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P 124 Auricular vagus nerve stimulation in subjects with major depression – Pulsatile vs. continuous stimulation
Abstracts / Clinical Neurophysiology 128 (2017) e305–e412
Introduction: Sleep onset REM periods (SOREMP) and sleep latency on the Multiple Sleep Latency Test (MSLT) are crucial to distinguish narcolepsy from other conditions with excessive daytime sleepiness (EDS) but SOREMP may also be found in behaviorally induced inadequate sleep syndrome (BIIS), sleep deprivation, and circadian rhythm disorders. Sleep stage sequence analysis in MSLT recordings has been reported to be useful in identifying patients with narcolepsy. We aimed to confirm this hypothesis in a large cohort with special regard to HLA haplotype and CSF hypocretin (Hcrt) levels. Patients and methods: 458 patients with EDS (and sleepdisordered breathing/SDB excluded) underwent nocturnal polysomnography (PSG) and MSLT. Hcrt was measured in 181 patients, and HLA haplotyping results were available in 254 individuals. A total of 1887 naps was recorded containing 272 SOREMP. Results: Mean age was 36.2 (13.5) years, and 57.4% of patients were female. According to ICSD-3 criteria, 47 patients were diagnosed with type 1 narcolepsy (NL1), 30 individuals with type 2 narcolepsy (NL2), 78 patients with idiopathic hypersomnia, 9 with BIIS, 11 with circadian rhythm disorders, and 70 with other sleep disorders such as NREM parasomnia, insomnia, periodic limb movements, or unexpected SDB. Secondary CNS hypersomnia was diagnosed in 16 patients, 67 patients had hypersomnia associated with a psychiatric disorder, and in 102 participants, EDS was unexplained. SOREMP arising from sleep stage N1 (N1-SOREMP) was extremely rare in non-narcoleptic patients (n = 2), but was present in 45.5% of patients with narcolepsy. The number of N1-SOREMP was significantly higher in patients with NL1 than with NL2. 42.1% of SOREMP in the NL1 group arose from N1 compared to 15.5% in the NL2 group. In patients with narcolepsy, the number of N1-SOREMP showed negative correlation with Hcrt levels, mean sleep latency on MSLT, and REM latency on PSG. Furthermore, it was significantly associated with HLA DQB1*06:02. N1-SOREMP occurred in 69% patients with Hcrt <110 pg/ml but in only 17% of patients with Hcrt >110 pg/ml. Conclusion: Both occurance and frequency of SOREMP arising from sleep stage N1 have high sensitivity for the diagnosis of narcolepsy and type 1 narcolepsy, in particular. The number of N1-SOREMP appears to be a marker of disease severity or instability of REM sleep, respectively. Sleep stage sequence analysis of SOREMP periods may support phenotyping of patients with central disorders of hypersomnolence. doi:10.1016/j.clinph.2017.06.194
Poster P 122 Stimulus-responsive myoclonic jerks of both levator palpebrae muscles in a comatose survivor of cardiopulmonary resuscitation may pretended awareness—F. Thömke (Klinikum Worms, Worms, Germany)
Comatose survivors of cardiopulmonary resuscitation (CPR), who develop myoclonus within 1–2 days after CPR, usually have a poor prognosis. Typically, such myoclonus occurs or increases on sensory stimuli like touching the patient or acoustic stimuli. Myclonic jerks mainly occur in the muscles of the face, shoulder girdle and diaphragm. Sometimes, such jerks may be restricted to one muscle like the diaphragm leading to hiccups. We report one comatose survivor of CPR with stimulus-sensitive myoclonus, which was restricted to both levator palpebrae muscles leading to eye opening on acoustic stimulation and by doing so pretending awareness. Report of a case: A 76-year-old female survivor of CPR opened her eyes on acoustic or sensory stimuli followed by a short period of
e389
blinking, which pretended awareness. EEG documented polymorph spike-slow waves after acoustic stimuli and was otherwise flat. Eye opening and blinking were coupled to spike-slow waves discharges and interpreted as restricted myoclonus of the levator palpebare muscles. This was a transient phenomenon for 24 h, and after another day, the patient was brain dead. Conclusion: Early myoclonus in comatose survivors of a CPR usually indicate a poor prognosis, although recent data indicate, that patients with focal myoclonus may have a better prognosis than those with more generalized myoclonus. Bouwes et al. (2012) reported a good outcome in 8 of 48 patients with focal myoclonus compared to 1 of 31 with generalized myoclonus. As shown by our patient, focal or restricted stimulus-sensitive myoclonus may pretend awareness and causes diagnostic problems, which can be solved by EEG. doi:10.1016/j.clinph.2017.06.195
Poster P 123 Prefrontal transcranial magnetic stimulation in children with attention deficit/hyperactivity disorder (ADHD)—S. Bender (Uniklinik Köln, Kinder- und Jugendpsychiatrie, Köln, Germany)
Background: Attention deficit/ hyperactivity disorder (ADHD) is characterized by a preference of immediate over delayed rewards. 1 Hz inhibitory repetitive transcranial magentic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) has been shown to influence decisions of reward preference in adult subjects towards smaller immediate rewards. Methods: Here we examine the effects of high frequency (excitatory) DLPFC rTMS in a small sample of adult subjects with ADHD. A delay discounting task was applied before and after rTMS. Results: After rTMS the preference of subjects with ADHD was changed in a marginally significant way towards larger but more delayed rewards compared to sham stimulation. Discussion/Significance: These are pilot data which encourage further research on whether rTMS is not only able to discrupt the cortical circuits involved in attentional top-down control and the ability to wait longer times for larger rewards, but whether rTMS is able to both decrease as well as increase cortical excitability leading to different behavioral effects. Such behavioral effects could represent a clinically valuable therapeutic tool. However, a replication of our finding is needed in a larger independent sample. doi:10.1016/j.clinph.2017.06.196
Poster P 124 Auricular vagus nerve stimulation in subjects with major depression – Pulsatile vs. continuous stimulation—T. Polak, M. Götzelmann, A. Katzorke, J.B. M. Zeller, M.J. Herrmann (Universitätsklinikum Würzburg, Klinik für Psychiatrie, Psychosomatik und Psychotherapie, Würzburg, Germany)
Background: Conventional vagus nerve stimulation (cVNS) is approved to treat major depression. Within this context, auricular VNS (aVNS) is of increasing interest due to its non-invasiveness. Still, the question of optimum stimulation parameters has to be solved.
e390
Abstracts / Clinical Neurophysiology 128 (2017) e305–e412
Method: 50 subjects with major depressive disorder were stimulated over 20 min. in the area of the auricular branch of the vagus nerve. Control stimulation (CS) was done at the ear lobe. Before and after each stimulation the participants were asked to rate their actual affective state. 30 participants were stimulated continuously, while in 20 subjects, stimulation was interrupted every 5 min. for 30 s. (pulsatile stimulation). Results: Only using pulsatile stimulation, participants significantly more often rated to feel better (F1;18 ¼ 12:35; p = 0.002) and to be more optimistic (F1;18 ¼ 12:24; p = 0.003) after aVNS than after CS. Using pulsatile as well as using continuous stimulation, subjects indicated to be more happy (F1;18 ¼ 24:61; p < 0.001 and F1;28 ¼ 8:03; p = 0.008, resp.). Rating of pictures of the Internatonal Affective Picture System (IAPS) showed no statistical significant difference between the stimulation methods. Conclusion: Stimulating in a pulsatile way showed more difference between aVNS and CS than stimulating in a continuous way. Self rating of the emotional state by means of a visual analogue scale seems to be a reliable tool for the examination of non-invasive stimulation techniques. doi:10.1016/j.clinph.2017.06.197
Conclusion: Consistent with the literature, our patients showed severe drug-resistant epilepsies with an electro-clinical complex of a fronto-temporal epilepsy with frequent, long-lasting or continuous subclinical seizure patterns and/or NCSE. Rhythmic theta as a ‘‘characteristic” EEG pattern was, however, only observed in 2/4 of our patients. Therefore, a rchr20es should be suspected in such patients also in the absence of this EEG feature. This information will help in an early identification of rchr20es, which is especially important since, without this specific diagnosis, many affected patients are considered candidates for pre-surgical diagnostics or even epilepsy surgery. doi:10.1016/j.clinph.2017.06.198
Poster P 126 Congruence of first out-patient routine EEG and in-patient EEG diagnostics in a specialized epilepsy center—B. Steinhoff *, M. Bacher, T. Intravooth, J. Stockinger, A. Staack (Epilepsiezentrum Kork, Kehl-Kork, Germany) ⇑
Poster P 125 Ring chromosome 20 Epilepsy syndrome in children Variable EEG- and electro-clinical pattern—A. Eger 1,*, T. Pieper 2, G. Kluger 3, U. Koehler 3, T. Herberhold 2, A. Zsoter 2, H. Holthausen 2, M. Staudt 2 (1 Städtisches Klinikum Dessau, Klinik für Kinder- und Jugendmedizin, Dessau, Germany, 2 Schön Klinik Vogtareuth, Epilepsiezentrum für Kinder und Jugendliche, Klinik für Neuropädiatrie und Neurologische Rehabilitation, Vogtareuth, Germany, 3 MGZ Medizinisch Genetisches Zentrum München, Zytogenetik, Microarray-Diagnostik, München, Germany) ⇑
Corresponding author.
Background: Children with ring chromosome 20 epilepsy syndrome (rchr20es) typically show severe, drug-resistant focal epilepsies characterized by frontal semiology, high susceptibility for non-convulsive status epilepticus (NCSE) and epilepsyassociated cognitive and behavioral deteriorations. EEG has been reported to show frequent or continuous subclinical seizure patterns together with characteristic rhythmic theta waves (Caneveni et al. 1998). Here, we report on clinical and EEG data in four patients. Patients and methods: Retrospective analysis of clinical and videoEEG-long-term-monitoring data of four patients (all female) with rchr20es. Age at onset of epilepsy ranged from 5 to 8 years, the number of antiepileptic drugs already used ranged from 6 to 10, and all four patients had suffered NCSE previously. Semiology: all four patients showed auras (epigastric: 2, fear: 2, visual: 1, somatosensory: 1) and seizures (hypermotor: 3, tonic: 3, dialeptic: 2, psychomotor: 2). Clinical epilepsy syndromes were frontal lobe epilepsies (n = 3) and frontal/ temporal lobe epilepsy (n = 1). EEG showed regional abnormalities in frontal (n = 4), temporal (n = 3) and parieto-occiptal (n = 1) areas, with subclinical seizure patterns and/ or EEG-status elements (with serial spikes, polyspikes, sharp waves, or spike wave complexes; n = 3), rhythmic theta (n = 2), 1–2 Hz slow sharp wave complexes (n = 1), spike wave complexes/low amplitude fast activity +high amplitude delta burst (n = 1), alpha/theta seizure activity (n = 1). MRI was essentially normal in all patients, with minor abnormalities in frontal (2) or temporal areas (2).
Corresponding author.
Background/Objective: In our epilepsy center we always perform a routine EEG in out-patients who are referred for the first time. We investigated in how many cases additional EEG diagnostics including long-term video EEG delivered additional clinically relevant information if in-patient diagnostics followed. Methods: We retrospectively assessed, how many out-patients seen for the first time were admitted to a hospital stay. In these cases we compared the EEG findings of the initial out-patient routine EEG with the in-patient data including long-term video EEG. Results: Total number of out-patients was 77. Ten patients (13%) were hospitalized with the purpose of a better diagnostic classification. In 4 of 10 epilepsy cases we found confirming epileptiform discharges in the long-term video EEG that had not been recording with the initial routine EEG. In one patient we found a normal variant where epileptiform discharges had been falsely supposed in the routine EEG. In the remaining cases no clinically relevant further information was obtained. Discussion/Conclusions: Additional hospitalizations are usually not necessary after out-patient visits of new referrals to a specialized epilepsy center. In half of these hospitalized patients additional EEG diagnostics beyond routine EEG render clinically relevant additional information. doi:10.1016/j.clinph.2017.06.199
Poster P 127 Vigilance regulation in adult ADHD—M. Strauß *, M. Paucke, C. Sander, U. Hegerl (Universitätsklinikum Leipzig AöR, Klinik für Psychiatrie und Psychotherapie, 04103, Germany) ⇑
Corresponding author.
Background: Functional regulation of vigilance or wakefulness is crucial for interaction with the environment and can be described as a unique, situation-dependent characteristic. Disorders of wakefulness regulation manifest themselves as delayed or rash declines in vigilance under calm settings.
Introduction: Sleep onset REM periods (SOREMP) and sleep latency on the Multiple Sleep Latency Test (MSLT) are crucial to distinguish narcolepsy from other conditions with excessive daytime sleepiness (EDS) but SOREMP may also be found in behaviorally induced inadequate sleep syndrome (BIIS), sleep deprivation, and circadian rhythm disorders. Sleep stage sequence analysis in MSLT recordings has been reported to be useful in identifying patients with narcolepsy. We aimed to confirm this hypothesis in a large cohort with special regard to HLA haplotype and CSF hypocretin (Hcrt) levels. Patients and methods: 458 patients with EDS (and sleepdisordered breathing/SDB excluded) underwent nocturnal polysomnography (PSG) and MSLT. Hcrt was measured in 181 patients, and HLA haplotyping results were available in 254 individuals. A total of 1887 naps was recorded containing 272 SOREMP. Results: Mean age was 36.2 (13.5) years, and 57.4% of patients were female. According to ICSD-3 criteria, 47 patients were diagnosed with type 1 narcolepsy (NL1), 30 individuals with type 2 narcolepsy (NL2), 78 patients with idiopathic hypersomnia, 9 with BIIS, 11 with circadian rhythm disorders, and 70 with other sleep disorders such as NREM parasomnia, insomnia, periodic limb movements, or unexpected SDB. Secondary CNS hypersomnia was diagnosed in 16 patients, 67 patients had hypersomnia associated with a psychiatric disorder, and in 102 participants, EDS was unexplained. SOREMP arising from sleep stage N1 (N1-SOREMP) was extremely rare in non-narcoleptic patients (n = 2), but was present in 45.5% of patients with narcolepsy. The number of N1-SOREMP was significantly higher in patients with NL1 than with NL2. 42.1% of SOREMP in the NL1 group arose from N1 compared to 15.5% in the NL2 group. In patients with narcolepsy, the number of N1-SOREMP showed negative correlation with Hcrt levels, mean sleep latency on MSLT, and REM latency on PSG. Furthermore, it was significantly associated with HLA DQB1*06:02. N1-SOREMP occurred in 69% patients with Hcrt <110 pg/ml but in only 17% of patients with Hcrt >110 pg/ml. Conclusion: Both occurance and frequency of SOREMP arising from sleep stage N1 have high sensitivity for the diagnosis of narcolepsy and type 1 narcolepsy, in particular. The number of N1-SOREMP appears to be a marker of disease severity or instability of REM sleep, respectively. Sleep stage sequence analysis of SOREMP periods may support phenotyping of patients with central disorders of hypersomnolence. doi:10.1016/j.clinph.2017.06.194
Poster P 122 Stimulus-responsive myoclonic jerks of both levator palpebrae muscles in a comatose survivor of cardiopulmonary resuscitation may pretended awareness—F. Thömke (Klinikum Worms, Worms, Germany)
Comatose survivors of cardiopulmonary resuscitation (CPR), who develop myoclonus within 1–2 days after CPR, usually have a poor prognosis. Typically, such myoclonus occurs or increases on sensory stimuli like touching the patient or acoustic stimuli. Myclonic jerks mainly occur in the muscles of the face, shoulder girdle and diaphragm. Sometimes, such jerks may be restricted to one muscle like the diaphragm leading to hiccups. We report one comatose survivor of CPR with stimulus-sensitive myoclonus, which was restricted to both levator palpebrae muscles leading to eye opening on acoustic stimulation and by doing so pretending awareness. Report of a case: A 76-year-old female survivor of CPR opened her eyes on acoustic or sensory stimuli followed by a short period of
e389
blinking, which pretended awareness. EEG documented polymorph spike-slow waves after acoustic stimuli and was otherwise flat. Eye opening and blinking were coupled to spike-slow waves discharges and interpreted as restricted myoclonus of the levator palpebare muscles. This was a transient phenomenon for 24 h, and after another day, the patient was brain dead. Conclusion: Early myoclonus in comatose survivors of a CPR usually indicate a poor prognosis, although recent data indicate, that patients with focal myoclonus may have a better prognosis than those with more generalized myoclonus. Bouwes et al. (2012) reported a good outcome in 8 of 48 patients with focal myoclonus compared to 1 of 31 with generalized myoclonus. As shown by our patient, focal or restricted stimulus-sensitive myoclonus may pretend awareness and causes diagnostic problems, which can be solved by EEG. doi:10.1016/j.clinph.2017.06.195
Poster P 123 Prefrontal transcranial magnetic stimulation in children with attention deficit/hyperactivity disorder (ADHD)—S. Bender (Uniklinik Köln, Kinder- und Jugendpsychiatrie, Köln, Germany)
Background: Attention deficit/ hyperactivity disorder (ADHD) is characterized by a preference of immediate over delayed rewards. 1 Hz inhibitory repetitive transcranial magentic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) has been shown to influence decisions of reward preference in adult subjects towards smaller immediate rewards. Methods: Here we examine the effects of high frequency (excitatory) DLPFC rTMS in a small sample of adult subjects with ADHD. A delay discounting task was applied before and after rTMS. Results: After rTMS the preference of subjects with ADHD was changed in a marginally significant way towards larger but more delayed rewards compared to sham stimulation. Discussion/Significance: These are pilot data which encourage further research on whether rTMS is not only able to discrupt the cortical circuits involved in attentional top-down control and the ability to wait longer times for larger rewards, but whether rTMS is able to both decrease as well as increase cortical excitability leading to different behavioral effects. Such behavioral effects could represent a clinically valuable therapeutic tool. However, a replication of our finding is needed in a larger independent sample. doi:10.1016/j.clinph.2017.06.196
Poster P 124 Auricular vagus nerve stimulation in subjects with major depression – Pulsatile vs. continuous stimulation—T. Polak, M. Götzelmann, A. Katzorke, J.B. M. Zeller, M.J. Herrmann (Universitätsklinikum Würzburg, Klinik für Psychiatrie, Psychosomatik und Psychotherapie, Würzburg, Germany)
Background: Conventional vagus nerve stimulation (cVNS) is approved to treat major depression. Within this context, auricular VNS (aVNS) is of increasing interest due to its non-invasiveness. Still, the question of optimum stimulation parameters has to be solved.
e390
Abstracts / Clinical Neurophysiology 128 (2017) e305–e412
Method: 50 subjects with major depressive disorder were stimulated over 20 min. in the area of the auricular branch of the vagus nerve. Control stimulation (CS) was done at the ear lobe. Before and after each stimulation the participants were asked to rate their actual affective state. 30 participants were stimulated continuously, while in 20 subjects, stimulation was interrupted every 5 min. for 30 s. (pulsatile stimulation). Results: Only using pulsatile stimulation, participants significantly more often rated to feel better (F1;18 ¼ 12:35; p = 0.002) and to be more optimistic (F1;18 ¼ 12:24; p = 0.003) after aVNS than after CS. Using pulsatile as well as using continuous stimulation, subjects indicated to be more happy (F1;18 ¼ 24:61; p < 0.001 and F1;28 ¼ 8:03; p = 0.008, resp.). Rating of pictures of the Internatonal Affective Picture System (IAPS) showed no statistical significant difference between the stimulation methods. Conclusion: Stimulating in a pulsatile way showed more difference between aVNS and CS than stimulating in a continuous way. Self rating of the emotional state by means of a visual analogue scale seems to be a reliable tool for the examination of non-invasive stimulation techniques. doi:10.1016/j.clinph.2017.06.197
Conclusion: Consistent with the literature, our patients showed severe drug-resistant epilepsies with an electro-clinical complex of a fronto-temporal epilepsy with frequent, long-lasting or continuous subclinical seizure patterns and/or NCSE. Rhythmic theta as a ‘‘characteristic” EEG pattern was, however, only observed in 2/4 of our patients. Therefore, a rchr20es should be suspected in such patients also in the absence of this EEG feature. This information will help in an early identification of rchr20es, which is especially important since, without this specific diagnosis, many affected patients are considered candidates for pre-surgical diagnostics or even epilepsy surgery. doi:10.1016/j.clinph.2017.06.198
Poster P 126 Congruence of first out-patient routine EEG and in-patient EEG diagnostics in a specialized epilepsy center—B. Steinhoff *, M. Bacher, T. Intravooth, J. Stockinger, A. Staack (Epilepsiezentrum Kork, Kehl-Kork, Germany) ⇑
Poster P 125 Ring chromosome 20 Epilepsy syndrome in children Variable EEG- and electro-clinical pattern—A. Eger 1,*, T. Pieper 2, G. Kluger 3, U. Koehler 3, T. Herberhold 2, A. Zsoter 2, H. Holthausen 2, M. Staudt 2 (1 Städtisches Klinikum Dessau, Klinik für Kinder- und Jugendmedizin, Dessau, Germany, 2 Schön Klinik Vogtareuth, Epilepsiezentrum für Kinder und Jugendliche, Klinik für Neuropädiatrie und Neurologische Rehabilitation, Vogtareuth, Germany, 3 MGZ Medizinisch Genetisches Zentrum München, Zytogenetik, Microarray-Diagnostik, München, Germany) ⇑
Corresponding author.
Background: Children with ring chromosome 20 epilepsy syndrome (rchr20es) typically show severe, drug-resistant focal epilepsies characterized by frontal semiology, high susceptibility for non-convulsive status epilepticus (NCSE) and epilepsyassociated cognitive and behavioral deteriorations. EEG has been reported to show frequent or continuous subclinical seizure patterns together with characteristic rhythmic theta waves (Caneveni et al. 1998). Here, we report on clinical and EEG data in four patients. Patients and methods: Retrospective analysis of clinical and videoEEG-long-term-monitoring data of four patients (all female) with rchr20es. Age at onset of epilepsy ranged from 5 to 8 years, the number of antiepileptic drugs already used ranged from 6 to 10, and all four patients had suffered NCSE previously. Semiology: all four patients showed auras (epigastric: 2, fear: 2, visual: 1, somatosensory: 1) and seizures (hypermotor: 3, tonic: 3, dialeptic: 2, psychomotor: 2). Clinical epilepsy syndromes were frontal lobe epilepsies (n = 3) and frontal/ temporal lobe epilepsy (n = 1). EEG showed regional abnormalities in frontal (n = 4), temporal (n = 3) and parieto-occiptal (n = 1) areas, with subclinical seizure patterns and/ or EEG-status elements (with serial spikes, polyspikes, sharp waves, or spike wave complexes; n = 3), rhythmic theta (n = 2), 1–2 Hz slow sharp wave complexes (n = 1), spike wave complexes/low amplitude fast activity +high amplitude delta burst (n = 1), alpha/theta seizure activity (n = 1). MRI was essentially normal in all patients, with minor abnormalities in frontal (2) or temporal areas (2).
Corresponding author.
Background/Objective: In our epilepsy center we always perform a routine EEG in out-patients who are referred for the first time. We investigated in how many cases additional EEG diagnostics including long-term video EEG delivered additional clinically relevant information if in-patient diagnostics followed. Methods: We retrospectively assessed, how many out-patients seen for the first time were admitted to a hospital stay. In these cases we compared the EEG findings of the initial out-patient routine EEG with the in-patient data including long-term video EEG. Results: Total number of out-patients was 77. Ten patients (13%) were hospitalized with the purpose of a better diagnostic classification. In 4 of 10 epilepsy cases we found confirming epileptiform discharges in the long-term video EEG that had not been recording with the initial routine EEG. In one patient we found a normal variant where epileptiform discharges had been falsely supposed in the routine EEG. In the remaining cases no clinically relevant further information was obtained. Discussion/Conclusions: Additional hospitalizations are usually not necessary after out-patient visits of new referrals to a specialized epilepsy center. In half of these hospitalized patients additional EEG diagnostics beyond routine EEG render clinically relevant additional information. doi:10.1016/j.clinph.2017.06.199
Poster P 127 Vigilance regulation in adult ADHD—M. Strauß *, M. Paucke, C. Sander, U. Hegerl (Universitätsklinikum Leipzig AöR, Klinik für Psychiatrie und Psychotherapie, 04103, Germany) ⇑
Corresponding author.
Background: Functional regulation of vigilance or wakefulness is crucial for interaction with the environment and can be described as a unique, situation-dependent characteristic. Disorders of wakefulness regulation manifest themselves as delayed or rash declines in vigilance under calm settings.