- Email: [email protected]
WS-2-3 Single fiber EMG (SFEMG) in the diagnosis and management of myasthenia gravis (MG)
Workshop 2. Single fiber EMG
$24
to midbrain as well as in the more caudal structures such as the medulla oblongata. G e n e r a t o r sources of far-field P30 and N33 components produced by posterior tibial nerve stimulation were compared with those of the P14 and N18 components of median nerve stimulated SSEPs. Intracranial spacio-temporal distributions of P30 and N33 were similar to those of the P14 and N18. In clinical cases, the changes in P30 and N33 were correlated with those in P14 and N18, indicative that P30 and N33 are derived from activities similar to those that produce P14 a n d N18.
In ALS, jitter values increase with stimulation rates of up to 20 Hz that indicate involvement of nerve terminal. In neuropathies, S F E M G is useful in detecting and quantitating axonal degeneration in demyelinating neuropathy. In myopathy, fiber density may increase slightly due to involvement of intramuscular nerve and fiber splitting. Jitter is sometimes increased in voluntary S F E M G due to velocity recovery function (VRF). A n o t h e r advantage of S-SFEMG is its ability to exclude the V R F effect due to stable firing rate. The combined application of voluntary S F E M G and S-SFEMG is useful to study the neurogenic nature in myopathy.
•
•
Far-field potentials in surface EMG
Dick F. Stegeman, Karin Roeleveld, Dick M. Vingerhoets.
Institute of Neurology, Department of Clinical Neurophysiology, University Hospital Nijmegen, The Netherlands Most potentials recorded in neuromuscular electrophysiology change in amplitude, wave shape and even polarity when the recording electrode is moved over a small distance. First in the electroencephalogram, components were described which hardly change their characteristics with electrode position over the body or over the scalp. In this contribution it will be shown that these "far-fields" also form a part of surface E M G recordings during voluntary contractions. From basic electric field theory it can be concluded that these far-field p h e n o m e n a are generated by dipolar sources in any finite volume conductor. Propagating action potentials of nerve and muscle fibres are composed of two equal dipoles of opposite direction. For such a source the far-field contributions cancel. Therefore, propagating nerve and muscle fibre action potentials are not expected to generate far-fields. However, when the constant propagation of an action potential is disturbed in the widest sense of the word, far-field potentials are generated. This can be understood from an incomplete cancellation for some time. Such a disturbance can be caused by: 1) A change in the size of the extracellular medium, 2) a changing extracellular conductivity, 3) the generation or the blocking of an action potential and 4) a change in the direction of action potential propagation. It is evident that situations described in the above are numerous all over the neuromuscular system. It will be shown that far-field components in E M G records are predominantly caused by the blocking of action potentials at the fibre-tendon transition (see cause 3) above).
WS-2. SINGLE FIBER EMG
IW~2-~
Single fiber EMG in neuromuscular disorders
Stimulation SFEMG: a diagnostic method and a tool in research Jo2e V. Trontelj 1, Erik V. Sffdberg 2. 1 Institute of Clinical Neurophysiology, Ljubljana University Medical Center, Slovenia; 2 Department of Clinical Neurophysiology, University Hospital, Uppsala Stimulation S F E M G has evolved into a useful modification of the original method introduced in the 60s by Ekstedt and St/tlberg. It is based on a combination of well controllable, highly selective activation with highly selective recording. A m o n g the advantages of the method is its greater precision, since only single neuromuscular junctions rather than pairs are studied, and the often disturbing effect of muscle fiber velocity recovery function can be eliminated. The main use of stimulation S F E M G remains in the diagnosis of neuromuscular transmission disorders, in which it offers additional sensitivity (close to 100%). Moreover, the study of individual neuromuscular junctions at different stimulation rates allows a better differentiation between the pre- and post-synaptic abnormalities. The method is suitable to detect muscle fiber splitting, a common finding in certain neuromuscular disorders. Direct intrafascicular muscle fiber stimulation allows precise measurement of propagation velocity (a function of muscle fiber diameter) and its recovery function (abnormal in muscular dystrophies). The p h e n o m e n o n of action potential recovery function may provide a useful and sensitive parameter in evaluating depolarisation/repolarisation abnormalities, such as in genetically determined or drug-induced myotonic disorders. Myogenic block of conduction can be detected in ion channel abnormalities. Stimulation S F E M G allows reliable identification of the various late responses to nerve stimulation, e.g., differentiation between the recurrent (F) and H-reflex responses. The measurement of reflex jitter allows the recognition of monosynaptic, oligosynaptic and polysynaptic reflex responses. The method has been used to identify the monosynaptic and oligosynaptic contacts between the cortico-spinal tract neurons and the lower motor neurons of different limb and cranial muscles.
Kimiyoshi Arimura. The Third Department of lnternal Medicine,
Kagoshima University School of Medicine Single fiber E M G ( S F E M G ) has gained importance in the study of motor unit microphysiology in neuromuscular disorders. Among other features, determination of fiber density, indicating reinnervation and jitter, indicating abnormality of neuromuscular transmission, have been applied clinically. In anterior horn cell disease, abnormal jitter and blocking are usually prominent in ALS indicating rapid progression, whereas increased fiber density is prominent in spinal muscular atrophy. Decremental response in ALS may suggest lowering safety factor due to presynaptic involvement. Stimulation S F E M G (S-SFEMG) is a new method for jitter measurement. The main advantage of S-SFEMG over voluntary S F E M G is its ability to study in detail the pathomechanism of neuromuscular transmission at different stimulation frequencies.
•
Single fiber EMG (SFEMG) in the diagnosis and management of myasthenla gravis (MG) Donald B. Sanders. Duke University Medical Center, Durham, NC, USA S F E M G demonstrates abnormal jitter in virtually all patients with MG, but in some patients it may be necessary to examine several muscles to demonstrate the characteristic findings. Jitter is abnormal in the extensor digitorum communis muscle (EDC) in about 85% of M G patients overall, in over 60% of those with ocular M G and in over 50% of patients in clinical remission. Jitter is abnormal in a face muscle in almost all patients with MG: the EDC, frontalis or both are abnormal in over 95% of patients at the initial evaluation. Jitter is usually greater in facial muscles than
Workshop3. Motorlearningand plasticily in limb muscles, but this pattern is reversed in about 5% of patients with MG. Very rarely, abnormal jitter can be demonstrated in the orbicularis oculi muscle when it is normal in the EDC and frontalis. In about 5% of patients with MG weakness is limited to a few limb muscles. In these patients jitter may be normal in the EDC but abnormal in a weak limb muscle. Thus, if jitter is normal in the E D C and frontalis muscles, the orbicularis oculi (in ocular MG) or a weak limb muscle should be examined. Jitter is usually abnormal even when the patient with MG is taking cholinesterase inhibitors. However, in rare patients with ocular or mild limb weakness, increase jitter can be demonstrated only after these medications have been discontinued. Abnormal jitter may be suppressed by immunosuppressant treatment for MG. Changes in MG severity usually correlate with changes in jitter measurements and serial S F E M G studies may be of value in predicting or confirming changes in disease severity under certain circumstances. For example, when the jitter values in one muscle have been constant for several months, any subsequent increase in jitter usually accompanies or heralds clinical deterioration. In patients who improve while receiving chronic immunosuppressant medications, jitter usually improves but remains elevated after clinical remission has occurred, then fall slowly toward normal values if effective immunosuppression continues.
~ - ~
SFEMG in Lambert-Eaton myasthenic syndrome and botulism Shin J. Oh. Department of Neurology, The University of Alabama at Birmingham, Birmingham, Alabama, USA We have analyzed the SFEMG in 16 patients with clinically and electrophysiologically well-established Lambert-Eaton Myasthenic Syndrome (LEMS). Fiber density (FD) was normal in all patients except one, in which FD was just above the normal limit. Jitter was abnormal in all 16 cases regardless of the strength of the EDC muscle or severity of disease: mean MCD was 154.3 /zs; 97% of potential pairs (PP), > 53 #s in MCD; and 73% of PP, blocking. In four patients, MCDs were analyzed in relation to the firing rate of PP In all four cases, MCD improved with increasing firing rates, indicating a pre-synaptic block. S F E M G findings are well correlated with clinical severity of diseases. Mean MCDs are significantly (P < 0.03) improved with clinical improvement. Number of PP with > 53 #s and with blocking is also improved with clinical improvement. However, the jitter became rarely normalized even in asymptomatic stage. MCDs are better (R > --0.64), though inversely, correlated with the incremental responses at high rate of stimulation (HRS) in the logarithmic scale, than the CMAPs. Both of these are the best electrophysiological indicators of severity of disease. In five cases with the serial SFEMGs, MCD was a better prognosticator in disease status than the CMAP or HRS response. In botulism, the S F E M G findings are essentially same with those observed in LEMS in four reported cases. Thus, the SFEMG is extremely helpful for diagnosis and follow-up of patients with presynaptic disorders.
$25
WS-3. MOTOR LEARNING AND PLASTICITY
~
Learning of sequential procedures in monkeys
Okihide Hikosaka, Shigehiro Miyachi, Kae Miyashita.
Department of Physiology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan Recent clinical studies have suggested that the basal ganglia, among other areas, might be involved in procedural/motor learning. However, it is unknown how and where learning takes place and how and where the memory is stored? As a first step to answer these questions, we designed a new experimental paradigm (called '2 by 5 task') for monkeys. Upon pressing of a home key, two of 16 (4 x 4) LED buttons (called 'set') were illuminated and the monkey had to press them in a predetermined order which he had to find by trial and error. A total of 5 sets (called 'hyperset') were presented in a fixed order for completion of a trial. Learning took place for each hyperset within a block of experiment (short-term learning) as well as across days of practice (longterm learning), which was evident as the decrease in the number of errors and the decrease in performance time. We found that the procedural learning was correlated with the development of anticipatory eye movements. Initially, a saccade occurred to one of the two LED targets after their onset; after long-term practice (20-30 days), the targeting saccades started before the target onset. Using this task we started to examine the effects of reversible blockade of the monkey striatum on learning of new procedures and execution of learned procedures. At the time of the experiment the monkey had experienced more than 700 hypersets, 14 of which were chosen for everyday practice and therefore were highly learned. The task also allowed us to examine new hypersets, after each injection, by computer-generated random numbers. For the injection, we implanted 12 guide tubes directing at the striatum (caudate and putamen, left and right) at three anteroposterior levels in one monkey. The blockade of the anterior striaturn and the anterior pallidum led to deficits in learning of new hypersets while execution of learned hypersets remained intact. By contrast, the blockade of the posterior striatum led to deficits in execution of learned hypersets while learning of new hypersets was unaffected. These results suggest that the neural mechanisms for procedural learning and the neural mechanisms for memory storage are separate and that the anterior and posterior parts of the basal ganglia contribute to them differentially.
•
Reorganization of cortical motor outputs in the acquisition of new motor skills Alvaro Pascual-Leone. Unidad de Neurobiologia, Dept. Fisiologla, Univ. Valencia, Spain
We have used serial transcranial magnetic stimulation (TMS) mapping of the motor cortical outputs to study the plasticity of the adult human cortex during the acquisition of new motor skills. Learning to perform a five-finger exercise on the piano given strict performance constraints requires several days of practice. Using a MIDI-keyboard and computerized analysis of the subject's performance we have quantified the performance improvement and have correlated it with the changes in cortical output maps demonstrated with daily TMS mapping studies. Acquisition of the new skill is associated with an enlargement of the area of cortical output to the muscles involved in the task and a reduction in the cortical motor threshold for their activation. These changes
$24
to midbrain as well as in the more caudal structures such as the medulla oblongata. G e n e r a t o r sources of far-field P30 and N33 components produced by posterior tibial nerve stimulation were compared with those of the P14 and N18 components of median nerve stimulated SSEPs. Intracranial spacio-temporal distributions of P30 and N33 were similar to those of the P14 and N18. In clinical cases, the changes in P30 and N33 were correlated with those in P14 and N18, indicative that P30 and N33 are derived from activities similar to those that produce P14 a n d N18.
In ALS, jitter values increase with stimulation rates of up to 20 Hz that indicate involvement of nerve terminal. In neuropathies, S F E M G is useful in detecting and quantitating axonal degeneration in demyelinating neuropathy. In myopathy, fiber density may increase slightly due to involvement of intramuscular nerve and fiber splitting. Jitter is sometimes increased in voluntary S F E M G due to velocity recovery function (VRF). A n o t h e r advantage of S-SFEMG is its ability to exclude the V R F effect due to stable firing rate. The combined application of voluntary S F E M G and S-SFEMG is useful to study the neurogenic nature in myopathy.
•
•
Far-field potentials in surface EMG
Dick F. Stegeman, Karin Roeleveld, Dick M. Vingerhoets.
Institute of Neurology, Department of Clinical Neurophysiology, University Hospital Nijmegen, The Netherlands Most potentials recorded in neuromuscular electrophysiology change in amplitude, wave shape and even polarity when the recording electrode is moved over a small distance. First in the electroencephalogram, components were described which hardly change their characteristics with electrode position over the body or over the scalp. In this contribution it will be shown that these "far-fields" also form a part of surface E M G recordings during voluntary contractions. From basic electric field theory it can be concluded that these far-field p h e n o m e n a are generated by dipolar sources in any finite volume conductor. Propagating action potentials of nerve and muscle fibres are composed of two equal dipoles of opposite direction. For such a source the far-field contributions cancel. Therefore, propagating nerve and muscle fibre action potentials are not expected to generate far-fields. However, when the constant propagation of an action potential is disturbed in the widest sense of the word, far-field potentials are generated. This can be understood from an incomplete cancellation for some time. Such a disturbance can be caused by: 1) A change in the size of the extracellular medium, 2) a changing extracellular conductivity, 3) the generation or the blocking of an action potential and 4) a change in the direction of action potential propagation. It is evident that situations described in the above are numerous all over the neuromuscular system. It will be shown that far-field components in E M G records are predominantly caused by the blocking of action potentials at the fibre-tendon transition (see cause 3) above).
WS-2. SINGLE FIBER EMG
IW~2-~
Single fiber EMG in neuromuscular disorders
Stimulation SFEMG: a diagnostic method and a tool in research Jo2e V. Trontelj 1, Erik V. Sffdberg 2. 1 Institute of Clinical Neurophysiology, Ljubljana University Medical Center, Slovenia; 2 Department of Clinical Neurophysiology, University Hospital, Uppsala Stimulation S F E M G has evolved into a useful modification of the original method introduced in the 60s by Ekstedt and St/tlberg. It is based on a combination of well controllable, highly selective activation with highly selective recording. A m o n g the advantages of the method is its greater precision, since only single neuromuscular junctions rather than pairs are studied, and the often disturbing effect of muscle fiber velocity recovery function can be eliminated. The main use of stimulation S F E M G remains in the diagnosis of neuromuscular transmission disorders, in which it offers additional sensitivity (close to 100%). Moreover, the study of individual neuromuscular junctions at different stimulation rates allows a better differentiation between the pre- and post-synaptic abnormalities. The method is suitable to detect muscle fiber splitting, a common finding in certain neuromuscular disorders. Direct intrafascicular muscle fiber stimulation allows precise measurement of propagation velocity (a function of muscle fiber diameter) and its recovery function (abnormal in muscular dystrophies). The p h e n o m e n o n of action potential recovery function may provide a useful and sensitive parameter in evaluating depolarisation/repolarisation abnormalities, such as in genetically determined or drug-induced myotonic disorders. Myogenic block of conduction can be detected in ion channel abnormalities. Stimulation S F E M G allows reliable identification of the various late responses to nerve stimulation, e.g., differentiation between the recurrent (F) and H-reflex responses. The measurement of reflex jitter allows the recognition of monosynaptic, oligosynaptic and polysynaptic reflex responses. The method has been used to identify the monosynaptic and oligosynaptic contacts between the cortico-spinal tract neurons and the lower motor neurons of different limb and cranial muscles.
Kimiyoshi Arimura. The Third Department of lnternal Medicine,
Kagoshima University School of Medicine Single fiber E M G ( S F E M G ) has gained importance in the study of motor unit microphysiology in neuromuscular disorders. Among other features, determination of fiber density, indicating reinnervation and jitter, indicating abnormality of neuromuscular transmission, have been applied clinically. In anterior horn cell disease, abnormal jitter and blocking are usually prominent in ALS indicating rapid progression, whereas increased fiber density is prominent in spinal muscular atrophy. Decremental response in ALS may suggest lowering safety factor due to presynaptic involvement. Stimulation S F E M G (S-SFEMG) is a new method for jitter measurement. The main advantage of S-SFEMG over voluntary S F E M G is its ability to study in detail the pathomechanism of neuromuscular transmission at different stimulation frequencies.
•
Single fiber EMG (SFEMG) in the diagnosis and management of myasthenla gravis (MG) Donald B. Sanders. Duke University Medical Center, Durham, NC, USA S F E M G demonstrates abnormal jitter in virtually all patients with MG, but in some patients it may be necessary to examine several muscles to demonstrate the characteristic findings. Jitter is abnormal in the extensor digitorum communis muscle (EDC) in about 85% of M G patients overall, in over 60% of those with ocular M G and in over 50% of patients in clinical remission. Jitter is abnormal in a face muscle in almost all patients with MG: the EDC, frontalis or both are abnormal in over 95% of patients at the initial evaluation. Jitter is usually greater in facial muscles than
Workshop3. Motorlearningand plasticily in limb muscles, but this pattern is reversed in about 5% of patients with MG. Very rarely, abnormal jitter can be demonstrated in the orbicularis oculi muscle when it is normal in the EDC and frontalis. In about 5% of patients with MG weakness is limited to a few limb muscles. In these patients jitter may be normal in the EDC but abnormal in a weak limb muscle. Thus, if jitter is normal in the E D C and frontalis muscles, the orbicularis oculi (in ocular MG) or a weak limb muscle should be examined. Jitter is usually abnormal even when the patient with MG is taking cholinesterase inhibitors. However, in rare patients with ocular or mild limb weakness, increase jitter can be demonstrated only after these medications have been discontinued. Abnormal jitter may be suppressed by immunosuppressant treatment for MG. Changes in MG severity usually correlate with changes in jitter measurements and serial S F E M G studies may be of value in predicting or confirming changes in disease severity under certain circumstances. For example, when the jitter values in one muscle have been constant for several months, any subsequent increase in jitter usually accompanies or heralds clinical deterioration. In patients who improve while receiving chronic immunosuppressant medications, jitter usually improves but remains elevated after clinical remission has occurred, then fall slowly toward normal values if effective immunosuppression continues.
~ - ~
SFEMG in Lambert-Eaton myasthenic syndrome and botulism Shin J. Oh. Department of Neurology, The University of Alabama at Birmingham, Birmingham, Alabama, USA We have analyzed the SFEMG in 16 patients with clinically and electrophysiologically well-established Lambert-Eaton Myasthenic Syndrome (LEMS). Fiber density (FD) was normal in all patients except one, in which FD was just above the normal limit. Jitter was abnormal in all 16 cases regardless of the strength of the EDC muscle or severity of disease: mean MCD was 154.3 /zs; 97% of potential pairs (PP), > 53 #s in MCD; and 73% of PP, blocking. In four patients, MCDs were analyzed in relation to the firing rate of PP In all four cases, MCD improved with increasing firing rates, indicating a pre-synaptic block. S F E M G findings are well correlated with clinical severity of diseases. Mean MCDs are significantly (P < 0.03) improved with clinical improvement. Number of PP with > 53 #s and with blocking is also improved with clinical improvement. However, the jitter became rarely normalized even in asymptomatic stage. MCDs are better (R > --0.64), though inversely, correlated with the incremental responses at high rate of stimulation (HRS) in the logarithmic scale, than the CMAPs. Both of these are the best electrophysiological indicators of severity of disease. In five cases with the serial SFEMGs, MCD was a better prognosticator in disease status than the CMAP or HRS response. In botulism, the S F E M G findings are essentially same with those observed in LEMS in four reported cases. Thus, the SFEMG is extremely helpful for diagnosis and follow-up of patients with presynaptic disorders.
$25
WS-3. MOTOR LEARNING AND PLASTICITY
~
Learning of sequential procedures in monkeys
Okihide Hikosaka, Shigehiro Miyachi, Kae Miyashita.
Department of Physiology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan Recent clinical studies have suggested that the basal ganglia, among other areas, might be involved in procedural/motor learning. However, it is unknown how and where learning takes place and how and where the memory is stored? As a first step to answer these questions, we designed a new experimental paradigm (called '2 by 5 task') for monkeys. Upon pressing of a home key, two of 16 (4 x 4) LED buttons (called 'set') were illuminated and the monkey had to press them in a predetermined order which he had to find by trial and error. A total of 5 sets (called 'hyperset') were presented in a fixed order for completion of a trial. Learning took place for each hyperset within a block of experiment (short-term learning) as well as across days of practice (longterm learning), which was evident as the decrease in the number of errors and the decrease in performance time. We found that the procedural learning was correlated with the development of anticipatory eye movements. Initially, a saccade occurred to one of the two LED targets after their onset; after long-term practice (20-30 days), the targeting saccades started before the target onset. Using this task we started to examine the effects of reversible blockade of the monkey striatum on learning of new procedures and execution of learned procedures. At the time of the experiment the monkey had experienced more than 700 hypersets, 14 of which were chosen for everyday practice and therefore were highly learned. The task also allowed us to examine new hypersets, after each injection, by computer-generated random numbers. For the injection, we implanted 12 guide tubes directing at the striatum (caudate and putamen, left and right) at three anteroposterior levels in one monkey. The blockade of the anterior striaturn and the anterior pallidum led to deficits in learning of new hypersets while execution of learned hypersets remained intact. By contrast, the blockade of the posterior striatum led to deficits in execution of learned hypersets while learning of new hypersets was unaffected. These results suggest that the neural mechanisms for procedural learning and the neural mechanisms for memory storage are separate and that the anterior and posterior parts of the basal ganglia contribute to them differentially.
•
Reorganization of cortical motor outputs in the acquisition of new motor skills Alvaro Pascual-Leone. Unidad de Neurobiologia, Dept. Fisiologla, Univ. Valencia, Spain
We have used serial transcranial magnetic stimulation (TMS) mapping of the motor cortical outputs to study the plasticity of the adult human cortex during the acquisition of new motor skills. Learning to perform a five-finger exercise on the piano given strict performance constraints requires several days of practice. Using a MIDI-keyboard and computerized analysis of the subject's performance we have quantified the performance improvement and have correlated it with the changes in cortical output maps demonstrated with daily TMS mapping studies. Acquisition of the new skill is associated with an enlargement of the area of cortical output to the muscles involved in the task and a reduction in the cortical motor threshold for their activation. These changes