Jpn J Rehabil Med 2009 ; 46 : 611.615

2009 年／第 46 回 日本リハビリテーション医学会学術集会／静岡

《Invited Lecture》

Traumatic to Peripheral ＊1

Lawrence R. ROBINSON, MD＊2

been proposed for classification of peripheral Epidemiology of Peripheral Nerve Trauma traumatic : that of Seddon 11） and that of Sun- Traumatic injury to peripheral nerves results in derland.14） The former is more commonly used in considerable disability across the world. In peace- the literature. Seddon has used the terms“ neuraprax- time, peripheral nerve injuries commonly result ia,”“,” and“ ” to describe from trauma due to motor vehicle accidents and less peripheral nerve injuries.11） is a com- commonly from penetrating trauma, falls, and indus- paratively mild injury with motor and sensory loss trial accidents. Of all patients admitted to Level I but no evidence of . The trauma centers, it is estimated that roughly 2 to 3％ nerve distally conducts normally. Focal demyelina- have peripheral nerve injuries.9,12） If plexus and root tion and／or are thought to be the etiologies injuries are also included, the incidence is about of the conduction block. Recovery may occur within 5％.9） hours, days, weeks, or up to a few months. Axonot- In the upper limb, the nerve most commonly re- mesis is commonly seen in crush injuries, nerve ported injured is the radial nerve, followed by ulnar stretch injuries（ such as from motor vehicle acci- and median nerves.9,12） Lower limb peripheral nerve dents and falls）, or percussion injuries（ such as from injuries are less common, with the sciatic most fre- gunshot wounds）. The and their quently injured, followed by peroneal and rarely tibi- sheaths are broken, yet the surrounding stroma（ i.e., al or femoral nerves. Fractures of nearby bones are the Schwann tubes, , and ） commonly associated, such as humeral fractures remains partially or fully intact. Wallerian degenera- with radial neuropathy. tion occurs, but subsequent axonal regrowth may In wartime, peripheral nerve trauma is much proceed along the intact endoneurial tubes. Recov- more common, and much of the knowledge about ery ultimately depends upon the degree of internal peripheral , repair, and recovery comes disorganization in the nerve as well as the distance to from experience derived in the American Civil War, the end organ. Sunderland’s classification（ see be- World Wars I and II, and subsequent wars.6,11,14） low） further divides this category. Neurotmesis de- scribes a nerve that has been either completely sev- Classification of Nerve Injuries ered or is so markedly disorganized by tissue There are two predominant schemes that have that axonal regrowth is impossible. Examples are

＊1 This paper is based on the invited lecture（ chairperson : Masahiro Ohashi） in the 46th Annual Meeting of the Japanese Association of Rehabilitation at Shizuoka on June 4, 2009 ＊2 Department of Rehabilitation Medicine, University of Washington, 1959 NE Pacifi c Street, C-414 , Box 356380, Seattle, WA 98195.6380, USA E-mail : [email protected]

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sharp injury, some traction injuries, and percussion to either loss of faster-conducting fibers or demyeli- injuries, or injection of noxious drugs. Prognosis for nation of surviving fibers. All these changes in the spontaneous recovery is extremely poor without sur- CMAP will generally persist until recovery takes gical intervention. place, typically by no more than a few months postin- jury. Most importantly, the distal CMAP will never Compound Muscle drop in amplitude in purely neurapraxic injuries, be- 1．Neurapraxia cause no loss or Wallerian degeneration occurs In purely neurapraxic lesions, the CMAP will and the distal nerve segment remains excitable. change immediately after injury, assuming one can 2．Axonotmesis and Neurotmesis stimulate both above and below the site of the lesion Electrodiagnostically, complete axonotmesis （Figure）. When recording from distal muscles and （equivalent to Sunderland grades 2, 3, and 4） and stimulating distal to the site of the lesion, the CMAP complete neurotmesis look the same, because the should always be normal because no axonal loss and difference between these types of lesions is in the in- no Wallerian degeneration has occurred. Moving the tegrity of the supporting structures, which have no site of stimulation proximal to the lesion will produce electrophysiological function. Thus, these lesions a smaller or absent CMAP, as conduction in some or can be grouped together as axonotmesis for the pur- all fibers is blocked In addition to conduction block, pose of this discussion. partial lesions also often demonstrate concomitant Immediately after axonotmesis and for a“ few days” slowing across the lesion. This slowing may be due thereafter, the CMAP and motor conduction studies look the same as those seen in a neurapraxic lesion. Nerve segments distal to the lesion remain excitable and demonstrate normal conduction, whereas proxi- mal stimulation results in an absent or small re- sponse from distal muscles. Early on, this picture looks the same as conduction block and can be con- fused with neurapraxia. Hence, neurapraxia and ax- onotmesis cannot be distinguished until sufficient time for Wallerian degeneration in all motor fibers has occurred, typically about 9 days postinjury.6） Af- ter enough time has passed for Wallerian degenera- tion to occur, the amplitude of the CMAP elicited with distal stimulation will fall. This starts at about day 3 and is complete by about day 9.6）

Compound or Sensory Nerve Action Potentials

1．Neurapraxia The SNAP and compound nerve action potential will show changes similar to the CMAP after focal nerve injury. In the setting of neurapraxia, there is a focal conduction block at the site of the lesion, with preserved distal amplitude. However, the criteria for Figure establishing conduction block in sensory nerve fi- Response of CMAP to stimulation below left panel and （ ） bers are substantially different than that for the above（ right panel） a nerve lesion of different types imme- diately（ day 1） and 10 days after injury. CMAP. When recording nerve action potentials,

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there is normally a greater drop in amplitude over in- 10 to 14 days for fibrillations to develop. With a lon- creasing distance between stimulating and recording ger distal stump（ e.g., ulnar-innervated hand mus- electrodes, due to temporal dispersion and phase cles in a brachial plexopathy）, 21 to 30 days is re- cancellation.7） Amplitude drops of 50 to 70％ over a quired for full development of fibrillation potentials 25-cm distance are not unexpected, and it is less and positive sharp waves.15） Thus, the electrodiag- clear just what change in amplitude is abnormal. nostic medicine consultant needs to be acutely aware 2．Axonotmesis and Neurotmesis of the time since injury so that severity is not under- Immediately after axonotmesis and for a few days estimated when a study is performed early after inju- thereafter, the SNAP looks the same as seen in a ry and so that development of increased fibrillation neurapraxic lesion. Nerve segments distal to the le- potentials over time is not misinterpreted as a wors- sion remain excitable and demonstrate normal con- ening of the injury. duction, whereas proximal stimulation results in an Density of fibrillation potentials and positive sharp absent or small response. Hence, neurapraxia and waves is usually graded on a four-point scale. This is axonotmesis cannot be distinguished until sufficient an ordinal scale, meaning that as numbers increase, time for Wallerian degeneration in all sensory fibers the findings are worse. However, it is not an interval has occurred, typically about 11 days postinjury.3） It or ratio scale, i.e., 4＋ is not twice as bad as 2＋ or takes slightly longer for sensory nerve studies to four times as bad as 1＋. Moreover, 4＋ fibrillation demonstrate loss of amplitude than for motor stud- potentials does not indicate complete axon loss and ies, i.e., 11 days versus 9 days, due to the earlier fail- in fact may represent only a minority of axons lost.1,4） ure of neuromuscular junction transmission com- Evaluation of recruitment and particularly of distally pared with nerve conduction. elicited CMAP amplitude is necessary before one can decide whether complete axon loss has oc- Needle Electromyography curred. 1．Neurapraxia Fibrillations may also occur after direct muscle in- The needle EMG examination in purely neurap- jury as well as nerve injury. Partanen and Danner 10） raxic lesions will show changes in recruitment with have demonstrated that patients after muscle biopsy debatable abnormalities in spontaneous activity. The have persistent fibrillation potentials starting after 6 most apparent change on needle EMG will be chang- to 7 days and extending for up to 11 months. In pa- es in recruitment. These occur immediately after in- tients who have undergone multiple trauma, coexist- jury. In complete lesions（ i.e., complete conduction ing direct muscle injury is common and can be po- block）, there will be no motor unit action potentials tentially misleading when trying to localize a lesion. （MUAPs）. In incomplete neurapraxic lesions, there When there are surviving axons after an incom- will be reduced numbers of MUAPs firing more rap- plete axonal injury, remaining MUAPs are initially idly than normal（ i.e., reduced or discrete recruit- normal in morphology but demonstrate reduced or ment）. Because no axon loss occurs in neurapraxic discrete recruitment. Axonal sprouting will be mani- injuries, there will be no axonal sprouting and no fested by changes in morphology of existing motor changes in MUAP morphology（ e.g., duration, am- units. Amplitude will increase, duration will become plitude, or phasicity） at any time after injury. prolonged, and the percentage of polyphasic MUAPs 2．Axonotmesis and Neurotmesis will increase as motor unit territory increases.4,5） With an axon-loss lesion, needle EMG will demon- This process occurs soon after injury. strate fibrillation potentials and positive sharp waves In complete lesions, the only possible mechanism a number of days after injury. The time between inju- of recovery is axonal regrowth. The earliest needle ry and onset of fibrillation potentials will be depen- EMG finding in this case is the presence of small, dent in part upon the length of the distal nerve polyphasic, often unstable MUAPs previously re- stump. When the distal stump is short, it takes only ferred to as“ nascent potentials.”（ This term is now

Jpn J Rehabil Med VOL. 46 NO. 10 2009 613 Lawrence R. ROBINSON discouraged because it implies an etiology ; it is pre- mentioned earlier, direct muscle trauma can result in ferred to simply describe the size, duration, and pha- positive sharp waves and fibrillations for months or sicity of the MUAP.） Observation of these potentials longer after injury.10） Practically speaking, this can is dependent upon establishing axon regrowth as result in erroneously proximal lesion sites or error well as new neuromuscular junctions, and this obser- in diagnosing more than one lesion. For example, in vation represents the earliest evidence of reinnerva- the setting of humeral fracture with radial neuropa- tion, usually preceding the onset of clinically evident thy, the triceps not infrequently demonstrates fibril- voluntary movement.4） lation potentials, due to direct muscle trauma. How- ever, one could be misled to localize the lesion to the Localization of Traumatic Nerve Injuries axilla or higher rather than spiral groove, if the tri- The localization of peripheral nerve injuries is ceps findings are not recognized to come from direct sometimes straightforward but may be complicated muscle rather than nerve injury. by a variety of possible pitfalls. Localization is usually Third, the problem of partial lesions can make for performed by two methods :（ 1） detecting focal misdiagnosis to more distal sites. In partial ulnar slowing or conduction block on NCSs, or（ 2） assess- nerve lesions at the elbow, for example, the forearm ing the pattern of denervation on needle EMG. ulnar innervated muscles are often spared.2） This is Localizing peripheral nerve lesions by NCSs usu- thought to be at least partially due to sparing of the ally requires that there be a focal slowing or conduc- fascicles in the nerve that are preparing to branch to tion block as one stimulates above and below the le- the flexor digitorum profundus and the flexor carpi sion. To see such a change, there must be either ulnaris, i.e., they are in a relatively protected posi- focal demyelination or ischemia or the lesion should tion. This finding could lead one to inadvertently lo- be so acute that degeneration of the distal stump has calize the lesion to the distal forearm or wrist. Simi- not yet occurred. Thus, lesions with partial or com- larly, a lesion involving the median nerve in the arm plete neurapraxia（ due to either demyelination or （above the elbow） has been reported to cause find- ischemia） can be well localized with motor NCSs, as ings only in the anterior interosseous distribution.17） can very acute axonal injuries. Intraneural topography needs to be considered when The other major electrodiagnostic method of de- making a diagnosis based on branching.16） termining the site of nerve injury is by needle EMG. Electrodiagnostic Evaluation of Prognosis Conceptually, if one knows the branching order to various muscles under study, one can determine that Determining the pathophysiology of a peripheral the nerve injury is between the branches to the most nerve traumatic injury can help with estimating distal normal muscle and the most proximal abnor- prognosis. Those injuries that are completely or mal muscle. There are, however, a number of poten- largely neurapraxic have a good prognosis for recov- tial problems with this approach. First, the branching ery within a few months（ usually up to 3 months and innervation for muscles is not necessarily con- postinjury）. Resolution of ischemia and remyelina- sistent from one person to another. Sunderland 40） tion should be complete by this time. demonstrated a great deal of variability in branching Mixed injuries typically have two or more phases order to muscles in the limbs, variability in the num- of recovery. The neurapraxic component resolves ber of branches going to each muscle, and variability quickly（ as above） and muscle fiber hypertrophy in which nerve or nerves supply each muscle. Thus, can provide additional recovery, but the axonal com- the typical branching scheme may not apply to the ponent is slower, because it depends upon distal ax- patient being studied, and, consequently, the lesion onal sprouting and upon axonal regeneration from site can be misconstrued. the site of the lesion. Thus, patients usually experi- Second, the problem of muscle trauma and associ- ence a relatively rapid but incomplete recovery fol- ated needle EMG findings can be misleading. As lowed by a slower further recovery. Sensory recov-

614 Jpn J Rehabil Med VOL. 46 NO. 10 2009 Traumatic Injury to Peripheral Nerves ery may proceed for a longer time than motor. neuropathy at the elbow. Muscle Nerve 1989 ;12 : 965.967 Partial axon-loss lesions usually represent axonot- 3） Chaudry V, Cornblath DR : Wallerian degeneration in human nerves : serial electrophysiological studies. Mus- mesis, though a partial neurotmesis e.g., a lacera- （ cle Nerve 1992 ; 15 : 687.693 tion through part of the nerve） cannot always be ex- 4） Dorfman LJ : Quantitative clinical electrophysiology in cluded in such cases. In axonotmesis, recovery will the evaluation of nerve injury and regeneration. Muscle . depend upon axonal sprouting and regeneration. Nerve 1990 ; 13 : 822 828 5） Erminio F, Buchthal F, Rosenfalck P : Motor unit territo- Hence, there will be some early recovery followed ry and muscle fi ber concentration in paresis due to pe- possibly by a later recovery if or when regenerating ripheral nerve injury and anterior horn cell involve- axons reach their end organs. The amplitude of the ment. 1959 ; 9 : 657.671 6 Haymaker W, Woodhall B : Peripheral Nerve Injuries. CMAP provides some guide to prognosis. In facial ） WB Saunders, Philadelphia, 1953 ; p 333 nerve lesions, it has been demonstrated that patients 7） Kimura J, Machida M, Ishida T, Yamada T, Rodnitzky with CMAP amplitudes 30％ or more of the other RL, Kudo Y, Suzuki S : Relation between size of com- side have an excellent outcome, those with 10 to pound sensory or muscle action potential, and length of nerve segment. Neurology 1986 ; 36 : 647.652 30％ have good but not always complete recovery, 8） Kline DG : Surgical repair of peripheral nerve injury. 13） and those with ＜10％ have a poor outcome. Muscle Nerve 1990 ; 13 : 843.852 Complete axonotmesis and neurotmesis have the 9） Noble J, Munro CA, Prasad VSSV, Midha R : Analysis of worst prognosis. Recovery depends solely upon ax- upper and lower extremity peripheral nerve injuries in a population of patients with multiple injuries. J Trauma onal regeneration, which may or may not occur, de- 1998 ; 45 : 116.122 pending upon the degree of injury to the nerve. In 10） Partanen JV, Danner R : Fibrillation potentials after mus- many cases of complete axon loss, it is not possible cle injury in humans. Muscle Nerve 1982 ; 5 : S70.S73 to know the degree of nerve injury except by surgi- 11） Seddon HJ : Surgical Disorders of the Peripheral Nerves. 2nd Ed, Churchill Livingstone, New York, 1975 ; pp 21.23 cal exploration with or without intraoperative record- 12） Selecki BR, Ring IT, Simpson DA, Vanderfi eld GK, Sewell ing or looking for evidence of early reinnervation af- MF : Trauma to the central and peripheral nervous sys- ter the lesion. tems. Part II : a statistical profi le of surgical treatment in New South Wales 1977. Aust NZ J Surg 1982 ; : 111.116 As a consequence, it is often recommended to wait 52 13） Sillman JS, Niparko JK, Lee SS, Kileny PR : Prognostic 2 to 4 months and look for evidence of reinnervation value of evoked and standard electromyography in acute in previously completely denervated muscles near facial . Otolaryngol Head Neck Surg 1992 ; 107 : the site of the lesion.8,18） Those lesions that have 377.381 14） Sunderland S : Nerves and Nerve Injuries. 2nd Ed. some spontaneous recovery are usually treated con- Churchill Livingstone, New York, 1978 ; pp 133.138 servatively, because operative repair is unlikely to 15） Thesleff S : Physiological effects of denervation of mus- improve upon natural recovery. Those with no evi- cle. Ann NY Acad Sci 1974 ; 228 : 89.103 dence of axonal regrowth usually have operative ex- 16） Wertsch JJ, Oswald TA, Roberts MM : Role of intraneural topography in diagnosis and localization in electrodiag- ploration with possible grafting. nostic medicine. Phys Med Rehabil Clin N Am 1994 ; 5 : 465.475 References 17） Wertsch JJ, Sanger JR, Matloub HS : Pseudo-anterior in- terosseous nerve syndrome. Muscle Nerve 1985 ; 8 : 68.70 1） Buchthal F : Fibrillations : clinical electrophysiology. in 18） Wood MB : Surgical approach to peripheral nervous sys- Abnormal Nerves and Muscle Generators（ ed by Culp WJ, tem trauma. in 1998 AAEM Course C : Electrodiagnosis Ochoa J）. Oxford University Press, New York, 1982 ; pp in Traumatic Conditions. American Association of Elec- 632.662 trodiagnostic Medicine, Rochester, 1998 ; pp 27.36 2） Campbell WW, Pridgeon RM, Riaz G, Astruc J, Leahy M, Crostic EG : Sparing of the flexor carpi ulnaris in ulnar

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