Forty patients with ALS underwent cortical magnetic stimulation. Twelve had marked pseudobulbar signs; in these motor evoked potentials (MEPs) could not be elicited. Mean MEP latencies in the others, who had predominantnantly lower motor neuron signs, measured 23.3 i 2.1 msec (thenar), 18.7 t 5.3 msec (EDC), and 13.4 5 2.9 msec (biceps), respectively. These values were significantly longer (P > 0.001) compared with normal values (n = 35), which measured 20.2 k 1.6, 14.2 t 1.7, and 9.4 2 1.7 msec, respectively. MEP amplitude was often markedly reduced (less than 15% of the M wave) compared with a normal mean of 39.5 13.0%. Overall abnormal MEPs (delayed, absent, or reduced in amplitude) approached 100%. It is argued that measuring central motor delay, which was not significantly different in the patients compared with normals, is subject to error in ALS. Key words: magnetic stimulation ALS MUSCLE 81 NERVE 13:146-151 1990
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CORTICAL MAGNETIC STIMULATION IN AMYOTROPHIC LATERAL SCLEROSIS ANDREW EISEN, WAYNE SHYTBEL, KIRSTEN MURPHY, and MAUREEN HOIRCH
Amyotrophic lateral sclerosis (ALS) typically involves both the upper and lower motor neurons. Electrophysiological methods, especially needle EMG and motor unit counting techniques, have proved valuable in confirming the diagnosis, delineating the extent of disease and evaluating its progress and prognosis."*- 10922*32,33However, upper motor neuron signs may predominant early in the course of ALS and rarely patients are seen in whom these features occur to the exclusion of overt lower motor neuron signs.2GWhen this happens needle EMG and motor unit counting techniques have a limited or no useful role. Stimulation, using electrical pulses applied to the intact, awake, human cortex, has been available since 1980 and allows assessment of central motor The, technique is uncomfortable or painful even when unifocal as opposed to bipolar stimulation is employed precluding widespread clinical use.28729
From the Neurornuscular Diseases Unrt (EMG), The Vancouver General Hospital, Vancouver, BC Acknowledgment Funded by a grant from the British Columbia Health Care Research Foundation Address reprint requests to Dr Eisen at The Neuromuscular Diseases Unit (EMG), The Vancouver General Hospital, 855 West 12th Avenue, Vancouver, BC V5Z 1M9. Canada Accepted for publication December 7, 1988 0148-639W90/020146-06 $04 00 0 1990 John Wiley & Sons, Inc
146
Magnetic Stimulation in ALS
Magnetic stimulation, available since 1985, is virtually free of discomfort when applied to the intact cortex."' It has already been used to clinical advantage in E ~ r o p e . ~ , ' , ' ~ ~ ' ~ , ~ ~ ~ ~ ~ Here we report the use of cortical magnetic stimulation in 40 cases of amyotrophic lateral sclerosis. METHODS
T h e patients were all examined by one of us (AE) and gave informed consent for study. 'I'heir ages ranged from 38 to 76 years (mean 62.8 years). Thirty two were men. All had both upper and lower motor neuron abnormalities in conjunction with at least one, and usually several, abnormal needle electromyographic studies that were characteristic of anterior horn cell disease. Most had radiological studies (either a C T scan and/or an MRI) to rule out a structural lesion causing their disease. A Dantec magnetic stimulator was used. It has a maximum field strength of 2.3 T induced by charging up 4,3600 FF capacitors, each shunted by a 22 R resistor. T h e device generates 1420 V at 90% maximum output. The stimulating coil used has 15 concentric turns of copper wire with outer and central diameters of 14.0 and 2.5 cm, respectively. The coil was placed tangentially to the vertex with its center just anterior to the vertex. In most patients the coil was positioned so that the inducing current flowed clockwise when viewed from
MUSCLE & NERVE
February 1990
above. This preferentially excited the right cortex, and motor potentials were recorded from the left arm. We attempted to record motor evoked potentials (MEPs) from the thenar, extensor digitorum communis, and biceps muscles. MEPs were recorded using surface, gold disk, electrogel-filled electrodes attached over the muscle endplate (G1) and a distant relatively inactive site (G2), respectively. Subjects were instructed to activate the target muscle using minimal voluntary contraction, qualitatively monitored by visual and auditory EMG feedback. Voluntary contraction facilitates the MEP so that latencies and amplitudes are respectively shorter and higher than when recorded from a relaxed muscle.25 When a response could be elicited five traces were superimposed. The one with the shortest latency was measured and normalized for arm length, where MEP latency = 0.2 x arm length + 6.9." The one with the greatest amplitude was also measured. Amplitude was expressed in absolute terms and, For the thenar and EDC muscles, as a percentage of their maximum M waves. Central motor delay was measured in 15 patients using both "root" stimulation and F wave rcsponses. In the former method the coil was placed laterally over the base of the neck so that the maximum magnetic field was over the C7 spinous process ipsilateral to the side of recording. MEPs were recorded simultaneously from the biceps, EDC, and thenar muscles using the same recording sites as for cortical stimulation. Central delay was derived from subtraction of' the cortical and neck latencies. The latter method employed subtraction of the shortest latency F wave and was limited to the thenar muscle ~ n l y . " ~ ' " , 'Central ~ * ~ ~ delay was derived by [Flat-1+M lat] [MEP lat] 2 Results were compared with a normal control group (n = 35) mean age 53.7 years (19-82). Normal values for this laboratory for some of the muscles used have been the subject of a previous communication." Central delay was measured in 15 subjects. RESULTS
No significant side effects were encountered, and the cortical stimulus delivered via the magnetic coil was well tolerated. Mean duration of clinical disease was 2.4 years (range 4 months to 8 years).
Magnetic Stimulation in ALS
Twelve patients had severe pseudobulbar symptoms and signs consisting of a spastic dysarthria or anarthria, excessive salivation, hyperactive gag and jaw reflexes, and difficulty swallowing. In these, despite increasing the output of the stimulator to 90% of its maximum, it was not possible to elicit a MEP from any of the 3 muscles studied. In the others a MEP was elicited in at least one of the muscles. There was no obvious correlation between the extent of clinical deficit and the degree of abnormality of the ALS In all but three cases the MEP latency was prolonged in at least one muscle (Figs. 1 and 2). Prolongation was usually modest, but mean latencies differed significantly from controls (Table 1) for each of the muscles studied (P > 0.001). Thenar MEP latencies were abnormally prolonged in 14/18 (77.8%) of cases, EDC MEP latencies in 15/20 (75%) cases, and biceps MEP latencies in 8/18 (44.4%) cases. The overall incidence of abnormal (absent or prolonged) MEPs was 37/40 (92.5%). An additional 2 patients had MEPs of normal latency which, however, had reduced amplitudes (
*
CORTICAL MAGNETIC STIMULATION IN AMYOTROPHIC LATERAL SCLEROSIS ANDREW EISEN, WAYNE SHYTBEL, KIRSTEN MURPHY, and MAUREEN HOIRCH
Amyotrophic lateral sclerosis (ALS) typically involves both the upper and lower motor neurons. Electrophysiological methods, especially needle EMG and motor unit counting techniques, have proved valuable in confirming the diagnosis, delineating the extent of disease and evaluating its progress and prognosis."*- 10922*32,33However, upper motor neuron signs may predominant early in the course of ALS and rarely patients are seen in whom these features occur to the exclusion of overt lower motor neuron signs.2GWhen this happens needle EMG and motor unit counting techniques have a limited or no useful role. Stimulation, using electrical pulses applied to the intact, awake, human cortex, has been available since 1980 and allows assessment of central motor The, technique is uncomfortable or painful even when unifocal as opposed to bipolar stimulation is employed precluding widespread clinical use.28729
From the Neurornuscular Diseases Unrt (EMG), The Vancouver General Hospital, Vancouver, BC Acknowledgment Funded by a grant from the British Columbia Health Care Research Foundation Address reprint requests to Dr Eisen at The Neuromuscular Diseases Unit (EMG), The Vancouver General Hospital, 855 West 12th Avenue, Vancouver, BC V5Z 1M9. Canada Accepted for publication December 7, 1988 0148-639W90/020146-06 $04 00 0 1990 John Wiley & Sons, Inc
146
Magnetic Stimulation in ALS
Magnetic stimulation, available since 1985, is virtually free of discomfort when applied to the intact cortex."' It has already been used to clinical advantage in E ~ r o p e . ~ , ' , ' ~ ~ ' ~ , ~ ~ ~ ~ ~ Here we report the use of cortical magnetic stimulation in 40 cases of amyotrophic lateral sclerosis. METHODS
T h e patients were all examined by one of us (AE) and gave informed consent for study. 'I'heir ages ranged from 38 to 76 years (mean 62.8 years). Thirty two were men. All had both upper and lower motor neuron abnormalities in conjunction with at least one, and usually several, abnormal needle electromyographic studies that were characteristic of anterior horn cell disease. Most had radiological studies (either a C T scan and/or an MRI) to rule out a structural lesion causing their disease. A Dantec magnetic stimulator was used. It has a maximum field strength of 2.3 T induced by charging up 4,3600 FF capacitors, each shunted by a 22 R resistor. T h e device generates 1420 V at 90% maximum output. The stimulating coil used has 15 concentric turns of copper wire with outer and central diameters of 14.0 and 2.5 cm, respectively. The coil was placed tangentially to the vertex with its center just anterior to the vertex. In most patients the coil was positioned so that the inducing current flowed clockwise when viewed from
MUSCLE & NERVE
February 1990
above. This preferentially excited the right cortex, and motor potentials were recorded from the left arm. We attempted to record motor evoked potentials (MEPs) from the thenar, extensor digitorum communis, and biceps muscles. MEPs were recorded using surface, gold disk, electrogel-filled electrodes attached over the muscle endplate (G1) and a distant relatively inactive site (G2), respectively. Subjects were instructed to activate the target muscle using minimal voluntary contraction, qualitatively monitored by visual and auditory EMG feedback. Voluntary contraction facilitates the MEP so that latencies and amplitudes are respectively shorter and higher than when recorded from a relaxed muscle.25 When a response could be elicited five traces were superimposed. The one with the shortest latency was measured and normalized for arm length, where MEP latency = 0.2 x arm length + 6.9." The one with the greatest amplitude was also measured. Amplitude was expressed in absolute terms and, For the thenar and EDC muscles, as a percentage of their maximum M waves. Central motor delay was measured in 15 patients using both "root" stimulation and F wave rcsponses. In the former method the coil was placed laterally over the base of the neck so that the maximum magnetic field was over the C7 spinous process ipsilateral to the side of recording. MEPs were recorded simultaneously from the biceps, EDC, and thenar muscles using the same recording sites as for cortical stimulation. Central delay was derived from subtraction of' the cortical and neck latencies. The latter method employed subtraction of the shortest latency F wave and was limited to the thenar muscle ~ n l y . " ~ ' " , 'Central ~ * ~ ~ delay was derived by [Flat-1+M lat] [MEP lat] 2 Results were compared with a normal control group (n = 35) mean age 53.7 years (19-82). Normal values for this laboratory for some of the muscles used have been the subject of a previous communication." Central delay was measured in 15 subjects. RESULTS
No significant side effects were encountered, and the cortical stimulus delivered via the magnetic coil was well tolerated. Mean duration of clinical disease was 2.4 years (range 4 months to 8 years).
Magnetic Stimulation in ALS
Twelve patients had severe pseudobulbar symptoms and signs consisting of a spastic dysarthria or anarthria, excessive salivation, hyperactive gag and jaw reflexes, and difficulty swallowing. In these, despite increasing the output of the stimulator to 90% of its maximum, it was not possible to elicit a MEP from any of the 3 muscles studied. In the others a MEP was elicited in at least one of the muscles. There was no obvious correlation between the extent of clinical deficit and the degree of abnormality of the ALS In all but three cases the MEP latency was prolonged in at least one muscle (Figs. 1 and 2). Prolongation was usually modest, but mean latencies differed significantly from controls (Table 1) for each of the muscles studied (P > 0.001). Thenar MEP latencies were abnormally prolonged in 14/18 (77.8%) of cases, EDC MEP latencies in 15/20 (75%) cases, and biceps MEP latencies in 8/18 (44.4%) cases. The overall incidence of abnormal (absent or prolonged) MEPs was 37/40 (92.5%). An additional 2 patients had MEPs of normal latency which, however, had reduced amplitudes (
