Supplement

Transcranial magnetic stimulation: Summary

Mamede de CarvalhoHospital de Santa Maria, Lisbon, Portugal

ALS and other motor neuron disorders 2002 (suppl 1), S117–S118© 2002 ALS and other motor neuron disorders. All rights reserved. ISSN 1466-0822 S117

Over the last 15 years, transcranial magnetic stimulation(TMS) has been established as a useful method of studyingthe upper motor neuron (UMN) function in many disor-ders, notably ALS. The parameters most often investigatedcan be obtained easily: cortical motor threshold (CMT),central conduction time (CCT), and motor-evoked poten-tial (MEP), generally expressed as a percentage of the com-pound muscle action potential amplitude obtained byelectrical stimulation of the peripheral nerve (MEP/CMAPamplitude). Other parameters can be studied, but they aretime-consuming and require special software and expertiseonly available in particular laboratories, the variability ofthe results is probably larger and certainly dependent onthe subtle technical details, and their application is limitedto those patients able to cooperate fully. In this group ofother parameters we can include the silence period, doublestimulation paradigms, peristimulus time histogram,motor area mapping and triple stimulation technique.

A good measure for following the ALS progressionshould be well tolerated, easy and quick to perform, sensi-tive and reliable, and the changes must re�ect UMN lossand be signi�cant in a short period of time, such as oneyear. Speci�city is not necessary in this regard.1 CMT, CCTand MEP/CMAP amplitude are well tolerated, easy andrapid. Probably CMT and MEP/CMAP amplitude re�ectUMN loss.1 CMT is reliable,2 but is not sensitive and doesnot change signi�cantly in a short period of time.3 CCT isnot sensitive, not very reliable, is not directly related to thenumber of UMN, and remains normal over time in ALS.3,4

MEP/CMAP amplitude can change early in some patients;however it lacks reliability, which makes it dif�cult to useto measure progression.1

The cortical silence period is mainly dependent on themuscle investigated and the TMS stimulus intensity, andless on the degree of muscular contraction. It was reported

to be shorter in ALS patients by some authors;5 however,other studies showed con�icting results.6 No informationexists relating this neurophysiological abnormality withclinical �ndings or disease progression. Double stimula-tion paradigms revealed a decreased corticocortical inhibi-tion in ALS patients.7 The available scienti�c informationdoes not permit us to propose this as a method to evaluatedisease progression. The peristimulus time histograminvestigates the effects of TMS on single motor units.8

Since it is impossible to be sure of reassessing the samemotor unit on a second investigation, it is not useful formeasuring disease progression. Mapping studies in ALSpatients suggested that diminishing of the motor area is amore sensitive parameter than CMT, CCT, and MEP/CMAPto detect disease progression.3 Nonetheless it is a time-con-suming method, and only one paper was published onALS. Triple stimulation technique can provide informationon the percentage of lower motor neurons that can be acti-vated by UMN stimulation;9 it is a very recent method, andother groups must con�rm its potentialities.

The greatest advantage of TMS is that it is the only non-invasive, painless, neurophysiological method of investi-gating UMN function. Different techniques of TMS alreadydescribed can be useful in increasing our understandingon the pathophysiology of ALS. TMS �ndings can recog-nize particular subsets of patients, who may show differentresponses to treatment.

At this moment no TMS method has been describedwhich has the required conditions to be used as a surro-gate marker of UMN dysfunction or loss. It is very neces-sary for the development of a simple technique, applicablein many centres, reproducible, and sensitive to diseaseprogression. More investigation should be done on thisnew neurophysiological tool.

References

1. Pouget J, Trefouret S, Attarian S. Transcranial magnetic stim-ulation (TMS): compared sensitivity of different motorresponse parameters in ALS. ALS 2000; 1(Suppl 2): S45–S49.

2. de Carvalho M, Miranda PC, Jardim L, Gabriel F, Falcão F.Reproductibility of corticomotor threshold: some observa-tions. Muscle Nerve 1999; 22: 538–539.

3. de Carvalho M, Miranda PC, Sales-Luís MML, Ducla-SoaresE. Cortical muscle representation in ALS patients: changesover the disease evolution. Muscle Nerve 1999; 22:1684–1692.

4. Claus D, Brunholzl C, Kerling FP, Henschel S. Transcranialmagnetic stimulation as a diagnostic and prognostic test inamyotrophic lateral sclerosis. J Neurol Sci 1995; 129(Suppl):30–34.

5. Desiato MT, Caramia MD. Towards a neurophysiologicalmarker of amyotrophic lateral sclerosis as revealed bychanges in cortical excitability. Electroencephalogr Clin Neu-rophysiol 1997; 105: 1–7.

6. Prout AJ, Eisen A. The cortical silent period and amyotrophiclateral sclerosis. Muscle Nerve 1994; 17: 217–223.

Am

yotr

oph

Lat

eral

Scl

er D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y U

nive

rsity

of

New

cast

le U

pon

Tyn

e on

12/

19/1

4Fo

r pe

rson

al u

se o

nly.

7. Yokota T, Yoshino A, Inaba A, Saito Y. Double cortical stim-ulation in amyotrophic lateral sclerosis. J Neurol NeurosurgPsychiatry 1996; 61: 596–600.

8. Weber M, Eisen A. Peristimulus time histograms (PSTHs) – amarker for upper motor neuron involvement in ALS ? ALS2000; 1(Suppl 2): S51–S56.

9. Magistris MR, Rosler KM, Truffert A, Myers JP. Transcranialmagnetic stimulation virtually excites all motor neurons sup-plying the target muscle. a demonstration and a methodimproving the study of motor evoked potentials. Brain 1998;121: 437–450.

S118 M de Carvalho

Supplement

Am

yotr

oph

Lat

eral

Scl

er D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y U

nive

rsity

of

New

cast

le U

pon

Tyn

e on

12/

19/1

4Fo

r pe

rson

al u

se o

nly.