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W22 Activity-dependent conduction failure in a peripheral nerve lesion
Workshop 3. Magnetoencephalography
340
ing transcranial doppler (TCD) and by other means. An early warning of vasospasm may help the clinician to treat this serious complication more aggressively and more early, thereby preventing and avoiding some long-term neurologic sequelae of vasospasm. Trending ICU EEG also allows for identification of subclinical epileptic seizures and other neuro-ICU complications, frequently prompting changes in clinical patient management. With current advances in digital EEG technology, ICU EEG monitoring and trending can be a valuable tool for clinicians in the neuro-ICU.
2. Nerve excitability and pathophysiology
•
CONTRIBUTIONS FROM EXCITABILITYTESTING TO NERVE PHYSIOLOGY AND PATHOPHYSIOLOGY:THRESHOLD ELECTROTONUS AND LATENT ADDITION
H. Bostock. Institute of Neurology, Queen Square, London WCIN 3BG,
UK Two related EMG techniques exploit the close relationship between the membrane potential of an axon and the threshold current required to just excite it. In Threshold Electrotonus (TE), the electrotonic responses of a nerve to 100 or 200 ms subthreshold current pulses are determined by tracking the changes in threshold for a 1 ms test stimulus. In Latent Addition (LA), the local responses to 60 # s current pulses are tracked with 60/zs test pulses. LA to hyperpolarizing pulses provides an estimate of nodal time constant (normally close to 45/zs) and evidence on voltage-dependent 'threshold' Na channels active at the resting potential. TE depends on internodal as well as nodal parameters: depolarizing responses reveal the activation of slow K channels, modified by the action of fast K channels, while hyperpolarizing responses show inward rectification. TE is extremely sensitive to ischaemic depolarization, or to the electrogenic hyperpolarization following ischaemia or impulse activity. Clinical studies have shown distinctive changes in ALS, MS and diabetic neuropathy, which have suggested more or less specific abnormalities in different types of ion channel. TE and LA are non-invasive and painless and provide new perspectives on peripheral nerve function in vivo.
~-~
ACTIVITY-DEPENDENTCONDUCTION FAILURE IN A PERIPHERAL NERVE LESION
D. Burke, M.C. Kiernan, I. Mogyoros, T.A. Miller. Prince of Wales
Medical Research Institute, Sydney, Australia When the safety margin for impulse conduction is reduced by, for example, demyelination, axons may fail to conduct any impulses or may not be able to sustain normal impulse traffic. The normal phenomenon of activity-dependent hyperpolarization can produce conduction block at sites of lowered safety margin for impulse conduction (Bostock & Grafe, 1985), and conduction may be restored by treatment with ouabain to block the electrogenic Na+/K + pump (Kaji & Sumner, 1989). In microneurographic studies, we have seen evidence for activity-dependent conduction failure in axons transmitting impulses past the site of myelin impalement by the microelectrode. We have therefore sought evidence of activity-dependent conduction failure in patients with carpal tunnel syndrome and focal conduction slowing, possibly due to compression-induced disturbance to the myelin sheath. In two series of studies, one designed to produce hyperpolarization due to activation of nodal slow K + conductances and the other designed to produce hyperpolarization due to activation of the Na + pump, we have failed to find convincing evidence of activity-dependent conduction failure. These findings suggest that the conduction slowing in carpal tunnel syndrome is not associated with a significant impairment of the safety margin for impulse conduction, and this questions whether the slowing results from focal demyelination.
~-~
ELECTROPHYSIOLOGICALAND PHARMACOLOGICAL EXPERIMENTS ON HUMAN SURAL NERVE BIOPSIES IN VITRO
S. Quasthoff. Dept. of Neurology, Technical Univ., Munich, Germany Histological examination of biopsied human sural nerve is an important diagnostic tool in the classification of neuropathies. However, electrophysiological studies on isolated sural nerve fascicles to elucidated the functional aspects and regional distribution of neuropathies are new. The combination of electrophysiological in vitro techniques with specific pharmacological tools have provide important information about the ionic conductances underlying action potential generation in myelinated and unmyelinated human sural nerve axons. Especially the ionic conductances of unmyelinated human C-fibres in human sural nerves are normally not accessible to classical in vivo neurography. Compound action potential measurements of unmyelinated C-fibres have revealed tetrodotoxin-resistant sodium and calcium currents which could be responsible for chronic pain. Additional immunohistochemical studies on sural nerve preparations demonstrated the existence of calcium channels on unmyelinated C fibres (Quasthoff et al. 1995 Neuroscience 69:955-965 and 1996 Brain Research). Furthermore, excitability of C fibres could be tested by means of the new "thresholdelectrotonus" tracing method in vitro which indicated an important function of the inwardly rectifying current (Ih) in unmyelinated C fibres. The functional aspects of the current (lh) might be a key to the understanding of autonomic neuropathy. In summary, electrophysiological in vitro experiments on human sural nerve fascicles could provide additional information about the functional deficits in peripheral neuropathies. - Supported by the Wilhelm Sander
Stiftung ~4--~
-
THRESHOLD ELECTROTONUS IN EXPERIMENTAL MODELS OF NEUROPATHIESAND NEURONOPATHIES
R. Kaji, N. Hirota, T. Takagi, C. Yan, Y. Kojima, N. Kohara, J. Kimura, H. Bostock i. Kyoto University School of Medicine, Japan; ~Institute of
Neurology, London, UK Threshold electrotonus (TE) assesses ion channel functions and membrane potential changes non-invasively in human subjects. We developed a model of TE recording using Wistar rats, in which various forms of nerve pathology could be induced. Under pentobarbital anesthesia, surface stimulating electrodes were placed proximally on the tail, and needle recording electrodes inserted distally in a tail muscle. Tall temperature was maintained at 30--34°C, and TE was recorded as previously described (Bostock, Sharief, Reid & Murray, Brain 118,217-225, 1995). TE was compared in 4 groups of animals: 'young' (body weight < 300 g, n = 9), 'mature' (> 400 g, n -- 6), 'dying-back' (mature rats intoxicated with bromophenylaeetylurea for 14-21 days, n = 6) and 'diabetic' (mature rats treated with streptozocin for 2-5 months, n = 10). The 'young' and 'dyingback' rats had significantly more early accommodation to depolarizing pulses than the 'mature' controls, suggesting greater expression or exposure of potassium channels, while the 'diabetic' group had significantly less inward rectification on hyperpolarization, as recently found in human diabetic neuropathy (Horn, Quasthoff, Grafe, Bostock et al., Muscle Nerve, in press). This method provides a new tool to study the pathophysiology of experimental nerve lesions and should aid interpretation of abnormal TE recordings from patients.
3. Magnetoencephalography ~-~
MOVEMENT RELATED MAGNETIC FIELDS AND MULTI-MODAL INTEGRATION
L. Deecke. University Clinic of Neurology A-f090 Vienna, Austria Modem muttimodal techniques enable us to study changes in cortical activity in association with specific motor or cognitive tasks. Such functional brain topography (DC-EEG, MEG, Emission-CTs, FMRI) can in fact confirm the classic localisasionists' findings of cortical functional areas in which lesions produce the famous a-syndromes (agnosia, aphasia, apraxia,
340
ing transcranial doppler (TCD) and by other means. An early warning of vasospasm may help the clinician to treat this serious complication more aggressively and more early, thereby preventing and avoiding some long-term neurologic sequelae of vasospasm. Trending ICU EEG also allows for identification of subclinical epileptic seizures and other neuro-ICU complications, frequently prompting changes in clinical patient management. With current advances in digital EEG technology, ICU EEG monitoring and trending can be a valuable tool for clinicians in the neuro-ICU.
2. Nerve excitability and pathophysiology
•
CONTRIBUTIONS FROM EXCITABILITYTESTING TO NERVE PHYSIOLOGY AND PATHOPHYSIOLOGY:THRESHOLD ELECTROTONUS AND LATENT ADDITION
H. Bostock. Institute of Neurology, Queen Square, London WCIN 3BG,
UK Two related EMG techniques exploit the close relationship between the membrane potential of an axon and the threshold current required to just excite it. In Threshold Electrotonus (TE), the electrotonic responses of a nerve to 100 or 200 ms subthreshold current pulses are determined by tracking the changes in threshold for a 1 ms test stimulus. In Latent Addition (LA), the local responses to 60 # s current pulses are tracked with 60/zs test pulses. LA to hyperpolarizing pulses provides an estimate of nodal time constant (normally close to 45/zs) and evidence on voltage-dependent 'threshold' Na channels active at the resting potential. TE depends on internodal as well as nodal parameters: depolarizing responses reveal the activation of slow K channels, modified by the action of fast K channels, while hyperpolarizing responses show inward rectification. TE is extremely sensitive to ischaemic depolarization, or to the electrogenic hyperpolarization following ischaemia or impulse activity. Clinical studies have shown distinctive changes in ALS, MS and diabetic neuropathy, which have suggested more or less specific abnormalities in different types of ion channel. TE and LA are non-invasive and painless and provide new perspectives on peripheral nerve function in vivo.
~-~
ACTIVITY-DEPENDENTCONDUCTION FAILURE IN A PERIPHERAL NERVE LESION
D. Burke, M.C. Kiernan, I. Mogyoros, T.A. Miller. Prince of Wales
Medical Research Institute, Sydney, Australia When the safety margin for impulse conduction is reduced by, for example, demyelination, axons may fail to conduct any impulses or may not be able to sustain normal impulse traffic. The normal phenomenon of activity-dependent hyperpolarization can produce conduction block at sites of lowered safety margin for impulse conduction (Bostock & Grafe, 1985), and conduction may be restored by treatment with ouabain to block the electrogenic Na+/K + pump (Kaji & Sumner, 1989). In microneurographic studies, we have seen evidence for activity-dependent conduction failure in axons transmitting impulses past the site of myelin impalement by the microelectrode. We have therefore sought evidence of activity-dependent conduction failure in patients with carpal tunnel syndrome and focal conduction slowing, possibly due to compression-induced disturbance to the myelin sheath. In two series of studies, one designed to produce hyperpolarization due to activation of nodal slow K + conductances and the other designed to produce hyperpolarization due to activation of the Na + pump, we have failed to find convincing evidence of activity-dependent conduction failure. These findings suggest that the conduction slowing in carpal tunnel syndrome is not associated with a significant impairment of the safety margin for impulse conduction, and this questions whether the slowing results from focal demyelination.
~-~
ELECTROPHYSIOLOGICALAND PHARMACOLOGICAL EXPERIMENTS ON HUMAN SURAL NERVE BIOPSIES IN VITRO
S. Quasthoff. Dept. of Neurology, Technical Univ., Munich, Germany Histological examination of biopsied human sural nerve is an important diagnostic tool in the classification of neuropathies. However, electrophysiological studies on isolated sural nerve fascicles to elucidated the functional aspects and regional distribution of neuropathies are new. The combination of electrophysiological in vitro techniques with specific pharmacological tools have provide important information about the ionic conductances underlying action potential generation in myelinated and unmyelinated human sural nerve axons. Especially the ionic conductances of unmyelinated human C-fibres in human sural nerves are normally not accessible to classical in vivo neurography. Compound action potential measurements of unmyelinated C-fibres have revealed tetrodotoxin-resistant sodium and calcium currents which could be responsible for chronic pain. Additional immunohistochemical studies on sural nerve preparations demonstrated the existence of calcium channels on unmyelinated C fibres (Quasthoff et al. 1995 Neuroscience 69:955-965 and 1996 Brain Research). Furthermore, excitability of C fibres could be tested by means of the new "thresholdelectrotonus" tracing method in vitro which indicated an important function of the inwardly rectifying current (Ih) in unmyelinated C fibres. The functional aspects of the current (lh) might be a key to the understanding of autonomic neuropathy. In summary, electrophysiological in vitro experiments on human sural nerve fascicles could provide additional information about the functional deficits in peripheral neuropathies. - Supported by the Wilhelm Sander
Stiftung ~4--~
-
THRESHOLD ELECTROTONUS IN EXPERIMENTAL MODELS OF NEUROPATHIESAND NEURONOPATHIES
R. Kaji, N. Hirota, T. Takagi, C. Yan, Y. Kojima, N. Kohara, J. Kimura, H. Bostock i. Kyoto University School of Medicine, Japan; ~Institute of
Neurology, London, UK Threshold electrotonus (TE) assesses ion channel functions and membrane potential changes non-invasively in human subjects. We developed a model of TE recording using Wistar rats, in which various forms of nerve pathology could be induced. Under pentobarbital anesthesia, surface stimulating electrodes were placed proximally on the tail, and needle recording electrodes inserted distally in a tail muscle. Tall temperature was maintained at 30--34°C, and TE was recorded as previously described (Bostock, Sharief, Reid & Murray, Brain 118,217-225, 1995). TE was compared in 4 groups of animals: 'young' (body weight < 300 g, n = 9), 'mature' (> 400 g, n -- 6), 'dying-back' (mature rats intoxicated with bromophenylaeetylurea for 14-21 days, n = 6) and 'diabetic' (mature rats treated with streptozocin for 2-5 months, n = 10). The 'young' and 'dyingback' rats had significantly more early accommodation to depolarizing pulses than the 'mature' controls, suggesting greater expression or exposure of potassium channels, while the 'diabetic' group had significantly less inward rectification on hyperpolarization, as recently found in human diabetic neuropathy (Horn, Quasthoff, Grafe, Bostock et al., Muscle Nerve, in press). This method provides a new tool to study the pathophysiology of experimental nerve lesions and should aid interpretation of abnormal TE recordings from patients.
3. Magnetoencephalography ~-~
MOVEMENT RELATED MAGNETIC FIELDS AND MULTI-MODAL INTEGRATION
L. Deecke. University Clinic of Neurology A-f090 Vienna, Austria Modem muttimodal techniques enable us to study changes in cortical activity in association with specific motor or cognitive tasks. Such functional brain topography (DC-EEG, MEG, Emission-CTs, FMRI) can in fact confirm the classic localisasionists' findings of cortical functional areas in which lesions produce the famous a-syndromes (agnosia, aphasia, apraxia,