stimuli. When measuring the RS, the peripheral muscles contract frequently and thereby in this study, we evaluated whether RS is influenced by the muscle metabolism. Methods: The metabolic profiles of 73 subjects (37 females) were measured from serum samples and TMS was targeted on the cortical representation of the right abductor pollicis brevis muscle on the primary motor cortex. The RS protocol included repeating trains of 4 pulses at 110% of the resting motor threshold with a 1s interstimulus interval and 20s inter-train interval. Results: Serum creatine levels were found to correlate negatively with the magnitude of RS (r = 0.43, p = 0.2). Discussion: Creatine is an important metabolite relating to energy requiring situations in the muscles. Therefore, the results suggest that large amounts of fast energy reservoir may be needed to keep up the muscle contraction in response to repeated TMS pulses.
Conclusions: Subjects with different metabolic profiles of creatine responded differently to repeated TMS pulses. Significance: The possible influence of different individual metabolic profiles on repeated MEPs should be taken into account in TMS motor paradigms involving pulse repetition. Keywords: Transcranial magnetic stimulation, Motor evoked response, Metabolomics, Creatine doi:10.1016/j.clinph.2017.07.225
P218 Motor cortical adaptation to external stimuli is altered in unverricht-lundborg type myoclonus epilepsy—Petro Julkunen 1, Olli Löfberg 1, Elisa Kallioniemi 1, Reetta Kälviäinen 2, Esa Mervaala 1 (1 Kuopio University Hospital, Department of Clinical Neurophysiology, Kuopio, Finland, 2 Kuopio University Hospital, Department of Neurology, Kuopio, Finland) Objectives: Unverricht-Lundborg disease, or progressive myoclonus epilepsy type 1 (EPM1), affects cortical excitability and inhibition, and neuroanatomy of the thalamocortical system. Stimulus sensitive myoclonus with potentially disabling features associates with EPM1. Our objective was to assess neurophysiological adaptation in EPM1 to further understand the role of the impaired thalamocortical system in the characteristic features of the disease. Methods: Eight EPM1 patients and 10 controls were studied using navigated transcranial magnetic stimulation (nTMS). We studied adaptation of motor cortex to excitatory external stimuli using nTMS with repetition suppression (RS) study-protocol adapted from our previous study [1]. Results: We found that the reactivity and adaptation to external stimuli was highly abnormal in EPM1 patients compared to healthy controls. EPM1 group exhibited no RS effect (F = 1.07, p = 0.385), while such effect was observed in controls (F = 53.01, p < 0:001). In controls, the RS effect was seen as 50–55% reduction in motor evoked potentials of the right hand after the first stimulus in RS stimulus protocol. Conclusions: Neural processing of stimuli received by the motor cortex is severely impaired in EPM1. This may be due to anatomic changes seen in the thalamocortical system, potentially impairing connective control between the thalamic nuclei and the cortex. Significance: The abnormal adaption to external stimuli observed in the present study may contribute to the expression of the EPM1’s motor symptoms. This study helps to further understand the neurophysiological appearance of EPM1 in common neural functions. Keywords: Transcranial magnetic stimulation, Epilepsy References Löfberg O et al. Neuroscience 2013. doi:10.1016/j.clinph.2017.07.226
P219 Cortical excitability in Dystrophia Myotonica type 1—Vildan Yayla 1, Arsida Bajrami 1, Filiz Azman 2, Nejla Sozer 1, Sultan Cagirici 3 (1 Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Department of Clinical Neurophysiology and Neurology, Istanbul, Turkey, 2 Sirnak State Hospital, Department of Neurology, Sirnak, Turkey, 3 Denizli Servergazi State Hospital, Department of Neurology, Denizli, Turkey)
Abstracts / Clinical Neurophysiology 128 (2017) e178–e303
Objectives: Dystrophia Myotonica type 1 (DM1) is characterized by distal muscle weakness, atrophy, myotonia and CNS involvement. Electrophysiological assessment of CNS involvement in DM1 patient refers to multimodal evoked potential studies. Herein we investigated the function of central motor pathways in DM1 patients by transcranial magnetic stimulation (TMS) and the possible relationships with disease duration, muscular impairment and MRI findings. Methods: Eight right-handed DM1 patients and 10 healthy adult volunteers (control group) were included in the study. Fazekas scale was used to quantify the amount of white matter lesion (WMLs) in MRI performed to all DM1 patients. TMS test battery consisted of AMT, RMT, central conduction time (CCT), cortical silent period (SP), and paired-pulse TMS paradigm. Results: Mean age and disease durations of patients’ were 37.2 and 7.02 years, respectively. WMLs were found in 62.5% of the patients. There were no significant differences between DM1 and control group in terms of AMT, RMT and SP (p 6 0.05). DM1 cases showed statistically significant lower long interval intracortical inhibitions (LICI) as compared to the control group. Discussion: The number of cortical excitability studies in neuromuscular and especially DM1 patients is limited. In this study, lower LICI in DM1 patients suggests that cortical excitability in these patients is less inhibited. Also, WML incidence in DM1 patients was found relatively high. The nature, significance and relationship of these findings can be investigated further by different cohorts and TMS protocols. Conclusion: TMS might help demonstrate the nature of CNS involvements. Significance: Cortical excitability changes in DM1. Keywords: Dystrophia Myotonica type 1, Transcranial magnetic stimulation, White matter lesion doi:10.1016/j.clinph.2017.07.227
P220 Extraction and decoding of vagus nerve mediated blood pressure and respiratory information for bioelectronic medicine purposes—Cristian Sevcencu, T.N. Nielsen, J.J. Struijk (Aalborg University, Department of Health Science and Technology, Aalborg, Denmark) Objectives: The bioelectronic medicines are envisioned as implantable devices treating impaired functions by closed-loop (CL) stimulation of nerves involved in regulation of those functions. One application of such devices could be the treatment of hypertension and an ideal target for this usage is the left vagus nerve (LVN). Indeed, whereas it is well-known that LVN stimulation (LVNS) results in decrease of blood pressure (BP), we here define an antihypertensive CL-LVNS system which uses LVN-mediated BP signals and respiratory signals to adapt this therapy to the actual BP and physical activity of the patients. Methods: In anesthetized pigs, BP and respiratory signals were recorded from the LVN with cuff electrodes, the BP waves with carotid catheters and the respiratory cycles (RCs) with pressure transducers attached to the system ventilating those pigs. Results & discussion: Calculating the power of the BP- and RCrelated LVN signals resulted in neural profiles resembling the BP and RC waveforms and comprising full information on BP and ventilatory changes, respectively. Those neural waveforms could thus be implemented in an ideal CL-LVNS system for BP control in
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hypertensive patients to monitor the BP and physical activity of those patients and drive that system accordingly. Further acute and chronic experiments with a prototype CL-LVNS system are necessary to validate this principle scheme of action of such a system. Conclusions & significance: A bioelectronic medicine for treating hypertension by CL-LVNS may be in reach. Keywords: Bioelectronic medicine, Vagus nerve, Blood pressure, Respiration doi:10.1016/j.clinph.2017.07.228
P222 Diagnostic and therapeutic possibilities of transcranial magnetic stimulation in patients after traumatic brain injury— Miroslav Kopachka 1, Elena Troshina 1, Elena Sharova 2, Oleg Zaitsev 3, Marina Chelyapina 2, Lubov Oknina 2 (1 Federal State Autonomous Institution «N.N. Burdenko National Scientific and Practical Center for Neurosurgery» the Ministry of Healthcare of the Russian Federation, Clinical Neurophysiology, Moscow, 2 Russia, Institute of Higher Nervous Activity and Neurophysiology of RAS (IHNA&NPh RAS), Clinical Neurophysiology, Moscow, Russia, 3 Federal State Autonomous Institution «N.N. Burdenko National Scientific and Practical Center for Neurosurgery» the Ministry of Healthcare of the Russian Federation, Department of Psychiatry, Moscow, Russia) Objectives: Recovery of both mental and motor functions is one of the key problems of neurorehabilitation of patients with traumatic brain injury (TBI), accompanied by posttraumatic unconsciousness state (PUS). The purpose of pilot study is to clarify the diagnostic and therapeutic potential of TMS in patients after TBI with impaired motor activity and consciousness. Methods: Observation groups: (1) 15 patients after TBI at the age of 17–56, in which the diagnostic TMS (cortical motor areas (M1) bilaterally, CVII bilaterally, registration of MEPs from musculus abductor pollicis brevis) was performed; (2) 9 patients after TBI at the age of 16–44 with a prolonged (from 60 to 220 days) unconscious state in which the rhythmic TMS was performed; (3) Control group: 5 healthy men aged 22–28. Diagnostic TMS evaluated cortical, radicular latency and amplitude of MEPs,time of central motor conduction. In the second and third groups changes of neurological status, indicators of the memory and attention, and N100, N200 and P300 components of auditory ERP hour before and hour after stimulation were estimated. Results: Diagnostic TMS in patients with positive or ambiguous clinical dynamics showed initial difference of conductivity of tracts in comparison with normal data by 20–30% or 30–40%, respectively, with progressive improvement as motor and cognitive functions recovered. In patients with negative clinical dynamics TMS values had significantly larger deviation of cortical latency and amplitudes of MEPs (over 45%), and also the time of central motor conduction. Statistical analysis of acquired data revealed the greatest prognostic significance for determining the level of the amplitudes of MEPs with undeniable importance for the indicators of cortical latency and the time of central motor conduction. Therapeutic TMS of the sagittal premotor cortex areas in groups 2 and 3 concurred with improvement of any attention and normalization of amplitude and latency of all ERP components, as well as indicators of their spatial synchronism, especially for P300.
Abstracts / Clinical Neurophysiology 128 (2017) e178–e303
stimulation (rTMS) over the left DLPFC in treating patients with primary chronic daily headaches (chronic tension type headache and chronic migraine). Methods: Twenty-seven patients participated in the study, divided into two groups: a study group (sixteen patients) and a control group (eleven patients). Treatment consisted of twelve high frequency (5 Hz) real rTMS sessions, delivered over the left DLPFC, every other day excluding weekends, whereas sham rTMS was used for the control group. Measures of attack frequency, headache intensity and headache index were recorded before and after treatment. Results: Patients of the study group, after real rTMS stimulation, showed a high statistically significant reduction of the measured headache parameters compared to the control group (Pvalue < 0.001) and the percentage of improvement was 94.5%. No significant reduction of headache parameters, after sham rTMS stimulation, was observed in the control group (P-value > 0.05) and percentage of improvement was 7.9%. Discussion: Results came in agreement with most of other studies done in this field. Conclusion: High-frequency rTMS is effective in reducing chronic tension headache and chronic migraine. Significance: This finding runs with the approval of the suggested role of DLPFC in pain control. This might open opinions for new treatment strategies in tension type headache and migraine prevention. Keywords: Repetitive transcranial magnetic stimulation (rTMS), Chronic tension type headache (CTTH), Chronic migraine (CM) doi:10.1016/j.clinph.2017.07.224
P217 Serum metabolic profile of creatine correlates with repeated motor evoked potentials: A study on TMS-induced repetition suppression—Elisa Kallioniemi 1, Olli Kärkkäinen 2, Sara Määttä 1, Mervi Könönen 1, Petri Kivimäki 3, Outi Kaarre 4, Virve Kekkonen 4, Eila Laukkanen 4, Tommi Tolmunen 4 (1 Kuopio University Hospital, Department of Clinical Neurophysiology, Kuopio, Finland, 2 University of Eastern Finland, School of Pharmacy, Kuopio, Finland, 3 University of Eastern Finland, School of Medicine, Kuopio, Finland, 4 Kuopio University Hospital, Department of Adolescent Psychiatry, Kuopio, Finland) Objectives: The motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) mainly reflect the electrophysiological characteristics of the motor system. Although the MEP amplitude is a peripheral response, it can be applied to study several neural phenomena, such as repetition suppression (RS). In RS, a train of TMS pulses is repeated and the induced MEP amplitudes suppress after the first MEP. RS is suggested to be a general response of the brain to repeated stimuli. When measuring the RS, the peripheral muscles contract frequently and thereby in this study, we evaluated whether RS is influenced by the muscle metabolism. Methods: The metabolic profiles of 73 subjects (37 females) were measured from serum samples and TMS was targeted on the cortical representation of the right abductor pollicis brevis muscle on the primary motor cortex. The RS protocol included repeating trains of 4 pulses at 110% of the resting motor threshold with a 1s interstimulus interval and 20s inter-train interval. Results: Serum creatine levels were found to correlate negatively with the magnitude of RS (r = 0.43, p = 0.2). Discussion: Creatine is an important metabolite relating to energy requiring situations in the muscles. Therefore, the results suggest that large amounts of fast energy reservoir may be needed to keep up the muscle contraction in response to repeated TMS pulses.
Conclusions: Subjects with different metabolic profiles of creatine responded differently to repeated TMS pulses. Significance: The possible influence of different individual metabolic profiles on repeated MEPs should be taken into account in TMS motor paradigms involving pulse repetition. Keywords: Transcranial magnetic stimulation, Motor evoked response, Metabolomics, Creatine doi:10.1016/j.clinph.2017.07.225
P218 Motor cortical adaptation to external stimuli is altered in unverricht-lundborg type myoclonus epilepsy—Petro Julkunen 1, Olli Löfberg 1, Elisa Kallioniemi 1, Reetta Kälviäinen 2, Esa Mervaala 1 (1 Kuopio University Hospital, Department of Clinical Neurophysiology, Kuopio, Finland, 2 Kuopio University Hospital, Department of Neurology, Kuopio, Finland) Objectives: Unverricht-Lundborg disease, or progressive myoclonus epilepsy type 1 (EPM1), affects cortical excitability and inhibition, and neuroanatomy of the thalamocortical system. Stimulus sensitive myoclonus with potentially disabling features associates with EPM1. Our objective was to assess neurophysiological adaptation in EPM1 to further understand the role of the impaired thalamocortical system in the characteristic features of the disease. Methods: Eight EPM1 patients and 10 controls were studied using navigated transcranial magnetic stimulation (nTMS). We studied adaptation of motor cortex to excitatory external stimuli using nTMS with repetition suppression (RS) study-protocol adapted from our previous study [1]. Results: We found that the reactivity and adaptation to external stimuli was highly abnormal in EPM1 patients compared to healthy controls. EPM1 group exhibited no RS effect (F = 1.07, p = 0.385), while such effect was observed in controls (F = 53.01, p < 0:001). In controls, the RS effect was seen as 50–55% reduction in motor evoked potentials of the right hand after the first stimulus in RS stimulus protocol. Conclusions: Neural processing of stimuli received by the motor cortex is severely impaired in EPM1. This may be due to anatomic changes seen in the thalamocortical system, potentially impairing connective control between the thalamic nuclei and the cortex. Significance: The abnormal adaption to external stimuli observed in the present study may contribute to the expression of the EPM1’s motor symptoms. This study helps to further understand the neurophysiological appearance of EPM1 in common neural functions. Keywords: Transcranial magnetic stimulation, Epilepsy References Löfberg O et al. Neuroscience 2013. doi:10.1016/j.clinph.2017.07.226
P219 Cortical excitability in Dystrophia Myotonica type 1—Vildan Yayla 1, Arsida Bajrami 1, Filiz Azman 2, Nejla Sozer 1, Sultan Cagirici 3 (1 Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Department of Clinical Neurophysiology and Neurology, Istanbul, Turkey, 2 Sirnak State Hospital, Department of Neurology, Sirnak, Turkey, 3 Denizli Servergazi State Hospital, Department of Neurology, Denizli, Turkey)
Abstracts / Clinical Neurophysiology 128 (2017) e178–e303
Objectives: Dystrophia Myotonica type 1 (DM1) is characterized by distal muscle weakness, atrophy, myotonia and CNS involvement. Electrophysiological assessment of CNS involvement in DM1 patient refers to multimodal evoked potential studies. Herein we investigated the function of central motor pathways in DM1 patients by transcranial magnetic stimulation (TMS) and the possible relationships with disease duration, muscular impairment and MRI findings. Methods: Eight right-handed DM1 patients and 10 healthy adult volunteers (control group) were included in the study. Fazekas scale was used to quantify the amount of white matter lesion (WMLs) in MRI performed to all DM1 patients. TMS test battery consisted of AMT, RMT, central conduction time (CCT), cortical silent period (SP), and paired-pulse TMS paradigm. Results: Mean age and disease durations of patients’ were 37.2 and 7.02 years, respectively. WMLs were found in 62.5% of the patients. There were no significant differences between DM1 and control group in terms of AMT, RMT and SP (p 6 0.05). DM1 cases showed statistically significant lower long interval intracortical inhibitions (LICI) as compared to the control group. Discussion: The number of cortical excitability studies in neuromuscular and especially DM1 patients is limited. In this study, lower LICI in DM1 patients suggests that cortical excitability in these patients is less inhibited. Also, WML incidence in DM1 patients was found relatively high. The nature, significance and relationship of these findings can be investigated further by different cohorts and TMS protocols. Conclusion: TMS might help demonstrate the nature of CNS involvements. Significance: Cortical excitability changes in DM1. Keywords: Dystrophia Myotonica type 1, Transcranial magnetic stimulation, White matter lesion doi:10.1016/j.clinph.2017.07.227
P220 Extraction and decoding of vagus nerve mediated blood pressure and respiratory information for bioelectronic medicine purposes—Cristian Sevcencu, T.N. Nielsen, J.J. Struijk (Aalborg University, Department of Health Science and Technology, Aalborg, Denmark) Objectives: The bioelectronic medicines are envisioned as implantable devices treating impaired functions by closed-loop (CL) stimulation of nerves involved in regulation of those functions. One application of such devices could be the treatment of hypertension and an ideal target for this usage is the left vagus nerve (LVN). Indeed, whereas it is well-known that LVN stimulation (LVNS) results in decrease of blood pressure (BP), we here define an antihypertensive CL-LVNS system which uses LVN-mediated BP signals and respiratory signals to adapt this therapy to the actual BP and physical activity of the patients. Methods: In anesthetized pigs, BP and respiratory signals were recorded from the LVN with cuff electrodes, the BP waves with carotid catheters and the respiratory cycles (RCs) with pressure transducers attached to the system ventilating those pigs. Results & discussion: Calculating the power of the BP- and RCrelated LVN signals resulted in neural profiles resembling the BP and RC waveforms and comprising full information on BP and ventilatory changes, respectively. Those neural waveforms could thus be implemented in an ideal CL-LVNS system for BP control in
e249
hypertensive patients to monitor the BP and physical activity of those patients and drive that system accordingly. Further acute and chronic experiments with a prototype CL-LVNS system are necessary to validate this principle scheme of action of such a system. Conclusions & significance: A bioelectronic medicine for treating hypertension by CL-LVNS may be in reach. Keywords: Bioelectronic medicine, Vagus nerve, Blood pressure, Respiration doi:10.1016/j.clinph.2017.07.228
P222 Diagnostic and therapeutic possibilities of transcranial magnetic stimulation in patients after traumatic brain injury— Miroslav Kopachka 1, Elena Troshina 1, Elena Sharova 2, Oleg Zaitsev 3, Marina Chelyapina 2, Lubov Oknina 2 (1 Federal State Autonomous Institution «N.N. Burdenko National Scientific and Practical Center for Neurosurgery» the Ministry of Healthcare of the Russian Federation, Clinical Neurophysiology, Moscow, 2 Russia, Institute of Higher Nervous Activity and Neurophysiology of RAS (IHNA&NPh RAS), Clinical Neurophysiology, Moscow, Russia, 3 Federal State Autonomous Institution «N.N. Burdenko National Scientific and Practical Center for Neurosurgery» the Ministry of Healthcare of the Russian Federation, Department of Psychiatry, Moscow, Russia) Objectives: Recovery of both mental and motor functions is one of the key problems of neurorehabilitation of patients with traumatic brain injury (TBI), accompanied by posttraumatic unconsciousness state (PUS). The purpose of pilot study is to clarify the diagnostic and therapeutic potential of TMS in patients after TBI with impaired motor activity and consciousness. Methods: Observation groups: (1) 15 patients after TBI at the age of 17–56, in which the diagnostic TMS (cortical motor areas (M1) bilaterally, CVII bilaterally, registration of MEPs from musculus abductor pollicis brevis) was performed; (2) 9 patients after TBI at the age of 16–44 with a prolonged (from 60 to 220 days) unconscious state in which the rhythmic TMS was performed; (3) Control group: 5 healthy men aged 22–28. Diagnostic TMS evaluated cortical, radicular latency and amplitude of MEPs,time of central motor conduction. In the second and third groups changes of neurological status, indicators of the memory and attention, and N100, N200 and P300 components of auditory ERP hour before and hour after stimulation were estimated. Results: Diagnostic TMS in patients with positive or ambiguous clinical dynamics showed initial difference of conductivity of tracts in comparison with normal data by 20–30% or 30–40%, respectively, with progressive improvement as motor and cognitive functions recovered. In patients with negative clinical dynamics TMS values had significantly larger deviation of cortical latency and amplitudes of MEPs (over 45%), and also the time of central motor conduction. Statistical analysis of acquired data revealed the greatest prognostic significance for determining the level of the amplitudes of MEPs with undeniable importance for the indicators of cortical latency and the time of central motor conduction. Therapeutic TMS of the sagittal premotor cortex areas in groups 2 and 3 concurred with improvement of any attention and normalization of amplitude and latency of all ERP components, as well as indicators of their spatial synchronism, especially for P300.