Summary
Previous studies on sural nerves were extended to human femoral, ulnar, facial and trochlear nerves. An asynchronous development of axon diameter and myelin sheath thickness was noted in all nerves studied. Whereas axons reach their maximal diameter by or before 5 years of age, maximal myelin sheath thickness is not attained before 16–17 years of age, i.e., more than 10 years later. The slope of the regression lines for the ratio between axon diameter and myelin thickness is significantly steeper in older than in younger individuals; it also differs if small and large fibers with more or less than 50 myelin lamellae are evaluated separately. The number of Schmidt-Lanterman incisures during later stages of development is related to myelin thickness, but the length of the spiral of the myelin lamella, thought to unrolled, in relation to its width, i.e., internodal length, varies considerably during development. The changes of the relationship between axons and myelin sheath thickness during normal human development have to be taken into account if hypomyelination is considered as a significant pathological phenomenon in peripheral neuropathies, especially in children. The implications of the present findings concerning conduction velocity of peripheral nerve fibers and other electrophysiologic parameters are discussed.
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References
Aguayo AJ, Bray GM, Perkins S, Duncan ID (1979) Axonsheath cell interactions in peripheral and central nervous system transplants. Soc Neurosci Symp 4:361–383
Arbuthnott ER, Boyd IA, Kalu KU (1980) Ultrastructural dimensions of myelinated peripheral nerve fibers in the cat and their relation to conduction velocity. J Physiol (Lond) 308:125–157
Bagust J (1974) Relationship between motor nerve conduction velocities and motor unit contraction characteristics in a slow twitch muscle of the cat. J Physiol (Lond) 238:269–278
Berthold CH (1978) Morphology of normal peripheral axons. In: Waxman SG (ed) Physiology and pathology of axons. Raven Press, New York, pp 3–63
Beuche W, Friede RL (1985) A new approach toward analyzing peripheral nerve fiber populations. II. Foreshortening of regenerated internodes corresponds to reduced sheath thickness. J Neuropathol Exp Neurol 44:73–84
Blight AR (1985) Computer simulation of action potentials and after potentials in mammalian myelinated axons: the case for a lower resistance sheath. Neuroscience 15:13–31
Boyd IA, Davey MR (1968) Composition of peripheral nerves. Livingstone, Edinburgh, 57 pp
Boyd IA, Kalu KU (1979) Scaling factor relating conduction velocity and diameter for myelinated afferent nerve fibers in the cat hind limb. J Physiol (Lond) 289:277–297
Buchthal F, Rosenfalck A, Behse F (1984) Sensory potentials of normal and diseased nerves. In: Dyck PJ, Thomas PK, Lambert EH, Bunge R (eds) Peripheral neuropathy, vol 1. Saunders, Philadelphia London Toronto, pp 981–1015
Burke RE (1967) Motor units types of cat triceps surae muscle. J Physiol (Lond) 193:141–160
Burke RE (1986) Physiology of motor units. In: Engel AG, Banker BQ (eds) Myology, vol 1. McGraw-Hill, New York St. Louis San Francisco, pp 419–443
Chiu SY, Low PA (1984) Voltage clamp of mammalian myelinated fibers. In: Dyck PJ, Thomas PK, Lambert EJ, Bunge R (eds) Peripheral neuropathy, vol 1. Saunders, Philadelphia London Toronto, pp 885–899
Cooper BJ, Duncan I, Cummings J, Lahunta A de (1984) Defective Schwann cell function in canine inherited hypertrophic neuropathy. Acta Neuropathol (Berl) 63:51–56
Cooper NA, Kidman AD (1984) Quantitation of the Schmidt-Lanterman incisures in juvenile, adult, remyelinated and regenerated fibers of the chicken sciatic nerve. Acta Neuropathol (Berl) 64:251–258
Cottrell L (1940) Histologic variations with age in apparently normal peripheral nerve trunks. Arch Neurol Psychiat 43:1138–1150
Culheim S (1978) Relations between cell body size, axon diameter and axon conduction velocity of cat sciatic motoneurons stained with horseradish peroxidase. Neurosci Lett 8:17–20
Dum RP, Kennedy TT (1980) Physiological and histochemical characteristics of motor units in cat tibialis anterior and extensor digitorum longus muscles. J Neurophysiol 43:1615–1630
Dyck PJ, Lambert EH, Sanders K, O'Brien PC (1971) Severe hypomyelination and marked abnormality of conduction in Dejerine-Sottas hypertrophic neuropathy: myelin thickness and compound action potential of sural nerve in vitro. Mayo Clin Proc 46:432–436
Dyck PJ, Lais AC, Sparks MF, Oviatt KF, Hexum LA, Steinmuller D (1979) Nerve xenografts to apportion the role of axon and Schwann cell in myelinated fiber absence in hereditary sensory neuropathy, type II. Neurology 29:1215–1221
Dyck PJ, Thomas PK, Lambert EH, Bunge R (eds) (1984) Peripheral neuropathy. W. B. Saunders, Philadelphia London Toronto, p 2323
Eccles JC, Eccles RM, Lundberg A (1958) The action potentials of the alpha motoneurons supplying fast and slow muscles. J Physiol (Lond) 142:275–291
Fernand VSV, Young JZ (1951) The sizes of the nerve fibers of muscle nerves. Proc R Soc Lond [Biol] 139:38–58
Friede RL (1984) Cochlear axon calibres are adjusted to characteristic frequencies. J Neurol Sci 66:193–200
Friede RL (1986) Relation between sheath thickness, internode geometry, and sheath resistance. Exp Neurol 92:234–247
Friede RL, Beuche W (1985) Combined scatter diagrams of sheath thickness and fibre calibre in human sural nerves: changes with age and neuropathy. J Neurol Neurosurg Psychiatry 48:749–756
Friede RL, Beuche W (1985) A new approach toward analyzing peripheral nerve fiber populations. I. Variance in sheath thickness corresponds to different geometric proportions of the internodes. J Neuropathol Exp Neurol 44:60–72
Friede RL, Bischhausen R (1980) The precise geometry of large internodes. J Neurol Sci 48:367–381
Friede RL, Bischhausen R (1982) How are sheath dimensions affected by axon caliber and internode length? Brain Res 235:335–350
Friede RL, Meier T, Diem M (1981) How is the exact length of an internode determined? J Neurol Sci 50:217–228
Friede RL, Benda M, Dewitz A, Stoll P (1984) Relations between axon length and axon caliber. “Is maximum conduction velocity the factor controlling the evolution of nerve structure? J Neurol Sci 63:369–380
Friede RL, Brzoska J, Hartmann U (1985) Changes in myelin sheath thickness and internode geometry in the rabbit phrenic nerve during growth. J Anat 143:103–113
Funch PG, Faber DS (1984) Measurement of myelin sheath resistances: implications for axonal conduction and pathophysiology. Science 225:538–540
Gamstorp I (1963) Normal condution velocity of ulnar, median and peroneal nerves in infancy, childhood and adolescence. Acta Paediat [Suppl] 46:68–76
Guzetta F, Ferriere G, Lyon G (1982) Congenital hypomyelination polyneuropathy. Pathological findings compared with polyneuropathies starting later in life. Brain 105:395–416
Hakamada S, Kumagai T, Watanabe K, Koike Y, Hara K, Miyazaki S (1982) The conduction velocity of slower and the fastes fibres in infancy and childhood. J Neurol Neurosurg Pschiatry 45:851–853
Hiscoe HB (1947) Distributions of odes and incisures in normal and regenerated nerve fibres. Anat Rec 99:447–475
Jacobs JM, Love S (1985) Qualitative and quantitative morphology of human nerve at different ages. Brain 108:897–924
Kimura J (1971) An evaluation of the facial and trigeminal nerves in polyneuropathy: electrodiagnostic study in Charcot-Marie-Tooth disease, Guillain-Barre syndrome, and diabetic neuropathy. Neurology 21:745–752
Kimura J (1974) F-wave velocity in the central segment of the median and ulnar nerves. A study in normal subjects and in patients with Charcot-Marie-Tooth disease. Neurology 24:539–546
Largo RH, Gasser T, Prader A, Stuetzle W, Huber PJ (1978) Analysis of the adolescent growth spurt using smoothing spline functions. Ann Human Biol 5:421–434
Matthews PBC (1972) Mammalian muscle receptors and their central action. Arnold, London, 630 pp
Moore JW, Joyner RW, Brill MH, Waxmann SG, Najar-Joa M (1978) Simulations of conduction in uniform myelinated fibers. Relative sensitivity of changes in nodal and internodal parameters. Biophys J 21:147–160
Niebroi-Dobosz I, Fidzianska A, Rafalowska J, Sawicka E (1980) Correlative biochemical and morphological studies of myelination in human ontogenesis. II. Myelination of the nerve roots. Acta Neuropathol (Berl) 49:153–158
Palix C, Coignet J (1978) Un cas de polyneuropathie peripherique neo-natale par amyelinisation. Pediatrie 33:201–207
Quilliam TA (1956) Some characteristics of myelinated fibre populations. J Anat 90:172–187
Rushton WAH (1951) A theory of the effects of fibre size inmedullated nerve. J Physiol 115:101–122
Schröder JM (1972) Altered ratio between axon diameter and myelin sheath thickness in regenerated nerve fibers. Brain Res 45:49–65
Schröder JM (1974) Two-dimensional reconstruction of Schwann cell changes following remyelination of regenerated nerve fibres. In: Hausmanowa-Petrusewicz I, Jedrzejowska H (eds) Proceedings of the symposium on structure and function of normal and diseased muscle and peripheral nerve. Polish Medical Publishers, Warsaw (Poland), pp. 299–304
Schröder JM (1982) Feinstrukturell-morphometrische Analyse anaboler Myelinisationsstörungen im peripheren Nerven. Verh Dtsch Ges Pathol 66:272–275
Schröder JM (1984) Zur Morphologie hereditärer Polyneuropathien. In: W. Mortier (ed) Moderne Diagnostik und Therapie bei Kindern. Grosse, Berlin, pp 14–22
Schröder JM (1987) Pathomorphologie der peripheren Nerven. In: Neundörfer B (ed) Polyneuritiden und Polyneuropathien. Verlag Chemie, Weinheim, pp 11–104
Schröder JM, Bohl J (1978) Altered ratio between axon caliber and myelin thickness in sural nerves of children. In: Canal N (ed) Peripheral neuropathies. Elsevier, Amsterdam, pp 49–62
Schröder JM, Bohl J, Brodda K (1978) Changes of the ratio between myelin thickness and axon diameter in the human developing sural nerve. Acta Neuropathol (Berl) 43:169–178
Smith KJ, Blakemore WF, Murry JA, Patterson RC (1982) Internodal myelin volume and axon surface area. J Neurol Sci 55:231–245
Smith RS, Koles ZJ (1970) Myelinated nerve fibers: computed effect of myelin thickness on conduction velocity. Am J Physiol 219:1256–1258
Thomas JE, Lambert EH (1960) Ulnar nerve conduction velocity and H-reflex in infants and children. J Appl Physiol 15:1–9
Thomas PK, Sears TA, Gilliatt RW (1959) The range of conduction velocity in normal motor nerve fibres to the small muscles of the hand and foot. J Neurol Neurosurg Psychiatry 22:175–181
Tomasch J, Schwarzacher HG (1952) Die innere Struktur peripherer menschlicher Nerven im Lichte faseranalytischer Untersuchungen. Acta Anat (Basel) 16:315–354
Tuczinski JH, Friede RL (1984) Internodal length in ventral roots of bovine spinal nerves varies independently of fibre calibre. J Anat 138:423–433
Van Buskirk C (1945) The seventh nerve complex. J Comp Neurol 82:330–333
Waxman SG (1980) Determinants of conduction velocity in myelinated nerve fibers. Muscle Nerve 3:141–150
Webster H deF (1971) The geometry of peripheral myelin sheaths during their formation and growth in rat sciatic nerves. J Cell Biol 48:348–367
Whitteridge D (1955) A separate afferent nerve supply from the extraocular muscles of goats. Q J Exp Physiol 40:331–336
Wuerker RB, McPhedran AM, Henneman E (1965) Properties of motor units in a heterogeneous pale muscle (M. gastrocnemius) of the cat. J Neurophysiol 28:85–99
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Supported in part by a grant from the Deutsche Forschungsgemeinschaft, Bonn-Bad Godesberg (Schr 195/5-7)
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Schröder, J.M., Bohl, J. & von Bardeleben, U. Changes of the ratio between myelin thickness and axon diameter in human developing sural, femoral, ulnar, facial, and trochlear nerves. Acta Neuropathol 76, 471–483 (1988). https://doi.org/10.1007/BF00686386
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DOI: https://doi.org/10.1007/BF00686386