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Posterior cervical N13 in median nerve SEP has two components
Electroencephalography and cfinical Neurophysiology, 1990, 77:28-38
28
Elsevier Scientific Publishers Ireland, Ltd. EVOPOT 89007
Posterior cervical N 1 3 in median nerve S E P has two components M. Sonoo, T. Shimpo, K. Genba, M. Kunimoto and T. Mannen Department o/Neurology, Institute of Brain Research, School of Medicine, University of Tokyo, Bunkyo, Tokyo 113 (Japan) (Accepted for publication: 4 May 1989)
Summary Somatosensory evoked potentials (SEPs) to median nerve stimulation were investigated in normal controls and patients with cervical lesions. Attention was paid primarily to the N13 and P13 components in the posterior and anterior cervical records with non-cephalic references. In normal subjects the CV2 and CV6 electrodes registered N13 with almost the same amplitude. Dissociation between N13 at the CV2 electrode (ucN13) and N13 at the CV6 electrode (1cN13) was observed in the patients. In 4 patients with cervical dorsal column lesions, lcN13 was preserved but ucNl3 was almost completely absent. Anterior cervical P13 (acP13) was preserved. In a patient with syringomyelia, lcNl3 and acP13 were greatly attenuated while ucN13 was relatively well preserved. These results suggested that the origins of ucN13 and lcN13 are different. The generator of lcN13-acP13 was assumed to be the postsynaptic potential of the dorsal horn intemeurons. Upon comparison with previous animal studies and intraoperative studies, it was concluded that the generator of ucN13 is the postsynaptic potential of the cuneate nucleus.
Key words: Somatosensory evoked potential; Median nerve; N13; Cuneate nucleus
Short-latency somatosensory evoked potentials (SEPs) to median nerve stimulation are now widely used in clinical practice. However, not all the generators of individual components have been identified. In particular, there has been much debate about the origin of the so-called 'N13' component of the cervical-scalp recording. The dorsal horn of the cervical spinal cord (Jones 1977), the dorsal column (Cracco 1972, 1973; Lesser et al. 1981) and the cuneate nucleus (Jones 1977; Hume and Cant 1978; Leandri et al. 1981; Favale et al. 1982) were all postulated as the generator of N13 in cervical-scalp records. Cracco and Cracco (1976) first recorded SEPs with a non-cephalic reference. They noted that the scalp electrodes which had been used as reference in previous studies, such as the frontal electrode, were also active when recorded with a non-ce-
Correspondence to: Dr. M. Sonoo, Department of Neurology, Institute of Brain Research, School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113 (Japan).
phalic reference. A negative potential (N13) was recorded at the cervical electrode with a non-cephalic reference, while a positive potential (named P13, P13-14 or P14 by various authors) is recorded simultaneously at scalp electrodes. At first, cervical N13 and scalp P13-14 were thought to be generated by the same generator (Jones 1977; Yamada et al. 1980). Using esophageal recording, Desmedt and Cheron (1981) found a prevertebral P13 which represented phase reversal of N13 at the posterior cervical electrodes. They interpreted this N13-P13 dipole to be the postsynaptic potential of the dorsal horn interneurons and argued that it should be differentiated from the scaIp P14 which originates in the medial lemniscus. Later they found that the prevertebral P13 can also be recorded from the skin surface of the anterior neck region (Desmedt and Huy 1984). Although their opinion is now widely accepted, an animal study pointed out the dual origin of the posterior cervical N13, that is, one part from the interneurons of the dorsal horn and the other
0168-5597/90/$03.50 © 1990 Elsevier Scientific Publishers Ireland, Ltd.
POSTERIOR CERVICAL N13
29
from the cuneate nucleus (Allison and H u m e 1981). However, these authors used a frontal reference and this point has not been clarified in records with a non-cephalic reference. The aim of this study is to investigate the dual nature of the posterior cervical N13 with a non-cephalic reference in clinical cases where a dissociated loss of the two components was expected from clinical and M R I (magnetic resonance imaging) findings.
Subjects We studied 17 normal volunteers without history of neurological disease and 5 neurological patients. Informed consent was obtained from all subjects. N o r m a l subjects were divided into 2 groups according to age: the younger (n = 9, 6 men and 3 women) had a mean age of 27.8 years (23-32 years) and the older group (n = 8, 5 men and 3 women) had a mean age of 72.3 years (65-81 years). Patients were divided into 2 groups according to the site of the lesion. Table I presents some of the clinical details of the patients. Cases 1 - 4 had cervical dorsal column lesions above the entry zone of the median nerve (C6, C7,
C8 and Thl). Cases 1 - 3 had definite disturbances of deep sensation in the upper extremities and showed impaired skilled movements of the hands. High to middle cervical lesions were demonstrated by M R I (Figs. 4B, 5B, 6B and 6C). Case 4 had only a mild dysesthesia of the palms while deep sensation of the hands was intact. Nevertheless, M R I clearly demonstrated a lesion of the high cervical dorsal column (Fig. 7B). Case 5, a patient with syringomyelia, had a lesion of cervical grey matter. His pain and thermal sensations were lost in the right upper extremity, although deep sensations were intact. M R I showed a syrinx of the cervical cord (Fig. 8B).
Methods The median nerve was stimulated at the wrist through felt electrodes using square wave pulses of 0.2 msec duration at a rate of 5/sec. Stimulus intensity was adjusted to produce a consistent thumb twitch. In order to assure that the stimulus intensity was comparable interpersonally and the amplitude of the evoked potential was nearly maximal, sensory nerve action potentials (SNAPs) were monitored simultaneously. Ring electrodes were
TABLE 1 Case no.
Age
Sex
Diagnosis
Main symptoms
Duration of illness
1
62
F
cervical spondylosis
10 years
2
66
F
rheumatoid arthritis atlanto-axial dislocation
3
19
M
myelitis
4
29
F
multiple sclerosis
5
40
M
posttraumatic syringomyelia
impaired position sense and vibratory sense of both hands impaired skilled movement of hands sensory disturbances hands > legs position sense dominant bilateral pyramidal sign sensory disturbances hands >> legs position sense dominant impaired skilled movement of both hands dementia, ataxia, pyramidal signs, impaired deep sensation of lower extremities mild dysesthesia of palms impaired pain and thermal sensation of right arm and trunk
2 months
3 weeks
2 years
8 months
30
placed over the index finger and the antidromic SNAP was shown on an oscilloscope. Then, the stimulus intensity was further regulated so that the amplitude of the SNAP would exceed at least half of the maximal amplitude. It was confirmed in some normal subjects that stronger stimulation would produce little change in the amplitude of the posterior cervical N13. The stimulus which produced the SNAP with the maximal amplitude was rather painful. Disk electrodes were placed at the following sites. The CV6 electrode was placed over the spinous process of the CV6. The 'CV2' electrode was placed at the midpoint of the inion and the CV6 electrode taking into consideration that the spinous process of the CV2 was hardly felt in some subjects. The anterior cervical electrode (AC) was placed contralateral to the stimulated side 5 cm from the midline at the midpoint of the rostro-caudal length of the neck. This deviation was employed because the root spike (which continues from N9) interferes considerably with the midline electrode (Desmedt and Huy 1984). Other electrodes included Fz, contralateral hand sensory area (named 'HS') and inion. The non-cephalic reference electrode (NC) was placed on the contralateral shoulder. Evoked potentials were amplified and filtered between 5.3 and 1500 Hz ( - 3 dB). Averaging was performed on 2000-3500 responses over an analysis time of 50 msec, using a sampling rate of 10,000 Hz. Two averages were superimposed. Samples showing excessive artifact were rejected on-line from the average. As a rule, bipolar montages were obtained directly by measuring potential difference between two electrodes, although off-fine subtraction between two waves of non-cephalic reference was substituted in some cases.
Results
Normal subjects Left median nerve stimulation was performed in all subjects. Right median nerve stimulation was performed in 6 subjects. Because the latter response was generally of poor quality due to
M. SONOO ET AL.
ECG artifact, we considered primarily the records to left median nerve stimulation. An example of wave forms in a normal subject is shown in Fig. 1. Both in CV2 and CV6 leads with non-cephalic reference, P9 far-field potential and subsequent negativity were noted in all sub-
Lt median N.
Fz-NC
10. 6 P9 Pll P13-14 ( 11.6) ucN13 N11 .,i T ~
CV2-NC ~ CV6-NC AC-NC
I-lpV
acP13
,.p
inion-CV2 12.3
CV2-CV6
A
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0
E
I
10
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20
~
30 ms
Fig. 1. A normal control (25-year-old male). The upper 4 traces are recorded with non-cephalic reference. The lower two traces are bipolar records. Both the CV2 and CV6 electrodes register N13 potentials and preceding N l l potentials. N13 at the CV2 electrode is n a m e d ucN13 and N13 at the CV6 electrode is n a m e d lcN13. The amplitude of ucN13 is almost the same as or slightly larger than that of lcN13. P13 is present at the anterior cervical (AC) electrode, which is named acP13. A scalp electrode (Fz) registers 3 far-field potentials: P9, P l l and P13-14. The onset of P l l is earlier than that of acP13. Two bipolar leads show peaks traveling caudo-rostrally which correspond to scalp P11. The termination of the scalp P11 coincides with the termination of N l l at posterior cervical electrodes (dashed line). Figures represent latencies expressed in milliseconds.
POSTERIOR CERVICAL N13
jects. This negative potential was assumed to be a composite of N l l and N13, although two peaks could not be discerned in some subjects. However, as is discussed later, N13 was considered to determine the main configuration of this negativity, especially its peak and descending slope. We named N13 in the CV2 lead 'ucN13' (upper cervical N13) and N13 in the CV6 lead 'lcN13' (lower cervical N13). In the anterior cervical (AC) lead, P9 and P13 were identified in all subjects. The anterior cervical P13 was named 'acP13' (anterior cervical P13) in order to distinguish it from the scalp P13-14 far-field potential. In scalp leads, P9, P l l and P13-14 far-field potentials were noted in all cases. We discerned the following two characteristics of P l l , which were employed as the criteria for the presence of P l l in clinical cases. First, the onset of P l l invariably preceded the onset of acP13. Second, bipolar derivations from CV2-CV6 and inion-CV2 showed the traveling of a peak corresponding to P l l , which was supposed to be an ascending dorsal column volley (Desmedt and Cheron 1980; Favale et al. 1982). In order to quantify the abnormality of N13, we tried to evaluate its amplitude. Because N l l and N13 overlapped in the posterior cervical records, we could only measure the combined amplitudes of N l l + N13. This, however, seemed to be a rough estimate of the amplitude of N13 which is the dominant component. The method of measuring the N l l + N13 amplitude is illustrated in Fig. 2. The results are shown in Fig. 3. In normal subjects, the amplitude of N l l + N13 was almost the same in the CV2 and CV6 leads or slightly greater in the former. Although old subjects had a significantly smaller amplitude, the CV2/CV6 ratio of the amplitude of N l l + N13 was fairly constant irrespective of age. Patients
In each of the 4 patients with a dorsal column lesion (Figs. 4A, 5A, 6A and 7A), N13 in the CV2 electrode (ucN13) was almost completely absent, while the CV6 electrode registered a definite broad negative potential which was thought to represent lcN13 (later discussed). Both N l l and lcN13 peak could definitely be identified in case 4 (Fig. 7A)
31
Fz
CV2 i i
f /
CV6
Fig. 2. Methods of measuring the amplitude of N l l + N13. The latency of the scalp P l l onset was marked on the wave in a posterior cervical lead. A line was drawn from this point to the termination of the N13. The greatest distance between this line and the negative wave was defined as the amplitude of N l l + N13. Because the shock artifact may interfere with the earlier wave configuration, neither prestimulus baseline nor baseline before P9 was employed.
and questionably in case 3 (Fig. 6A). The acP13 was also preserved in all 4 cases. In these patients, the CV2/CV6 ratios of the amplitude of N l l + N13 were clearly lower than those of normal subjects (Fig. 3). In case 1 (Fig. 4A), scalp electrodes registered only P9 and a positive potential following P9. The onset of the positivity did not precede the onset of acP13 and posterior cervical bipolar leads did not show the latency shift of a peak. In view of the aforesaid criteria for the presence of P l l , we judged that this positivity was not P l l . Moreover, the scalp P13-14 is rather unlikely to be present without P l l or later components. Because the onset and the configuration of the positivity coincided well with those of acP13, we assumed that acP13 could be recorded over the scalp in this patient.
32
M. SONOO ET AL. CV6
CV2
pV 2.0-
CV2/CV6
uv 2.0
Discussion
2.0-
S o m e r e m a r k s on wave identification 1.5 ¸
0.5
I
1.0
0
0.5
o o
I *2SD
o
g
o cases 1 - 4 Acase 5
o
0.5
• control
young p
ojId
young
L
p
old
young
__
old
n.s.
j
Fig. 3. The amplitude of N11+N13 at the CV6 and CV2 electrodes and the CV2/CV6 ratio of the amplitude of N l l + N13 are shown. Closed circles represent normal subjects. Young and old subjects are considered separately. Old subjects have significantly smaller amplitudes at both the CV6 and CV2 electrodes, but the amplitude ratio is constant irrespective of age. Open circles represent patients with a dorsal column lesion (cases 1-4). They clearly have small amplitude ratios. Open triangles represent case 5. He has a large amplitude ratio. Case 5, who is 40 years old, is included in the young group.
In 3 other cases (Figs. 5A, 6A and 7A), definite P l l scalp far-field potentials with earlier onset than that of acP13 were present. As for the later components, delayed P13-14 was noted in case 4 (Fig. 7A) and delayed N20 potentials were noted in cases 2 and 4 (Figs. 5A and 7A). In case 4, a patient with long-standing multiple sclerosis, who had a clear but delayed P13-14 at the scalp electrodes, a rather flat negativity, probably intercalated by P13-14, was noted at the CV2 electrode, which was assumed to be a delayed ucN13 (Fig. 7A). In a patient with a cervical grey matter lesion (case 5, Fig. 8A), both acP13 and lcN13 had very small amplitudes. It was judged that the negative potential at the CV2 electrode mainly represented ucN13 and not N l l since its peak was behind the termination of the scalp P l l (see the following section). The ucN13 was also attenuated but was relatively well preserved in comparison with lcN13. The C V 2 / C V 6 ratio of the amplitude of N l l + N13 was therefore higher than in normal subjects (Fig. 3). Scalp far-field potentials were normal in this patient.
As is mentioned above, the posterior cervical negative wave with non-cephalic reference is thought to be composed of N l l and N13. In order to discuss N13 at all, one must be able to identify N l l and N13 separately. N l l is thought to be generated by the near-field potential of the ascending dorsal column volley (Desmedt and Cheron 1980). Therefore, the duration of N l l must be relatively short, reflecting the time for the impulses to go up the dorsal column. In normal subjects where two peaks of N l l and N13 could be clearly distinguished, termination of N l l coincided with the termination of scalp P l l (Fig. 1), which supports the theory that the scalp Pl1 sees the approaching front of depolarization of the dorsal column volley (Desmedt and Cheron 1980). The peak of N13, which usually represented the major peak of the overall negativity, existed behind the termination of N l l and scalp P l l (Fig. 1). In subjects where the two peaks could not be discerned, the peak of the overall negativity was also behind the termination of scalp P l l . From these findings, the authors concluded that the peak and the gentle descending slope of the posterior cervical negative potential are free from the influence of N l l and represent principally N13. N l l was thus estimated as a rather small potential located on the ascending limb of N13. This opinion agrees with Desmedt and Cheron (1980) and is also supported by the findings with epidural recording (Beri6 et al. 1986). On this ground, N13 was judged to be lost when the characteristic broad descending slope was lost, such as in the CV2 electrodes in present cases 1-4, Conversely, N13 was most probably preserved when the broad descending slope was preserved, although of small amplitude, such as at the CV6 electrodes in cases 1 and 2. It seems unlikely that N l l , which was originally a small steep potential analogous to a sensory nerve action potential, would assume such a clear prolonged shape even if it was metamorphosed. Moreover, if the negative potential is interpreted as N l l , it is difficult to explain the fact that acP13, which is thought to be the counterpart of the posterior cervical N13
POSTERIOR CERVICAL N13
33
Lt median N. V ~11\\ lo.1 Fz-NC I!ii "~'~ • !I\
A p~ ucN 13(-)
ii~~
cV2-NC ;!i
ov -.c I "a i"
~/9.9
;, . . . . . . . . . . . . . . .
_ A
1
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4
,r,,or,-CV !! cw-cv61i l!', I
A
0
1 1.3 I
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10
~.+lyV I
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20
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30 m8
Fig. 4. Case 1. A 62-year-old woman with high cervical spondylosis. A: N13 at CV6 (lcN13) is preserved although it is of small amplitude. N13 at CV2 (ucN13) is absent. Anterior cervical P13 (acP13) is preserved. A scalp electrode (Fz) registers a positivity which resembles acP13. This is not thought to be P l l since its onset does not precede the onset of acP13 and posterior cervical bipolar leads do not show traveling of the peak. B: magnetic resonance imaging (MRI) shows posterior compression of the spinal cord, mainly at the C 3 - 4 vertebral level.
(Desmedt and Cheron 1981), is preserved in these cases.
Two generators of N13 The present study revealed that N13 potentials at CV2 and CV6 electrodes are of almost the same size in normal subjects. However, the CV2 electrode is far from the level of the median nerve entry where Desmedt and Cheron (1981) demonstrated that prevertebral P13 has its maximal amplitude. In the present clinical cases, dissociation between N13 potentials in the high and low posterior cervical electrodes was observed. In the patients with cervical dorsal column lesions, N13 at the CV6 electrode (lcN13) was preserved although N13 at the CV2 electrode (ucN13) was
almost completely absent. In one case (case 4), a possible delayed ucN13 was noted just before the scalp P13-14. In a patient with a syringomyelia, lcN13 was greatly attenuated although ucN13 was relatively well preserved. The acP13 potential behaved similarly to the lcN13. We concluded from these results that the origins of lcN13 and ucN13 are different. Of course, significant overlap may exist between the distribution of the potentials generated by the two generators. This is suggested by the fact that the amplitude of lcN13 in some patients with dorsal column lesions (cases 1 and 2) was decreased and also by the fact that the amplitude of ucN13 was decreased and 1cN13 was still present with a small amplitude in case 5. Another
34
M. SONOO ET AL.
Lt median N. V
N2o(19.9)
HS-NC 4
A
P9(6.9) P1 1(9.9)
CV2-NC
CV6-NC
I-1/JV
AC-NC
-t-
acP13 I
A
0
I
I
10
I
I
20
I
I
30
ms
Fig. 5. Case 2. A 66-year-old woman with atlanto-axial dislocation. A: lcN13 is preserved although it is of rather small amplitude. ucN13 is absent, acP13 is preserved. The electrode at the contralateral hand sensory area (HS) registers Pll and N20. P13-14 is absent. Pll has a rather broad configuration. Its onset precedes the onset of acP13. N20 is delayed in this short-stature patient since P9-N20 interpeak latency is clearly prolonged (13.0 msec. Average and standard deviation of normal subjects; 10.36+0.65 msec, n = 17). B: sagittal section of MRI showing posterior compression of the spinal cord at the C1-2 level due to the displaced posterior arch of the atlas.
possibility to explain the above results is that a subclinical partial disturbance of each generator is present in such cases. It seems clear that the generator of l c N 1 3 acP13 is the postsynaptic potential of the dorsal h o r n interneurons which was studied b y D e s m e d t and Cheron (1981). The generator of ucN13 is assumed to be located more rostrally. Its location should be at or above the C 1 - 2 level since it was lost in cases 2, 3 and 4 with lesions at the C 1 - 2 level. In normal subjects, the latency of ucN13 is the same or just less than that of the scalp P 1 3 - 1 4 , the main generator of which is n o w accepted to be the medial lemniscus. Therefore, its generator should be caudal to the medial lemniscus since it is supposed that no sensory impulses ascend more rapidly than in the dorsal column-lemniscal system. Considering these two facts, the location of the ucN13 generator must be between the C 1 - 2
level and the medial lemniscus. The most conspicuous anatomical structure of the sensory system near there is the cuneate nucleus. The authors therefore considered the cuneate nucleus as the first candidate for the ucN13 generator.
The potential generated by the cuneate nucleus - review of the literature T h e r m a n (1941) first described in cats a negative-positive biphasic potential at the dorsal aspect of the cuneate nucleus when the peripheral nerve was electrically stimulated. A n d e r s e n et al. (1964) recorded a similar potential and studied it in detail. The slow negative potential was shown to have its maximal amplitude precisely over the dorsal aspect of the cuneate nucleus. The results of depth recording led them to conclude that the negative potential reflects the E P S P of the neurons of the cuneate nucleus p r o d u c e d by the dorsal
POSTERIOR CERVICAL N13
35
Lt median N. VI
HS-NC
~ I+
~,~ 10.9
cv2-Nc L: y//
cv
-.c
,o-.c
ICN13
v
!7 e' J :I
v
f
acP13
I-I~v ÷
I ......
A
0
I'
10
I
I
20
I
I
30
ms
Fig. 6. Case 3. A 19-year-old man with myelitis. A: the negative potential at CV6 electrode appears to be composed of a questionable steep N l l peak and subsequent lcN13, acP13 is preserved, ucN13 is absent. A scalp electrode (HS) registers only P9 and Pll. B: sagittal section of MRI (T2 intensified image). A high signal region is present at the C1-2 level. C: horizontal section of MRI (T2 intensified image) at the C1-2 level. The lesion mainly affects the dorsal column.
column afferent impulses. Allison and Hume (1981) and Kaji et al. (1986) also recorded a similar potential. Kaji et al. (1986) described an electrical dipole around the cuneate nucleus, dorso-caudally negative and ventro-rostraUy positive. Allison and Hume (1981) argued from the
animal study that their N13b in the CV2-Fz lead in humans is generated by the cuneate nucleus while their N13a in the CV7-Fz lead reflects the activity of the dorsal horn neurons. Their conclusion is quite similar to ours, although the Fz reference makes the aforesaid confusion unavoidable.
36
M. SONOO ET AL.
N20(24.7)
Lt median N. V
HS-NC
7.2 °
V CV2-NC
CV6-NC
!!i'Nll,,z
AC-NC
I-I~V 4-
I
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I
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80 m8
Fig. 7. Case 4. A 29-year-old woman with multiple sclerosis. A: lcN13 and acP13 are preserved. The HS electrode registers P9, P l l and delayed but clear P13-14 and N20. In the CV2 electrode, a broad and rather flat negativity probably intercalated by P13-14 is noted long after lcN13, which is thought to be a delayed ucN13. B: horizontal section of MRI (T 2 intensified image) at the C2 level. A high intensity region which mainly affects the dorsal column is noted.
Rt median N. V
Fz-NC
I1 I '~ =r~
~, . f
"v'
~P13-14 -P11 .....
i, ~:~
I:
p9
'1!
I
ucN 13 (13"0~c:"'~
;i
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i~/ A
I I 0
-
acP 13
I ljuV -IF-
I
I
10
I
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20
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,30
ms Fig. 8. Case 5. A 40-year-old man with posttraumatic syringomyelia. A: 1cN13 and acP13 are greatly attenuated, ucN13 in CV2 is relatively well preserved. Its peak lies behind the termination of scalp P l l . Scalp far-field potentials are normal. B: sagittal section of MRI. Syrinx is noted from the foramen magnum level to the thoracic spine.
POSTERIOR CERVICAL N13
Similar negative waves at the dorsal medulla were recorded intraoperatively in human subjects by several authors (Lesser et al. 1981; Suzuki and Mayanagi 1984; Urasaki et al. 1984; Yasue et al. 1985; Moiler et al. 1986; Jacobson and Tew 1988), although they were interpreted as the postsynaptic activity of cuneate nucleus only by 2 authors (Suzuki and Mayanagi 1984; Urasaki et al. 1984). Lesser et al. (1981) and Yasue et al. (1985) interpreted their origin to be the presynaptic activity of the dorsal column. In clinical studies, the dissociation between spinal N13-P13 and scalp P13-14 was reported by several authors (Mauguirre and IbaYaez 1985; Emerson and Pedley 1986; Urasaki et al. 1988). Neither study, however, paid attention to the high cervical N13. Using bipolar recording, Kaji and Sumner (1987) distinguished between a horizontal dipole (their N13a) and an axial dipole (N13b) and showed that each was selectively affected by intramedullary (N13a) and high cervical (N13b) lesions, respectively. They attributed the origin of N13b to the caudal medial lemniscus and the cuneate nucleus. However, because they employed bipolar leads (corresponding to our inion-CV2 derivation), their N13b is assumed to be a summation of N13 at the high cervical electrode and the scalp P13-14 already present at the electrode on the inion. High cervical N13 proper was not separately identified in their study. The broad configuration of ucN13 in the present study resembles the negative potential at the dorsal aspect of the cuneate nucleus shown by animal studies and intraoperative studies, which was suggested by Andersen et al. (1964) to be the postsynaptic potential of the neurons of the cuneate nucleus. On these grounds, we concluded that the most probable generator of ucN13 is the postsynaptic potential of the cuneate nucleus. Our hypothesis of the generators of these components is illustrated in Fig. 9.
The generators of the scalp P13-14 The present study made some implications of the generators of scalp P13-14. If ucN13 is generated by the cuneate nucleus, the positive pole of this dipole should exist somewhere in the upper and anterior region. The contribution of the
37
Fig. 9. Schematic representation of our hypothesis concerning the generators of median nerve SEPs at the cervical spine and the cuneate nucleus.
cuneate nucleus to the scalp P13-14 has been suggested by some authors (Suzuki and Mayanagi 1984; Urasaki et al. 1984; Kaji et al. 1986). Besides, it was suggested by the present case 1 that even the acP13 of the dorsal horn origin can be recorded over the scalp, in contrast to the opinion of Desmedt and Cheron (1981). Multiple generators have been postulated for the scalp P13-14 because it is frequently bilobed (Cracco and Cracco 1976). This point requires further investigation. We wish to thank H. Yoshikawa, M.D., for MRI examination.
References Allison, T. and Hume, A.L. A comparative analysis of shortlatency somatosensory evoked potentials in man, monkey, cat, and rat. Exp. Neurol., 1981, 72: 592-611. Andersen, P., Eccles, J.C., Schmidt, R.F. and Yokota, T. Slow potential waves produced in the cuneate nucleus by cutaneous volleys and cortical stimulation. J. Neurophysiol., 1964, 27: 78-91. Berir, A., Dimitrijevi~, M.R., Prevec, T.S. and Sherwood, A.M. Epidurally recorded cervical somatosensory evoked poten-
38 tial in humans. Electroenceph. clin. Neurophysiol., 1986, 65: 94-101. Cracco, R.Q. The initial positive potential of the human scalprecorded somatosensory evoked response. Electroenceph. clin. Neurophysiol., 1972, 32: 623-629. Cracco, R.Q. Spinal evoked response: peripheral nerve stimulation in man. Electroenceph. clin. Neurophysiol., 1973, 35: 379-386. Cracco, R.Q. and Cracco, J.B. Somatosensory evoked potential in man: far field potentials. Electroenceph. clin. Neurophysiol., 1976, 41: 460-466. Desmedt, J.E. and Cheron, G. Central somatosensory conduction in man: neural generators and interpeak latencies of the far-field components recorded from neck and right or left scalp and earlobes. Electroenceph. clin. Neurophysiol., 1980, 50: 382-403. Desmedt, J.E. and Cheron, G. Prevertebral (oesophageal) recording of subcortical somatosensory evoked potentials in man: the spinal P13 component and the dual nature of the spinal generators. Electroenceph. clin. Neurophysiol., 1981, 52: 257-276. Desmedt, J.E. and Huy, N.T. Bit-mapped colour imaging of the potential fields of propagated and segmental subcortical components of somatosensory evoked potentials in man. Electroenceph. clin. Neurophysiol., 1984, 58: 481-497. Emerson, R.G. and Pedley, A.T. Effects of cervical spinal cord lesions on early components of the median nerve somatosensory evoked potential. Neurology, 1986, 36: 20-26. Favale, E., Ratto, S., Leandri, M. and Abbruzzese, M. Investigation on the nervous mechanisms underlying the somatosensory cervical response in man. J. Neurol. Neurosurg. Psychiat., 1982, 45: 796-801. Hume, A.L. and Cant, B.R. Conduction time in central somatosensory pathways in man. Electroenceph. clin. Neurophysiol., 1978, 45: 361-375. Jacobson, G.P. and Tew, J.M. The origin of the scalp recorded P14 following electrical stimulation of the median nerve; intraoperative observations. Electroenceph. clin. Neurophysiol., 1988, 71: 73-76. Jones, S.J. Short latency potentials recorded from the neck and scalp following median nerve stimulation in man. Electroenceph, clin. Neurophysiol., 1977, 43: 853-863. Kaji, R. and Sumner, A.J. Bipolar recording of short-latency somatosensory evoked potentials after median nerve stimulation. Neurology, 1987, 37: 410-418.
M. SONOO ET AL, Kaji, R., Tanaka, R., Kawaguchi, S., McCormick, F. and Kameyama, M. Origin of short-latency somatosensory evoked potentials to median nerve stimulation in the cat, Brain, 1986, 109: 443-468. Leandri, M., Favale, E., Ratto, S. and Abbruzzese, M. Conducted and segmental components of the somatosensory cervical response. J. Neurol. Neurosurg. Psychiat., 1981, 44: 718-722. Lesser, R.P., Lueders, H., Hahn, J. and Klem, G. Early somatosensory potentials evoked by median nerve stimulation: intraoperative monitoring. Neurology, 1981, 31: 1519-1523. Maugui~re, F. and Ibafiez, V. The dissociation of early SEP components in lesions of the cervicomedullary junction; a cue for routine interpretation of abnormal cervical responses to median nerve stimulation. Electroenceph. clin. Neurophysiol., 1985, 62: 406-420. Moller, A.R., Jannetta, P.J. and Burgess, J.E. Neural generator of the somatosensory evoked potentials: recording from the cuneate nucleus in man and monkeys. Electroenceph. clin. Neurophysiol., 1986, 65: 241-248. Suzuki, I. and Mayanagi, Y. Intracranial recording of short latency somatosensory evoked potentials in man: identification of origin of each component. Electroenceph. clin. Neurophysiol., 1984, 59: 286-296. Therman, P.O. Transmission of impulses through the Burdach nucleus. J. Neurophysiol., 1941, 4: 153-166. Urasaki, E., Matsukado, Y., Wada, S., Nagashiro, S., Yamaguchi, T. and Yadomi, C. Origins of components PI 1 and P13 in short latency somato-sensory evoked potentials (SSEP): correlative study of SSEP and intraoperative evoked potentials. Brain Nerve (Jpn.), 1984, 36: 681-688. Urasaki, E., Fukumura, A., Ito, Y. et al. Scalp recorded P13 and spinal recorded N13 in short latency somatosensory evoked potentials. Brain Nerve (Jpn.), 1988, 40: 1081-1088. Yamada, T., Kimura, J. and Nitz, D.M. Short latency somatosensory evoked potentials following median nerve stimulation in man. Electroenceph. clin. Neurophysiol., 1980, 48: 367-376. Yasue, M., Takahashi, H. and Ishijima, B. Consideration about generators of short latency somatosensory potential to median nerve stimulation. Clin. Electroenceph. (Jpn.), 1985, 27: 353-360.
28
Elsevier Scientific Publishers Ireland, Ltd. EVOPOT 89007
Posterior cervical N 1 3 in median nerve S E P has two components M. Sonoo, T. Shimpo, K. Genba, M. Kunimoto and T. Mannen Department o/Neurology, Institute of Brain Research, School of Medicine, University of Tokyo, Bunkyo, Tokyo 113 (Japan) (Accepted for publication: 4 May 1989)
Summary Somatosensory evoked potentials (SEPs) to median nerve stimulation were investigated in normal controls and patients with cervical lesions. Attention was paid primarily to the N13 and P13 components in the posterior and anterior cervical records with non-cephalic references. In normal subjects the CV2 and CV6 electrodes registered N13 with almost the same amplitude. Dissociation between N13 at the CV2 electrode (ucN13) and N13 at the CV6 electrode (1cN13) was observed in the patients. In 4 patients with cervical dorsal column lesions, lcN13 was preserved but ucNl3 was almost completely absent. Anterior cervical P13 (acP13) was preserved. In a patient with syringomyelia, lcNl3 and acP13 were greatly attenuated while ucN13 was relatively well preserved. These results suggested that the origins of ucN13 and lcN13 are different. The generator of lcN13-acP13 was assumed to be the postsynaptic potential of the dorsal horn intemeurons. Upon comparison with previous animal studies and intraoperative studies, it was concluded that the generator of ucN13 is the postsynaptic potential of the cuneate nucleus.
Key words: Somatosensory evoked potential; Median nerve; N13; Cuneate nucleus
Short-latency somatosensory evoked potentials (SEPs) to median nerve stimulation are now widely used in clinical practice. However, not all the generators of individual components have been identified. In particular, there has been much debate about the origin of the so-called 'N13' component of the cervical-scalp recording. The dorsal horn of the cervical spinal cord (Jones 1977), the dorsal column (Cracco 1972, 1973; Lesser et al. 1981) and the cuneate nucleus (Jones 1977; Hume and Cant 1978; Leandri et al. 1981; Favale et al. 1982) were all postulated as the generator of N13 in cervical-scalp records. Cracco and Cracco (1976) first recorded SEPs with a non-cephalic reference. They noted that the scalp electrodes which had been used as reference in previous studies, such as the frontal electrode, were also active when recorded with a non-ce-
Correspondence to: Dr. M. Sonoo, Department of Neurology, Institute of Brain Research, School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113 (Japan).
phalic reference. A negative potential (N13) was recorded at the cervical electrode with a non-cephalic reference, while a positive potential (named P13, P13-14 or P14 by various authors) is recorded simultaneously at scalp electrodes. At first, cervical N13 and scalp P13-14 were thought to be generated by the same generator (Jones 1977; Yamada et al. 1980). Using esophageal recording, Desmedt and Cheron (1981) found a prevertebral P13 which represented phase reversal of N13 at the posterior cervical electrodes. They interpreted this N13-P13 dipole to be the postsynaptic potential of the dorsal horn interneurons and argued that it should be differentiated from the scaIp P14 which originates in the medial lemniscus. Later they found that the prevertebral P13 can also be recorded from the skin surface of the anterior neck region (Desmedt and Huy 1984). Although their opinion is now widely accepted, an animal study pointed out the dual origin of the posterior cervical N13, that is, one part from the interneurons of the dorsal horn and the other
0168-5597/90/$03.50 © 1990 Elsevier Scientific Publishers Ireland, Ltd.
POSTERIOR CERVICAL N13
29
from the cuneate nucleus (Allison and H u m e 1981). However, these authors used a frontal reference and this point has not been clarified in records with a non-cephalic reference. The aim of this study is to investigate the dual nature of the posterior cervical N13 with a non-cephalic reference in clinical cases where a dissociated loss of the two components was expected from clinical and M R I (magnetic resonance imaging) findings.
Subjects We studied 17 normal volunteers without history of neurological disease and 5 neurological patients. Informed consent was obtained from all subjects. N o r m a l subjects were divided into 2 groups according to age: the younger (n = 9, 6 men and 3 women) had a mean age of 27.8 years (23-32 years) and the older group (n = 8, 5 men and 3 women) had a mean age of 72.3 years (65-81 years). Patients were divided into 2 groups according to the site of the lesion. Table I presents some of the clinical details of the patients. Cases 1 - 4 had cervical dorsal column lesions above the entry zone of the median nerve (C6, C7,
C8 and Thl). Cases 1 - 3 had definite disturbances of deep sensation in the upper extremities and showed impaired skilled movements of the hands. High to middle cervical lesions were demonstrated by M R I (Figs. 4B, 5B, 6B and 6C). Case 4 had only a mild dysesthesia of the palms while deep sensation of the hands was intact. Nevertheless, M R I clearly demonstrated a lesion of the high cervical dorsal column (Fig. 7B). Case 5, a patient with syringomyelia, had a lesion of cervical grey matter. His pain and thermal sensations were lost in the right upper extremity, although deep sensations were intact. M R I showed a syrinx of the cervical cord (Fig. 8B).
Methods The median nerve was stimulated at the wrist through felt electrodes using square wave pulses of 0.2 msec duration at a rate of 5/sec. Stimulus intensity was adjusted to produce a consistent thumb twitch. In order to assure that the stimulus intensity was comparable interpersonally and the amplitude of the evoked potential was nearly maximal, sensory nerve action potentials (SNAPs) were monitored simultaneously. Ring electrodes were
TABLE 1 Case no.
Age
Sex
Diagnosis
Main symptoms
Duration of illness
1
62
F
cervical spondylosis
10 years
2
66
F
rheumatoid arthritis atlanto-axial dislocation
3
19
M
myelitis
4
29
F
multiple sclerosis
5
40
M
posttraumatic syringomyelia
impaired position sense and vibratory sense of both hands impaired skilled movement of hands sensory disturbances hands > legs position sense dominant bilateral pyramidal sign sensory disturbances hands >> legs position sense dominant impaired skilled movement of both hands dementia, ataxia, pyramidal signs, impaired deep sensation of lower extremities mild dysesthesia of palms impaired pain and thermal sensation of right arm and trunk
2 months
3 weeks
2 years
8 months
30
placed over the index finger and the antidromic SNAP was shown on an oscilloscope. Then, the stimulus intensity was further regulated so that the amplitude of the SNAP would exceed at least half of the maximal amplitude. It was confirmed in some normal subjects that stronger stimulation would produce little change in the amplitude of the posterior cervical N13. The stimulus which produced the SNAP with the maximal amplitude was rather painful. Disk electrodes were placed at the following sites. The CV6 electrode was placed over the spinous process of the CV6. The 'CV2' electrode was placed at the midpoint of the inion and the CV6 electrode taking into consideration that the spinous process of the CV2 was hardly felt in some subjects. The anterior cervical electrode (AC) was placed contralateral to the stimulated side 5 cm from the midline at the midpoint of the rostro-caudal length of the neck. This deviation was employed because the root spike (which continues from N9) interferes considerably with the midline electrode (Desmedt and Huy 1984). Other electrodes included Fz, contralateral hand sensory area (named 'HS') and inion. The non-cephalic reference electrode (NC) was placed on the contralateral shoulder. Evoked potentials were amplified and filtered between 5.3 and 1500 Hz ( - 3 dB). Averaging was performed on 2000-3500 responses over an analysis time of 50 msec, using a sampling rate of 10,000 Hz. Two averages were superimposed. Samples showing excessive artifact were rejected on-line from the average. As a rule, bipolar montages were obtained directly by measuring potential difference between two electrodes, although off-fine subtraction between two waves of non-cephalic reference was substituted in some cases.
Results
Normal subjects Left median nerve stimulation was performed in all subjects. Right median nerve stimulation was performed in 6 subjects. Because the latter response was generally of poor quality due to
M. SONOO ET AL.
ECG artifact, we considered primarily the records to left median nerve stimulation. An example of wave forms in a normal subject is shown in Fig. 1. Both in CV2 and CV6 leads with non-cephalic reference, P9 far-field potential and subsequent negativity were noted in all sub-
Lt median N.
Fz-NC
10. 6 P9 Pll P13-14 ( 11.6) ucN13 N11 .,i T ~
CV2-NC ~ CV6-NC AC-NC
I-lpV
acP13
,.p
inion-CV2 12.3
CV2-CV6
A
11.6 I
0
E
I
10
I
g
20
~
30 ms
Fig. 1. A normal control (25-year-old male). The upper 4 traces are recorded with non-cephalic reference. The lower two traces are bipolar records. Both the CV2 and CV6 electrodes register N13 potentials and preceding N l l potentials. N13 at the CV2 electrode is n a m e d ucN13 and N13 at the CV6 electrode is n a m e d lcN13. The amplitude of ucN13 is almost the same as or slightly larger than that of lcN13. P13 is present at the anterior cervical (AC) electrode, which is named acP13. A scalp electrode (Fz) registers 3 far-field potentials: P9, P l l and P13-14. The onset of P l l is earlier than that of acP13. Two bipolar leads show peaks traveling caudo-rostrally which correspond to scalp P11. The termination of the scalp P11 coincides with the termination of N l l at posterior cervical electrodes (dashed line). Figures represent latencies expressed in milliseconds.
POSTERIOR CERVICAL N13
jects. This negative potential was assumed to be a composite of N l l and N13, although two peaks could not be discerned in some subjects. However, as is discussed later, N13 was considered to determine the main configuration of this negativity, especially its peak and descending slope. We named N13 in the CV2 lead 'ucN13' (upper cervical N13) and N13 in the CV6 lead 'lcN13' (lower cervical N13). In the anterior cervical (AC) lead, P9 and P13 were identified in all subjects. The anterior cervical P13 was named 'acP13' (anterior cervical P13) in order to distinguish it from the scalp P13-14 far-field potential. In scalp leads, P9, P l l and P13-14 far-field potentials were noted in all cases. We discerned the following two characteristics of P l l , which were employed as the criteria for the presence of P l l in clinical cases. First, the onset of P l l invariably preceded the onset of acP13. Second, bipolar derivations from CV2-CV6 and inion-CV2 showed the traveling of a peak corresponding to P l l , which was supposed to be an ascending dorsal column volley (Desmedt and Cheron 1980; Favale et al. 1982). In order to quantify the abnormality of N13, we tried to evaluate its amplitude. Because N l l and N13 overlapped in the posterior cervical records, we could only measure the combined amplitudes of N l l + N13. This, however, seemed to be a rough estimate of the amplitude of N13 which is the dominant component. The method of measuring the N l l + N13 amplitude is illustrated in Fig. 2. The results are shown in Fig. 3. In normal subjects, the amplitude of N l l + N13 was almost the same in the CV2 and CV6 leads or slightly greater in the former. Although old subjects had a significantly smaller amplitude, the CV2/CV6 ratio of the amplitude of N l l + N13 was fairly constant irrespective of age. Patients
In each of the 4 patients with a dorsal column lesion (Figs. 4A, 5A, 6A and 7A), N13 in the CV2 electrode (ucN13) was almost completely absent, while the CV6 electrode registered a definite broad negative potential which was thought to represent lcN13 (later discussed). Both N l l and lcN13 peak could definitely be identified in case 4 (Fig. 7A)
31
Fz
CV2 i i
f /
CV6
Fig. 2. Methods of measuring the amplitude of N l l + N13. The latency of the scalp P l l onset was marked on the wave in a posterior cervical lead. A line was drawn from this point to the termination of the N13. The greatest distance between this line and the negative wave was defined as the amplitude of N l l + N13. Because the shock artifact may interfere with the earlier wave configuration, neither prestimulus baseline nor baseline before P9 was employed.
and questionably in case 3 (Fig. 6A). The acP13 was also preserved in all 4 cases. In these patients, the CV2/CV6 ratios of the amplitude of N l l + N13 were clearly lower than those of normal subjects (Fig. 3). In case 1 (Fig. 4A), scalp electrodes registered only P9 and a positive potential following P9. The onset of the positivity did not precede the onset of acP13 and posterior cervical bipolar leads did not show the latency shift of a peak. In view of the aforesaid criteria for the presence of P l l , we judged that this positivity was not P l l . Moreover, the scalp P13-14 is rather unlikely to be present without P l l or later components. Because the onset and the configuration of the positivity coincided well with those of acP13, we assumed that acP13 could be recorded over the scalp in this patient.
32
M. SONOO ET AL. CV6
CV2
pV 2.0-
CV2/CV6
uv 2.0
Discussion
2.0-
S o m e r e m a r k s on wave identification 1.5 ¸
0.5
I
1.0
0
0.5
o o
I *2SD
o
g
o cases 1 - 4 Acase 5
o
0.5
• control
young p
ojId
young
L
p
old
young
__
old
n.s.
j
Fig. 3. The amplitude of N11+N13 at the CV6 and CV2 electrodes and the CV2/CV6 ratio of the amplitude of N l l + N13 are shown. Closed circles represent normal subjects. Young and old subjects are considered separately. Old subjects have significantly smaller amplitudes at both the CV6 and CV2 electrodes, but the amplitude ratio is constant irrespective of age. Open circles represent patients with a dorsal column lesion (cases 1-4). They clearly have small amplitude ratios. Open triangles represent case 5. He has a large amplitude ratio. Case 5, who is 40 years old, is included in the young group.
In 3 other cases (Figs. 5A, 6A and 7A), definite P l l scalp far-field potentials with earlier onset than that of acP13 were present. As for the later components, delayed P13-14 was noted in case 4 (Fig. 7A) and delayed N20 potentials were noted in cases 2 and 4 (Figs. 5A and 7A). In case 4, a patient with long-standing multiple sclerosis, who had a clear but delayed P13-14 at the scalp electrodes, a rather flat negativity, probably intercalated by P13-14, was noted at the CV2 electrode, which was assumed to be a delayed ucN13 (Fig. 7A). In a patient with a cervical grey matter lesion (case 5, Fig. 8A), both acP13 and lcN13 had very small amplitudes. It was judged that the negative potential at the CV2 electrode mainly represented ucN13 and not N l l since its peak was behind the termination of the scalp P l l (see the following section). The ucN13 was also attenuated but was relatively well preserved in comparison with lcN13. The C V 2 / C V 6 ratio of the amplitude of N l l + N13 was therefore higher than in normal subjects (Fig. 3). Scalp far-field potentials were normal in this patient.
As is mentioned above, the posterior cervical negative wave with non-cephalic reference is thought to be composed of N l l and N13. In order to discuss N13 at all, one must be able to identify N l l and N13 separately. N l l is thought to be generated by the near-field potential of the ascending dorsal column volley (Desmedt and Cheron 1980). Therefore, the duration of N l l must be relatively short, reflecting the time for the impulses to go up the dorsal column. In normal subjects where two peaks of N l l and N13 could be clearly distinguished, termination of N l l coincided with the termination of scalp P l l (Fig. 1), which supports the theory that the scalp Pl1 sees the approaching front of depolarization of the dorsal column volley (Desmedt and Cheron 1980). The peak of N13, which usually represented the major peak of the overall negativity, existed behind the termination of N l l and scalp P l l (Fig. 1). In subjects where the two peaks could not be discerned, the peak of the overall negativity was also behind the termination of scalp P l l . From these findings, the authors concluded that the peak and the gentle descending slope of the posterior cervical negative potential are free from the influence of N l l and represent principally N13. N l l was thus estimated as a rather small potential located on the ascending limb of N13. This opinion agrees with Desmedt and Cheron (1980) and is also supported by the findings with epidural recording (Beri6 et al. 1986). On this ground, N13 was judged to be lost when the characteristic broad descending slope was lost, such as in the CV2 electrodes in present cases 1-4, Conversely, N13 was most probably preserved when the broad descending slope was preserved, although of small amplitude, such as at the CV6 electrodes in cases 1 and 2. It seems unlikely that N l l , which was originally a small steep potential analogous to a sensory nerve action potential, would assume such a clear prolonged shape even if it was metamorphosed. Moreover, if the negative potential is interpreted as N l l , it is difficult to explain the fact that acP13, which is thought to be the counterpart of the posterior cervical N13
POSTERIOR CERVICAL N13
33
Lt median N. V ~11\\ lo.1 Fz-NC I!ii "~'~ • !I\
A p~ ucN 13(-)
ii~~
cV2-NC ;!i
ov -.c I "a i"
~/9.9
;, . . . . . . . . . . . . . . .
_ A
1
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4
,r,,or,-CV !! cw-cv61i l!', I
A
0
1 1.3 I
I
10
~.+lyV I
I
20
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I
30 m8
Fig. 4. Case 1. A 62-year-old woman with high cervical spondylosis. A: N13 at CV6 (lcN13) is preserved although it is of small amplitude. N13 at CV2 (ucN13) is absent. Anterior cervical P13 (acP13) is preserved. A scalp electrode (Fz) registers a positivity which resembles acP13. This is not thought to be P l l since its onset does not precede the onset of acP13 and posterior cervical bipolar leads do not show traveling of the peak. B: magnetic resonance imaging (MRI) shows posterior compression of the spinal cord, mainly at the C 3 - 4 vertebral level.
(Desmedt and Cheron 1981), is preserved in these cases.
Two generators of N13 The present study revealed that N13 potentials at CV2 and CV6 electrodes are of almost the same size in normal subjects. However, the CV2 electrode is far from the level of the median nerve entry where Desmedt and Cheron (1981) demonstrated that prevertebral P13 has its maximal amplitude. In the present clinical cases, dissociation between N13 potentials in the high and low posterior cervical electrodes was observed. In the patients with cervical dorsal column lesions, N13 at the CV6 electrode (lcN13) was preserved although N13 at the CV2 electrode (ucN13) was
almost completely absent. In one case (case 4), a possible delayed ucN13 was noted just before the scalp P13-14. In a patient with a syringomyelia, lcN13 was greatly attenuated although ucN13 was relatively well preserved. The acP13 potential behaved similarly to the lcN13. We concluded from these results that the origins of lcN13 and ucN13 are different. Of course, significant overlap may exist between the distribution of the potentials generated by the two generators. This is suggested by the fact that the amplitude of lcN13 in some patients with dorsal column lesions (cases 1 and 2) was decreased and also by the fact that the amplitude of ucN13 was decreased and 1cN13 was still present with a small amplitude in case 5. Another
34
M. SONOO ET AL.
Lt median N. V
N2o(19.9)
HS-NC 4
A
P9(6.9) P1 1(9.9)
CV2-NC
CV6-NC
I-1/JV
AC-NC
-t-
acP13 I
A
0
I
I
10
I
I
20
I
I
30
ms
Fig. 5. Case 2. A 66-year-old woman with atlanto-axial dislocation. A: lcN13 is preserved although it is of rather small amplitude. ucN13 is absent, acP13 is preserved. The electrode at the contralateral hand sensory area (HS) registers Pll and N20. P13-14 is absent. Pll has a rather broad configuration. Its onset precedes the onset of acP13. N20 is delayed in this short-stature patient since P9-N20 interpeak latency is clearly prolonged (13.0 msec. Average and standard deviation of normal subjects; 10.36+0.65 msec, n = 17). B: sagittal section of MRI showing posterior compression of the spinal cord at the C1-2 level due to the displaced posterior arch of the atlas.
possibility to explain the above results is that a subclinical partial disturbance of each generator is present in such cases. It seems clear that the generator of l c N 1 3 acP13 is the postsynaptic potential of the dorsal h o r n interneurons which was studied b y D e s m e d t and Cheron (1981). The generator of ucN13 is assumed to be located more rostrally. Its location should be at or above the C 1 - 2 level since it was lost in cases 2, 3 and 4 with lesions at the C 1 - 2 level. In normal subjects, the latency of ucN13 is the same or just less than that of the scalp P 1 3 - 1 4 , the main generator of which is n o w accepted to be the medial lemniscus. Therefore, its generator should be caudal to the medial lemniscus since it is supposed that no sensory impulses ascend more rapidly than in the dorsal column-lemniscal system. Considering these two facts, the location of the ucN13 generator must be between the C 1 - 2
level and the medial lemniscus. The most conspicuous anatomical structure of the sensory system near there is the cuneate nucleus. The authors therefore considered the cuneate nucleus as the first candidate for the ucN13 generator.
The potential generated by the cuneate nucleus - review of the literature T h e r m a n (1941) first described in cats a negative-positive biphasic potential at the dorsal aspect of the cuneate nucleus when the peripheral nerve was electrically stimulated. A n d e r s e n et al. (1964) recorded a similar potential and studied it in detail. The slow negative potential was shown to have its maximal amplitude precisely over the dorsal aspect of the cuneate nucleus. The results of depth recording led them to conclude that the negative potential reflects the E P S P of the neurons of the cuneate nucleus p r o d u c e d by the dorsal
POSTERIOR CERVICAL N13
35
Lt median N. VI
HS-NC
~ I+
~,~ 10.9
cv2-Nc L: y//
cv
-.c
,o-.c
ICN13
v
!7 e' J :I
v
f
acP13
I-I~v ÷
I ......
A
0
I'
10
I
I
20
I
I
30
ms
Fig. 6. Case 3. A 19-year-old man with myelitis. A: the negative potential at CV6 electrode appears to be composed of a questionable steep N l l peak and subsequent lcN13, acP13 is preserved, ucN13 is absent. A scalp electrode (HS) registers only P9 and Pll. B: sagittal section of MRI (T2 intensified image). A high signal region is present at the C1-2 level. C: horizontal section of MRI (T2 intensified image) at the C1-2 level. The lesion mainly affects the dorsal column.
column afferent impulses. Allison and Hume (1981) and Kaji et al. (1986) also recorded a similar potential. Kaji et al. (1986) described an electrical dipole around the cuneate nucleus, dorso-caudally negative and ventro-rostraUy positive. Allison and Hume (1981) argued from the
animal study that their N13b in the CV2-Fz lead in humans is generated by the cuneate nucleus while their N13a in the CV7-Fz lead reflects the activity of the dorsal horn neurons. Their conclusion is quite similar to ours, although the Fz reference makes the aforesaid confusion unavoidable.
36
M. SONOO ET AL.
N20(24.7)
Lt median N. V
HS-NC
7.2 °
V CV2-NC
CV6-NC
!!i'Nll,,z
AC-NC
I-I~V 4-
I
A
I
I
0
I
I
10
I
I
20
80 m8
Fig. 7. Case 4. A 29-year-old woman with multiple sclerosis. A: lcN13 and acP13 are preserved. The HS electrode registers P9, P l l and delayed but clear P13-14 and N20. In the CV2 electrode, a broad and rather flat negativity probably intercalated by P13-14 is noted long after lcN13, which is thought to be a delayed ucN13. B: horizontal section of MRI (T 2 intensified image) at the C2 level. A high intensity region which mainly affects the dorsal column is noted.
Rt median N. V
Fz-NC
I1 I '~ =r~
~, . f
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i, ~:~
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I
,30
ms Fig. 8. Case 5. A 40-year-old man with posttraumatic syringomyelia. A: 1cN13 and acP13 are greatly attenuated, ucN13 in CV2 is relatively well preserved. Its peak lies behind the termination of scalp P l l . Scalp far-field potentials are normal. B: sagittal section of MRI. Syrinx is noted from the foramen magnum level to the thoracic spine.
POSTERIOR CERVICAL N13
Similar negative waves at the dorsal medulla were recorded intraoperatively in human subjects by several authors (Lesser et al. 1981; Suzuki and Mayanagi 1984; Urasaki et al. 1984; Yasue et al. 1985; Moiler et al. 1986; Jacobson and Tew 1988), although they were interpreted as the postsynaptic activity of cuneate nucleus only by 2 authors (Suzuki and Mayanagi 1984; Urasaki et al. 1984). Lesser et al. (1981) and Yasue et al. (1985) interpreted their origin to be the presynaptic activity of the dorsal column. In clinical studies, the dissociation between spinal N13-P13 and scalp P13-14 was reported by several authors (Mauguirre and IbaYaez 1985; Emerson and Pedley 1986; Urasaki et al. 1988). Neither study, however, paid attention to the high cervical N13. Using bipolar recording, Kaji and Sumner (1987) distinguished between a horizontal dipole (their N13a) and an axial dipole (N13b) and showed that each was selectively affected by intramedullary (N13a) and high cervical (N13b) lesions, respectively. They attributed the origin of N13b to the caudal medial lemniscus and the cuneate nucleus. However, because they employed bipolar leads (corresponding to our inion-CV2 derivation), their N13b is assumed to be a summation of N13 at the high cervical electrode and the scalp P13-14 already present at the electrode on the inion. High cervical N13 proper was not separately identified in their study. The broad configuration of ucN13 in the present study resembles the negative potential at the dorsal aspect of the cuneate nucleus shown by animal studies and intraoperative studies, which was suggested by Andersen et al. (1964) to be the postsynaptic potential of the neurons of the cuneate nucleus. On these grounds, we concluded that the most probable generator of ucN13 is the postsynaptic potential of the cuneate nucleus. Our hypothesis of the generators of these components is illustrated in Fig. 9.
The generators of the scalp P13-14 The present study made some implications of the generators of scalp P13-14. If ucN13 is generated by the cuneate nucleus, the positive pole of this dipole should exist somewhere in the upper and anterior region. The contribution of the
37
Fig. 9. Schematic representation of our hypothesis concerning the generators of median nerve SEPs at the cervical spine and the cuneate nucleus.
cuneate nucleus to the scalp P13-14 has been suggested by some authors (Suzuki and Mayanagi 1984; Urasaki et al. 1984; Kaji et al. 1986). Besides, it was suggested by the present case 1 that even the acP13 of the dorsal horn origin can be recorded over the scalp, in contrast to the opinion of Desmedt and Cheron (1981). Multiple generators have been postulated for the scalp P13-14 because it is frequently bilobed (Cracco and Cracco 1976). This point requires further investigation. We wish to thank H. Yoshikawa, M.D., for MRI examination.
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