- Email: [email protected]
SEPs to median nerve stimulation: normative data for paediatrics
Electroencephalography and clinical Neurophysiology, 1988, 71 : 323-330
323
Elsevier Scientific Publishers Ireland, Ltd. EEG03424
S E P s to median nerve stimulation: normative data for paediatrics M.J. Taylor and E.R. Fagan 1 Division of Neurology, and Research Institute, Hospital for Sick Children, University of Toronto, Toronto M5G 1X8 (Canada) (Accepted for publication: 5 January 1988)
Summary Somatosensory evoked potentials (SEPs) provide neurologists with an assessment of the neuraxis from peripheral nerve to sensory cortex. Their value is particularly relevant in paediatric neurology as sensory clinical examination can be difficult in young infants and children. The clinical utility of SEPs, however, requires knowledge of the alterations in wave form which occur with growth and development. This study presents normative SEP data from 4 months-35 years. Different non-linear maturational patterns were seen in spinal and central segments of the nervous system. The cervical components (N12, N13) changed little in latency until 2-3 years, the N20 decreased in latency until 2-3 years and P22 decreased in latency until 6-8 years, after which latencies increased until adulthood. The greatest latency changes occurred in N12 and N13, the least in N20. Wave form morphology and interpeak latencies also changed with age. Adult morphology was achieved early (from 1 year), but central conduction time (N13-N20) reached adult values only at 6 - 8 years. This study provides normative values of SEPs during maturation and a functional assessment of pathways known to myelinate and mature at varying rates. Key words: Somatosensory evoked potential; (Normative data); (Infants); (Children)
Somatosensory evoked potentials (SEPs) provide neurologists with an objective tool with which to assess the neuraxis from peripheral nerve to cerebral cortex. The neural generators of SEPs along this pathway have been investigated and, although controversy remains, there is some consensus about their origins. N9 recorded at midclavicle is a travelling wave generated in the afferent nerve proximal to the axilla and distal to the nerve roots (Jones 1979). N12 and N13 recorded at the cervical spine (C7) are a travelling wave in the dorsal column and a postsynaptic response in the dorsal h o r n / c u n e a t e nucleus, respectively (Allison and H u m e 1981; Desmedt and Cheron 1981a; Taylor et al. 1985). P14 and P16 (often referred to
1 Current address: Department of Neurology, Royal Alexandra Children's Hospital, Camperdown, N.S.W. 2050, Australia.
Correspondence to: Dr. Margo Taylor, Division of Neurology, Hospital for Sick Children, University of Toronto, Toronto, Ont. M5G 1X8 (Canada).
as P15) are the first components recorded over the contralateral somatosensory cortex with a cephalic reference and probably reflect activity in the medial lemniscus (Allison and H u m e 1981; Taylor and Black 1984; Delestre et al. 1986). N18 is also a subcortical wave, probably thalamic in origin (Desmedt and Cheron 1981b; K i m u r a and Y a m a d a 1982). N20 is a cortical response generated in the posterior wall of the central sulcus, areas 3b (Allison 1982; Wood et al. 1985). P22 (often referred to as P25 or P27) is also cortical, generated in the crown of the posterior central sulcus, area 1 (Allison et al. 1986). However, some uncertainty still exists about the sources of both N20 (Chiappa 1983) and P22 (Eisen 1982; Desmedt et al. 1987). In paediatric neurology the use of SEPs to assess somatosensory pathways is of particular relevance, as the clinical examination of the sensory system is often difficult in young patients. The clinical utility of SEPs, however, depends on a number of factors including reproducibility, ease
0168-5597/88/$03.50 © 1988 Elsevier Scientific Publishers Ireland, Ltd.
324
M.J. TAYLOR, E.R. F A G A N
TABLE I Ages
S E P latencies X S.D. (n = 19) U. limits
Arm (cm)
N12
N13
P14
P16
N18
N20
P22
4-8 m
26
6.11 0.54 7.46
8.27 0.53 9.60
10.60 1.11 13.37
12.88 1.00 15.38
15.78 0.76 17.68
17.74 0.85 19.86
24.14 0.89 26.36
X S.D. (n = 14) U. limits
9-15 m
30
6.09 0.32 6.89
8.01 0.50 9.26
9.45 0.95 11.83
11.71 0.76 13.61
14.12 1.09 16.84
15.71 0.94 18.06
21.30 1.27 24.48
X S.D. (n = 11) U. limits
16-22 m
33
6.04 0.45 7.17
7.82 0.32 8.62
10.13 0.52 11.43
11.83 0.87 14.00
13.65 0.73 15.48
15.41 0.63 16.98
20.37 0.91 22.64
X S.D. (n = 8) U. limits
2-3 y
37
6.33 0.22 6.88
7.77 0.30 8.52
14.88 0.93 17.20
19.34 0.92 21.64
X S.D. (n = 16) U. limits
3-5 y
44
7.19 0.46 8.34
8.62 0.45 9.74
10.82 0.51 12.09
12.41 0.51 13.68
13.88 0.54 15.23
15.28 0.58 16.73
19.14 0.62 20.69
X S.D. (n = 13) U. limits
6-8 y
54
8.34 0.40 9.34
9.63 0.43 10.71
11.56 0.45 12.69
13.08 0.51 14.36
14.16 0.50 15.41
15.52 0.54 16.87
18.47 0.82 20.52
X S.D. (n = 18) U. limits
9-11 y
60
9.42 0.44 10.52
10.70 0.37 11.63
12.63 0.50 13.88
14.15 0.51 15.43
15.24 0.41 16.27
16.53 0.60 18.03
19.42 0.59 20.90
X S.D. (n = 18) U. limits
12-16 y
66
10.25 0.72 12.05
11.60 0.68 13.30
13.36 0.61 14.88
14.91 0.64 16.51
16.04 0.62 17.59
17.24 0.69 18.97
20.06 0.76 21.96
X S.D. (n = 19) U. limits
14-18 y
73
10.84 0.85 12.96
12.21 0.89 14.43
13.94 0.83 16.01
15.34 0.83 17.41
16.39 0.74 18.24
17.73 0.79 19.70
20.88 0.88 23.24
X S.D. (n = 50) U. limits
Adult
74
11.26 0.68 12.96
12.72 0.67 14.40
14.39 0.73 16.22
15.79 0.80 17.79
17.16 0.92 19.46
18.38 0.89 20.61
21.18 1.13 24.01
N12-N13
N13-N20
N20-P22
-
S E P interpeak latencies X 4 - 8 rn S.D. U. limits
2.17 0.59 3.64
9.63 0.94 11.98
6.48 0.76 8.38
X S.D. U. limits
9-15 m
2.07 0.34 2.92
7.89 0.97 10.31
5.58 1.40 9.08
X S.D. U. limits
16-22 m
1.83 0.31 2.60
7.76 0.44 8.86
4.72 0.65 6.34
X S.D. U. limits
2-3 y
1.46 0.33 2.28
7.10 1.04 9.70
4.45 1.09 7.17
X S.D. U. limits
3-5y
1.46 0.31 2.23
6.69 0.49 7.91
3.91 0.65 5.53
11.26 0.41 12.28
-
325
PAEDIATRIC NORMS FOR MEDIAN NERVE SEPs TABLE I (continued) Ages
N12-N13
N13-N20
N20-P22
X S.D. U. limits
6-8 y
1.30 0.28 2.00
5.71 0.47 6.89
2.93 0.54 4.28
X S.D. U. limits
9-11 y
1.29 0.33 2.12
5.84 0.43 6.92
2.91 0.46 4.06
X S.D. U. limits
12-16 y
1.33 0.29 2.06
5.64 0.40 6.64
2.81 0.38 3.76
X S.D. U. limits
14-18 y
1.35 0.26 2.00
5.60 0.48 6.80
3.13 0.67 4.80
X S.D. U. limits
Adults
1.43 0.31 2.20
5.55 0.47 6.73
2.89 0.70 4.64
x = mean; S.D. = standard deviation; U. limits = X + (2.5 x S.D.); - = insufficient numbers; arm = mean arm length; m = months; y = years.
of m e a s u r e m e n t a n d a k n o w l e d g e of the altera t i o n s in wave' f o r m s which o c c u r with g r o w t h a n d d e v e l o p m e n t . This k n o w l e d g e c a n o n l y b e o b t a i n e d b y s t u d y i n g large n u m b e r s o f n e u r o l o g i cally n o r m a l c h i l d r e n of differing ages a n d sizes. F r o m the p r e s e n t l i t e r a t u r e it is very difficult to o b t a i n useful n o r m a t i v e d a t a for c h i l d r e n of a given age a n d / o r l i m b length. N o r m a t i v e d a t a a c q u i r e d over a 4 y e a r p e r i o d in o u r clinical l a b o r a t o r y are p r e s e n t e d . M a t u r a t i o n a l c h a n g e s in SEPs f r o m i n f a n c y t h r o u g h c h i l d h o o d are d e m o n strated. Results are p r e s e n t e d in such a m a n n e r t h a t they c a n be used b y o t h e r l a b o r a t o r i e s t h a t m a y n o t have the resources to o b t a i n a d e q u a t e p a e d i a t r i c norms.
Materials and methods T h e subjects were 136 n e u r o l o g i c a l l y n o r m a l c h i l d r e n (4 m o n t h s - 1 8 y e a r s old) w i t h n o a b n o r m a l i t i e s of g r o w t h o r d e v e l o p m e n t . F i f t y n o r m a l a d u l t s ( 2 0 - 3 5 years old) were also studied. SEPs in c h i l d r e n y o u n g e r t h a n 4 m o n t h s o l d will b e p r e s e n t e d elsewhere ( G e o r g e a n d T a y l o r in prep.). T h e studies were p e r f o r m e d in a quiet r o o m
with the subject lying a w a k e b u t r e l a x e d o n a bed. S o m e of the infants were h e l d b y their m o t h e r s while SEPs were r e c o r d e d . A l l the c h i l d r e n were tested w i t h o u t sedation, b o t h for ethical r e a s o n s a n d in light of the k n o w n effects o f sedatives on cortical SEP c o m p o n e n t s ( F a g a n et al. 1987). SEPs were r e c o r d e d over the cervical s p i n e at C7 a n d the c o n t r a l a t e r a l sensory c o r t e x ( C 3 ' a n d C 4 ' ) , r e f e r e n c e d to Fpz. O n l y 2 c h a n n e l s were r e c o r d e d b e c a u s e of e q u i p m e n t l i m i t a t i o n s . W e n o w r o u t i n e l y r e c o r d at E r b ' s p o i n t a n d r e c o m m e n d this for clinical studies. R e c o r d i n g s were m a d e with gold cup electrodes. I m p e d a n c e s were always b e l o w 2 kI2. T h e b a n d p a s s was 3 0 - 3 0 0 0 Hz, the g a i n was 40 K a n d the sweep 50 msec. Stimuli were 0.2 m s e c electrical i m p u l s e s p r e s e n t e d at 4.1 H z to the m e d i a n nerve at the wrist. S t i m u l u s i n t e n s i t y was j u s t a b o v e m o t o r threshold. E a c h average c o n t a i n e d 256 a r t e f a c t - f r e e trials a n d replications were always o b t a i n e d . E a c h a r m was tested separately.
Results SEPs were easily r e c o r d e d in all the c h i l d r e n in the age r a n g e studied. M e a n s a n d s t a n d a r d devia-
326
M.J. T A Y L O R , E . R . F A G A N 26-
18
•0 24
=:~
N18 P16
17
P22
~ N20 ,4=- N13
\
~j~
14 20 12
1
E 8 |
i
-
i
•
|
•
!
•
|
.
i
•
|
•
i
|
•
i to
14
•
age
Fig. 2. A v e r a g e latencies f o r s u b c o r t i c a l c o m p o n e n t s ( P I 4 , P16, N 1 8 ) over the a g e s s t u d i e d . T h e m a t u r a t i o n a l c h a n g e s in l a t e n c y in t h e s e p e a k s p r o v i d e a s m o o t h t r a n s i t i o n b e t w e e n the s p i n a l a n d c e n t r a l c o m p o n e n t s in Fig. 1.
10
8
creases with age and size. Interpeak latencies also changed developmentally, with the central conduction time (N13-N20) reaching adult values by
6
i
•
•
i
•
i
•
i
•
i
•
i
•
i
i
•
i
,
10
age
Fig. 1. A v e r a g e latencies f o r s p i n a l c o m p o n e n t s r e c o r d e d a t C 7 ) N 1 2 a n d N 1 3 , c o r t i c a l c o m p o n e n t s ( r e c o r d e d at C 3 ' a n d C 4 ' ) N 2 0 a n d P22, a c r o s s the a g e r a n g e s t u d i e d , s h o w i n g the d i f f e r i n g m a t u r a t i o n a l p a t t e r n s f o r the 4 peaks.
8
-0- N13-N20
~ . N20-P22 N12-N13
6-
tions of peak and interpeak latencies are shown in Table I. Fig. 1 shows non-linear maturational patterns of change in the spinal and central segments of the nervous system across the ages studied. Despite steady increases in physical size, N12 changed little in latency until after 16-22 months, N13 decreased slightly in latency until 2-3 years, N20 decreased until 2-3 years and P22 decreased until 6-8 years, after which ages all the latencies increased towards adult values. The greatest changes in absolute latencies occurred with N12 and N13; the least with N20. Age-related changes in subcortical components (P14, P16, N18) lay between the spinal and central components (Fig. 2), showing slight decreases in latencies over the first several years, then subsequent in-
4o
2"
0
i
• i • i • i • i • i • i • i • i
. i .
age Fig. 3. D e v e l o p m e n t a l c h a n g e s in i n t e r p e a k l a t e n c i e s s h o w i n g the slight d e c r e a s e in N 1 2 - N 1 3 l a t e n c i e s o n l y o v e r t h e first few y e a r s o f life, a n d s i m i l a r p a t t e r n s o f c h a n g e in the N 1 3 - N 2 0 and N20-P22 components.
PAEDIATRIC NORMS FOR MEDIAN NERVE SEPs
327
¥ ~Av
l/
~
1y
~
3y
3y
A
6y
~
13 y
P16
~ N2o
i
i
I
i
i
i
i
i
i
0
10
20
30
40
50
0
10
20
ms
adutl i
!
i
30
4O
5O
ms
Fig. 4. Cervical (a) and cortical (b) SEPs over the age range studied, showing morphologicalchanges with age. 6 - 8 years. Interestingly, the N20-P22 interpeak latencies were parallel to those of N13-N20 (Fig. 3). Wave morphology also changed with age. N12 and N13 were widely spaced in the infants, coming closer together during early childhood until
the more typically adult pattern, of N12 being a shoulder on N13, was seen consistently in teenagers (Fig. 4a). In contrast, the wave definition of the cortical SEPs was less clear in the youngest children, with the bifid appearance of the N18-N20 starting to appear after 1 year of
328
age, but appearing reliably only after 3-5 years of age (Fig. 4b). This and the bifld appearance of P15 (P14/P16) were seen in virtually all normal children over 3 years old, such that the absence of these subcomponents is considered abnormal. Their absence in younger children, however, may be more a result of age than of physiological factors as, with children who are somewhat active whilst being tested, the prominent components are still easily recorded while smaller inflections can be difficult or impossible to discern from background noise.
Discussion These studies provide functional assessment of the pathways which are known to myelinate and mature at varying rates (Yakovlev and Lecours 1967). Hence, the SEPs recorded from peripheral and central segments of the nervous system can be expected to change differentially with growth and development. The latencies of the responses vary with the length and conduction velocity of the pathways and the number of synapses traversed. Conduction velocity in turn depends on factors such as fibre diameter and degree of myelination. Increase in SEP latency with increasing body size begins earlier in the peripheral/spinal components, as myelination of the peripheral fibres progresses more rapidly and is completed earlier than that of the central segments of the pathway. In contrast, the components recorded at the cortical electrodes initially decrease in latency with maturation of the pathways and then increase in latency with increasing body size, conduction velocities remaining stable. The different maturational patterns of N20 and P22 over the first 6-8 years of life suggest that, although both arise in closely adjacent cortical areas (areas 3b and 1 of the postcentral gyms), either maturation of the cortical neurones differs between 2 areas or the afferent pathways (which differ in fibre density and thickness, Kaas 1983) have different maturational rates. It must be kept in mind, however, that the measurement of these waves from scalp electrodes is not independent; hence, they are not uncontaminated measures of neuronal maturation.
M.J. TAYLOR, E.R. FAGAN
There have been a number of reports in the literature documenting developmental changes in SEPs and relating these to the physiological changes of maturation. Desmedt et al. (1976) reported cortical SEPs in 29 full-term infants and 35 children between 1 month and 9 years old. Their results indicated that there was a reduction in the latency and duration of the N20 and an increase in the size of the P22 with postnatal development; the adult pattern was approached by 8 years of age. Hashimoto et al. (1983) studied SEPs in children up to 16 years old and found that after 2 years the latencies of the short latency SEPs were positively related to body length and arm length. Based on differences in the age at which various components matured, they suggested that the maturation of the lemniscal pathways proceeds at a slower rate than that of peripheral sensory fibres; this is consistent with other studies. Similarly, Sitzoglou and Fotiou (1984) reported decreasing latencies of both cortical components and interpeak latencies between cervical and cortical waves, while the absolute latency of the cervical SEP increased with age. In studies by Allison et al. (1983, 1984) maturational changes in both peripheral and central SEPs, as well as changes in rate of change, were documented. Despite the thoroughness of these studies, however, these data are not readily applicable as normative data for a clinical paediatric lab, as there were no subjects under 4 years old and the linear, age-related regressions were done on the 4-17 year olds as a single group. Unfortunately, in the largest developmental series reported (Laget et al. 1976), the recording parameters were not described and the emphasis and analyses were on long latency SEPs rather than the currently more clinically used short latency components. A recent study by Tomita et al. (1986) reported normative developmental trends in SEPs, but their study included only 46 children over a 16 year range, and although their graphs show developmental changes in latencies with age, actual latencies are not included. Also, we have found that unlike general anaesthetics (Coles et al. 1984), sedatives such as chloral hydrate can affect the cortical SEPs (when recorded while a child is in sedated sleep, there can be smoothing out of the
PAEDIATRIC NORMS FOR MEDIAN NERVE SEPs
wave forms, i.e., a loss of the smaller components such as P16 and N18, prolongation in latencies of N20 and P22 and in some cases a complete loss of all cortically recorded components, Fagan et al. 1987). Hence, the use of sedatives when recording SEPs in young children (Hashimoto et al. 1983; Tomita et al. 1986) may affect the reported normative values. In the analysis of published reports, it is important to note that when considering latency values, comparable methodology is critical. Desmedt et al. (1976) used random finger stimulation while most other authors stimulated the median nerve; bandpasses varied from study to study. Some grouped together children of differing ages and sizes and reported results without reference to height or arm length. Changes in the SEPs with age argue strongly against arranging children in groups that span more than several months in younger, or a few years, in older children. Arm length must always be considered also, although this is less important in the youngest age groups where maturation is the dominant effect. The grouping of Sitzoglou and Fotiou (1984) of infants from 10 days to 2 years, and 2 - 1 2 years, for example, could obscure much of the developmental change in SEPs. It is also not recommended to use norms from only a few children at each age, as SEP variability is such that small numbers of subjects do not provide adequate data for reliable normal values. SEPs reflect different rates of change as a function of the neural system involved, with different latency profiles in the spinal and the central components. We have attempted to present our results in a manner which will enable them to be used as a reference source of normative data across age and size parameters, given consistency in the method used to perform SEP studies.
References Allison, T. Scalp and cortical recordings of initial somatosensory cortex activity to median nerve stimulation in man. Ann. NY Acad. Sci., 1982, 388: 671-677. 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.
329 Allison, T., Wood, C.C. and Golf, W.R. Brain stem auditory, pattern-reversal visual, and short-latency somatosensory evoked potentials: latencies in relation to age, sex, and brain and body size. Electroenceph. clin. Neurophysiol., 1983, 55: 619-636. Allison, T., Hume, A.L., Wood, C.C. and Goff, W.R. Developmental and aging changes in somatosensory, auditory and visual evoked potentials. Electroenceph. clin. Neurophysiol., 1984, 58: 14-24. Allison, T., Wood, C.C. and McCarthy, G. The central nervous system. In: M.G.H. Coles, E. Donchin and S.W. Porges (Eds.), Psychophysiology. Guildford Press, New York, 1986: 5-25. Chiappa, K.H. Evoked Potentials in Clinical Medicine. Raven Press, New York, 1983: 259-262. Coles, J.G., Taylor, M.J., Pearce, J.M. et al. Cerebral monitoring of somatosensory evoked potentials during profoundly hypothermic circulatory arrest. Circulation, 1984, 70 (Suppl. 1): 196-102. Delestre, J., Lonchampt, P. and Dubas, F. Neural generator of P14 far-field somatosensory evoked potential studied in a patient with a pontine lesion. Electroenceph. clin. Neurophysiol., 1986, 65: 227-230. 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., 1981a, 52: 257-275. Desmedt, J.E. and Cheron, G. Non-cephalic reference recording of early somatosensory potentials to finger stimulation in adult or aging normal man: differentiation of widespread N18 and contralateral N20 from the prerolandic P22 and N30 components. Electroenceph. clin. Neurophysiol., 1981b, 52: 553-570. Desmedt, J.E., Brunko, E. and Debecker, J. Maturation of the somatosensory evoked potential in normal infants and children, with special reference to the early N1 component. Electroenceph. clin. Neurophysiol., 1976, 40: 43-58. Desmedt, J.E., Nguyen, T.H. and Bourguet, M. Bit-mapped color imaging of human evoked potentials with reference to the N20, P22, P27 and N30 somatosensory responses. Electroenceph, clin. Neurophysiol., 1987, 68: 1-19. Eisen, A. The somatosensory evoked potential. Can. J. Neurol. Sci., 1982, 9: 65-77. Fagan, E.R., Taylor, M.J. and Logan, W.J. Somatosensory evoked potentials. Part I. A review of neural generators and special considerations in paediatrics. Pediat. Neurol., 1987, 3: 189-196. George, S.R. and Taylor, M.J. Somatosensory evoked potentials in young infants: normative data. Manuscript in preparation. Hashimoto, T., Tayama, M., Hiura, K., Endo, S. et al. Short latency somatosensory evoked potential in children. Brain Dev., 1983, 5: 390-396. Jones, S.F. Investigation of brachial plexus traction lesions by peripheral and spinal somatosensory evoked potentials. J. Neurol. Neurosurg. Psychiat., 1979, 42: 104-116.
330 Kaas, J.H. What, if anything, is SI? Organization of first somatosensory area of cortex. Physiol. Rev., 1983, 63: 206-231. Kimura, J. and Yamada, T. Short-latency somatosensory evoked potentials following median nerve stimulation. Ann. NY Acad. Sci., 1982, 388: 689-694. Laget, P., Raimbault, J., D'Allest, A.M., Flores-Guerara, R., Mariani, J. et Thieriot-Prevost, G. La maturation des potentiels 6voqu6s somesth~siques (PES) chez l'homme. Electroenceph. din. Neurophysiol., 1976, 40: 499-515. Sitzoglou, C. and Fotiou, F. A study of the maturation of the somatosensory pathway by evoked potentials. Neuropaediatrie, 1984, 43: 205-208. Taylor, M.J. and Black, S.E. Lateral asymmetries and thalamic components in far-field somatosensory evoked potentials. Can. J. Neurol. Sci., 1984, 11: 252-256.
M.J. TAYLOR, E.R. FAGAN Taylor, M.J, Borrett, D.S. and Coles, J.C. The effects of profound hypothermia on the cervical SEP in humans: evidence of dual generators. Electroenceph. clin. Neurophysiol., 1985, 62: 184-192. Tomita, Y., Nishimura, S. and Tanaka, T. Short latency SEPs in infants and children: developmental changes and maturational index of SEPs. Electroenceph. clin. Neurophysiol., 1986, 65: 335-343. Wood, C.C., Cohen, D., Cuffin, B.N. et al. Electrical sources of the human somatosensory cortex: identification by combined magnetic and potential recordings. Science, 1985, 227: 1051-1053. Yakovlev, P.I. and Lecours, A.R. The myelogenetic cycles of regional maturation of the brain. In: A. Minkowski (Ed.), Regional Development of the Brain in Early Life. Blackwell, Oxford, 1967: 3-70.
323
Elsevier Scientific Publishers Ireland, Ltd. EEG03424
S E P s to median nerve stimulation: normative data for paediatrics M.J. Taylor and E.R. Fagan 1 Division of Neurology, and Research Institute, Hospital for Sick Children, University of Toronto, Toronto M5G 1X8 (Canada) (Accepted for publication: 5 January 1988)
Summary Somatosensory evoked potentials (SEPs) provide neurologists with an assessment of the neuraxis from peripheral nerve to sensory cortex. Their value is particularly relevant in paediatric neurology as sensory clinical examination can be difficult in young infants and children. The clinical utility of SEPs, however, requires knowledge of the alterations in wave form which occur with growth and development. This study presents normative SEP data from 4 months-35 years. Different non-linear maturational patterns were seen in spinal and central segments of the nervous system. The cervical components (N12, N13) changed little in latency until 2-3 years, the N20 decreased in latency until 2-3 years and P22 decreased in latency until 6-8 years, after which latencies increased until adulthood. The greatest latency changes occurred in N12 and N13, the least in N20. Wave form morphology and interpeak latencies also changed with age. Adult morphology was achieved early (from 1 year), but central conduction time (N13-N20) reached adult values only at 6 - 8 years. This study provides normative values of SEPs during maturation and a functional assessment of pathways known to myelinate and mature at varying rates. Key words: Somatosensory evoked potential; (Normative data); (Infants); (Children)
Somatosensory evoked potentials (SEPs) provide neurologists with an objective tool with which to assess the neuraxis from peripheral nerve to cerebral cortex. The neural generators of SEPs along this pathway have been investigated and, although controversy remains, there is some consensus about their origins. N9 recorded at midclavicle is a travelling wave generated in the afferent nerve proximal to the axilla and distal to the nerve roots (Jones 1979). N12 and N13 recorded at the cervical spine (C7) are a travelling wave in the dorsal column and a postsynaptic response in the dorsal h o r n / c u n e a t e nucleus, respectively (Allison and H u m e 1981; Desmedt and Cheron 1981a; Taylor et al. 1985). P14 and P16 (often referred to
1 Current address: Department of Neurology, Royal Alexandra Children's Hospital, Camperdown, N.S.W. 2050, Australia.
Correspondence to: Dr. Margo Taylor, Division of Neurology, Hospital for Sick Children, University of Toronto, Toronto, Ont. M5G 1X8 (Canada).
as P15) are the first components recorded over the contralateral somatosensory cortex with a cephalic reference and probably reflect activity in the medial lemniscus (Allison and H u m e 1981; Taylor and Black 1984; Delestre et al. 1986). N18 is also a subcortical wave, probably thalamic in origin (Desmedt and Cheron 1981b; K i m u r a and Y a m a d a 1982). N20 is a cortical response generated in the posterior wall of the central sulcus, areas 3b (Allison 1982; Wood et al. 1985). P22 (often referred to as P25 or P27) is also cortical, generated in the crown of the posterior central sulcus, area 1 (Allison et al. 1986). However, some uncertainty still exists about the sources of both N20 (Chiappa 1983) and P22 (Eisen 1982; Desmedt et al. 1987). In paediatric neurology the use of SEPs to assess somatosensory pathways is of particular relevance, as the clinical examination of the sensory system is often difficult in young patients. The clinical utility of SEPs, however, depends on a number of factors including reproducibility, ease
0168-5597/88/$03.50 © 1988 Elsevier Scientific Publishers Ireland, Ltd.
324
M.J. TAYLOR, E.R. F A G A N
TABLE I Ages
S E P latencies X S.D. (n = 19) U. limits
Arm (cm)
N12
N13
P14
P16
N18
N20
P22
4-8 m
26
6.11 0.54 7.46
8.27 0.53 9.60
10.60 1.11 13.37
12.88 1.00 15.38
15.78 0.76 17.68
17.74 0.85 19.86
24.14 0.89 26.36
X S.D. (n = 14) U. limits
9-15 m
30
6.09 0.32 6.89
8.01 0.50 9.26
9.45 0.95 11.83
11.71 0.76 13.61
14.12 1.09 16.84
15.71 0.94 18.06
21.30 1.27 24.48
X S.D. (n = 11) U. limits
16-22 m
33
6.04 0.45 7.17
7.82 0.32 8.62
10.13 0.52 11.43
11.83 0.87 14.00
13.65 0.73 15.48
15.41 0.63 16.98
20.37 0.91 22.64
X S.D. (n = 8) U. limits
2-3 y
37
6.33 0.22 6.88
7.77 0.30 8.52
14.88 0.93 17.20
19.34 0.92 21.64
X S.D. (n = 16) U. limits
3-5 y
44
7.19 0.46 8.34
8.62 0.45 9.74
10.82 0.51 12.09
12.41 0.51 13.68
13.88 0.54 15.23
15.28 0.58 16.73
19.14 0.62 20.69
X S.D. (n = 13) U. limits
6-8 y
54
8.34 0.40 9.34
9.63 0.43 10.71
11.56 0.45 12.69
13.08 0.51 14.36
14.16 0.50 15.41
15.52 0.54 16.87
18.47 0.82 20.52
X S.D. (n = 18) U. limits
9-11 y
60
9.42 0.44 10.52
10.70 0.37 11.63
12.63 0.50 13.88
14.15 0.51 15.43
15.24 0.41 16.27
16.53 0.60 18.03
19.42 0.59 20.90
X S.D. (n = 18) U. limits
12-16 y
66
10.25 0.72 12.05
11.60 0.68 13.30
13.36 0.61 14.88
14.91 0.64 16.51
16.04 0.62 17.59
17.24 0.69 18.97
20.06 0.76 21.96
X S.D. (n = 19) U. limits
14-18 y
73
10.84 0.85 12.96
12.21 0.89 14.43
13.94 0.83 16.01
15.34 0.83 17.41
16.39 0.74 18.24
17.73 0.79 19.70
20.88 0.88 23.24
X S.D. (n = 50) U. limits
Adult
74
11.26 0.68 12.96
12.72 0.67 14.40
14.39 0.73 16.22
15.79 0.80 17.79
17.16 0.92 19.46
18.38 0.89 20.61
21.18 1.13 24.01
N12-N13
N13-N20
N20-P22
-
S E P interpeak latencies X 4 - 8 rn S.D. U. limits
2.17 0.59 3.64
9.63 0.94 11.98
6.48 0.76 8.38
X S.D. U. limits
9-15 m
2.07 0.34 2.92
7.89 0.97 10.31
5.58 1.40 9.08
X S.D. U. limits
16-22 m
1.83 0.31 2.60
7.76 0.44 8.86
4.72 0.65 6.34
X S.D. U. limits
2-3 y
1.46 0.33 2.28
7.10 1.04 9.70
4.45 1.09 7.17
X S.D. U. limits
3-5y
1.46 0.31 2.23
6.69 0.49 7.91
3.91 0.65 5.53
11.26 0.41 12.28
-
325
PAEDIATRIC NORMS FOR MEDIAN NERVE SEPs TABLE I (continued) Ages
N12-N13
N13-N20
N20-P22
X S.D. U. limits
6-8 y
1.30 0.28 2.00
5.71 0.47 6.89
2.93 0.54 4.28
X S.D. U. limits
9-11 y
1.29 0.33 2.12
5.84 0.43 6.92
2.91 0.46 4.06
X S.D. U. limits
12-16 y
1.33 0.29 2.06
5.64 0.40 6.64
2.81 0.38 3.76
X S.D. U. limits
14-18 y
1.35 0.26 2.00
5.60 0.48 6.80
3.13 0.67 4.80
X S.D. U. limits
Adults
1.43 0.31 2.20
5.55 0.47 6.73
2.89 0.70 4.64
x = mean; S.D. = standard deviation; U. limits = X + (2.5 x S.D.); - = insufficient numbers; arm = mean arm length; m = months; y = years.
of m e a s u r e m e n t a n d a k n o w l e d g e of the altera t i o n s in wave' f o r m s which o c c u r with g r o w t h a n d d e v e l o p m e n t . This k n o w l e d g e c a n o n l y b e o b t a i n e d b y s t u d y i n g large n u m b e r s o f n e u r o l o g i cally n o r m a l c h i l d r e n of differing ages a n d sizes. F r o m the p r e s e n t l i t e r a t u r e it is very difficult to o b t a i n useful n o r m a t i v e d a t a for c h i l d r e n of a given age a n d / o r l i m b length. N o r m a t i v e d a t a a c q u i r e d over a 4 y e a r p e r i o d in o u r clinical l a b o r a t o r y are p r e s e n t e d . M a t u r a t i o n a l c h a n g e s in SEPs f r o m i n f a n c y t h r o u g h c h i l d h o o d are d e m o n strated. Results are p r e s e n t e d in such a m a n n e r t h a t they c a n be used b y o t h e r l a b o r a t o r i e s t h a t m a y n o t have the resources to o b t a i n a d e q u a t e p a e d i a t r i c norms.
Materials and methods T h e subjects were 136 n e u r o l o g i c a l l y n o r m a l c h i l d r e n (4 m o n t h s - 1 8 y e a r s old) w i t h n o a b n o r m a l i t i e s of g r o w t h o r d e v e l o p m e n t . F i f t y n o r m a l a d u l t s ( 2 0 - 3 5 years old) were also studied. SEPs in c h i l d r e n y o u n g e r t h a n 4 m o n t h s o l d will b e p r e s e n t e d elsewhere ( G e o r g e a n d T a y l o r in prep.). T h e studies were p e r f o r m e d in a quiet r o o m
with the subject lying a w a k e b u t r e l a x e d o n a bed. S o m e of the infants were h e l d b y their m o t h e r s while SEPs were r e c o r d e d . A l l the c h i l d r e n were tested w i t h o u t sedation, b o t h for ethical r e a s o n s a n d in light of the k n o w n effects o f sedatives on cortical SEP c o m p o n e n t s ( F a g a n et al. 1987). SEPs were r e c o r d e d over the cervical s p i n e at C7 a n d the c o n t r a l a t e r a l sensory c o r t e x ( C 3 ' a n d C 4 ' ) , r e f e r e n c e d to Fpz. O n l y 2 c h a n n e l s were r e c o r d e d b e c a u s e of e q u i p m e n t l i m i t a t i o n s . W e n o w r o u t i n e l y r e c o r d at E r b ' s p o i n t a n d r e c o m m e n d this for clinical studies. R e c o r d i n g s were m a d e with gold cup electrodes. I m p e d a n c e s were always b e l o w 2 kI2. T h e b a n d p a s s was 3 0 - 3 0 0 0 Hz, the g a i n was 40 K a n d the sweep 50 msec. Stimuli were 0.2 m s e c electrical i m p u l s e s p r e s e n t e d at 4.1 H z to the m e d i a n nerve at the wrist. S t i m u l u s i n t e n s i t y was j u s t a b o v e m o t o r threshold. E a c h average c o n t a i n e d 256 a r t e f a c t - f r e e trials a n d replications were always o b t a i n e d . E a c h a r m was tested separately.
Results SEPs were easily r e c o r d e d in all the c h i l d r e n in the age r a n g e studied. M e a n s a n d s t a n d a r d devia-
326
M.J. T A Y L O R , E . R . F A G A N 26-
18
•0 24
=:~
N18 P16
17
P22
~ N20 ,4=- N13
\
~j~
14 20 12
1
E 8 |
i
-
i
•
|
•
!
•
|
.
i
•
|
•
i
|
•
i to
14
•
age
Fig. 2. A v e r a g e latencies f o r s u b c o r t i c a l c o m p o n e n t s ( P I 4 , P16, N 1 8 ) over the a g e s s t u d i e d . T h e m a t u r a t i o n a l c h a n g e s in l a t e n c y in t h e s e p e a k s p r o v i d e a s m o o t h t r a n s i t i o n b e t w e e n the s p i n a l a n d c e n t r a l c o m p o n e n t s in Fig. 1.
10
8
creases with age and size. Interpeak latencies also changed developmentally, with the central conduction time (N13-N20) reaching adult values by
6
i
•
•
i
•
i
•
i
•
i
•
i
•
i
i
•
i
,
10
age
Fig. 1. A v e r a g e latencies f o r s p i n a l c o m p o n e n t s r e c o r d e d a t C 7 ) N 1 2 a n d N 1 3 , c o r t i c a l c o m p o n e n t s ( r e c o r d e d at C 3 ' a n d C 4 ' ) N 2 0 a n d P22, a c r o s s the a g e r a n g e s t u d i e d , s h o w i n g the d i f f e r i n g m a t u r a t i o n a l p a t t e r n s f o r the 4 peaks.
8
-0- N13-N20
~ . N20-P22 N12-N13
6-
tions of peak and interpeak latencies are shown in Table I. Fig. 1 shows non-linear maturational patterns of change in the spinal and central segments of the nervous system across the ages studied. Despite steady increases in physical size, N12 changed little in latency until after 16-22 months, N13 decreased slightly in latency until 2-3 years, N20 decreased until 2-3 years and P22 decreased until 6-8 years, after which ages all the latencies increased towards adult values. The greatest changes in absolute latencies occurred with N12 and N13; the least with N20. Age-related changes in subcortical components (P14, P16, N18) lay between the spinal and central components (Fig. 2), showing slight decreases in latencies over the first several years, then subsequent in-
4o
2"
0
i
• i • i • i • i • i • i • i • i
. i .
age Fig. 3. D e v e l o p m e n t a l c h a n g e s in i n t e r p e a k l a t e n c i e s s h o w i n g the slight d e c r e a s e in N 1 2 - N 1 3 l a t e n c i e s o n l y o v e r t h e first few y e a r s o f life, a n d s i m i l a r p a t t e r n s o f c h a n g e in the N 1 3 - N 2 0 and N20-P22 components.
PAEDIATRIC NORMS FOR MEDIAN NERVE SEPs
327
¥ ~Av
l/
~
1y
~
3y
3y
A
6y
~
13 y
P16
~ N2o
i
i
I
i
i
i
i
i
i
0
10
20
30
40
50
0
10
20
ms
adutl i
!
i
30
4O
5O
ms
Fig. 4. Cervical (a) and cortical (b) SEPs over the age range studied, showing morphologicalchanges with age. 6 - 8 years. Interestingly, the N20-P22 interpeak latencies were parallel to those of N13-N20 (Fig. 3). Wave morphology also changed with age. N12 and N13 were widely spaced in the infants, coming closer together during early childhood until
the more typically adult pattern, of N12 being a shoulder on N13, was seen consistently in teenagers (Fig. 4a). In contrast, the wave definition of the cortical SEPs was less clear in the youngest children, with the bifid appearance of the N18-N20 starting to appear after 1 year of
328
age, but appearing reliably only after 3-5 years of age (Fig. 4b). This and the bifld appearance of P15 (P14/P16) were seen in virtually all normal children over 3 years old, such that the absence of these subcomponents is considered abnormal. Their absence in younger children, however, may be more a result of age than of physiological factors as, with children who are somewhat active whilst being tested, the prominent components are still easily recorded while smaller inflections can be difficult or impossible to discern from background noise.
Discussion These studies provide functional assessment of the pathways which are known to myelinate and mature at varying rates (Yakovlev and Lecours 1967). Hence, the SEPs recorded from peripheral and central segments of the nervous system can be expected to change differentially with growth and development. The latencies of the responses vary with the length and conduction velocity of the pathways and the number of synapses traversed. Conduction velocity in turn depends on factors such as fibre diameter and degree of myelination. Increase in SEP latency with increasing body size begins earlier in the peripheral/spinal components, as myelination of the peripheral fibres progresses more rapidly and is completed earlier than that of the central segments of the pathway. In contrast, the components recorded at the cortical electrodes initially decrease in latency with maturation of the pathways and then increase in latency with increasing body size, conduction velocities remaining stable. The different maturational patterns of N20 and P22 over the first 6-8 years of life suggest that, although both arise in closely adjacent cortical areas (areas 3b and 1 of the postcentral gyms), either maturation of the cortical neurones differs between 2 areas or the afferent pathways (which differ in fibre density and thickness, Kaas 1983) have different maturational rates. It must be kept in mind, however, that the measurement of these waves from scalp electrodes is not independent; hence, they are not uncontaminated measures of neuronal maturation.
M.J. TAYLOR, E.R. FAGAN
There have been a number of reports in the literature documenting developmental changes in SEPs and relating these to the physiological changes of maturation. Desmedt et al. (1976) reported cortical SEPs in 29 full-term infants and 35 children between 1 month and 9 years old. Their results indicated that there was a reduction in the latency and duration of the N20 and an increase in the size of the P22 with postnatal development; the adult pattern was approached by 8 years of age. Hashimoto et al. (1983) studied SEPs in children up to 16 years old and found that after 2 years the latencies of the short latency SEPs were positively related to body length and arm length. Based on differences in the age at which various components matured, they suggested that the maturation of the lemniscal pathways proceeds at a slower rate than that of peripheral sensory fibres; this is consistent with other studies. Similarly, Sitzoglou and Fotiou (1984) reported decreasing latencies of both cortical components and interpeak latencies between cervical and cortical waves, while the absolute latency of the cervical SEP increased with age. In studies by Allison et al. (1983, 1984) maturational changes in both peripheral and central SEPs, as well as changes in rate of change, were documented. Despite the thoroughness of these studies, however, these data are not readily applicable as normative data for a clinical paediatric lab, as there were no subjects under 4 years old and the linear, age-related regressions were done on the 4-17 year olds as a single group. Unfortunately, in the largest developmental series reported (Laget et al. 1976), the recording parameters were not described and the emphasis and analyses were on long latency SEPs rather than the currently more clinically used short latency components. A recent study by Tomita et al. (1986) reported normative developmental trends in SEPs, but their study included only 46 children over a 16 year range, and although their graphs show developmental changes in latencies with age, actual latencies are not included. Also, we have found that unlike general anaesthetics (Coles et al. 1984), sedatives such as chloral hydrate can affect the cortical SEPs (when recorded while a child is in sedated sleep, there can be smoothing out of the
PAEDIATRIC NORMS FOR MEDIAN NERVE SEPs
wave forms, i.e., a loss of the smaller components such as P16 and N18, prolongation in latencies of N20 and P22 and in some cases a complete loss of all cortically recorded components, Fagan et al. 1987). Hence, the use of sedatives when recording SEPs in young children (Hashimoto et al. 1983; Tomita et al. 1986) may affect the reported normative values. In the analysis of published reports, it is important to note that when considering latency values, comparable methodology is critical. Desmedt et al. (1976) used random finger stimulation while most other authors stimulated the median nerve; bandpasses varied from study to study. Some grouped together children of differing ages and sizes and reported results without reference to height or arm length. Changes in the SEPs with age argue strongly against arranging children in groups that span more than several months in younger, or a few years, in older children. Arm length must always be considered also, although this is less important in the youngest age groups where maturation is the dominant effect. The grouping of Sitzoglou and Fotiou (1984) of infants from 10 days to 2 years, and 2 - 1 2 years, for example, could obscure much of the developmental change in SEPs. It is also not recommended to use norms from only a few children at each age, as SEP variability is such that small numbers of subjects do not provide adequate data for reliable normal values. SEPs reflect different rates of change as a function of the neural system involved, with different latency profiles in the spinal and the central components. We have attempted to present our results in a manner which will enable them to be used as a reference source of normative data across age and size parameters, given consistency in the method used to perform SEP studies.
References Allison, T. Scalp and cortical recordings of initial somatosensory cortex activity to median nerve stimulation in man. Ann. NY Acad. Sci., 1982, 388: 671-677. 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.
329 Allison, T., Wood, C.C. and Golf, W.R. Brain stem auditory, pattern-reversal visual, and short-latency somatosensory evoked potentials: latencies in relation to age, sex, and brain and body size. Electroenceph. clin. Neurophysiol., 1983, 55: 619-636. Allison, T., Hume, A.L., Wood, C.C. and Goff, W.R. Developmental and aging changes in somatosensory, auditory and visual evoked potentials. Electroenceph. clin. Neurophysiol., 1984, 58: 14-24. Allison, T., Wood, C.C. and McCarthy, G. The central nervous system. In: M.G.H. Coles, E. Donchin and S.W. Porges (Eds.), Psychophysiology. Guildford Press, New York, 1986: 5-25. Chiappa, K.H. Evoked Potentials in Clinical Medicine. Raven Press, New York, 1983: 259-262. Coles, J.G., Taylor, M.J., Pearce, J.M. et al. Cerebral monitoring of somatosensory evoked potentials during profoundly hypothermic circulatory arrest. Circulation, 1984, 70 (Suppl. 1): 196-102. Delestre, J., Lonchampt, P. and Dubas, F. Neural generator of P14 far-field somatosensory evoked potential studied in a patient with a pontine lesion. Electroenceph. clin. Neurophysiol., 1986, 65: 227-230. 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., 1981a, 52: 257-275. Desmedt, J.E. and Cheron, G. Non-cephalic reference recording of early somatosensory potentials to finger stimulation in adult or aging normal man: differentiation of widespread N18 and contralateral N20 from the prerolandic P22 and N30 components. Electroenceph. clin. Neurophysiol., 1981b, 52: 553-570. Desmedt, J.E., Brunko, E. and Debecker, J. Maturation of the somatosensory evoked potential in normal infants and children, with special reference to the early N1 component. Electroenceph. clin. Neurophysiol., 1976, 40: 43-58. Desmedt, J.E., Nguyen, T.H. and Bourguet, M. Bit-mapped color imaging of human evoked potentials with reference to the N20, P22, P27 and N30 somatosensory responses. Electroenceph, clin. Neurophysiol., 1987, 68: 1-19. Eisen, A. The somatosensory evoked potential. Can. J. Neurol. Sci., 1982, 9: 65-77. Fagan, E.R., Taylor, M.J. and Logan, W.J. Somatosensory evoked potentials. Part I. A review of neural generators and special considerations in paediatrics. Pediat. Neurol., 1987, 3: 189-196. George, S.R. and Taylor, M.J. Somatosensory evoked potentials in young infants: normative data. Manuscript in preparation. Hashimoto, T., Tayama, M., Hiura, K., Endo, S. et al. Short latency somatosensory evoked potential in children. Brain Dev., 1983, 5: 390-396. Jones, S.F. Investigation of brachial plexus traction lesions by peripheral and spinal somatosensory evoked potentials. J. Neurol. Neurosurg. Psychiat., 1979, 42: 104-116.
330 Kaas, J.H. What, if anything, is SI? Organization of first somatosensory area of cortex. Physiol. Rev., 1983, 63: 206-231. Kimura, J. and Yamada, T. Short-latency somatosensory evoked potentials following median nerve stimulation. Ann. NY Acad. Sci., 1982, 388: 689-694. Laget, P., Raimbault, J., D'Allest, A.M., Flores-Guerara, R., Mariani, J. et Thieriot-Prevost, G. La maturation des potentiels 6voqu6s somesth~siques (PES) chez l'homme. Electroenceph. din. Neurophysiol., 1976, 40: 499-515. Sitzoglou, C. and Fotiou, F. A study of the maturation of the somatosensory pathway by evoked potentials. Neuropaediatrie, 1984, 43: 205-208. Taylor, M.J. and Black, S.E. Lateral asymmetries and thalamic components in far-field somatosensory evoked potentials. Can. J. Neurol. Sci., 1984, 11: 252-256.
M.J. TAYLOR, E.R. FAGAN Taylor, M.J, Borrett, D.S. and Coles, J.C. The effects of profound hypothermia on the cervical SEP in humans: evidence of dual generators. Electroenceph. clin. Neurophysiol., 1985, 62: 184-192. Tomita, Y., Nishimura, S. and Tanaka, T. Short latency SEPs in infants and children: developmental changes and maturational index of SEPs. Electroenceph. clin. Neurophysiol., 1986, 65: 335-343. Wood, C.C., Cohen, D., Cuffin, B.N. et al. Electrical sources of the human somatosensory cortex: identification by combined magnetic and potential recordings. Science, 1985, 227: 1051-1053. Yakovlev, P.I. and Lecours, A.R. The myelogenetic cycles of regional maturation of the brain. In: A. Minkowski (Ed.), Regional Development of the Brain in Early Life. Blackwell, Oxford, 1967: 3-70.