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S117 Excitability testing in the 21st century
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Abstracts / Clinical Neurophysiology 128 (2017) e178–e303
by Alfred Lee Loomis in the 1930s these oscillatory electrophysiological phenomena were gradually becoming one of the major focuses of sleep scientists. Although they were first considered as pure signs of cerebral inactivity, empirical findings suggested their involvement in the maintenance of a homeostasis between wake-related cerebral activity and sleep-related rest, restauration of wake-related wear and tear (including detoxification, tissue restoration and immunological functions), maintaining synaptic homeostasis (reducing synaptic strengths and cortical firing rate) and consolidation of memory traces (hippocamapo-neocortical replay). The precise homeostatic regulation of sleep slow wave activity is one of the best characterized aspects of sleep. Spectral power, wave amplitude and occurrence, as well as frequency and slope are the sleep slow wave features which are homeostatically regulated, mainly reflecting local plastic processes. The dichotomy of the cortically generated slow oscillation. Keywords: Sleep homeostasis, Slow oscillation, Delta waves, Up states, Down states doi:10.1016/j.clinph.2017.07.126
S116 The heterogeneity of sleep slow waves—Péter Ujma (Semmelweis University, Institute of Behavioural Sciences, Budapest, Hungary) NREM sleep slow waves reflect both the temporal dynamics of the synchronized onset and cessation of cortical neuron firing and the spatial extent of this synchronized firing pattern. This synchronization is crucially dependent on synaptic strength, and the renormalization of synaptic changes occurring in wakefulness is thought to be one of the main functions of NREM sleep. In line with this hypothesis, slow waves are more frequent, larger and steeper in cases when the synaptic load is high and the need for homeostatic synaptic renormalization is strong: early in the night, in younger subjects with greater neural plasticity and after prolonged or more intensive wakefulness. Slow waves exhibit substantial heterogeneity and may contribute to these processes to a differing degree. In NREM sleep, series of large-amplitude slow waves (Cyclic Alternating Pattern [CAP] A1) sometimes appear, either spontaneously with predictably cyclicity or after sensory stimulation. Slow waves in CAP A1 resemble slow waves normally recorded under high homeostatic sleep pressure: they are characterized by a greater spatial extent, larger amplitude, steeper slopes (even when correcting for amplitude) and higher EEG synchronization, even though their topography and propagation patterns are similar to ordinary (non-CAP) slow waves. These results indicate that CAP A1 represents a period of highly synchronous neuronal firing over large areas of the cortical mantle. This feature may contribute to the role CAP A1 plays in both normal synaptic homeostasis and – through greater synchronization – in the generation of epileptiform phenomena in epileptic patients. Keywords: Slow wave, NREM sleep, Synaptic homeostasis, Cyclic Alternating Pattern doi:10.1016/j.clinph.2017.07.127
Symposium XVIII. – Axonal excitability and diabetic polyneuropathy S117 Excitability testing in the 21st century—Hugh Bostock (Institute of Neurology, University College London, Sobell Department, London, United Kingdom)
In 1950, excitability testing of nerves and muscles had a leading role in neurological electrodiagnosis, but by the end of the century it had all but disappeared. In 2, the use of computerised threshold tracking to perform multiple nerve excitability tests in an efficient 10-min protocol provided a new research tool for those interested in the biophysical basis of neuropathies. This ‘TROND’ protocol has been taken up by several centres worldwide, and given rise to over a hundred research papers, because changes in membrane potential, ion channels, and other membrane properties, produce distinctive patterns of abnormal excitability. However, nerve excitability testing remains a specialized technique: it is not possible on regular EMG machines, it is not required for any common diagnostic test, and abnormal recordings are often difficult to interpret. It is to be hoped that this situation will change, with the accumulation of more patient studies and the development of more sophisticated software. The future may also see more widespread use of two extensions of excitability testing. Muscle fibres are unsuited to excitation by surface electrodes, but velocity recovery cycles, analogous to excitability recovery cycles in nerve, can be recorded almost painlessly with needle electrodes. This method is providing information about muscle membrane potential and other membrane properties not otherwise available from patients in vivo. Threshold-tracking has also been applied to cortical excitability testing with trans-cranial magnetic stimulation: cortical recovery cycles reveal early defects in intra-cortical inhibition in ALS that show promise as a diagnostic biomarker of disease progression.
Keywords: Nerve excitability, Threshold tracking, Recovery cycle, TMS doi:10.1016/j.clinph.2017.07.128
S118 Mechanisms of diabetic neuropathy—Hatice Tankisi (Aarhus University Hospital, Clinical Neurophysiology, Aarhus, Denmark) Objectives: Diabetic polyneuropathy (DPN) is the most common peripheral neuropathy representing a severe disabling condition. There is currently no disease modifying treatment, and development of targeted therapies depends on understanding the complex underlying mechanisms of DPN. The objective of this review is to discuss mechanisms of DPN. Methods: DPN is associated with disturbances in endoneurial metabolism and microvascular morphology, but the roles of these as the cause of DPN have been controversial. The scientific community has been divided into two groups, favoring either metabolic or neurovascular mechanisms. Results: Since DPN is decreased by improved metabolic control, hyperglycemia is assumed to be the main cause. Long lasting hyperglycemia leads to a downstream metabolic cascade which affects mitochondrial function and causes an excess formation of reactive oxygen species and exaggerated oxidative stress. Additionally, dyslipidemia, insulin resistance, autoimmunity, and epigenetics are suggested to contribute to metabolic mechanisms of DPN. The idea that microvascular changes cause DPN was challenged in early studies. There is, however, increasing evidence that changes in endoneurial capillary morphology and vascular reactivity may predate the development of DPN. In recent studies, disturbances in capillary function were shown to reduce the amount of oxygen and glucose that can be extracted by the tissue for a given blood flow. Discussion: The ability to show immediately the effects on patient axons of interventions such as ischemia makes excitability testing a powerful method to investigate disease pathophysiology.
Abstracts / Clinical Neurophysiology 128 (2017) e178–e303
by Alfred Lee Loomis in the 1930s these oscillatory electrophysiological phenomena were gradually becoming one of the major focuses of sleep scientists. Although they were first considered as pure signs of cerebral inactivity, empirical findings suggested their involvement in the maintenance of a homeostasis between wake-related cerebral activity and sleep-related rest, restauration of wake-related wear and tear (including detoxification, tissue restoration and immunological functions), maintaining synaptic homeostasis (reducing synaptic strengths and cortical firing rate) and consolidation of memory traces (hippocamapo-neocortical replay). The precise homeostatic regulation of sleep slow wave activity is one of the best characterized aspects of sleep. Spectral power, wave amplitude and occurrence, as well as frequency and slope are the sleep slow wave features which are homeostatically regulated, mainly reflecting local plastic processes. The dichotomy of the cortically generated slow oscillation. Keywords: Sleep homeostasis, Slow oscillation, Delta waves, Up states, Down states doi:10.1016/j.clinph.2017.07.126
S116 The heterogeneity of sleep slow waves—Péter Ujma (Semmelweis University, Institute of Behavioural Sciences, Budapest, Hungary) NREM sleep slow waves reflect both the temporal dynamics of the synchronized onset and cessation of cortical neuron firing and the spatial extent of this synchronized firing pattern. This synchronization is crucially dependent on synaptic strength, and the renormalization of synaptic changes occurring in wakefulness is thought to be one of the main functions of NREM sleep. In line with this hypothesis, slow waves are more frequent, larger and steeper in cases when the synaptic load is high and the need for homeostatic synaptic renormalization is strong: early in the night, in younger subjects with greater neural plasticity and after prolonged or more intensive wakefulness. Slow waves exhibit substantial heterogeneity and may contribute to these processes to a differing degree. In NREM sleep, series of large-amplitude slow waves (Cyclic Alternating Pattern [CAP] A1) sometimes appear, either spontaneously with predictably cyclicity or after sensory stimulation. Slow waves in CAP A1 resemble slow waves normally recorded under high homeostatic sleep pressure: they are characterized by a greater spatial extent, larger amplitude, steeper slopes (even when correcting for amplitude) and higher EEG synchronization, even though their topography and propagation patterns are similar to ordinary (non-CAP) slow waves. These results indicate that CAP A1 represents a period of highly synchronous neuronal firing over large areas of the cortical mantle. This feature may contribute to the role CAP A1 plays in both normal synaptic homeostasis and – through greater synchronization – in the generation of epileptiform phenomena in epileptic patients. Keywords: Slow wave, NREM sleep, Synaptic homeostasis, Cyclic Alternating Pattern doi:10.1016/j.clinph.2017.07.127
Symposium XVIII. – Axonal excitability and diabetic polyneuropathy S117 Excitability testing in the 21st century—Hugh Bostock (Institute of Neurology, University College London, Sobell Department, London, United Kingdom)
In 1950, excitability testing of nerves and muscles had a leading role in neurological electrodiagnosis, but by the end of the century it had all but disappeared. In 2, the use of computerised threshold tracking to perform multiple nerve excitability tests in an efficient 10-min protocol provided a new research tool for those interested in the biophysical basis of neuropathies. This ‘TROND’ protocol has been taken up by several centres worldwide, and given rise to over a hundred research papers, because changes in membrane potential, ion channels, and other membrane properties, produce distinctive patterns of abnormal excitability. However, nerve excitability testing remains a specialized technique: it is not possible on regular EMG machines, it is not required for any common diagnostic test, and abnormal recordings are often difficult to interpret. It is to be hoped that this situation will change, with the accumulation of more patient studies and the development of more sophisticated software. The future may also see more widespread use of two extensions of excitability testing. Muscle fibres are unsuited to excitation by surface electrodes, but velocity recovery cycles, analogous to excitability recovery cycles in nerve, can be recorded almost painlessly with needle electrodes. This method is providing information about muscle membrane potential and other membrane properties not otherwise available from patients in vivo. Threshold-tracking has also been applied to cortical excitability testing with trans-cranial magnetic stimulation: cortical recovery cycles reveal early defects in intra-cortical inhibition in ALS that show promise as a diagnostic biomarker of disease progression.
Keywords: Nerve excitability, Threshold tracking, Recovery cycle, TMS doi:10.1016/j.clinph.2017.07.128
S118 Mechanisms of diabetic neuropathy—Hatice Tankisi (Aarhus University Hospital, Clinical Neurophysiology, Aarhus, Denmark) Objectives: Diabetic polyneuropathy (DPN) is the most common peripheral neuropathy representing a severe disabling condition. There is currently no disease modifying treatment, and development of targeted therapies depends on understanding the complex underlying mechanisms of DPN. The objective of this review is to discuss mechanisms of DPN. Methods: DPN is associated with disturbances in endoneurial metabolism and microvascular morphology, but the roles of these as the cause of DPN have been controversial. The scientific community has been divided into two groups, favoring either metabolic or neurovascular mechanisms. Results: Since DPN is decreased by improved metabolic control, hyperglycemia is assumed to be the main cause. Long lasting hyperglycemia leads to a downstream metabolic cascade which affects mitochondrial function and causes an excess formation of reactive oxygen species and exaggerated oxidative stress. Additionally, dyslipidemia, insulin resistance, autoimmunity, and epigenetics are suggested to contribute to metabolic mechanisms of DPN. The idea that microvascular changes cause DPN was challenged in early studies. There is, however, increasing evidence that changes in endoneurial capillary morphology and vascular reactivity may predate the development of DPN. In recent studies, disturbances in capillary function were shown to reduce the amount of oxygen and glucose that can be extracted by the tissue for a given blood flow. Discussion: The ability to show immediately the effects on patient axons of interventions such as ischemia makes excitability testing a powerful method to investigate disease pathophysiology.