(Stroke. 1995;26:550-553.)
© 1995 American Heart Association, Inc.
Articles |
Transcranial Magnetic Stimulation–Evoked Inhibition of Voluntary Muscle Activity (Silent Period) Is Impaired in Patients With Ischemic Hemispheric Lesion
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.
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Abstract |
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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
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Introduction |
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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 electric5 or magnetic6 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.
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Subjects and Methods |
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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.
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Results |
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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.
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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).
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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).
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Discussion |
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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 coworkers12 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.
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- 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.
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