(Stroke. 1995;26:550-553.)
© 1995 American Heart Association, Inc.
Transcranial Magnetic StimulationEvoked Inhibition of Voluntary Muscle Activity (Silent Period) Is Impaired in Patients With Ischemic Hemispheric Lesion
Hans J. Braune, MD
Christof Fritz, MD
From the Department of Neurology, University of Marburg
(Germany).
Correspondence to Dr Hans-Joachim Braune, Neurologische Universitätsklinik und Poliklinik, Rudolf-Bultmann-Straße 8, D-35033 Marburg, Germany.
 |
Abstract
|
|---|
Background and Purpose Transcranial magnetic stimulation of
the
motor cortex is well established as a valuable method for
noninvasive
examination of the central motor system. In addition to
exciting
corticospinal cells and evoking a direct motor response, the
magnetic
stimulus delivered during voluntary activity produces a
prolonged
postexcitatory inhibition (silent period) of activity. We
investigated
silent period changes in patients with ischemic stroke of
different
clinical degrees.
Methods Standardized transcranial magnetic stimulation during
sustained muscle contraction was performed at the vertex.
Electromyographic activity was recorded via surface electrodes placed
over the abductor digiti minimi muscle on both sides. We examined 50
patients with stroke (divided into three subgroups according to the
degree of impairment) and 50 healthy control subjects.
Results In the control group we found no statistically
significant interside difference in the duration of the silent period,
whereas a marked interindividual variation was found. In patients with
prior minor stroke who showed no residual motor disturbance, we found a
significant prolongation of the postexcitatory inhibition recorded from
the affected side compared with the healthy side. This interside
discrepancy was even more pronounced in patients with minor hemiparesis
and patients with moderate hemiparesis.
Conclusions Our findings suggest that the measurement of the
silent period elicited by transcranial magnetic stimulation is a useful
and sensitive neurophysiological parameter in the management of stroke.
Particularly in the subgroup of patients with no residual clinical
signs of central motor impairment, it is capable of detecting
subclinical motor function disturbances.
Key Words: cerebral ischemia cerebral ischemia, transient motor activity stimulation, transcranial magnetic stroke assessment
 |
Introduction
|
|---|
Transcranial magnetic stimulation (TCMS)
of the motor cortex
has been established as a valuable noninvasive
method for examination
of the central motor system. TCMS has both
excitatory and inhibitory
effects. During a voluntary contraction TCMS
produces a motor
evoked potential (MEP) and a transient suppression of
muscle
action potentials thereafter. This silent period (SP) is a
transitory
suppression of electromyographic (EMG) activity during
sustained
voluntary contraction.
1 It can be induced by
supramaximal electric
stimulation of mixed peripheral
nerves,
2 3 unloading of the
spindles,
4 and
transcranial cortical electric
5 or
magnetic
6 7 stimulation. Although it is understandable
that large stimuli
such as TCMS elicit excitation as well as inhibition
and disruption
of movements, the underlying substrates and neuronal
mechanisms
of the SP are still unknown. Recently published data
indicate
that the SP is mainly due to a synchronous volley of
inhibitory
postsynaptic potentials induced by the electromagnetic
stimulator
at the cortical level.
7
Cerebrovascular disease often leads to an impairment of central motor
function. For this reason, TCMS has been introduced into the diagnostic
repertoire in patients with stroke. Most studies are limited to the
investigation of the excitatory effects of cortical magnetic
stimulation in the assessment of amplitudes and latencies of
MEP.8 9 Only a few studies have analyzed the inhibitory
effects of cortical stimulation,10 11 with controversial
results: After stimulation of the affected side, prolongation as well
as reduction of the SP in patients with stroke was
described.12 The aim of the present study was to
further investigate this controversy.
 |
Subjects and Methods
|
|---|
Subjects
The study was carried out after protocol approval by the ethics
committee
of the medical faculty of Philipps University in accordance
with
the Declaration of Helsinki as modified by the 35th World Medical
Assembly,
Venice, Italy, 1983. All subjects gave their informed consent
before
they were included in the study. Exclusion criteria were a
history
of epileptic seizures or prior intracranial operations
involving
the use of metallic clips, a cardiac pacemaker, acoustic
devices,
or the use of drugs involving the excitability threshold, eg,
antispastic,
anxiolytic, hypnotic, or antiepileptic agents. Fifty
patients
with upper motor neuron syndromes due to cerebrovascular
accidents
were examined (mean age, 56 years [SD, 5.5 years]; range,
45
to 79 years; 28 men, 22 women). Patients with a history of bilateral
motor
involvement, brain stem or spinal cord lesions, or peripheral
neuropathy
were excluded. Patients were divided in three subgroups
according
to the degree of impairment: group 1, 7 patients showing no
residual
clinical signs of motor disturbances after minor stroke; group
2,
22 patients with minor clinical signs of hemiparesis; and group
3,
21 patients with moderate hemiparesis. The diagnosis of cerebral
infarction
in the territory of the middle cerebral artery was made
clinically
and regularly confirmed by computed tomography. However, in
three
cases of a primarily normal cranial computed tomographic scan
at
the beginning of the disease, a second scan for determining
the exact
location of the lesion could not be performed. Patients
with clinical
or radiological evidence of further cerebral infarctions
were excluded.
All investigations were performed within 1 week
after the onset of
disease. The control group consisted of 50
healthy volunteers (mean
age, 47 years [SD, 9.2 years]; range,
17 to 80 years; 21 men, 29
women). None had a history of previous
neurological disorder.
Methods
Magnetic stimulation of the motor cortex was performed with the
use of a Novametrix Magstim 200 stimulator with a 14-cm outer diameter
flat coil that produced a maximal magnetic field of 1.5 T pulsed for
100 microseconds with a bipolar characteristic of the induced electric
current. A standardized stimulation procedure was used, positioning the
center of the magnetic coil over the vertex. The minimal time between
successive stimuli was 15 seconds. Either one or the other side of the
coil was applied to induce maximum response of the left or right
precentral hand area, as in MEP elicitation.11 Muscle
responses were recorded from the respective abductor digiti minimi
muscle via surface electrodes (9 mm in diameter) placed in a
belly-tendon montage after we lowered the electrode-skin impedance to
less than 5 k
by gently abrading the skin and placing conductive
jelly. A conventional four-channel EMG system (NIHON KOHDEN Neuropack
4) served as a recording unit, with a sensitivity of 0.5 mV per
division. The duration of the poststimulus analysis time was
usually 300 to 500 milliseconds. Cutoff frequency filters were set at 1
Hz and 10 kHz, respectively. Patients and control subjects were seated
comfortably in an armchair and asked to maintain a constant isometric
contraction of the contralateral muscle. The force of voluntary
activity was monitored by visual judgment of the surface EMG
interference pattern because it has been shown elsewhere that the
quantitative amount of preinnervation has no influence on the duration
of the SP.11 A standardized paradigm for stimulus
intensity was used because the duration of SP has been shown to
increase with increasing stimulus strength.10 Stimulation
thresholds were determined on each side by increasing stimulus
intensity in increments of 5%, starting at 20% and increasing to 50%
of the maximal output of the stimulator. After we determined the
individual threshold of the SP on the right and left sides, a stimulus
intensity of threshold plus 50% of threshold intensity was applied.
The actual amount of current reaching the cortical surface is regarded
to vary within subjects because of passive physical properties such as
skin resistance and skull thickness. Interside differences of the
individual threshold for SP elicitation did not exceed 5% of the
maximal coil output. We therefore used the same stimulus intensity for
both sides, thereby avoiding ambiguities when comparing interside
differences. Measurements were reproduced five times on each hand and
superimposed to demonstrate the constancy of the EMG suppression. Since
the exact time of the start of the SP was not known, the duration of SP
was measured from the beginning of the MEP to the return of
uninterrupted voluntary EMG, as recommended by Inghilleri et
al.13 This is the most reliable recording technique, since
the end of the MEP after TCMS is not constant enough for use as a
latency marker. The shortest SP was used for further calculations.
Statistical evaluation was performed with the parameter-free
U test (Mann-Whitney); graphic documentation was performed
with box and whisker plots. The 95th percentile was determined from our
control subjects. A minimal criterion for assumed abnormality in
patients was a test result value greater than the 95th percentile.
 |
Results
|
|---|
Control Group
The mean duration of the SP in the control group was 144
milliseconds,
with high interindividual variation (range, 100 to 219
milliseconds).
Intraindividually, a high interside symmetry of SP was
found,
with mean side-to-side SP duration differences of 10.5
milliseconds
(range, 0 to 60.5 milliseconds; Fig 1

). No
statistically significant
influence of sex or age was found. Thus, we
defined one normal
range for all ages. The cutoff value of interside
difference
was defined as the 95th percentile: 95% of all values of
the
control group were shorter than 22 milliseconds.

View larger version (15K):
[in this window]
[in a new window]
|
Figure 1. Tracings show silent period of a healthy subject
evoked during sustained contraction of abductor digiti minimi muscle.
Stimulus strength is 50% above the threshold to evoke a silent
period.
|
|
Patient Group
In group 1 (7 patients with minor stroke showing no clinical signs
of motor disturbances), a significant prolongation of the SP recorded
from the formerly affected side compared with the healthy side was
measured. The mean interside difference in these 7 patients was 33.2
milliseconds (range, 11 to 68.5 milliseconds; five values were out of
normal range, ie, >22 milliseconds). In group 2 (22 poststroke
patients with minor hemiparesis), this interside difference was even
more pronounced (Fig 2
). The mean interside difference
in this group was 58.3 milliseconds (range, 8 to 251 milliseconds; 19
values were out of normal range), with prolongation of the SP recorded
from the affected side compared with the healthy side. However, in 7
patients a reduction in the SP on the affected side was found. In group
3 (21 poststroke patients with moderate hemiparesis), measurements
revealed a mean interside difference of 104.7 milliseconds (range, 9 to
280 milliseconds; 17 values were out of normal range). Sixteen patients
in this group showed prolongation of the SP on the affected side, and 5
patients showed a reduction (Fig 3
).

View larger version (14K):
[in this window]
[in a new window]
|
Figure 2. Tracings show motor evoked potential (MEP) and
silent period (SP) in a 36-year-old patient with right hemispheric
transient ischemic attack 4 days before examination. At the time of
examination, the patient did not show any motor impairment.
|
|

View larger version (13K):
[in this window]
[in a new window]
|
Figure 3. Tracings show motor evoked potential (MEP) and
silent period (SP) in a 70-year-old patient with left hemispheric
infarction 3 days before examination. This patient showed a moderate
right-sided hemiparesis.
|
|
Comparison between control and patient groups revealed a highly
significant intergroup difference (P<.01), whereas no
statistical difference was found between patient groups (Fig 4
).

View larger version (13K):
[in this window]
[in a new window]
|
Figure 4. Bar graph shows interside difference of the evoked
postexcitatory inhibition (PI) period (of voluntary activity) in 50
healthy subjects (N), 7 stroke patients with no residual paresis (1),
22 patients with mild hemiparesis (2), and 21 patients with moderate
hemiparesis (3). **Highly significant (P<.01); -, not
significant (P>.05).
|
|
 |
Discussion
|
|---|
In concordance with former studies on the SP after TCMS, we
found
only a small interside difference in our healthy
subjects.
10 11 In the patient group we found an increasing
interside difference
according to the degree of motor impairment.
Although the majority
of measurements revealed an SP prolongation on
the affected
side, 12 of 50 patients exhibited a reduction. Published
data
concerning SP measurements in patients with stroke are divergent.
Uozumi
and coworkers
12 studied 12 patients with cerebral
infarction
and found a shortened SP duration. Other authors described a
prolongation
in 10 patients with previous stroke.
11
Similar to the results
of Haug and Kukowski,
14 we did not
find a constant pattern
of reduction or prolongation, although most
patients showed
a prolonged SP duration on the paretic side.
The diverging results in the literature and in our own study are still
unexplained. They could mainly be due to a different topographical
distribution of ischemic lesions. We confirmed the diagnosis of a
cerebral infarction in the territory of the middle cerebral artery by
computed tomography in all patients but three, who had primarily normal
cranial computed tomographic scans. Patients with infarctions in other
territories were excluded. A more detailed specification of different
distributions of cortical or subcortical lesions was not given since
statistical analysis showed no significant influence, probably
because of the small number of patients examined. It has been
speculated that cortical lesions lead to a reduction of the SP and
subcortical lesions to a prolongation of the SP.15 16 We
hope that a planned study with recruitment of more patients will
provide further evidence to answer this question.
Nevertheless, interside differences of the SP, most frequently with
prolongation on the affected side, seem to be a very sensitive
indicator of ischemic central motor deficits. Particularly in those
patients without clinical signs of motor impairment, we were able to
record subclinical central motor imbalances. Hence, measurement of the
SP is a useful and easily performed neurophysiological tool,
particularly when clinical, radiological, and established
neurophysiological methods fail to clearly detect suspected central
motor lesions.
Received October 20, 1994;
revision received January 12, 1995;
accepted January 12, 1995.
 |
References
|
|---|
-
Rossini PM, Barker AT, Berardelli A, Caramia MD, Caruso
G, Cracco RQ, Dimitrijevic MR, Hallett M, Katayama Y, Lücking CH,
Maertens de Noordhout AL, Marsden CD, Murray NMF, Rothwell JC, Swash M,
Tomberg C. Non-invasive electrical and magnetical stimulation of the
brain, spinal cord and roots: basic principles and procedures for
routine clinical application: report of an IFCN committee.
Electroencephalogr Clin Neurophysiol. 1994;91:79-92. [Medline]
[Order article via Infotrieve]
-
Shahani BT, Young RR. Studies of the normal ulnar silent
period. In: Desmedt JE, ed. New Developments in Electromyography
and Clinical Neurophysiology. Basel, Switzerland: Karger;
1973:589-602.
-
Leis AA, Ross MA, Matsue Y, Saito T. The silent period
produced by electrical stimulation of mixed peripheral nerves.
Muscle Nerve. 1991;14:1202-1208. [Medline]
[Order article via Infotrieve]
-
Struppler A, Burg D, Erbel F. The unloading reflex under
normal and pathological conditions in man. In: Desmedt JE, ed.
New Developments in Electromyography and Clinical
Neurophysiology. Basel, Switzerland: Karger; 1973:603-617.
-
Marsden CD, Merton PA, Morton HB. Direct electrical
stimulation of the corticospinal pathways through the intact scalp in
human subjects. In: Desmedt JE, ed. Advances in Neurology, Vol.
39: Motor Control Mechanism in Health and Disease. New York, NY:
Raven Press; 1983:387-391.
-
Wassermann EM, Fuhr P, Cohen L, Hallet M. Effects of
transcranial magnetic stimulation on ipsilateral muscles.
Neurology. 1991;41:1795-1799. [Abstract/Free Full Text]
-
Uncini A, Treviso M, DiMuzio A, Simone P, Pullman S.
Physiological basis of voluntary activity inhibition induced by
transcranial cortical stimulation. Electroencephalogr Clin
Neurophysiol. 1993;89:211-220. [Medline]
[Order article via Infotrieve]
-
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 neuron disease.
Electroencephalogr Clin Neurophysiol. 1991;81:389-396. [Medline]
[Order article via Infotrieve]
-
Kandler RH, Jarratt JA, Venables GS. Clinical value of
magnetic stimulation in stroke. Cerebrovasc Dis. 1991;1:239-244.
-
Kukowski B, Haug B. Quantitative evaluation of the silent
period, evoked by transcranial magnetic stimulation during sustained
muscle contraction, in normal man and in patients with stroke.
Electromyogr Clin Neurophysiol. 1992;32:373-378. [Medline]
[Order article via Infotrieve]
-
Haug BA, Schönle PW, Knobloch C, Köhne M. Silent
period measurement revives as a valuable diagnostic tool with
transcranial magnetic stimulation. Electroencephalogr Clin
Neurophysiol. 1992;85:158-160. [Medline]
[Order article via Infotrieve]
-
Uozumi T, Yoichi I, Tsuji S, Murai Y. Inhibitory period
following motor potentials evoked by magnetic cortical stimulation.
Electroencephalogr Clin Neurophysiol. 1992;85:273-279. [Medline]
[Order article via Infotrieve]
-
Inghilleri M, Berardelli A, Cruccu G, Manfredi M. Silent
period evoked by transcranial stimulation of the human cortex and
cervicomedullary junction. J Physiol (Lond). 1993;466:521-534. [Abstract/Free Full Text]
-
Haug B, Kukowski B. Latency and duration of the muscle silent
period following transcranial magnetic stimulation in multiple
sclerosis, cerebral ischemia, and upper motor neuron lesions.
Neurology. 1994;44:936-940. [Abstract/Free Full Text]
-
Roick H, von Giesen HJ, Benecke R. The origin of
postexcitatory inhibition after transcranial magnetic cortex
stimulation. Electroencephalogr Clin Neurophysiol. 1993;87:1P. Abstract.
-
von Giesen HJ, Roick H, Beneke R. Pathophysiologic aspects of
postexcitatory inhibition. Electroencephalogr Clin
Neurophysiol. 1993;87:1P-2P. Abstract.
This article has been cited by other articles:

|
 |

|
 |
 
O. B.C. Swayne, J. C. Rothwell, N. S. Ward, and R. J. Greenwood
Stages of Motor Output Reorganization after Hemispheric Stroke Suggested by Longitudinal Studies of Cortical Physiology
Cereb Cortex,
August 1, 2008;
18(8):
1909 - 1922.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. R. Kessler, A. Schnitzler, J. Classen, and R. Benecke
Reduced inhibition within primary motor cortex in patients with poststroke focal motor seizures
Neurology,
October 8, 2002;
59(7):
1028 - 1033.
[Abstract]
[Full Text]
[PDF]
|
 |
|