Main Articles
Cortical versus spinal dysfunction in amyotrophic lateral sclerosis
Shahram Attarian MD,
Jean-Pierre Vedel PhD,
Jean Pouget MD,
Annie Schmied PhD,
Corresponding Author
Shahram Attarian MD
Department of Neurology and Neuromuscular Diseases, CHU La Timone, 264 rue Saint-Pierre, 13385 Marseille, France
Department of Neurology and Neuromuscular Diseases, CHU La Timone, 264 rue Saint-Pierre, 13385 Marseille, FranceSearch for more papers by this authorJean-Pierre Vedel PhD
Plasticity and Pathophysiology of Movement, UMR 6196, CNRS, 31 Chemin Joseph Aiguier, 13402 Marseille, France
Search for more papers by this authorJean Pouget MD
Department of Neurology and Neuromuscular Diseases, CHU La Timone, 264 rue Saint-Pierre, 13385 Marseille, France
Search for more papers by this authorAnnie Schmied PhD
Plasticity and Pathophysiology of Movement, UMR 6196, CNRS, 31 Chemin Joseph Aiguier, 13402 Marseille, France
Search for more papers by this authorShahram Attarian MD,
Jean-Pierre Vedel PhD,
Jean Pouget MD,
Annie Schmied PhD,
Corresponding Author
Shahram Attarian MD
Department of Neurology and Neuromuscular Diseases, CHU La Timone, 264 rue Saint-Pierre, 13385 Marseille, France
Department of Neurology and Neuromuscular Diseases, CHU La Timone, 264 rue Saint-Pierre, 13385 Marseille, FranceSearch for more papers by this authorJean-Pierre Vedel PhD
Plasticity and Pathophysiology of Movement, UMR 6196, CNRS, 31 Chemin Joseph Aiguier, 13402 Marseille, France
Search for more papers by this authorJean Pouget MD
Department of Neurology and Neuromuscular Diseases, CHU La Timone, 264 rue Saint-Pierre, 13385 Marseille, France
Search for more papers by this authorAnnie Schmied PhD
Plasticity and Pathophysiology of Movement, UMR 6196, CNRS, 31 Chemin Joseph Aiguier, 13402 Marseille, France
Search for more papers by this authorAbstract
Little is known about the possible link between cortical and spinal motor neuron dysfunction in amyotrophic lateral sclerosis (ALS). We correlated the characteristics of the responses to transcranial magnetic stimulation (TMS) with the electromechanical properties and firing pattern of single motor units (MUs) tested in nine ALS patients, three patients with Kennedy's disease, and 15 healthy subjects. In Kennedy's disease, 19 of 22 MUs were markedly enlarged with good electromechanical coupling and discharged with great variability. Their excitatory responses increased with MU size. In ALS, 17 of 34 MUs with excitatory responses behaved as in Kennedy's disease. By contrast, 28 MUs with nonsignificant responses showed poor electromechanical coupling and high firing rates, whereas 28 MUs with inhibitory responses showed moderate functional alterations. This result indicates that in ALS as in Kennedy's disease, sprouting of corticospinal axons may occur on surviving motoneurons. A clear relationship exists between the responsiveness of MUs to TMS and their functional state. Muscle Nerve, 2006
REFERENCES
- 1 Allen C, Stevens CF. An evaluation of causes for unreliability of synaptic transmission. Proc Natl Acad Sci USA 1994; 91: 10380–10383.
- 2 Attarian S, Azulay JP, Lardillier D, Verschueren A, Pouget J. Transcranial magnetic stimulation in lower motor neuron diseases. Clin Neurophysiol 2005; 116: 35–42.
- 3 Awiszus F, Feistner H. Abnormal EPSPs evoked by magnetic brain stimulation in hand muscle motoneurons of patients with amyotrophic lateral sclerosis. Electroencephalogr Clin Neurophysiol 1993; 89: 408–414.
- 4 Awiszus F, Feistner H. Comparison of single motor unit responses to transcranial magnetic and peroneal nerve stimulation in the tibialis anterior muscle of patients with amyotrophic lateral sclerosis. Electroencephalogr Clin Neurophysiol 1995; 97: 90–95.
- 5 Awiszus F, Feistner H. Correlations between size parameters and the amplitude of the excitatory postsynaptic potential evoked by magnetic brain stimulation in human hand muscle motoneurons. Exp Brain Res 1994; 98: 128–134.
- 6 Bawa P, Lemon RN. Recruitment of motor units in response to transcranial magnetic stimulation in man. J Physiol (Lond) 1993; 471: 445–464.
- 7 Boniface SJ, Mills KR, Schubert M. Responses of single spinal motoneurons to magnetic brain stimulation in healthy subjects and patients with multiple sclerosis. Brain 1991; 114: 643–662.
- 8 Brooks BR. El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. Subcommittee on Motor Neuron Diseases/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial “Clinical limits of amyotrophic lateral sclerosis” workshop contributors. J Neurol Sci 1994; 124: 96–107.
- 9 Brown WF, Strong MJ, Snow R. Methods for estimating numbers of motor units in biceps-brachialis muscles and losses of motor units with aging. Muscle Nerve 1988; 11: 423–432.
- 10 Bruijn LI, Miller TM, Cleveland DW. Unraveling the mechanisms involved in motor neuron degeneration in ALS. Annu Rev Neurosci 2004; 27: 723–749.
- 11 Calancie B, Nordin M, Wallin U, Hagbarth KE. Motor-unit responses in human wrist flexor and extensor muscles to transcranial cortical stimuli. J Neurophysiol 1987; 58: 1168–1185.
- 12 Calvin WH, Stevens CF. Synaptic noise and other sources of randomness in motoneuron interspike intervals. J Neurophysiol 1968; 31: 574–587.
- 13 Chan KM, Doherty TJ, Brown WF. Contractile properties of human motor units in health, aging, and disease. Muscle Nerve 2001; 24: 1113–1133.
- 14 Classen J, Benecke R. Inhibitory phenomena in individual motor units induced by transcranial magnetic stimulation. Electroencephalogr Clin Neurophysiol 1995; 97: 264–274.
- 15 Coers C, Telerman-Toppet N, Gerard JM. Terminal innervation ratio in neuromuscular disease. I. Methods and controls. Arch Neurol 1973; 29: 210–214.
- 16 Davey NJ, Romaiguere P, Maskill DW, Ellaway PH. Suppression of voluntary motor activity revealed using transcranial magnetic stimulation of the motor cortex in man. J Physiol (Lond) 1994; 477: 223–235.
- 17 Dengler R, Konstanzer A, Kuther G, Hesse S, Wolf W, Struppler A. Amyotrophic lateral sclerosis: macro-EMG and twitch forces of single motor units. Muscle Nerve 1990; 13: 545–550.
- 18 Desiato MT, Caramia MD. Towards a neurophysiological marker of amyotrophic lateral sclerosis as revealed by changes in cortical excitability. Electroencephalogr Clin Neurophysiol 1997; 105: 1–7.
- 19 Di Lazzaro V, Restuccia D, Oliviero A, Profice P, Ferrara L, Insola A, et al. Magnetic transcranial stimulation at intensities below active motor threshold activates intracortical inhibitory circuits. Exp Brain Res 1998; 119: 265–268.
- 20 Dupuis L, Gonzalez de Aguilar JL, di Scala F, Rene F, de Tapia M, Pradat PF, et al. Nogo provides a molecular marker for diagnosis of amyotrophic lateral sclerosis. Neurobiol Dis 2002; 10: 358–365.
- 21 Eccles JC, Libet B, Young RR. The behaviour of chromatolysed motoneurones studied by intracellular recording. J Physiol (Lond) 1958; 143: 11–40.
- 22 Eisen A, Entezari-Taher M, Stewart H. Cortical projections to spinal motoneurons: changes with aging and amyotrophic lateral sclerosis. Neurology 1996; 46: 1396–1404.
- 23 Eisen A, Kim S, Pant B. Amyotrophic lateral sclerosis (ALS): a phylogenetic disease of the corticomotoneuron? Muscle Nerve 1992; 15: 219–224.
- 24 Eisen A, Nakajima M, Weber M. Corticomotoneuronal hyper-excitability in amyotrophic lateral sclerosis. J Neurol Sci 1998; 160: S64–S68.
- 25 Eisen A, Pant B, Stewart H. Cortical excitability in amyotrophic lateral sclerosis: a clue to pathogenesis. Can J Neurol Sci 1993; 20: 11–16.
- 26 Ellaway PH. Cumulative sum technique and its application to the analysis of peristimulus time histograms. Electroencephalogr Clin Neurophysiol 1978; 45: 302–304.
- 27
Enterzari-Taher M,
Eisen A,
Stewart H,
Nakajima M.
Abnormalities of cortical inhibitory neurons in amyotrophic lateral sclerosis.
Muscle Nerve
1997;
20:
65–71.
10.1002/(SICI)1097-4598(199701)20:1<65::AID-MUS9>3.0.CO;2-F CAS PubMed Web of Science® Google Scholar
- 28 Garnett R, Stephens JA. The reflex responses of single motor units in human first dorsal interosseous muscle following cutaneous afferent stimulation. J Physiol (Lond) 1980; 303: 351–364.
- 29 Hirota N, Weber M, Eisen A. Temporal dispersion of cortically evoked single motor unit potentials in ALS. J Neurol Sci 2000; 180: 71–75.
- 30 Ingram DA, Davis GR, Schwartz MS, Swash M. The effect of continuous voluntary activation on neuromuscular transmission: a SFEMG study of myasthenia gravis and anterior horn cell disorders. Electroencephalogr Clin Neurophysiol 1985; 60: 207–213.
- 31 Kaji R, Kimura J. Amyotrophic lateral sclerosis: what makes the direct corticospinal tract so vulnerable. Muscle Nerve 1993; 16: 872–874.
- 32 Karpati G, Kimura J. Amyotrophic lateral sclerosis: a critique of a hypothesis. Muscle Nerve 1992; 15: 224–226.
- 33 Kiernan JA, Hudson AJ. Changes in sizes of cortical and lower motor neurons in amyotrophic lateral sclerosis. Brain 1991; 114: 843–853.
- 34 Klem GH, Luders HO, Jasper HH, Elger C. The ten-twenty electrode system of the International Federation. The International Federation of Clinical Neurophysiology. Electroencephalogr Clin Neurophysiol Suppl 1999; 52: 3–6.
- 35 Kohara N, Kaji R, Kojima Y, Kimura J. An electrophysiological study of the corticospinal projections in amyotrophic lateral sclerosis. Clin Neurophysiol 1999; 110: 1123–1132.
- 36 Kohara N, Kaji R, Kojima Y, Mills KR, Fujii H, Hamano T, et al. Abnormal excitability of the corticospinal pathway in patients with amyotrophic lateral sclerosis: a single motor unit study using transcranial magnetic stimulation. Electroencephalogr Clin Neurophysiol 1996; 101: 32–41.
- 37 Kujirai T, Caramia MD, Rothwell JC, Day BL, Thompson PD, Ferbert A, et al. Corticocortical inhibition in human motor cortex. J Physiol (Lond) 1993; 471: 501–519.
- 38 Ludolph AC, Meyer T, Riepe MW, Volkel H. Amyotrophic lateral sclerosis and glutamate. Restor Neurol Neurosci 1998; 13: 59–67.
- 39 Martin LJ. Neuronal death in amyotrophic lateral sclerosis is apoptosis: possible contribution of a programmed cell death mechanism. J Neuropathol Exp Neurol 1999; 58: 459–471.
- 40 Matthews PB. Relationship of firing intervals of human motor units to the trajectory of post-spike after-hyperpolarization and synaptic noise. J Physiol (Lond) 1996; 492: 597–628.
- 41 McComas AJ, Sica RE. Properties of motor units in normal and partly denervated human muscles. J Physiol (Lond) 1971; 212: 28P–29P.
- 42 Millard RE, McAnally KI, Clark GM. A gated differential amplifier for recording physiological responses to electrical stimulation. J Neurosci Methods 1992; 44: 81–84.
- 43 Mills KR. Excitatory and inhibitory effects on human spinal motoneurones from magnetic brain stimulation. Neurosci Lett 1988; 94: 297–302.
- 44 Mills KR. Motor neuron disease. Studies of the corticospinal excitation of single motor neurons by magnetic brain stimulation. Brain 1995; 118: 971–982.
- 45 Morrison BM, Morrison JH. Amyotrophic lateral sclerosis associated with mutations in superoxide dismutase: a putative mechanism of degeneration. Brain Res Brain Res Rev 1999; 29: 121–135.
- 46 Nakajima M, Eisen A, McCarthy R, Olney RK, Aminoff MJ. Reduced corticomotoneuronal excitatory postsynaptic potentials (EPSPs) with normal Ia afferent EPSPs in amyotrophic lateral sclerosis. Neurology 1996; 47: 1555–1561.
- 47
Nakajima M,
Eisen A,
Stewart H.
Comparison of corticomotoneuronal EPSPs and macro-MUPs in amyotrophic lateral sclerosis.
Muscle Nerve
1998;
21:
18–24.
10.1002/(SICI)1097-4598(199801)21:1<18::AID-MUS3>3.0.CO;2-J CAS PubMed Web of Science® Google Scholar
- 48 Nakajima M, Eisen A, Stewart H. Diverse abnormalities of corticomotoneuronal projections in individual patients with amyotrophic lateral sclerosis. Electroencephalogr Clin Neurophysiol 1997; 105: 451–457.
- 49 Nihei K, McKee AC, Kowall NW. Patterns of neuronal degeneration in the motor cortex of amyotrophic lateral sclerosis patients. Acta Neuropathol (Berl) 1993; 86: 55–64.
- 50 Pamphlett R, Kril J, Hng TM. Motor neuron disease: a primary disorder of corticomotoneurons? Muscle Nerve 1995; 18: 314–318.
- 51 Plaitakis A, Caroscio JT. Abnormal glutamate metabolism in amyotrophic lateral sclerosis. Ann Neurol 1987; 22: 575–579.
- 52 Pouget J, Trefouret S, Attarian S. Transcranial magnetic stimulation (TMS): compared sensitivity of different motor response parameters in ALS. Amyotroph Lateral Scler Other Motor Neuron Disord 2000; 1: S45–S49.
- 53 Rothstein JD, Tsai G, Kuncl RW, Clawson L, Cornblath DR, Drachman DB, et al. Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis. Ann Neurol 1990; 28: 18–25.
- 54 Schmied A, Pouget J, Vedel JP. Electromechanical coupling and synchronous firing of single wrist extensor motor units in sporadic amyotrophic lateral sclerosis. Clin Neurophysiol 1999; 110: 960–974.
- 55 Stalberg E. Electrophysiological studies of reinnervation in ALS. Adv Neurol 1982; 36: 47–59.
- 56 Stalberg E. Invited review: electrodiagnostic assessment and monitoring of motor unit changes in disease. Muscle Nerve 1991; 14: 293–303.
- 57 Swash M. Amyotrophic lateral sclerosis: a phylogenetic disease of the corticomotoneuron? Comments on the hypothesis. Muscle Nerve 1992; 15: 226–228.
- 58 Taylor AM, Steege JW, Enoka RM. Motor-unit synchronization alters spike-triggered average force in simulated contractions. J Neurophysiol 2002; 88: 265–276.
- 59 Thomas CK, Bigland-Ritchie B, Westling G, Johansson RS. A comparison of human thenar motor-unit properties studied by intraneural motor-axon stimulation and spike-triggered averaging. J Neurophysiol 1990; 64: 1347–1351.
- 60 Triggs WJ, Menkes D, Onorato J, Yan RS, Young MS, Newell K, et al. Transcranial magnetic stimulation identifies upper motor neuron involvement in motor neuron disease. Neurology 1999; 53: 605–611.
- 61 Venkatesh S, Shefner JM, Logigian EL. Does muscle reinnervation produce electromechanical dissociation in amyotrophic lateral sclerosis? Muscle Nerve 1995; 18: 1335–1337.
- 62
Weber M,
Eisen A.
Assessment of upper and lower motor neurons in Kennedy's disease: implications for corticomotoneuronal PSTH studies.
Muscle Nerve
1999;
22:
299–306.
10.1002/(SICI)1097-4598(199903)22:3<299::AID-MUS2>3.0.CO;2-D CAS PubMed Web of Science® Google Scholar
- 63 Weber M, Eisen A, Nakajima M. Corticomotoneuronal activity in ALS: changes in the peristimulus time histogram over time. Clin Neurophysiol 2000; 111: 169–177.
- 64 Yokota T, Yoshino A, Inaba A, Saito Y. Double cortical stimulation in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 1996; 61: 596–600.
- 65 Zanette G, Tamburin S, Manganotti P, Refatti N, Forgione A, Rizzuto N. Changes in motor cortex inhibition over time in patients with amyotrophic lateral sclerosis. J Neurol 2002; 49: 1723–1728.
- 66 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.
Citing Literature
