Motor evoked potential changes in ischaemic stroke depend on stroke location

JOURNAL

OF THE

NEUROLOGICAL SCIENCES

ELSEVIER

Journal

of the Neurological

Sciences

134 (1995)

67-72

Motor evoked potential changes in ischaemic stroke depend on stroke location U.K. Misra *, J. Kalita of Neurology,

Department

Sanjay Gandhi

Received

Postgraduate

17 June 1994; revised

Institute

of Medical

Sciences, Lucknow

226 014, India

12 June 1995; accepted 22 June 1995

Abstract This study was undertaken to evaluate the central motor conduction in ischaemic stroke and their role in predicting the short term prognosis. Fifty-six patients with CT proven infarction were examined after a mean duration of 9 (range l-30) days. Patients’ mean age was 54.6 years (range 22-80) and 44 of them were males. Motor evoked potentials (MEPs) on cortical stimulation were unrecordable in

57% and central motor conduction time (CMCT) was prolonged in 21% patients. Central motor conduction time was significantly related to the motoricity index and outcome of the patients, but not to the size of infarction. The involvement of the primary motor area or its connection seemed to be an important determinant of the motor dysfunction, MEP abnormalities and outcome. A recordable MEP on cortical stimulation predicted a better outcome than an unrecordable one. Changes in central motor conduction occurred in 14 out of 33 patients

who

were

followed

up for a mean

duration

of 5.7 months

(range

3-15).

patients, 5-12 weeks in eight, and after 12 weeks in four patients, highlighting Keywords:

Stroke;

Ischaemic;

Cortical

stimulation;

Recovery;

Motor

The commonest disability following stroke is the loss of motor functions, which can be evaluated by the technique of transcranial electrical or magnetic stimulation. There are only a few studies in which the motor pathways have been assessed in stroke employing this technique. Unrecordable or delayed MEP have been reported following ischaemic stroke (Thompson et al., 1987; Berardelli et al., 1987). The prolongation of CMCT in subcortical strokes and unrecordable MEP as a feature of cortical stroke have been highlighted (Macdonnel et al., 1989). These studies have limitation of a small number of patients, paucity of data in the acute stage, lack of serial follow-up and inclusion of a mixed population of infarction and haemorrhage (Thompson et al., 1987; Berardelli et al., 1987; Macdonnel et al., 1989; Tsai et al., 1992). In a recent study, comprising of 118 patients with acute stroke; absence, prolongation and normal CMCT have been reported (Heald et al., 1993a,b). The changes in CMCT correlated with clinical parameters

author.

Fax:

91-0522-259973;

Tel.:

91-0522-55009,

55007ext.

0022-510X/95/$09.50 0 1995 Elsevier SSDI 0022-510X(95)00216-2

the multiplicity

in CMCT

was noted

after

4 weeks

in two

of factors responsible for the recovery.

pathways

1. Introduction

* Corresponding 2167.

Improvement

Science B.V. All rights resewed

and the outcome (Heald et al., 1993a,b). The location of infarction may be an important determinant of the clinical picture and the outcome. None of the published studies however have evaluated the MEP changes in the infarctions at different locations and their role in predicting the prognosis. In this study, we have evaluated the MEP changes in different locations of ischaemic stroke and their role in predicting the prognosis.

2. Patients and methods Fifty-six patients with CT proven infarction within 30 days of the ictus have been included in this study. All the patients were hospitalised and informed consent was obtained. This study was approved by the local ethics committee. The patients’ age, sex, blood pressure, Glasgow Coma Scale, muscle tone, power and reflexes were recorded. Motor dysfunction was evaluated by the motoricity index (MI) which is a modification of the Medical Research Council (MRC) scale (Demeurisse et al., 1980). Pinprick, joint position, vibration sense and cortical sensations, i.e. tactile localisation, two point discrimination stereognosis, graphesthesia and ability to perceive sensa-

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force irrespective of the degree of weakness). For spinal stimulation, the patient was asked to relax. Three responses were obtained at 10-s intervals and the one with the shortest latency was measured. Motor evoked potentials were recorded by surface electrode at ADM bilaterally. The EMG signals were filtered through 20 Hz to 2 kHz. The stimulus intensity was 90-100% of the maximum output for cortical stimulation and 50-60% for spinal stimulation. Minimum onset latency and the amplitude of the negative phase were measured. Central motor conduction time (CMCT) was calculated by subtracting the latency of MEP on C7 stimulation from that on cortical stimulation (Misra and Sharma, 1994). Motor evoked potential studies were repeated at the time of clinical followup. Additional MEP studies were also undertaken depending upon the MEP abnormality and availability of the patient. Normal CMCT values were obtained from 32 healthy adult volunteers. Abnormality was defined as absence of MEP or significant prolongation of CMCT. The upper limit of normal CMCT was defined as mean + 2.5 SD of controls. The correlation between the size of infarction with various clinical and electrophysiological parameters were evaluated by x2 test.

tions simultaneously on either side were also tested. Activities of daily life were evaluated by the Barthel Index (Mahony and Barthel, 1965). Cranial CT scan was carried out in all the patients on admission employing a whole body third generation CT scanner (W400 Hitachi, Japan) with a display matrix of 512 X 512 and a spatial resolution of 3 mm at 0.5 contrast. The scan time for each slice was 4.5 s. To measure the size of the infarction, the largest diameter of the lesion was defined on serial 10mm slices parallel to orbitomeatal line. The infarction was classified into small, medium and large according to the largest diameter of less than 2 cm, 2-4 cm and more than 4 cm respectively (Homberg et al., 1991). The patients were re-evaluated 1, 3, 6 and 12 months after the stroke. The outcome was defined on the basis of the Barthel index (BI) at the end of 3 months. A BI of 20 was regarded as complete, 12-19 as partial and below 12 as poor recovery (Misra and Kalita, 1995a). 2.1. Motor evoked potential Motor evoked potentials (MEP) were recorded by stimulating the motor cortex by a high voltage electrical stimulator Digitimer D180, delivering a shock up to 750 V with a time constant of 50-100 ps. The stimulating electrode was l-cm diameter saline-soaked felt pads mounted on a plastic handle. To activate abductor digiti minimi (ADM), the cathode was placed at the vertex and the anode 7 cm laterally and 1 cm anterior to a line drawn from the vertex to the tragus. For cervical stimulation the cathode was placed below the spinous process of the 7th cervical (C7) vertebra and the anode proximal. In order to obtain the maximum response on cortical stimulation, the patient was asked to contract his ADM slightly (10% of the maximum

3. Results The mean age of the patients was 54.6 year (range 22-80), 44 of them were males and 12 females. The patients were examined after a mean duration of 9 (range l-30) days. On the basis of CT picture they were grouped into: (a) cortical-complete middle cerebral artery (MCA), (b) cortical-partial MCA, (c) corona radiata, (d) internal

Table 1 Distribution of MEP MEP(i) = initial motor

changes in ischaemic strokes in different locations of infarction. No. = number initially examined; evolved potential; MEP(f) = final motor evoked potential; A = absent; P = prolong; N = normal.

Infarction

No.

Total MCA

Mean motoricity index

MEP (i)

MEP (f)

N(f) = final

Recovery

numbers; N(f)

A

P

N

A

P

N

Complete

Partial

Poor

9

13

9

0

0

5

0

0

0

1

4

5

Partial MCA: Frontal Frontoparietal Parietotemporal Corona radiata

1 8 10 7

51 50 85 51

0 5 5 5

1 1 3 2

0 2 2 0

0 1 1 1

0 3 1 1

1 1 5 1

0 1 3 0

0 1 4 2

1 3 0 1

1 5 7 3

Capsular: Ant. limb/germ Posterior limb Thalamic

2 9 1

100 48 0

0 5 1

1 1 0

1 3 0

0 1 1

0 1 0

2 2 0

2 1 0

0 3 0

0 0 1

2 4 1

Brainstem: Medial Lateral Occipital

5 1 3

38 100 100

2 0 0

2 0 1

1 1 2

0 0 0

1 0 1

0 1 2

0 0 2

0 1 1

1 0 0

1 1 3

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of the Neurological

r-

Sciences 134 (1995)

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69

day 5

day 90

bdayl80 208 ms -I lOrn6 Fig. 1. Cranial CT scans of different types of infarction involving the primary motor area or its connections. a: complete MCA; b: partial MCA, c: corona radiata; d: posterior limb of internal capsule.

capsule, (e) thalamic, (f) brain stem, and (g) occipital infarction. Motor evoked potential was recorded in all the control subjects on cortical and spinal stimulation. The latency of MEP on cortical stimulation was 19.2 f 1.2 ms and that on spinal stimulation 13.9 + 1.0 ms. CMCT-ADM was 5.1 f 1.2 ms. The amplitude of MEP on cortical stimulation was 3.5 + 1.8 mV and on spinal stimulation 6.1 k 1.9 mV. The MEP abnormalities in different types of infarction and their relationship to motor dysfunction and outcome are shown in Table 1. Motor evoked potential was unrecordable in 57% and CMCT was prolonged in 21% patients. Central motor conduction depended on the location of infarction. Complete MCA, frontoparietal, posterior limb of internal capsular (Fig. 1) and medial brain stem infarctions were associated with a high frequency of persistent MEP abnormalities. The infarctions which did not directly involve the motor pathways like temporoparietal, anterior limb or genu of internal capsule, lateral brain stem and occipital infarction had fewer or transient MEP abnormalities. The MEP changes were serially followed up in 33 patients for a period of at least 3 months; 8 were followed up for 6 months, and 7 for 12 months or more. The mean duration of follow-up was 5.7 months (range 3-15). The MEP changes were of four types: (1) initially unrecordable MEP became recordable with a normal CMCT in four

2mv

Fig. 2. Initially unrecordable MEP becoming normal 6.2 ms) in a patient with corona radiata infarction.

on day 180 (CMCT

(Fig. 21, (2) ml ’ ‘t’ta 11y unrecordable MEP was followed by prolonged CMCT in five (Fig. 3), 3) initially prolonged CMCT returned to normal in three patients (Fig. 4), and (4) slight improvement in CMCT occurred in 2 patients, although both the initial and the final values were pro-

w

day 150

L-A-

day

356

day

L65

*:l3ms L-p27ms 2mv 10ms Fig. 3. Unrecordable MEP which became recordable with CMCT (12.2 ms) in a patient with complete MCA infarction.

prolonged

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4. Discussion 2mv (CMCT

5.2 ms) on

longed. The follow-up MEP revealed changes in 14 out of 33 patients which are summarised in Table 2. In follow-up, MEP changes occurred over a wide range of time. The improvement in MEP was noticed in 2 patients after 4 weeks, in 8 patients between 5 and 12 weeks and in 4 patients after 12 weeks. The role of ipsilateral motor pathways was studied by stimulating the unaffected hemisphere and recording from the hemiplegic side in 24 patients. The ipsilateral response was not recordable in any of the 22 patients with absent contralateral response and in 2 patients with prolonged CMCT. The ipsilateral response on the hemiplegic side was followed-up in 9 patients for a mean duration of 6.8 months (range 1-15). It remained unrecordable in all the patients in whom the contralateral response was absent. In 2 patients of complete MCA infarction in whom the MEP Table 2 Follow-up of central motor motor conduction time. Type of stroke

complete

Cortical

partial MCA

Corona Midbrain

radiata

MCA

in the patients

with ischaemic

In the patients with cerebral infarction two types of CMCT abnormalities have been reported: (1) unrecordable MEP on cortical stimulation, and (2) prolongation of CMCT. In the cortical infarctions the motor evoked potentials have an all or none phenomenon depending on the number of surviving neurons and corticospinal tracts. The response to cortical stimulation is often absent in the conditions affecting the motor cortex such as motor neuron disease and stroke (Thompson et al., 1987; Berardelli et al., 1987). In our study, MEP was unrecordable in all the patients with complete MCA infarction. Prolongation of CMCT has not been reported in cortical infarction (Macdonnel et al., 1989). In our study, however 5 out of 19 patients with partial MCA infarction had prolonged CMCT which may be due to lack of synchronisation of descending volleys in the motor pathways. The subcortical infarctions may result in the prolongation of CMCT by damaging or distorting the descending motor pathways due to infarction or oedema. The motor pathways if sufficiently damaged, the MEP is lost. Partial interruption of motor pathways results in reduction and temporal dispersion of

stroke

showing

No showing change

Duration follow-up

of (mo)

5

2

13

7

6

2

3

2

2

1

12 15 5 3 4 10 12 3 3 3 3 6 3 3

No.

Cortical

Capsular

conduction

67-72

became recordable after 12 months, the ipsilateral response was identical to the contralateral response. The MEP was significantly related to motoricity index (~~=14.1,df=2,p
10ms Fig. 4. Prolonged CMCT (9.8 ms) becoming normal day 102 in a patient with temporoparietal infarction.

Sciences 134 (1995)

change in CMCT. Change

MCA

in CMCT

= middle (ms)

cerebral

artery;

CMCI

Initial

Final

Improvement time (mo)

NR NR NR NR NR 8.2 9.8 8.8 NR 18.8 NR NR 9.2 NR/NR

6.2 12.2 10.6 8.4 9.6 5.6 5.2 7.2 5.4 13.2 7.8 6.2 8.2 9.2/9.4

12 12 5 3 4 10 3.5 2 3 3 1 3 1 2.5

= central

U.K. Misra,

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of the Neurological

descending volleys giving rise to a prolonged CMCT (Thompson et al., 1987). The prolongation of CMCT may also be due to a shift in the pyramidal fibre spectrum. The fast conducting fibres since are more vulnerable to ischaemia in such condition therefore remaining slow conducting fibres may result in prolongation of CMCT (Homberg et al., 1991). In our study, CMCT significantly correlated with motor dysfunction but not with the size of infarction, although such correlation has been reported in some studies (Valdimarsson et al., 1982; Brott et al., 1989; Heald et al., 1993a,b). Motor deficit has been reported to better correlate with CMCT than with CT scan (Hornberg et al., 1991). In our experience MEP abnormalities depended on the location rather than the size of infarction. The study of sequential changes in MEP has revealed a wide variety of changes which may occur due to a number of factors. Return of adequate perfusion, lysis of emboli and opening of collaterals account for the early improvement. In the present study, since the initial follow-up was done one month after the stroke, therefore, the role of these factors in the recovery of our patients cannot be assessed. The subsequent improvement is likely to be due to resolution of brain oedema which may persist up to eight weeks (Inoue et al., 1980). Most of the cerebral oedema resolves in the earlier stage. The other factors which contribute to the recovery include restitution of functions after diaschisis and functional substitution. The regeneration of damaged axons probably does not have an important role in the recovery (Fieschi et al., 1987). In our study, the clinical and CMCT recovery occurred over a wide range of time ranging between 1 and 12 months. The duration of follow-up although was not uniform but these changes highlight the multiplicity of factors responsible for Delayed improvement and MEP becoming recovery. recordable after 1 year in our patients may be due to neuronal plasticity (Jenkins and Merzenich, 1987). The prognosis of infarction seems to depend on the extent of damage to the motor pathways from different areas like primary, supplementary and premotor areas. The motor pathways from these areas maintain a topographic organisation. From supplementary motor area and limbic motor fields, the motor pathways pass through anterior limb; from premotor area through the anterior most part of posterior limb; and from primary motor cortex through the middle one third of posterior limb of internal capsule (Fries et al., 1993). Damage to these motor pathways at different levels may account for the variation in the degree of weakness and subsequent recovery. The weakness following pericentral gyrectomy (Jane et al., 1968) and selective ablation of supplementary motor area (Rostomiley et al., 1991) is associated with better outcome than those with damage to primary motor area (Fries et al., 1993). In our patients with partial MCA infarction involving the frontoparietal area, the motor dysfunction, MEP abnormalities and the outcome were worse than in those with parietotem-

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71

poral infarctions. The importance of connection to the primary motor area was also illustrated in the internal capsular infarctions. The posterior limb had more pronounced weakness and poorer outcome compared to genu and the anterior limb infarctions. The recovery following stroke is attributed to the operation of the different motor areas’ ability to substitute for each others functioning in parallel rather than in a higher-archial fashion (Fries et al., 1993). Recently electrophysiological evidence of functional reorganisation has been obtained in supplementary motor area after primary motor cortex lesion (Aizawa et al., 1991). The role of ipsilateral corticospinal fibres in the recovery has been suggested. In a large hemispheric infarction ipsilateral motor response on cortical stimulation has been reported (Hornberg et al., 1991). We, however, were unable to get a motor response on the hemiplegic side by ipsilateral cortical stimulation in any patient in whom the response to contralateral cortical stimulation was absent. During follow-up, the ipsilateral response in two patients with complete MCA infarction became recordable after one year. This may well be due to spurious stimulation because the latency and amplitude were identical bilaterally (Misra and Kalita, 1995b). Central motor conduction studies are an objective measure of motor dysfunction and provide useful information regarding its prognosis and possible mechanisms.

Acknowledgements We thank K.S. Bisht and S.P. Singh for technical assistance, V.K. Tripathi for typing the manuscript and Anil Kumar for preparing the illustrations.

References Aizawa, H., Inase, M., Mushiake, H., Shima, K. and Tanz, J. (1991) Reorganisation of activity in the supplementary motor area associated with motor learning and functional recovery. Exp. Brain Res., 84: 668-671. Berardelli, A., Inghilleri, M., Manfredi, M., Zamponi, A., Cecconi, V. and Dolce, G. (1987) Cortical and cervical stimulation after hemispheric infarction. J. Neurol. Neurosurg. Psychiat., 50: 861-865. Brott, T., Marler, J.R., Olinger, C.P., Adams, Jr., H.P., Tomsi, K.T., Barsan, W.G., Biller, J., Eberle, R., Hertzberg, V. and Walker, M. (1989) Measurement of acute cerebral infarction lesion size by computed tomography. Stroke, 20: 871-875. Demeurisse, G., Demol, 0. and Robaye, E. (1980) Motor evaluation of vascular hemiplegia. Eur. Neurol., 19: 382-389. Fieschi, C., Carole, A., Fiorelli, M., Argentino, C., Bozzao, L., Fazio, C., Salvetti, M. and Bastianello, S. (1987) Changing prognosis of intracerebral haemorrhage: results of a clinical and computed tomographic follow-up study of 104 patients. Stroke, 19: 192-195. Fries, W., Danek, A., Scheidtmann, K. and Hamburger, C. (1993) Motor recovery following capsular stroke - role of descending pathways from multiple motor areas. Brain, 116: 369-382. Heald, A., Bates, D., Cartlidge, N.E.F., French, J.M. and Miller, S. (1993a) Longitudinal study of central motor conduction time in

72

U.K. Misra,

J. Kalita /Journal

of the Neurological

stroke. I. Natural history of central motor conduction. Brain, 116: 1355-1370. Heald, A., Bates, D., Cartlidge, N.E.F., French, J.M. and Miller, S. (1993b) Longitudinal study of central motor conduction time following stroke. II. Central motor conduction measured within 72 h after stroke as a predictor of functional outcome at 12 months. Brain, 116: 1371-1385. Homberg, V., Stephan, K.M. and Netz, J. (1991) Transcranial stimulation of motor cortex in upper motor neurone syndrome: its relation to the motor deficit. Electroenceph. Clin. Neurophysiol., 81: 377-388. Inoue, Y., Takomoto, K., Miyamoto, T., Yoshikawa, N., Taniguchi, S., Sivai, S., Nashimura, Y. and Katsu, T. (19801 Sequential computed tomography scans in acute cerebral infarction. Radiology, 135: 655662. Jane, J.A., Yashon, D., Becker, D.P., Beatty, R. and Sugar, 0. (19681 The effect of destruction of the corticospinal tract in the human cerebral peduncle upon motor function and involuntary movements. Report of 11 cases. J. Neurosurg., 29: 581-585. Jenkins, W.M. and Merzenich, M.M. (1987) Reorganisation of neocortical representation after brain injury: a neurophysiological model of the basis of recovery from stroke. In: F.J. Seil, E. Herbert and B.M. Carlson (Eds.), Progress in Brain Research, Vol. 71, Elsevier, Amsterdam, pp. 249-266. Macdonnel, R.A.L., Donnan, A. and Bladin, P.F. (1989) A comparison of somatosensory evoked and motor evoked potentials in stroke. Ann. Neurol.. 25: 68-73.

Sciences 134 (1995)

67-72

Mahony, F.I. and Barthel, D.W. (19651 Functional evaluation: the Barthel index. Md. State Med. J., 14: 61-65. Misra, U.K. and Kalita, J. (1995a) Putaminal haemorrhage leading to pure motor hemiplegia. Acta Neurol. Stand., 91: 283-286. Misra, U.K. and Kalita, J. (1995b) Ipsilateral motor response: is it an artefact? Electroenceph. Clin. Neurophysiol., 97: 251-254. Misra, U.K. and Sharma, V.P. (19941 Central and peripheral conduction in neurolathyrism. J. Neurol. Neurosurg. Psychiat., 57: 572-577. Rostomiley, R.C., Berger, M.S., Ojemann, G.A. and Lettich, E. (1991) Postoperative deficits and functional recovery following removal of tumors involving the dominant hemisphere supplementary motor area. J. Neurosurg., 75: 62-68. Thompson, P.D., Day, B.L., Rothwell, J.C., Dick, J.P.R., Cowan, J.M.A., Asselman, P., Griffin, C.B., Sheeley, M.P. and Marsden, CD. (1987) The interpretation of electromyographic response to electrical stimulation of motor cortex in the diseases of upper motor neuron. J. Neurol. Sci., 80: 91-110. Tsai, S.Y., Tchen, P.H. and Chen, J.D. (1992) The relationship between motor evoked potential and clinical motor status in stroke patients. Electromyogr. Clin. Neurophysiol., 32 (12): 615-620. Valdimarsson, E., Bergvall, U. and Samuelsson, K. (1982) Prognostic significance of computed tomography results in supratentorial infarction. Acta Neurol. Stand., 65: 133-145.