Transcranial magnetic stimulation identifies upper motor neuron involvement in motor neuron disease
Abstract
Objective: To evaluate the sensitivity of transcranial magnetic stimulation (TMS) to identify upper motor neuron involvement in patients with motor neuron disease.
Background: Diagnosis of ALS depends on upper and lower motor neuron involvement. Lower motor neuron involvement may be documented with electromyography, whereas definite evidence of upper motor neuron involvement may be elusive. A sensitive, noninvasive test of upper motor neuron function would be useful.
Methods: TMS and clinical assessment in 121 patients with motor neuron disease.
Results: TMS revealed evidence of upper motor neuron dysfunction in 84 of 121 (69%) patients, including 30 of 40 (75%) patients with only probable upper motor neuron signs and unsuspected upper motor neuron involvement in 6 of 22 (27%) patients who had purely lower motor neuron syndromes clinically. In selected cases, upper motor neuron involvement identified with TMS was verified in postmortem examination. Increased motor evoked potential threshold was the abnormality observed most frequently and was only weakly related to peripheral compound muscle action potential amplitude. In a subset of 12 patients reexamined after 11 ± 6 months, TMS showed progression of abnormalities, including progressive inexcitability of central motor pathways and loss of the normal inhibitory cortical stimulation silent period.
Conclusions: TMS provides a sensitive means for the assessment and monitoring of excitatory and inhibitory upper motor neuron function in motor neuron disease.
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References
1.
Lambert EH. Electromyography in amyotrophic lateral sclerosis. In: Norris FH, Kurland LT, eds. Motor neuron diseases: research on amyotrophic lateral sclerosis and related disorders. New York:Grune & Stratton, 1969:135–153.
2.
Triggs WJ, Edgar MA. A 61-year-old man with increasing weakness and atrophy of all extremities. Case records of the Massachusetts General Hospital. N Engl J Med 1995;333:1406–1412.
3.
Elliott JL. A clearer view of upper motor neuron dysfunction in amyotrophic lateral sclerosis. Arch Neurol 1998;55:910–912.
4.
Thompson PD, Day BL, Rothwell JC, et al. The interpretation of electromyographic responses to electrical stimulation of the motor cortex in diseases of the upper motor neurone. J Neurol Sci 1987;80:91–110.
5.
Ingram DA, Swash M. Central motor conduction is abnormal in motor neuron disease. J Neurol Neurosurg Psychiatry 1987;50:159–166.
6.
Hugon J, Lubeau M, Tabaraud F, Chazot F, Vallat JM, Dumas M. Central motor conduction in motor neuron disease. Ann Neurol 1987;22:544–546.
7.
Schriefer TN, Hess CW, Mills KR, Murray NMF. Central motor conduction studies in motor neurone disease using magnetic brain stimulation. Electroencephalogr Clin Neurophysiol 1989;74:431–437.
8.
Eisen A, Shytbel W, Murphy K, Hoirch M. Cortical magnetic stimulation in amyotrophic lateral sclerosis. Muscle Nerve 1990;13:146–151.
9.
Berardelli A, Inghilleri M, Cruccu G, Mercuri B, Manfredi M. Electrical and magnetic transcranial stimulation in patients with corticospinal damage due to stroke or motor neurone disease. Electroencephalogr Clin Neurophysiol 1991;81:389–396.
10.
Caramia MD, Cicinelli P, Paradiso C, et al. “Excitability” changes of muscular responses to magnetic brain stimulation in patients with central motor disorders. Electroencephalogr Clin Neurophysiol 1991;81:243–250.
11.
Uozumi T, Tsuji S, Murai Y. Motor potentials evoked by magnetic stimulation of the motor cortex in normal subjects and patients with motor disorders. Electroencephalogr Clin Neurophysiol 1991;81:251–256.
12.
Triggs WJ, Macdonell RAL, Cros D, Chiappa KH, Shahani BT, Day BJ. Motor inhibition and excitation are independent effects of magnetic cortical stimulation. Ann Neurol 1992;32:345–351.
13.
Eisen A, Pant B, Stewart H. Cortical excitability in amyotrophic lateral sclerosis : a clue to pathogenesis. Can J Neurol Sci 1993;20:11–16.
14.
Younger DS, Rowland LP, Latov N, et al. Motor neuron disease and amyotrophic lateral sclerosis : relation of high CSF protein content to paraproteinemia and clinical syndromes. Neurology 1990;40:595–599.
15.
Kent Braun JA, Walker CH, Weiner MW, Miller RG. Functional significance of upper and lower motor neuron impairment in amyotrophic lateral sclerosis. Muscle Nerve 1998;21:762–768.
16.
Day BL, Rothwell JC, Thompson PD, et al. Delay in the execution of voluntary movement by electrical or magnetic brain stimulation in intact man. Brain 1989;112:649–663.
17.
Prout AJ, Eisen AA. The cortical silent period and amyotrophic lateral sclerosis. Muscle Nerve 1994;17:217–223.
18.
Claus D. Central motor conduction : method and normal results. Muscle Nerve 1990;13:1125–1132.
19.
Claus D, Brunholzl C, Kerling FP, Henschel S. Transcranial magnetic stimulation as a diagnostic and prognostic test in amyotrophic lateral sclerosis. J Neurol Sci 1995;129 (suppl):30–34.
20.
Pioro EP, Antel JP, Cashman NR, Arnold DL. Detection of cortical neuron loss in motor neuron disease by proton magnetic resonance spectroscopic imaging in vivo. Neurology 1994;44:1933–1938.
21.
Gredal O, Rosenbaum S, Topp S, Karlsborg M, Strange P, Werdelin L. Quantification of brain metabolites in amyotrophic lateral sclerosis by localized proton magnetic resonance spectroscopy. Neurology 1997;48:878–881.
22.
Block W, Karitzky J, Traber F, et al. Proton magnetic resonance spectroscopy of the primary motor cortex in patients with motor neuron disease. Arch Neurol 1998;55:931–936.
23.
Rooney WD, Miller RG, Gelinas D, Schuff N, Maudsley AA, Weiner MW. Decreased N-acetylaspartate in motor cortex and corticospinal tract in ALS. Neurology 1998;50:1800–1805.
24.
Ross MA, Miller RG, Berchert L, et al. Toward earlier diagnosis of amyotrophic lateral sclerosis : revised criteria. Neurology 1998;50:768–772.
25.
Brooks BR. El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. J Neurol Sci 1994;124 (suppl):96–107.
26.
Hess CW, Mills KR, Murray NMF. Responses in small hand muscles from magnetic stimulation of the human brain. J Physiol 1987;388:397–419.
27.
Mills KR. Motor neuron disease. Studies of the corticospinal excitation of single motor neurons by magnetic brain stimulation. Brain 1995;118:971–982.
28.
Mills KR, Nithi KA. Corticomotor threshold is reduced in early sporadic amyotrophic lateral sclerosis. Muscle Nerve 1997;20:1137–1141.
29.
Eisen A, Entezari Taher M, Stewart H. Cortical projections to spinal motoneurons : changes with aging and amyotrophic lateral sclerosis. Neurology 1996;46:1396–1404.
30.
Enterzari Taher M, Eisen A, Stewart H, Nakajima M. Abnormalities of cortical inhibitory neurons in amyotrophic lateral sclerosis. Muscle Nerve 1997;20:65–71.
31.
Kohara N, Kaji R, Kojima Y, et al. Magnetic stimulation in ALS : a single motor unit study. Electroencephalogr Clin Neurophysiol 1996;46:327–336.
32.
Yokota T, Yoshino A, Inaba A, Saito Y. Double cortical stimulation in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 1996;61:596–600.
33.
Ziemann U, Winter M, Reimers CD, Reimers K, Tergau F, Paulus W. Impaired motor cortex inhibition in patients with amyotrophic lateral sclerosis : evidence from paired transcranial magnetic stimulation. Neurology 1997;49:1292–1298.
34.
Eisen A, Stewart H, Schulzer M, Cameron D. Anti-glutamate therapy in amyotrophic lateral sclerosis : a trial using lamotrigine. Can J Neurol Sci 1993;20:297–301.
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Received: December 7, 1998
Accepted: March 9, 1999
Published online: August 1, 1999
Published in print: August 1, 1999
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