262

, Electroencephalography and clinical Neurophysiology, 80 (1991) 262-275

© 1991 Elsevier Scientific Publishers Ireland, Ltd. 0168-5597/91/$03.50
A D O N I S 016855979100084S
EVOPOT 02359

A prospective 1 year follow-up study with somatosensory potentials evoked
by stimulation of the posterior tibial nerve in patients with supratentorial
cerebral infarction
T. Kovala a, U. Tolonen a and J. Pyhtinen b
Departments of a Clinical Neurophysiology and h Radiology, Oulu University Central Hospital, Oulu (Finland)

(Accepted for publication: 16 August 1990)

Summary
Somatosensory potentials evoked by stimulation of the posterior tibial nerve (tibial nerve SEPs) were studied in 40 patients with
supratentorial non-haemorrhagic cerebral infarction and in 25 control subjects. SEPs were recorded twice in 39 patients and thrice in 35 patients.
The first examination was carried out 4-19 days after the onset of the symptoms, the second examination 56-100 days after the stroke, and the
third examination 348-393 days after the stroke. Increased side-to-side differences in the P57 and N75 peak latencies and absence of the P40 peak
were the most frequent abnormal findings. The latency abnormalities were associated with involvement of the subcortical white matter of the
rolandic region. The absence of the P40 peak was, in contrast, closely related to the extension of the infarcted area into the cortical gray matter of
the rolandic region. When all SEP abnormalities were taken into account 55% of patients showed at least one abnormality in the tibial nerve SEP
during the acute stage, 51% of patients had abnormal SEPs in the second examination and 43% of patients in the third examination. A nearly
significant decrease was observed in the number of latency abnormalities, but the number of amplitude abnormalities, including absent responses,
did not change during the 1 year follow-up period.
Key words: Somatosensory evoked potentials; Cerebral infarction; Ischemia; Posterior tibial nerve; (Man)

T h e clinical d i a g n o s t i c usefulness of s o m a t o s e n s o r y
p o t e n t i a l s e v o k e d b y lower limb s t i m u l a t i o n has m a i n l y
b e e n s t u d i e d in p a t i e n t s with lesions in the spinal c o r d
a n d with diffuse neurological diseases. This m e t h o d
seems to be p r o m i s i n g for the d e t e c t i o n of spinal c o r d
lesions in cervical s p o n d y l o s i s (Perlik a n d F i s h e r 1987;
H e i s k a r i et al. 1988). F u r t h e r m o r e , with diffuse lesions
SEPs to lower l i m b s t i m u l a t i o n a p p e a r to b e fairly
sensitive: e.g., subclinical d y s f u n c t i o n o f the spinal c o r d
has been attested in the early phases of d i a b e t e s ( G u p t a
a n d D o r f m a n 1981; C r a c c o et al. 1984). In p e r m a n e n t
subcortical ischaemic lesions lower limb SEPs seem to
be c o m p l e m e n t a r y to m e d i a n nerve SEPs, increasing the
n u m b e r of d e t e c t e d a b n o r m a l i t i e s ( C h u 1986a; Hassel
et al. 1986). T h e p r e s e n t s t u d y was c o n d u c t e d to establish the significance of the tibial nerve SEPs in p a t i e n t s
with local ischaemic lesions in the s u p r a t e n t o r i a l space,
a n d to establish the course of the changes in the tibial
nerve SEPs d u r i n g a p r o s p e c t i v e 1 y e a r follow-up study.

Correspondence to: Tero Kovala, Institute of Occupational Health,
Haartmaninkatu 1, 00290 Helsinki (Finland).

Patients and m e t h o d s

A 1 y e a r follow-up was c o n d u c t e d in the D e p a r t m e n t
of Clinical N e u r o p h y s i o l o g y of O u l u U n i v e r s i t y C e n t r a l
H o s p i t a l f r o m A u g u s t 1985 to A u g u s t 1988. F o r t y p a tients with n o n - h a e m o r r h a g i c s u p r a t e n t o r i a l c e r e b r a l infarction were e x a m i n e d . T i b i a l nerve SEPs were rec o r d e d 3 times a n d a n e u r o l o g i c a l e x a m i n a t i o n was
p e r f o r m e d 3 times: (1) w i t h i n 4 - 1 9 ( m e a n 9.8) d a y s
after the i n f a r c t i o n (40 patients); (2) within 5 6 - 1 0 0
( m e a n 69) d a y s (39 p a t i e n t s ) ; (3) within 3 4 8 - 3 9 3 ( m e a n
370) d a y s (35 patients). C e r e b r a l c o m p u t e d t o m o g r a p h y
(CT) was s t u d i e d at least once d u r i n g the acute stage,
1 - 2 1 ( m e a n 5.1) d a y s after the stroke.
T h e clinical n e u r o l o g i c a l e x a m i n a t i o n , using a f o r m
specially d e s i g n e d for this study, tested the following
variables: level of consciousness, receptive d y s p h a s i a ,
expressive d y s p h a s i a , sense of touch, sense of t e m p e r a ture, j o i n t p o s i t i o n sense, sense of v i b r a t i o n , stereognosis, neglect, a b i l i t y to move, m o t o r p e r f o r m a n c e in
u p p e r arm, muscle tone in the l i m b s of the affected side,
e n h a n c e m e n t of the b i c e p s reflex, e n h a n c e m e n t of the
p a t e l l a r reflex, B a b i n s k i sign. A l l variables were classi-

TIB1AL N E R V E SEPs IN C E R E B R A L I N F A R C T I O N

263

fied as either normal or abnormal. Twenty-four patients
(60%) had sensory and motor signs when the first SEPs
were registered, 7 patients (17.9%) had only motor signs,
7 patients (17.9%) had right-sided herniplegia and severe
aphasia which precluded sensory testing, 1 patient had
only sensory signs, and 1 patient had normal neurological signs.
CT was assessed by one of the authors (J.P.), who
had no knowledge of the results from the neurological
examination and SEPs, using a form specially designed
for this purpose. The following variables were assessed:
the presence of mass displacements and the presence of
infarction changes in the following areas: the regions of
arteria cerebri anterior, media and posterior, thalamus,
capsula interna, precentral, postcentral and prefrontal
white matter, white matter in the temporal and occipital
lobes, precentral, postcentral and prefrontal gray matter,
gray matter in the temporal and occipital lobes. All

TABLE

variables were classified as either negative or positive.
The CT was abnormal in 32 patients (80%; see Table I).
The control group consisted of 25 healthy volunteers
from the staff of the hospital. The mean age of the
controls was 43.3 years (S.D. 11.3) and of the patients
51.7 years (S.D. 12.6) ( P = 0.009 with Student's t test).
The mean height was 166.1 cm (S.D. 8.8) in the control
group and 172.1 cm (S.D. 7.7) in the patient group
( P = 0.005 with Student's t test). The ratio m a l e s /
females was 1 0 / 1 5 in the control group and 2 9 / 1 1 in
the patient group ( P = 0.009 with chi-square test). The
conduction velocity between the ankle and the popliteal
fossa was normal in all patients.
The "active" electrodes (grid 1) were situated in the
midline 2 cm behind the C z location of the 1 0 - 2 0
system (C~') and in the popliteal fossa. For the scalp site
a needle electrode made of platinum-iridium alloy was
used and in the popliteal fossa an Ag/AgCI surface

I

T h e findings in the cerebral computed tomography (CT) for all patients with abnormal C T s ( 3 2 patients). The classification is based on the

presence or absence of the abnormal CT findings in the region of thalamus, capsula interna, subcortical white and cortical gray matter in the
precentral and postcentral area. W = white matter, G = gray matter, T H A L = t h a l a m u s , P O S T C = p o s t c e n t r a l , P R E C = p r e c e n t r a l , T E M P
temporal lobe, P R E F = prefrontal area, OCC = occipital lobe. + = the patient had infarction in that area.
C T class

Age S e x T H A L

a: thalamus

16

m

+

+

68

f

+

+

+

CAPS

POSTC.W

PREC.W

POSTC.G

PREC.G

TEMP.W

TEMP.G

PREF.W

PREF.G

+

29

f

b: capsula int.

54

f

+

58

f

+

c: capsula int.
+ PREC.W
d: capsula int.

45

m

+

+

60

m

+

+

60

m

+

e: capsula int.
+ PREC.W

59

m

+

+

+

58

m

+

+

+

+ POSTC.W

65

f

+

+

+

64

m

+

+

+

56

m

+

+

+

+

+

+

40

m

+

+

+

+

+

+

53

m

4-

4-

4-

+

+

+

+

+

33

m

4-

4-

4-

+

+

+

+

+

+ G 64

m

4-

+

4-

+

+

+

+

47

m

4-

4-

4-

+

÷

+

+

39

f

4-

4-

4-

+

+

+

+

66

f

4-

4-

4-

+

+

+

+

+

+

55

m

4-

4-

4-

+

+

+

+

+

+

33

m

+ POSTC.W

h: P R E C . W + G
i: P O S T C . W

4-

m

4-

44
71

m

4-

m

4-

+

+ POSTC,W

57

f

4-

+

1: P R E C . W + G

54

m

4-

+

+

+

+

+

+ POSTC.W

+ G 66

m

4-

4-

+

+

+

+

36

f

4-

4-

+

+

52

m

41

f

+ G

+

+
+

+

m

m: occipital I.

+

+

4-

30

k: PREC.W

+

+

53
j: POSTC.W

+

+ G

g: capsula int.
+ PREC.W + G
+ POSTC.W

OCC.G

+

+ G

f: capsula int.
+ PREC.W
+ POSTC.W

+

OCC.W

+

+
+
+

264

T. KOVALA ET AL.

electrode was used. Linked ears reference electrodes
(AIA2) were used for the scalp channel, Ag/AgC1
surface electrodes being placed on both earlobes and
both electrodes being connected to the grid 2 of the
amplifier. In the second channel (popliteal fossa) an
Ag/AgC1 surface electrode placed 4 cm above the "act i v e " e l e c t r o d e w a s u s e d as t h e r e f e r e n c e . S E P s w e r e
recorded using a 4-channel Disa 1500 D electromyog r a p h , w h i c h i n c l u d e d a D i s a 15 G 21 a v e r a g e r . T h e
sampling frequency was 5 kHz. Trials with excessive
artifacts were rejected automatically. The bandpass was
2 H z - 2 k H z i n all c h a n n e l s . 1 5 0 0 t r i a l s w e r e a v e r a g e d ,
a n d t h i s p r o c e d u r e w a s p e r f o r m e d t w i c e o n b o t h sides.
The posterior tibial nerve was stimulated at the ankle
with surface electrodes. The strength of the stimulus
was adjusted to slightly over the motor threshold so that

it d i d n o t p r o d u c e p a i n ; t h e d u r a t i o n w a s 2 0 0 / x s e c , t h e
frequency was 3 Hz. Analysis time was 200 msec.
Latencies were measured on the oscilloscope screen
with a cursor, and the pictures were then made with an
analog x-y plotter. The amplitudes were measured on
the paper. The peak latencies of the components P40,
N 4 8 , P57, N 7 5 a n d p e a k - t o - p e a k a m p l i t u d e s N 3 2 - P 4 0 ,
P40-N48, P57-N75 were measured (if N32 was not
present, the N32-P40 amplitude was measured from the
baseline to the peak of the P40 wave). On both sides
means of the latency and amplitude values from both
averages were calculated (averaging was done twice on
b o t h sides). S i d e - t o - s i d e d i f f e r e n c e s o f t h e l a t e n c i e s a n d
interpeak latency P40-N75 were calculated from the
mean latencies. Amplitudes were transformed to logarithms and side-to-side differences in the amplitudes

TABLE I1
The intersession stability studied in 5 control subjects. The amplitude values in the table are logarithms of the measured amplitudes. Time lapse
between the first and second examinations is presented as months.

P40
Right:

Left:

N75
Right:

Left:

P40-N75 IPL
Right:

Left:

P40-N48 ampl.
Right:

Left:

P57-N75 ampl.
Right:

Left:

Age (years)
Gender
Time lapse (months)

37
female
47

38
female
33

40
female
34

48
female
37

48
female
32

first
second
change
first
second
change

38.0
38.0
0.0%
38.0
38.4
+ 1.1%

37.5
36.3
- 3.2%
37.5
37.3
-0.5%

39.0
37.6
- 3.6%
39.0
37.8
- 3.1%

35.5
34.7
- 2.3%
33.5
34.4
+ 2.7%

38.7
38.5
- 0.5%
39.4
39.1
- 0.8%

first
second
change
first
second
change

75.0
77.0
+ 2.7%
77.5
80.0
+ 3.2%

74.0
77.0
+ 4.1%
74.5
74.5
0.0%

78.5
78.5
0.0%
79.0
78.5
- 0.6%

80.5
82.5
+ 2.5%
85.0
87.0
+ 2.4%

81.0
81.5
+ 0.6%
87.0
86.5
- 0.6%

first
second
change
first
second
change

37.0
39.0
+ 5.4%
39.5
41.7
+ 5.6%

36.5
40.8
+ 11.8%
37.0
37.3
+ 0.8%

39.5
40.9
+ 3.5%
40.0
40.7
+ 1.8%

45.0
47.8
+ 6.2%
51.5
52.7
+ 2.3%

42.3
43.1
+ 1.9%
47.6
47.4
- 0.4%

first
second
change
first
second
change

0.564
0.559
-0.9%
0.609
0.694
+ 14.0%

0.457
0.396
- 13.3%
0.555
0.485
- 12.6%

0.423
0.385
- 9.0%
0.269
0.512
+ 90.3%

1.106
1.126
+ 1.8%
1.097
1.201
+ 9.5%

0.966
0.986
+ 2.1%
0.665
0.677
+ 1.8%

first
second
change
first
second
change

0.643
0.563
- 12.4%
0.688
0.694
+ 0.9%

0.548
0.551
+ 0.5 %
0.672
0.540
- 19.6%

0.574
0.528
- 8.0%
0.619
0.628
+ 1.5%

1.075
1.118
+ 4.0%
1.183
1.243
+ 5.1%

0.981
0.764
- 22.1%
0.900
0.694
- 22.9%

TIBIAL NERVE SEPs IN CEREBRAL I N F A R C T I O N

265

TABLE I11
The variables used as criteria of abnormality. 'Affected side' was drawn randomly by lot in the control group. Amplitudes were transformed to
logarithms, and side-by-side differences in the amplitudes were transformed to decibels by the formula: 10Xlog(amplau/amplnon), where
amplar f = amplitude on the 'affected' side and amplnon = amplitude on the 'non-affected' side (both as microvolts); side-by-side differences in the
latencies were calculated latarr - latnon, where lat,u = latency on the 'affected' side and latno n = latency on the 'non-affected' side. Normal limits
of amplitudes as microvolts and normal limits of side-by-side differences in the amplitudes as amplitude ratios (higher amplitude per lower
amplitude) are in parentheses.
Statistics in the control group

Limits of normality

Mean

S.D.

Median

Range

40.9
0.36
0.54
0.67

3.8
0.28
0.25
0.21

39.5
0.42
0.49
0.65

34.5-49.0
- 0.50-0.91
0.03-1.11
0.17-1.07

- 0.31
-0.12
-0.64
- 1.34
0.13
0.46
-0.38

1.31
1.72
1.81
4.28
1.99
2.06
1.37

0
0
- 1.0
- 1.0
0.41
0.28
-0.45

- 3.5-2.0
-4.0-4.0
- 3.5-3.5
- 14.0-8.0
-4.1-3.9
- 3.7-4.4
-2.9-3.5

Mean - 3 S.D.

Mean + 3 S.D.

- 0 . 4 8 (0.33 ~tV)
- 0 . 2 1 (0.62 #V)
0.04 (1.10 pN)

52.4 msec
1.20 (15.8 #V)
1.29 (19.5 #V)
1.30 (20.0 #V)

3 S.D.

Affected side
P40-N75 IPL (msec)
log(N32-P40 amplitude)
log(P40-N48 amplitude)
log(P57-N75 amplitude)

Side-by-side differences
P40 latency (msec)
N48 latency (msec)
P57 latency (msec)
N75 latency (msec)
N32-P40 amplitude (dB)
P40-N48 amplitude (dB)
P57-N75 amplitude (dB)

3.93 msec
5.16 msec
5.43 msec
12.84 msec
+5.97 dB (3.95*)
+6.18 dB (4.15")
+4.11 dB (2.57*)

8O

Right foot

Left foot
First average

First average
64
126

i

o.63

pV

20 ms

46 65
second

a v e r a g e BO
63

second
123
0.63

average

pv
0 . 6 3 pV

I

20 ms

55

20 ms

51

4
46

Fig. 1. Tibial nerve SEPs of a 33-year-old male (the second patient in group g in Tables I, IV and V) recorded at C z (in the midline, 2 cm behind
Cz) with AIA 2 reference. The responses to stimulation of the right foot are on the left and of the left foot on the right of the figure. The first
average on each side is in the upper half and the second average is in the lower half of the figure. The P40-N75 IPL, and also the side-to-side
differences in the P40, N48, P57 and N75 peak latencies were abnormal when the right foot was stimulated. The amplitudes were normal.

266

T. KOVALA ET AL.

were transformed to decibels by the formula: 10 ×
log(ampl afr/ampl,o, ), where ampl aff amplitude in the
affected side, amplno . = amplitude in the non-affected
side. These transformations resulted in normal (i.e.,
gaussian) distributions (the Shapiro-Wilk test for normality). In 5 control subjects, a second tibial nerve SEP
record was made after an interval of 2 years 8 months
(32 months) to 3 years 11 months (47 months) from the
first recording (Table II). In these subjects, the latency
values were slightly more stable than the amplitude
values, and the consistency of the later waves (P57 and
N75) was about as good as that of the earlier waves
(P40 and N48).
Group differences in the peak latencies were studied
by analysis of covariance adjusted for height, age and
gender, and in the P40-N75 interpeak latency and the
amplitudes by analysis of covariance adjusted for age
and gender. The changes in peak latencies, interpeak
latencies and amplitudes between the first, second and
third examinations were analysed with a paired t test,
and the changes in the number of abnormalities with a
chi-square test. Statistical analyses were performed with
=

Right f o o t
85

firsL

a P C / X T compatible microcomputer and a S A S /
STAT T M version 6.03 statistical software package. The
interpeak latency P40-N75 on the affected side, the
side-to-side differences of P40, N48, P57 and N75 peak
latencies, the peak-to-peak amplitudes N32-P40, P40N48, P57-N75 on the affected side, and the side-to-side
differences of N32-P40, P40-N48, P57-N75 amplitudes
were used as criteria of normality. The limits of normality were: mean + 3 S.D. in the interpeak latencies, mean
- 3 S.D. in the amplitudes (after logarithmic transformation), zero + 3 S.D. in the side-to-side differences
(where the values were distributed symmetrically around
zero) calculated from the control group. The absence of
a peak was classified as amplitude abnormality. The
normal limits are presented in Table III.

Results

The tibial nerve SEPs recorded in the scalp channel
of 3 patients are presented in Figs. 1-3.
Case 1 (Fig. 1): the patient was a 33-year-old male
LefL

foot

first

average

average
1.zspv

[

48

~

l.zspv

20 ms

20 ms

39.4

60
6O

;econd

77

average

~

47

pv

;econd

average

20 ms

20

ms

6O

59

Fig. 2. Tibial nerve SEPs of a 30-year-old male (the first patient in group i in Tables I, IV and V) recorded at (2' with A I A 2 reference. The
arrangement as in Fig. 1. The P40-N75 IPL and also the side-to-side differences in peak latencies were normal. The P40-N48 peak-to-peak
amplitude was abnormal when the left foot was stimulated (both the absolute value and the side-to-side difference were abnormal). The P57-N75
amplitude was normal.

TIBIAL NERVE SEPs IN CEREBRAL INFARCTION

267

( t h e s e c o n d p a t i e n t in g r o u p g in T a b l e s I, I V a n d V).
T h e C T was d o n e 2 d a y s a f t e r t h e o n s e t o f t h e s y m p t o m s . T h e r e was e x t e n s i v e i n f a r c t i o n in t h e left h e m i s p h e r e : in the c a p s u l a i n t e r n a , in the p r e f r o n t a l , t e m p o r a l , p r e c e n t r a l a n d p o s t c e n t r a l w h i t e m a t t e r , a n d in
the temporal, precentral and postcentral gray matter. A
n e u r o l o g i c a l e x a m i n a t i o n was p e r f o r m e d 10 d a y s a f t e r
the stroke. T h e p a t i e n t h a d t o t a l a p h a s i a ( w h i c h p r e cluded sensory examination), and there were no volunt a r y m o v e m e n t s in t h e l i m b s of t h e r i g h t side; t h e b i c e p s
a n d p a t e l l a r r e f l e x e s w e r e e n h a n c e d o n the r i g h t side,
a n d the B a b i n s k i sign was p o s i t i v e o n t h e r i g h t side. I n
the tibial n e r v e S E P s r e c o r d e d 11 d a y s a f t e r t h e stroke,

the P 4 0 - N 7 5 I P L was a b n o r m a l w h e n the r i g h t f o o t w a s
s t i m u l a t e d , a n d t h e s i d e - t o - s i d e d i f f e r e n c e s in t h e P40,
N 4 8 , P57 a n d N 7 5 p e a k l a t e n c i e s w e r e a b n o r m a l , b u t
all a m p l i t u d e s w e r e n o r m a l .
C a s e 2 (Fig. 2): t h e p a t i e n t was a 3 0 - y e a r - o l d m a l e
( t h e first p a t i e n t in g r o u p i in T a b l e s I, I V a n d V). T h e
CT was done 1 day after the onset of the symptoms.
T h e r e was i n f a r c t i o n in t h e r i g h t h e m i s p h e r e : o f t h e
postcentral white matter, the white matter of the temp o r a l lobe, a n d o f b o t h the w h i t e a n d g r a y m a t t e r in t h e
o c c i p i t a l lobe. A n e u r o l o g i c a l e x a m i n a t i o n w a s p e r f o r m e d 4 d a y s a f t e r t h e stroke, t h e o n l y a b n o r m a l sign
b e i n g a d e f e c t in t h e v i s u a l field o f t h e left side. T h e

TABLE IV
Abnormalities of the latencies of the tibial nerve SEP during the acute stage in relation to the findings in the CT (see Table I). abn = abnormal,
m = male, f = female.
CT class

Age

Sex

a: thalamus

16
68
29
54
58
45
60
60

m
f
f
f
f
m
m
m

abn

59
58
65
64
56
40

m
m
f
m
m
m

abn

53
33
64
47
39
66
55
33
30
53
44
71
57
54
66
36
52
41
55
68
52
53
56
39
64
54

m
m
m
m
f
f
m
m
m
m
m
m
f
m
m
f
m
f
m
m
m
f
m
m
m
m

b: capsula int.
c: capsula int.
+ PREC.W
d: capsula int.
+ POSTC.W + G
e: capsula int.
+ PREC.W
+ POSTC.W
f: capsula int.
+ PREC.W
+ POSTC.W + G
g: capsula int.
+ PREC.W + G
+ POSTC.W + G

h: PREC.W + G
i: POSTC.W
j: POSTC.W + G
k: PREC.W
+ POSTC.W
I: PREC.W + G
+ POSTC.W + G
m: occipital 1.
n: normal

P40-N75 IPL
(aft. side)

Side-by-side differences
P40

N48

P57

N75

abn

abn

abn

abn

abn

abn

abn
abn

abn
abn

abn
abn

abn

abn

abn

abn

abn
abn
abn
abn

abn
abn
abn
abn

abn

abn

abn

abn

abn

abn
abn

abn

abn

abn
abn

abn

abn

abn

268

T. K O V A L A E T A L .

TABLE V
A b n o r m a l i t i e s o f the a m p l i t u d e s o f the tibial n e r v e S E P d u r i n g the a c u t e s t a g e in r e l a t i o n to the f i n d i n g s in the C T (see T a b l e If). a t t = a t t e n u a t e d ,
a b s = a b s e n t , e n h = e n h a n c e d , aff.side = a f f e c t e d side, s.-b.-s.d. = s i d e - b y - s i d e d i f f e r e n c e , m = m a l e , f = female.
C T class

a: t h a l a m u s

b: c a p s u l a int.
c: c a p s u l a int.
+ PREC.W
d: c a p s u l a int.
+ POSTC.W + G
e: c a p s u l a int:
+ PREC.W
+ POSTC.W
f: c a p s u l a int.
+ PREC.W
+ POSTC.W + G
g: c a p s u l a int.
+ PREC.W + G
+ POSTC.W + G

h: P R E C . W + G
i: P O S T C . W
j: P O S T C . W + G
k: P R E C . W
+ POSTC.W
1: P R E C . W + G
+ POSTC.W + G
m: o c c i p i t a l 1.
n: n o r m a l

Age

Sex

16
68
29
54
58
45
60
60

m
f
f
f
f
m
m
m

59
58
65
64
56
40

m
m
f
m
m
m

53
33
64
47
39
66
55
33
30
53
44
71
57
54
66
36
52
41
55
68
52
53
56
39
64
54

m
m
m
m
f
f
m
m
m
m
m
m
f
m
m
f
m
f
m
m
m
f
m
m
m
m

P40-N48 amplitude

P57-N75 amplitude

aff. side

s.-b.-s.d,

abs

abs

att

aff. side

s.-b.-s.d.

att

att

enh
abs

abs

abs

abs

abs

abs

abs

abs

abs
att

abs
att

abs
abs

abs
abs

att

att

abs
abs
abs

abs
abs
abs

tibial nerve SEPs were recorded 5 days after the stroke:
the P40-N75 IPL and also the side-to-side differences in
peak latencies were normal, but the P40-N48 peak-topeak amplitude was abnormally low when the left foot
was stimulated (both the absolute value and the sideto-side difference were abnormal).
Case 3 (Fig. 3): the patient was a 66-year-old female
(the sixth patient in group g in Tables I, IV and V). The
CT was done 21 days after the stroke. There was
extensive infarction of the left hemisphere: of the
capsula interna, the prefrontal, temporal, precentral and
postcentral white matter, and of the prefrontal, temporal, precentral and postcentral gray matter. A neuro-

att
att
abs

abs

att
abs

att
abs

logical examination was performed 6 days after the
stroke: the level of consciousness was still reduced; the
patient had deficiency on the right side of the sense of
light touch, temperature, joint position and vibration,
and of stereognosis, and there were no voluntary movements in the limbs of the right side; the biceps reflex
was enhanced on the right, and the Babinski sign was
positive on that side. The tibial nerve SEPs were recorded 7 days after the stroke: all cortical peaks were
absent when the right foot was stimulated.
Abnormalities in the peak latencies and in the P40N75 IPLs of the tibial nerve SEPs during the acute
stage are presented in Table IV (the classification of the

TIBIAL N E R V E SEPs IN C E R E B R A L I N F A R C T I O N

269

CT findings is described in Table I). Altogether 15
patients (38%) had abnormalities of latency. Most frequently they occurred in the side-to-side differences of
the P57 or N75 peak (13 patients). Only 4 patients with
normal side-to-side differences of the N75 latency had
abnormalities of the other latencies, and only 1 patient
with normal P57 and N75 side-to-side differences had
abnormal side-to-side differences of the earlier components. As many as 13 (87%) out of 15 patients with
abnormalities of the latencies had involvement of the
subcortical white matter in the postcentral region.
During the acute stage altogether 13 patients (33%)
had abnormalities of amplitudes (Table V). All patients
with abnormal N32-P40 amplitudes also had abnormalities of the P40-N48 or P57-N75 amplitudes, and hence
the N32-P40 amplitude was not included in the table.
The P40-N48 amplitude was abnormal in 12 patients
(30%) and the P57-N75 amplitude in 10 patients (25%).
All patients with an absent P40 peak in the first examination (9 patients) had evidence of involvement of
the cortical gray matter in the postcentral area in the
CT.
When both the latency and the amplitude abnormalities were taken into account, 22 patients (55%) during
the acute stage, 20 patients (51%) about 2 months later
and 15 patients (43%) about 12 months after the stroke

had abnormal tibial nerve SEPs (Fig. 4). The changes in
the number of amplitude abnormalities and in the total
number of abnormalities were not significant (chi-square
test), but nearly significant decreases between the second and the third examination (P = 0.034 with chisquare test), and between the first and the third examination (P = 0.023 with chi-square test) were found
in the number of latency abnormalities (Fig. 4).
All 6 patients with a lowered level of consciousness
at the time of the first recording showed abnormal SEPs
in all the 3 examinations (Fig. 5). In the subgroup of 15
patients with mass displacements as many as 13 patients (87%) had abnormal SEPs during the acute stage.
Furthermore, 12 (80%) out of 15 patients with involvement of both the cortical gray matter and the subcortical white matter in the rolandic region had abnormal
SEPs during the acute stage, whereas in the subgroup of
13 patients with involvement of the subcortical white
matter but not the cortical gray 8 patients (62%) had
abnormal SEPs.
The differences in the means of P40 and N75 peak
latencies, P40-N75 interpeak latency (IPL), P40-N48
and P57-N75 amplitudes between the control group and
certain CT groups for all the 3 examinations were tested
with analysis of covariance. Patients with absent peaks
could not be included in these statistical analyses. How-

Right foot

Left

foot

first

first

average

average

86
2.5
I

0.63

pV

20 ms

pV

46.7

20 ms

Z

61

second

second

average

average
2.5

1
io.63 pv

pV

20 ms

~I .2

20 ms

6)

Fig. 3. Tibial nerve SEPs of a 66-year-old female (the sixth patient in group g in Tables I, IV and V) recorded in C" with A1A 2 reference.
Arrangement as in Fig. 1. The P40, N48, P57 and N75 peaks were absent when the right foot was stimulated.

270

T. KOVALA ET AL.
22
60%.

40t.

20t

0t
N:

40

[Ifirat

T.~C
39

I F.~
35

~LITUI)ES
40
39
35

lucondimthird

~
'40 ~

J~S)l.
35

39

]

Fig. 4. The percentages of abnormal SEP findings in latencies and amplitudes as well as the total number of abnormal findings in the entire patient
group (OVERALL. ABN.) in the first examination (days 4-19), in the second examination (days 56-100) and in the third examination (days
348-393).

ever, some significant differences were observed between the control group a n d those patients with measurable peaks (Figs. 6 - 9 ) . The m e a n of the P40 latency
was still, a b o u t 1 year after the stroke, significantly
longer in the group of patients with i n v o l v e m e n t of the
r o l a n d i c cortex ( m e a n 44.3, S.D. 3.8) than in the control
group ( m e a n 39.8, S.D. 3.6, P = 0.007 b y the analysis of

covariance, adjusted for height, age a n d gender). I n the
P40-N75 IPL, only a n e a r l y significant difference was
f o u n d d u r i n g the acute stage b e t w e e n the entire p a t i e n t
group a n d the c o n t r o l group (Fig. 6). I n this acute stage
the subgroups of p a t i e n t s with mass d i s p l a c e m e n t s a n d
patients with i n v o l v e m e n t of the r o l a n d i c cortex differed highly significantly from the c o n t r o l group in the
6 6 5
100ZlOOZIO0~

7
100~

100%

80%

60%

40%

20%

o%

ALL

N:

40 39 35

[I

first

I

MASSDISP. CORTICAL SUBCORTICAL L.CONSC.

APHASIA PUREMOT. SENSOMOT.

15 14 11

7

second I

third

15 1,5 13

13

12 11

6

6

5

7

,5

7

7

7

24 23 21

]

Fig. 5. The total number of abnormal SEP findings in relation to the CT and the clinical examination in the first, second and third examinations.
ALL = all patients, MASS DISP. = patients with evidence of mass displacements in the CT, CORTICAL = patients with involvement of both the
cortical gray matter and the subcortical white matter in the rolandic region, SUBCORTICAL = patients with involvement of the subcortical white
matter but not the cortical gray matter in the rolandic region, LCONSC. = patients with lowered level of consciousness, APHASIA = patients with
fight-sided hemiplegia and severe aphasia, PURE MOT. = patients with pure motor hemiparesis, SENSOMOT. = patients with sensomotor stroke.

TIBIAL NERVE SEPs IN CEREBRALINFARCTION

271

P40-N75 IPL
absent
..... • ..,....E......

.......

°...°°

.........

.... .... ..,. ..... ..i...

........

.....,°...°°..,.

..... ......,.°

......

lO0
95
90
85
80

75
70
65
6O
55
5O
***

45

***

4O

35

.*****

****

*

*****

-********--

******

*********

****

*****

******

**

*****

*

**

*

3O

I
CONTROLS

I

first

I

second

I

first

second

(p--O.O16)

(p=o.oool)

(p--O.O02)

ALL PATIENTS

MASS DISPLACDIENTS IN CT

third

I

third

Fig. 6. The scatter of the P40-N75 IPLs in the control group, in the entire patient group, and in the subgroup of patients with evidence of mass
displacement in the CT. * = one patient, first = the first examination (days 3-15), second = the second examination (days 56-99), third = the third
examination (days 347-392). The levels of significancewere tested by analysis of covariance adjusted for age and gender.

P40-N75 IPL (Figs. 6 and 7). During the follow-up
period these differences diminished; in the second examination the patients with mass displacements differed
significantly and the patients with involvement of the
rolandic cortex only nearly significantly from the control group, and in the third examination no significant
differences were noted any more (Figs. 6 and 7). Thus,
the prolongations in the P40-N75 IPL were observed
mainly during the acute stage.
When considering the amplitudes, the changes in the
P40-N48 amplitude were more profound than those of
P57-N75. The difference between the subgroup with
mass displacements and the control group in the P40N48 amplitude was still significant in the third examination (Fig. 8). The subgroup of patients with involvement of the subcortical white matter in the rolandic region differed significantly from the control
group in the P40-N48 amplitude during the acute stage
and in the second examination, and the difference was
nearly significant in the third examination (Fig. 9). The

P40 peak was absent during the acute stage in 9 out of
15 patients (60%) with both cortical and subcortical
involvement in the rolandic region, but in the subgroup
of patients with only subcortical involvement, none had
an absent P40 peak in the first and second examinations, and only 1 patient had an absent P40 peak in the
third examination (Fig. 9).
The changes in the P40 and N75 latencies, in the
P40-N75 IPL and in the P40-N48 and P57-N75 amplitudes between the first, second and third examinations
were tested with paired t test in the same subgroups of
patients as in Figs. 6-9. In the entire patient group
there were no significant changes. In the subgroup of
patients with mass displacements there was a nearly
significant ( P = 0.037) decrease in the N75 peak latency
between the second and the third examinations: in the
third the N75 latency was on average 7.5 msec (S.D. 7.4
msec) shorter than in the second. In the subgroup of
patients with involvement of the subcortical white matter
in the rolandic region there was a small but significant

272

T. KOVALA ET AL.
P40-N75 IPL
*********

abf,eat
• ....

o,.,°,°o

******

*****

..o,,o°,,,,,o,,o,,,,oo,°,,,,,o°,,,o,o,,,,,o,,,o

H°,°,°°°°,°°°o,°,°°°°°°°°°,o°°°°°°.,°°°°°°,°°

i

100
95
90
85
80
75
70
65
60
55
50

*

45

*****

40

-********--

35

**

***

**

***

-*

**

*

-*.

***

***

*

30

t

C01TIDLS

I

I

first

second

(D=O.O001)

(p:O.Oll)

I

third

CORTICAL AID SI~COIfflCAL I~OLVE]i~T

I

i

first

see0nd

(p:0.011)

(p=0.035)

i

third

SI~C01~ICAL ONLY

Fig. 7. The scatter of the P40-N75 IPLs in the control group, and in the subgroups of patients with involvement of both the cortical gray matter and
the subcortical white matter in the rolandic region and patients with involvement of the subcortical white matter but not the cortical gray matter in
the rolandic region. * = one patient, first = the first examination (days 3-15), second = the second examination (days 56-99), third = the third
examination (days 347-392). The levels of significance were tested by analysis of covariance adjusted for age and gender.
d i m i n u t i o n o f the P57-N75 a m p l i t u d e f r o m the first to
the s e c o n d e x a m i n a t i o n (the m e a n c h a n g e in the logar i t h m i c a m p l i t u d e = - 0 . 1 1 , S.D. = 0.12, N = 12, P =
0.007) a n d f r o m the first to the third e x a m i n a t i o n s (the
m e a n change in the l o g a r i t h m i c a m p l i t u d e = - 0 . 1 4 ,
S.D. = 0 . 1 3 , N = 1 0 ,
P = 0 . 0 0 6 ) , b u t no significant
c h a n g e s b e t w e e n the s e c o n d a n d the third e x a m i n a t i o n s .

Discussion
T h e m o s t frequent a b n o r m a l findings in the tibial
nerve SEPs were high side-to-side differences in the P57
or N75 p e a k latencies a n d a b s e n c e of the P40 peak. T h e
l a t e n c y a b n o r m a l i t i e s were a s s o c i a t e d with i n v o l v e m e n t
of the s u b c o r t i c a l white m a t t e r in the r o l a n d i c region
when related to the findings in the C T scan. O n the
o t h e r hand, the a b s e n c e of the P40 p e a k was closely
c o n n e c t e d with e x t e n s i o n of the i n f a r c t e d a r e a into the
cortical g r a y m a t t e r of the r o l a n d i c region. It has been

e s t a b l i s h e d in earlier studies of the g e n e r a t o r s of the
tibial nerve SEPs that the source of the P40 p e a k is a
cortical g e n e r a t o r l o c a t e d in the i n t e r h e m i s p h e r i c fissure
(Cruse et al. 1982; Beri6 a n d Prevec 1983; Seyal et al.
1983; D e s m e d t a n d B o u r g u e t 1985; Lesser et al. 1987),
that the g e n e r a t o r s o f the P57 p e a k are p r o b a b l y s i t u a t e d
m o r e p o s t e r i o r l y in the p a r i e t a l lobe, a n d that the N75
p e a k has a w i d e s p r e a d negative field over b o t h the
frontal a n d p o s t e r i o r s c a l p ( D e s m e d t a n d B o u r g u e t
1985). T h e a b s e n c e o f t h e P40 p e a k in s o m e p a t i e n t s
might thus reflect n e u r o n a l d a m a g e in the cortex o f the
r o l a n d i c area. H i g h s i d e - t o - s i d e differences in the P57
a n d N75 p e a k latencies could, in contrast, i n d i c a t e
i n v o l v e m e n t of the s u b c o r t i c a l white m a t t e r ( p o s s i b l y in
the c o r t i c o - c o r t i c a l c o n n e c t i o n s o r in the successive
t h a l a m o - c o r t i c a l loops). This suggestion c o n f i r m s the
o b s e r v a t i o n of C h u (1986a) that in s u b c o r t i c a l infarcts
m a i n l y m i d - a n d l o n g - l a t e n c y S E P c o m p o n e n t s a r e affected. Similar findings have b e e n r e p o r t e d in the literature a b o u t m e d i a n nerve SEPs: a c c o r d i n g to M a u g u i 6 r e

TIBIAL NERVE SEPs IN CEREBRAL I N F A R C T I O N

273

P40-N48 amplitude
)V
16.00

8.00

4.00

*

*

***

**

***

**

***

***

**

-******

**

2.00

***

*****
**

***

****

***

*
- * - -

1.00

**

*
*
**
*

*
*

0.50

*
*

*********

al~nt

I

first
COraLS

******

I

second

******

I

******

third
(p=O.O18)

ALL PATIDIT$

I

first
(p=0.043)

****

t

second
(p=O.OO7)

****

I

third
(p=O.O09)

HASS DISPI~C~EI~S IN CT

Fig. 8. The scatter of the P40-N48 peak-to-peak amplitudes in the control group, in the entire patient group, and in the subgroup of patients with
evidence of mass displacement in the CT. * = one patient, first = the first examination (days 3-15), second = the second examination (days 56-99),
third = the third examination (days 347-392). The levels of significance were tested by analysis of covariance adjusted for age and gender.

et al. (1983) typical abnormalities in patients with cortical lesions are changes in amplitude or changes in
duration of cortical SEP components, whereas the onset
latencies are either equal to those of the controls or only
slightly longer. The hypothesis that the absence of the
P40 peak might reflect cortical neuronal damage is
further supported by our finding about the persistence
of the amplitude abnormalities during the 1 year followup period (Fig. 4).
When the measured latencies and amplitudes of the
control group and the patient groups are compared by
analysis of covariance, it can also be noted that the
differences in the N75 peak latency and the P40-N75
IPL were concentrated in the acute stage, whereas the
differences in the early components were more perma-

nent. This is in accordance with our hypothesis that the
changes in the N75 peak latency indicate involvement
of the subcortical white matter.
The height of the subject correlates highly with the
peak latencies of tibial nerve SEPs. Using multiple
correlation and regression analysis, Chu (1986b) has
observed that height provides the best prediction of the
remaining latencies, whereas age alone does not correlate with latencies. In addition, Kakigi (1987) noted that
the interpeak latencies of cortical potentials following
"P35" (our P40) do not correlate with age, but that the
amplitudes of short- and middle-latency cortical potentials are slightly smaller in aged subjects than those in
young subjects. In the present study the problem of
interpreting the role of height in abnormalities was

274

T. KOVALA ET AL.
P40-H48 a~litude

~V
16.00
k

**

8.00

**

4.00

***
tik

***
i

*

***

2.00

**
i

i

,

i

1.00

i

**

*

0.50

. . ° . ° ° . o o , o ° o

,°°° .... °°°°°o,°°.o°oo°o°°°°°°o°

......

o°°°..°°,

ab6ent

I
CO~IOLS

I

first

I

second

i

third
(pffiO.026)

COBTICAL AND SUB~RTICAL INVOLV~(ERT

I

first
(p=O.O09)

I

second
(p=O.OlO)

I

third
(p=0.029)

StmCORTICAL ONLY

Fig. 9. The scatter of the P40-N48 peak-to-peak amplitudes in the control group, and in the subgroups of patients with involvement of both the
cortical gray matter and the subcortical white matter in the rolandic region and patients with involvement of the subcortical white matter but not
the cortical gray matter in the rolandic region. * = one patient, first = the first examination (days 3-15), second = the second examination (days
56-99), third = the third examination (days 347-392). The levels of significance were tested by analysis of covariance adjusted for age and gender.

a v o i d e d b y using o n l y the P40-N75 I P L a n d side-to-side
differences o f the p e a k latencies as criteria of a b n o r m a l ity o f the latencies. In the statistical analysis o f differences of m e a s u r e d values b e t w e e n different subg r o u p s a n d the c o n t r o l g r o u p we used analysis of cov a r i a n c e a d j u s t e d for height, age a n d g e n d e r for the
p e a k latencies, a n d a d j u s t e d for age a n d g e n d e r for the
P40-N75 I P L a n d the a m p l i t u d e s .
Studies have b e e n p u b l i s h e d which i n d i c a t e that SEPs
m a y have p r o g n o s t i c significance in c e r e b r a l infarct ( L a
Joie et al. 1982; Regli a n d D e s p l a n d 1982; P a v o t et al.
1986; D e W e e r d et al. 1987).
A l t h o u g h o n l y 55% o f p a t i e n t s with c e r e b r a l infarction h a d a b n o r m a l tibial nerve SEPs, in certain subg r o u p s a s u b s t a n t i a l p r o p o r t i o n o f p a t i e n t s revealed

a b n o r m a l findings. A g r e a t e r n u m b e r of a b n o r m a l i t i e s
w o u l d have b e e n d e t e c t e d if n a r r o w e r limits of n o r m a l ity t h a n ours (_+ 3 S.D.) h a d b e e n used. H o w e v e r , as
n a r r o w e r limits w o u l d i n e v i t a b l y l e a d to false positive
findings ( a l t o g e t h e r 11 p a r a m e t e r s were used as criteria
of a b n o r m a l i t y in 3 successive e x a m i n a t i o n s ) we preferred the use o f the _+ 3 S.D. limits.
P r o l o n g a t i o n of the p e a k N75 l a t e n c y a n d P40-N75
I P L of the tibial nerve SEPs c o r r e l a t e d with d a m a g e in
the s u b c o r t i c a l white m a t t e r of the r o l a n d i c area, o b served m a i n l y d u r i n g the a c u t e stage. T h e a b n o r m a l i t i e s
of a m p l i t u d e , especially the a b s e n c e of the P40 p e a k
a n d a t t e n u a t i o n of the P40-N48 p e a k - t o - p e a k a m p l i tude, were a s s o c i a t e d with the e x t e n s i o n o f the i n f a r c t e d
area i n t o the cortical g r a y m a t t e r of the r o l a n d i c region.

TIBIAL NERVE SEPs IN CEREBRAL INFARCTION
The amplitude abnormalities were relatively permanent
t h r o u g h o u t the 1 year follow-up period.

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