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Clinical Outcome Measures Following Peripheral Nerve Repair

The Future for Assessment of the Processes and Experiences of Nerve Injury

  • Living reference work entry
  • First Online:
Peripheral Nerve Tissue Engineering and Regeneration

Part of the book series: Reference Series in Biomedical Engineering ((TIENRE))

Abstract

The hope of translational medicine is to identify treatments that improve the rate and quality of neuronal recovery following peripheral nerve injuries (PNI). A major obstacle to the trial of new treatments for PNI is the absence of sensitive and responsive measures of clinical function, which are the ultimate outcome of the biological events of nerve regeneration.

The development of objective clinical measures of nerve regeneration that are sensitive, responsive, and valid is challenging for a number of reasons. The Peripheral Nervous System (PNS) allows us to have complex interactions with our surroundings (for example, the perception of pain, touch, and temperature). Developing objective measures that reflect the multimodal function of the PNS and separate it from psychological influences on that experience is difficult. Secondly, the recovery of function following PNI is dependent upon a number of biological processes at multiple levels including the end organ, the damaged nerve segments, as well as the Central Nervous System (CNS). Clinical measures that quantify these changes and relate them to the recovery of function are not well documented.

The biological process of neural regeneration is often assessed in the research arena through postmortem tissue assessment. However, the harvesting of vital nerve tissue for assessment of neural regeneration often risks the function that has been recovered. Therefore, this is not feasible when studying the biological process of regeneration in humans. This has necessitated the development of noninvasive methods to attain the same degree of assessment of biological regeneration.

In order to assess the biological mechanisms of tissue and cellular regeneration, the relationship of these processes with human clinical experiences needs to be explained. Correlating these new areas of human assessment will help establish the influence of the complex biological processes that underpin nerve regeneration on the lived experience of nerve injury.

This Chapter provides an overview of the clinical, neurophysiological, and imaging assessments that can provide pre-, intra-, and postoperative measures of nerve regeneration. This will inform the development of outcome measures that have the capacity to detect a meaningful cinical response in clinical trials which aim to detemine the efficacy of new therapies for PNI.

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References

  • (1917) Nerve wounds symptomatology of peripheral nerve lesions caused by War Wounds. By J. Tinel, late Chef de Clinique at La Salpêtrière, with Preface by Professor Dejerine, translated by Fred Rothwell, revised and edited by Cecil A. Joll. Pp. xii + 317, with 323 illustrations. London Baillière, Tindal & Cox. 15s. net. BJS 5(19):517

    Google Scholar 

  • (1986) Classification of chronic pain. Descriptions of chronic pain syndromes and definitions of pain terms. Prepared by the International Association for the Study of Pain, Subcommittee on Taxonomy. Pain Suppl 3:S1-226

    Google Scholar 

  • Aagaard BD, Lazar DA, Lankerovich L, Andrus K, Hayes CE, Maravilla K, Kliot M (2003) High-resolution magnetic resonance imaging is a noninvasive method of observing injury and recovery in the peripheral nervous system. Neurosurgery 53(1):199–203; discussion 203-194

    Google Scholar 

  • Aberg M, Ljungberg C, Edin E, Jenmalm P, Millqvist H, Nordh E, Wiberg M (2007) Considerations in evaluating new treatment alternatives following peripheral nerve injuries: a prospective clinical study of methods used to investigate sensory, motor and functional recovery. J Plast Reconstr Aesthet Surg 60(2):103–113

    Google Scholar 

  • Abraham A, Izenberg A, Dodig D, Bril V, Breiner A (2016) Peripheral nerve ultrasound imaging shows enlargement of peripheral nerves outside the brachial plexus in neuralgic amyotrophy. J Clin Neurophysiol 33(5):e31–e33

    Google Scholar 

  • Adams L, Carlson BM, Henderson L, Goldman D (1995) Adaptation of nicotinic acetylcholine receptor, myogenin, and MRF4 gene expression to long-term muscle denervation. J Cell Biol 131(5):1341–1349

    Google Scholar 

  • Alvarez-Linera J (2008) 3T MRI: advances in brain imaging. Eur J Radiol 67(3):415–426

    Google Scholar 

  • Aminoff MJ (2004) Electrophysiologic testing for the diagnosis of peripheral nerve injuries. Anesthesiology 100(5):1298–1303

    Google Scholar 

  • Ashley Z, Sutherland H, Lanmuller H, Russold MF, Unger E, Bijak M, Mayr W, Boncompagni S, Protasi F, Salmons S, Jarvis JC (2007) Atrophy, but not necrosis, in rabbit skeletal muscle denervated for periods up to one year. Am J Physiol Cell Physiol 292(1):C440–C451

    Google Scholar 

  • Baltodano PA, Tong AJ, Chhabra A, Rosson GD (2014) The role of magnetic resonance neurography in the postoperative management of peripheral nerve injuries. Neuroimag Clin N Am 24(1):235–244

    Google Scholar 

  • Barkhaus PE, Nandedkar SD (1994) Recording characteristics of the surface EMG electrodes. Muscle Nerve 17(11):1317–1323

    Google Scholar 

  • Bendszus M, Koltzenburg M (2001) Visualization of denervated muscle by gadolinium-enhanced MRI. Neurology 57(9):1709–1711

    Google Scholar 

  • Bendszus M, Stoll G (2003) Caught in the act: in vivo mapping of macrophage infiltration in nerve injury by magnetic resonance imaging. J Neurosci 23(34):10892–10896

    Google Scholar 

  • Bendszus M, Stoll G (2005) Technology insight: visualizing peripheral nerve injury using MRI. Nat Clin Pract Neurol 1(1):45–53

    Google Scholar 

  • Bendszus M, Koltzenburg M, Wessig C, Solymosi L (2002) Sequential MR imaging of denervated muscle: experimental study. AJNR Am J Neuroradiol 23(8):1427–1431

    Google Scholar 

  • Bendszus M, Wessig C, Reiners K, Bartsch AJ, Solymosi L, Koltzenberg M (2003) MR imaging in the differential diagnosis of neurogenic foot drop. AJNR Am J Neuroradiol 24(7):1283–1289

    Google Scholar 

  • Birch R (2011) Pain. In: Birch R (ed) Surgical disorders of the peripheral nerves. Springer, London, pp 527–561

    Google Scholar 

  • Bostock H, Sears TA (1976) Continuous conduction in demyelinated mammalian nerve fibers. Nature 263(5580):786–787

    Google Scholar 

  • Bostock H, Sears TA, Sherratt RM (1981) The effects of 4-aminopyridine and tetraethylammonium ions on normal and demyelinated mammalian nerve fibres. J Physiol 313:301–315

    Google Scholar 

  • Boyd JG, Gordon T (2003) Glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor sustain the axonal regeneration of chronically axotomized motoneurons in vivo. Exp Neurol 183(2):610–619

    Google Scholar 

  • Boyer RB, Kelm ND, Riley DC, Sexton KW, Pollins AC, Shack RB, Dortch RD, Nanney LB, Does MD, Thayer WP (2015) 4.7-T diffusion tensor imaging of acute traumatic peripheral nerve injury. Neurosurg Focus 39(3):E9–E9

    Google Scholar 

  • Brattain K (2012) Analysis of the peripheral nerve repair market in the US. Magellan Medical Technology Consultants, Minneapolis

    Google Scholar 

  • Bromberg MB (1999) Electronic myoanatomic atlas for clinical electromyography muscle localization for needle insertion in clinical EMG CD-ROM. Electronic atlas of electromyographic waveforms, EMG on CD. Vol. II, Parts I–IV. Muscle Nerve 22(10):1468–1469

    Google Scholar 

  • Bromberg MB (2007) Updating motor unit number estimation (MUNE). Clin Neurophysiol 118(1):1–8

    Google Scholar 

  • Bromberg MB, Abrams JL (1995) Sources of error in the spike-triggered averaging method of motor unit number estimation (MUNE). Muscle Nerve 18(10):1139–1146

    Google Scholar 

  • Brown WF, Milner-Brown HS (1976) Some electrical properties of motor units and their effects on the methods of estimating motor unit numbers. J Neurol Neurosurg Psychiatry 39(3):249–257

    Google Scholar 

  • Brown H, Johnson K, Gilbert A, Quick TJ (2018) The lived experience of motor recovery of elbow flexion following Oberlin nerve transfer: a qualitative analysis. Hand Therapy 23(4):130–138

    Google Scholar 

  • Buchthal F, Guld C, Rosenfalck P (1954a) Action potential parameters in normal human muscle and their dependence on physical variables. Acta Physiol Scand 32(2-3):200–218

    Google Scholar 

  • Buchthal F, Pinell P, Rosenfalck P (1954b) Action potential parameters in normal human muscle and their physiological determinants. Acta Physiol Scand 32(2-3):219–229

    Google Scholar 

  • Burnett MG, Zager EL (2004) Pathophysiology of peripheral nerve injury: a brief review. Neurosurg Focus 16(5):E1

    Google Scholar 

  • Campbell WW (2008) Evaluation and management of peripheral nerve injury. Clin Neurophysiol 119(9):1951–1965

    Google Scholar 

  • Carlson BM (2014) The biology of long-term denervated skeletal muscle. Eur J Trans Myol 24(1):3293–3293

    Google Scholar 

  • Chammas M, Micallef JP, Prefaut C, Allieu Y (1997) Fatigue analysis of human reinnervated muscle after microsurgical nerve repair. Clin Orthop Relat Res 334:144–149

    Google Scholar 

  • Chassard M, Pham E, Comtet JJ (1993) Two-point discrimination tests versus functional sensory recovery in both median and ulnar nerve complete transections. J Hand Surg Br Eur Vol 18(6):790–796

    Google Scholar 

  • Chaudhry V, Cornblath DR (1992) Wallerian degeneration in human nerves: serial electrophysiological studies. Muscle Nerve 15(6):687–693

    Google Scholar 

  • Chen Z-L, Yu W-M, Strickland S (2007) Peripheral regeneration. Ann Rev Neurosci 30:209–233

    Google Scholar 

  • Chong PST, Cros DP (2004) Technology literature review: quantitative sensory testing. Muscle Nerve 29(5):734–747

    Google Scholar 

  • Churchill JD, Arnold LL, Garraghty PE (2001) Somatotopic reorganization in the brainstem and thalamus following peripheral nerve injury in adult primates. Brain Res 910(1–2):142–152

    Google Scholar 

  • Ciaramitaro P, Mondelli M, Logullo F, Grimaldi S, Battiston B, Sard A, Scarinzi C, Migliaretti G, Faccani G, Cocito D (2010) Traumatic peripheral nerve injuries: epidemiological findings, neuropathic pain and quality of life in 158 patients. J Peripher Nerv Syst 15(2):120–127

    Google Scholar 

  • Clague JE, Roberts N, Gibson H, Edwards RH (1995) Muscle imaging in health and disease. Neuromuscul Disord 5(3):171–178

    Google Scholar 

  • Cluskey S, Ramsden DB (2001) Mechanisms of neurodegeneration in amyotrophic lateral sclerosis. Mol Pathol 54(6):386–392

    Google Scholar 

  • Cudlip SA, Howe FA, Griffiths JR, Bell BA (2002) Magnetic resonance neurography of peripheral nerve following experimental crush injury, and correlation with functional deficit. J Neurosurg 96(4):755–759

    Google Scholar 

  • Dailey AT, Tsuruda JS, Goodkin R, Haynor DR, Filler AG, Hayes CE, Maravilla KR, Kliot M (1996) Magnetic resonance neurography for cervical radiculopathy: a preliminary report. Neurosurgery 38(3):488–492. discussion 492

    Google Scholar 

  • Dailey AT, Tsuruda JS, Filler AG, Maravilla KR, Goodkin R, Kliot M (1997) Magnetic resonance neurography of peripheral nerve degeneration and regeneration. Lancet 350(9086):1221–1222

    Google Scholar 

  • Daube JR (1995) Estimating the number of motor units in a muscle. J Clin Neurophysiol 12(6):585–594

    Google Scholar 

  • de Carvalho M, Barkhaus PE, Nandedkar SD, Swash M (2018) Motor unit number estimation (MUNE): where are we now? Clin Neurophysiol 129(8):1507–1516

    Google Scholar 

  • Delgado DA, Lambert BS, Boutris N, McCulloch PC, Robbins AB, Moreno MR, Harris JD (2018) Validation of digital visual analog scale pain scoring with a traditional paper-based visual analog scale in adults. J Am Acad Orthop Surg Global Res Rev 2(3):e088–e088

    Google Scholar 

  • Dellon AL, Mackinnon SE (1988) Basic scientific and clinical applications of peripheral nerve regeneration. Surg Ann 20:59–100

    Google Scholar 

  • Deroide N, Bousson V, Lévy BI, Laredo JD, Kubis N (2010) L’imagerie du nerf et du muscle dans les atteintes nerveuses périphériques associée à l’électroneuromyographie: le couple idéal ? La Revue de Médecine Interne 31(4):287–294

    Google Scholar 

  • Does MD, Snyder RE (1996) Multiexponential T2 relaxation in degenerating peripheral nerve. Magn Reson Med 35(2):207–213

    Google Scholar 

  • Drobnjak I, Zhang H, Ianus A, Kaden E, Alexander DC (2016) PGSE, OGSE, and sensitivity to axon diameter in diffusion MRI: insight from a simulation study. Magn Reson Med 75(2):688–700

    Google Scholar 

  • Duff SV (2005) Impact of peripheral nerve injury on sensorimotor control. J Hand Ther 18(2):277–291

    Google Scholar 

  • Dumitru D, Zwarts MJ, Amato AA (2002) Peripheral nervous system’s reaction to injury. In: Electrodiagnostic medicine. Hanley & Belfus, Philadelphia

    Google Scholar 

  • Faroni A, Mobasseri SA, Kingham PJ, Reid AJ (2015) Peripheral nerve regeneration: experimental strategies and future perspectives. Adv Drug Deliv Rev 82–83:160–167

    Google Scholar 

  • Filler AG, Kliot M, Winn HR, Tsuruda JS, Hayes CE, Howe FA, Griffiths JR, Filler AG, Bell BA, Filler AG (1993) Magnetic resonance neurography. Lancet 341(8846):659–661

    Google Scholar 

  • Filler AG, Kliot M, Howe FA, Hayes CE, Saunders DE, Goodkin R, Bell BA, Winn HR, Griffiths JR, Tsuruda JS (1996) Application of magnetic resonance neurography in the evaluation of patients with peripheral nerve pathology. J Neurosurg 85(2):299–309

    Google Scholar 

  • Flasar J, Volk GF, Granitzka T, Geißler K, Irintchev A, Lehmann T, Guntinas-Lichius O (2017) Quantitative facial electromyography monitoring after hypoglossal-facial jump nerve suture. Laryngoscope Investig Otolaryngol 2(5):325–330

    Google Scholar 

  • Fu SY, Gordon T (1995) Contributing factors to poor functional recovery after delayed nerve repair: prolonged denervation. J Neurosci 15(5 Pt 2):3886–3895

    Google Scholar 

  • Fu SY, Gordon T (1997) The cellular and molecular basis of peripheral nerve regeneration. Mol Neurobiol 14(1–2):67–116

    Google Scholar 

  • Galea V, Fehlings D, Kirsch S, McComas A (2001) Depletion and sizes of motor units in spinal muscular atrophy. Muscle Nerve 24(9):1168–1172

    Google Scholar 

  • Gallagher TA, Simon NG, Kliot M (2015) Diffusion tensor imaging to visualize axons in the setting of nerve injury and recovery. Neurosurg Focus 39(3):E10

    Google Scholar 

  • Gaudet AD, Popovich PG, Ramer MS (2011) Wallerian degeneration: gaining perspective on inflammatory events after peripheral nerve injury. J Neuroinflammation 8:110–110

    Google Scholar 

  • Geuna S, Raimondo S, Ronchi G, Di Scipio F, Tos P, Czaja K, Fornaro M (2009) Chapter 3: Histology of the peripheral nerve and changes occurring during nerve regeneration. Int Rev Neurobiol 87:27–46

    Google Scholar 

  • Giannini C, Lais AC, Dyck PJ (1989) Number, size, and class of peripheral nerve fibers regenerating after crush, multiple crush, and graft. Brain Res 500(1):131–138

    Google Scholar 

  • Gooch CL, Harati Y (2000) Motor unit number estimation, ALS and clinical trials. Amyotroph Lateral Scler Other Motor Neuron Disorders 1(2):71–82

    Google Scholar 

  • Gooch CL, Doherty TJ, Chan KM, Bromberg MB, Lewis RA, Stashuk DW, Berger MJ, Andary MT, Daube JR (2014) Motor unit number estimation: a technology and literature review. Muscle Nerve 50(6):884–893

    Google Scholar 

  • Gordon T, Chan KM, Sulaiman OAR, Udina E, Amirjani N, Brushart TM (2009) Accelerating axon growth to overcome limitations in functional recovery after peripheral nerve injury. Neurosurgery 65(4 Suppl):A132–A144

    Google Scholar 

  • Gydikov A, Gerilovsky L, Kostov K, Gatev P (1980) Influence of some features of the muscle structure on the potentials of motor units, recorded by means of different types of needle electrodes. Electromyogr Clin Neurophysiol 20(4-5):299–321

    Google Scholar 

  • Hansson T, Brismar T (2003) Loss of sensory discrimination after median nerve injury and activation in the primary somatosensory cortex on functional magnetic resonance imaging. J Neurosurg 99(1):100–105

    Google Scholar 

  • He B, Zhu Z, Zhu Q, Zhou X, Zheng C, Li P, Zhu S, Liu X, Zhu J (2014) Factors predicting sensory and motor recovery after the repair of upper limb peripheral nerve injuries. Neural Regen Res 9(6):661–672

    Google Scholar 

  • Heckel A, Weiler M, Xia A, Ruetters M, Pham M, Bendszus M, Heiland S, Baeumer P (2015) Peripheral nerve diffusion tensor imaging: assessment of axon and myelin sheath integrity. PLoS One 10(6):e0130833

    Google Scholar 

  • Hilz MJ, Axelrod FB, Hermann K, Haertl U, Duetsch M, Neundorfer B (1998) Normative values of vibratory perception in 530 children, juveniles and adults aged 3–79 years. J Neurol Sci 159(2):219–225

    Google Scholar 

  • Hoffman H (1950) Local re-innervation in partially denervated muscle: a histo-physiological study. Aust J Exp Biol Med Sci 28(4):383–398

    Google Scholar 

  • Holzgrefe RE, Wagner ER, Singer AD, Daly CA (2019) Imaging of the peripheral nerve: concepts and future direction of magnetic resonance neurography and ultrasound. J Hand Surg 44(12):1066–1079

    Google Scholar 

  • Howe FA, Filler AG, Bell BA, Griffiths JR (1992) Magnetic resonance neurography. Magn Reson Med 28(2):328–338

    Google Scholar 

  • Hsueh IP, Lee MM, Hsieh CL (2002) The Action Research Arm Test: is it necessary for patients being tested to sit at a standardized table? Clin Rehabil 16(4):382–388

    Google Scholar 

  • Hughes SM, Taylor JM, Tapscott SJ, Gurley CM, Carter WJ, Peterson CA (1993) Selective accumulation of MyoD and myogenin mRNAs in fast and slow adult skeletal muscle is controlled by innervation and hormones. Development 118(4):1137–1147

    Google Scholar 

  • Hundepool CA, Bulstra LF, Kotsougiani D, Friedrich PF, Hovius SER, Bishop AT, Shin AY (2018) Comparable functional motor outcomes after repair of peripheral nerve injury with an elastase-processed allograft in a rat sciatic nerve model. Microsurgery 38(7):772–779

    Google Scholar 

  • Ikeda M, Oka Y (2012) The relationship between nerve conduction velocity and fiber morphology during peripheral nerve regeneration. Brain Behav 2(4):382–390

    Google Scholar 

  • Jacobsen AB, Bostock H, Tankisi H (2018) CMAP scan MUNE (MScan) – a novel motor unit number estimation (MUNE) method. J Vis Exp 136:56805

    Google Scholar 

  • Jayakumar P, Overbeek CL, Lamb S, Williams M, Funes C, Gwilym S, Ring D, Vranceanu AM (2018) What factors are associated with disability after upper extremity injuries? A systematic review. Clin Orthop Relat Res 476(11):2190–2215

    Google Scholar 

  • Jeon T, Fung MM, Koch KM, Tan ET, Sneag DB (2018) Peripheral nerve diffusion tensor imaging: overview, pitfalls, and future directions. J Magn Reson Imaging 47(5):1171–1189

    Google Scholar 

  • Jerosch-Herold C (2005) Assessment of sensibility after nerve injury and repair: a systematic review of evidence for validity, reliability and responsiveness of tests. J Hand Surg Br 30(3):252–264

    Google Scholar 

  • Jespersen SN (2012) Equivalence of double and single wave vector diffusion contrast at low diffusion weighting. NMR Biomed 25(6):813–818

    Google Scholar 

  • Jessen KR, Arthur-Farraj P (2019) Repair Schwann cell update: adaptive reprogramming, EMT, and stemness in regenerating nerves. Glia 67(3):421–437

    Google Scholar 

  • Jessen KR, Mirsky R (2019) The success and failure of the schwann cell response to nerve injury. Front Cell Neurosci 13:33–33

    Google Scholar 

  • Jiang X, Li H, Xie J, Zhao P, Gore JC, Xu J (2016) Quantification of cell size using temporal diffusion spectroscopy. Magn Reson Med 75(3):1076–1085

    Google Scholar 

  • Joyce NC, Carter GT (2013) Electrodiagnosis in persons with amyotrophic lateral sclerosis. PM R 5(5 Suppl):S89–S95

    Google Scholar 

  • Kadrie HA, Yates SK, Milner-Brown HS, Brown WF (1976) Multiple point electrical stimulation of ulnar and median nerves. J Neurol Neurosurg Psychiatry 39(10):973–985

    Google Scholar 

  • Kakkar LS, Bennett OF, Siow B, Richardson S, Ianus A, Quick T, Atkinson D, Phillips JB, Drobnjak I (2018) Low frequency oscillating gradient spin-echo sequences improve sensitivity to axon diameter: an experimental study in viable nerve tissue. Neuroimage 182:314–328

    Google Scholar 

  • Kamath S, Venkatanarasimha N, Walsh MA, Hughes PM (2008) MRI appearance of muscle denervation. Skeletal Radiol 37(5):397–404

    Google Scholar 

  • Kaya Y, Sarikcioglu L (2015) Sir Herbert Seddon (1903–1977) and his classification scheme for peripheral nerve injury. Childs Nerv Syst 31(2):177–180

    Google Scholar 

  • Kikuchi Y, Nakamura T, Takayama S, Horiuchi Y, Toyama Y (2003) MR imaging in the diagnosis of denervated and reinnervated skeletal muscles: experimental study in rats. Radiology 229(3):861–867

    Google Scholar 

  • Kline DG (2012) Chapter 16 – Operative neurophysiology of the brachial plexus intraoperative electrodiagnostic studies. In: Chung KC, Yang LJS, McGillicuddy JE (eds) Practical management of pediatric and adult brachial plexus palsies. W.B. Saunders, Philadelphia, pp 212–219

    Google Scholar 

  • Kline DG, Happel LT (1993) Penfield Lecture. A quarter century’s experience with intraoperative nerve action potential recording. Can J Neurol Sci 20(1):3–10

    Google Scholar 

  • Kobayashi J, Mackinnon SE, Watanabe O, Ball DJ, Gu XM, Hunter DA, Kuzon WM Jr (1997) The effect of duration of muscle denervation on functional recovery in the rat model. Muscle Nerve 20(7):858–866

    Google Scholar 

  • Koltzenburg M, Bendszus M (2004) Imaging of peripheral nerve lesions. Curr Opin Neurol 17(5):621–626

    Google Scholar 

  • Kostrominova T, Dow D, Dennis R, Miller R, Faulkner JA (2005) Comparison of gene expression of 2-mo denervated, 2-mo stimulated-denervated, and control rat skeletal muscles. Physiolo Genom 22:227–243

    Google Scholar 

  • Kraft GH (1990) Fibrillation potential amplitude and muscle atrophy following peripheral nerve injury. Muscle Nerve 13(9):814–821

    Google Scholar 

  • Krarup C, Boeckstyns M, Ibsen A, Moldovan M, Archibald S (2016) Remodeling of motor units after nerve regeneration studied by quantitative electromyography. Clin Neurophysiol 127(2):1675–1682

    Google Scholar 

  • Kullmer K, Sievers KW, Reimers CD, Rompe JD, Muller-Felber W, Nagele M, Harland U (1998) Changes of sonographic, magnetic resonance tomographic, electromyographic, and histopathologic findings within a 2-month period of examinations after experimental muscle denervation. Arch Orthop Trauma Surg 117(4-5):228–234

    Google Scholar 

  • Kuntz C t, Blake L, Britz G, Filler A, Hayes CE, Goodkin R, Tsuruda J, Maravilla K, Kliot M (1996) Magnetic resonance neurography of peripheral nerve lesions in the lower extremity. Neurosurgery 39(4):750–756. discussion 756-757

    Google Scholar 

  • Lawson VH, Gordon Smith A, Bromberg MB (2003) Assessment of axonal loss in Charcot-Marie-Tooth neuropathies. Exp Neurol 184(2):753–757

    Google Scholar 

  • Lee SK, Wolfe SW (2000) Peripheral nerve injury and repair. J Am Acad Orthop Surg 8(4):243–252

    Google Scholar 

  • Lee MB, David AH, Rajiv M, Erin W, Marco V (2004) Neurogenic motor evoked potentials: role in brachial plexus surgery. Neurosurg Focus FOC 16(5):607–610

    Google Scholar 

  • Li X, Chen J, Hong G, Sun C, Wu X, Peng MJ, Zeng G (2013) In vivo DTI longitudinal measurements of acute sciatic nerve traction injury and the association with pathological and functional changes. Eur J Radiol 82(11):e707–e714

    Google Scholar 

  • Li R, Liu Z, Pan Y, Chen L, Zhang Z, Lu L (2014) Peripheral nerve injuries treatment: a systematic review. Cell Biochem Biophys 68(3):449–454

    Google Scholar 

  • Lowitzsch K, Hopf HC, Galland J (1977) Changes of sensory conduction velocity and refractory periods with decreasing tissue temperature in man. J Neurol 216(3):181–188

    Google Scholar 

  • Lubinska L (1982) Patterns of Wallerian degeneration of myelinated fibres in short and long peripheral stumps and in isolated segments of rat phrenic nerve. Interpretation of the role of axoplasmic flow of the trophic factor. Brain Res 233(2):227–240

    Google Scholar 

  • Ma J, Shen J, Lee CA, Elsaidi GA, Smith TL, Walker FO, Rushing JT, Tan KH, Koman LA, Smith BP (2005) Gene expression of nAChR, SNAP-25 and GAP-43 in skeletal muscles following botulinum toxin A injection: a study in rats. J Orthop Res 23(2):302–309

    Google Scholar 

  • Ma J, Shen J, Garrett JP, Lee CA, Li Z, Elsaidi GA, Ritting A, Hick J, Tan KH, Smith TL, Smith BP, Koman LA (2007) Gene expression of myogenic regulatory factors, nicotinic acetylcholine receptor subunits, and GAP-43 in skeletal muscle following denervation in a rat model. J Orthop Res 25(11):1498–1505

    Google Scholar 

  • MacAvoy MC, Green DP (2007) Critical reappraisal of Medical Research Council muscle testing for elbow flexion. J Hand Surg Am 32(2):149–153

    Google Scholar 

  • Macdonald WM (1918) Tinel's sign in peripheral nerve lesions. Br Med J 2(3001):6–8

    Google Scholar 

  • Mackinnon, S. E. and A. L. Dellon (1988). Surgery of the peripheral nerve. New York; Stuttgart; New York, Thieme Medical Publishers ; G. Thieme Verlag. 

    Google Scholar 

  • Mackinnon SE, Novak CB, Myckatyn TM, Tung TH (2005) Results of reinnervation of the biceps and brachialis muscles with a double fascicular transfer for elbow flexion. J Hand Surg 30(5):978–985

    Google Scholar 

  • Maglioni S, Giraldo DL, Duarte J, Velasco N, Romero E (2018) Description of brain volumetric changes in Alzheimer disease using region-based morphometry. SPIE, 14th International Symposium on Medical Information Processing and Analysis, Mazatlán, Mexico

    Google Scholar 

  • Mallik A, Weir AI (2005) Nerve conduction studies: essentials and pitfalls in practice. J Neurol Neurosurg Psychiatry 76(suppl 2):ii23–ii31

    Google Scholar 

  • Mansukhani KA (2013) Electrodiagnosis in traumatic brachial plexus injury. Ann Indian Acad Neurol 16(1):19–25

    Google Scholar 

  • Mar FM, Bonni A, Sousa MM (2014) Cell intrinsic control of axon regeneration. EMBO Rep 15(3):254–263

    Google Scholar 

  • Maravilla KR, Bowen BC (1998) Imaging of the peripheral nervous system: evaluation of peripheral neuropathy and plexopathy. AJNR Am J Neuroradiol 19(6):1011–1023

    Google Scholar 

  • McComas AJ, Fawcett PRW, Campbell MJ, Sica REP (1971) Electrophysiological estimation of the number of motor units within a human muscle. J Neurol Neurosurg Psychiatry 34(2):121

    Google Scholar 

  • McDonnell M (2008) Action research arm test. Aust J Physiother 54(3):220

    Google Scholar 

  • Mendler L, Pintér S, Kiricsi M, Baka Z, Dux L (2007) Regeneration of reinnervated rat soleus muscle is accompanied by fiber transition toward a faster phenotype. J Histochemi Cytochem 56(2):111–123

    Google Scholar 

  • Menorca RMG, Fussell TS, Elfar JC (2013) Nerve physiology: mechanisms of injury and recovery. Hand Clin 29(3):317–330

    Google Scholar 

  • Mercredi M, Vincent TJ, Bidinosti CP, Martin M (2017) Assessing the accuracy of using oscillating gradient spin echo sequences with AxCaliber to infer micron-sized axon diameters. Magma 30(1):1–14

    Google Scholar 

  • Miledi R, Slater CR (1970) On the degeneration of rat neuromuscular junctions after nerve section. J Physiol 207(2):507–528

    Google Scholar 

  • Millesi H (1985) Peripheral nerve repair: terminology, questions, and facts. J Reconstr Microsurg 2(1):21–31

    Google Scholar 

  • Mitolo M, Stanzani-Maserati M, Capellari S, Testa C, Rucci P, Poda R, Oppi F, Gallassi R, Sambati L, Rizzo G, Parchi P, Evangelisti S, Talozzi L, Tonon C, Lodi R, Liguori R (2019) Predicting conversion from mild cognitive impairment to Alzheimer's disease using brain (1)H-MRS and volumetric changes: a two- year retrospective follow-up study. Neuroimage Clin 23:101843

    Google Scholar 

  • Morisaki S, Kawai Y, Umeda M, Nishi M, Oda R, Fujiwara H, Yamada K, Higuchi T, Tanaka C, Kawata M, Kubo T (2011) In vivo assessment of peripheral nerve regeneration by diffusion tensor imaging. J Magn Reson Imaging 33(3):535–542

    Google Scholar 

  • Moser T, Kremer S, Holl N (2009) Imagerie du nerf peripherique: anatomie, techniques d’exploration et principales pathologies. J Radiol 90(10):1448

    Google Scholar 

  • Murphy P, Koh DM (2010) Imaging in clinical trials. Cancer Imaging 10(1A):S74–S82

    Google Scholar 

  • Mydlarz WK, Boahene KO (2013) Sunderland classification of nerve injury. In: Kountakis SE (ed) Encyclopedia of otolaryngology, head and neck surgery. Springer, Berlin/Heidelberg, pp 2615–2616

    Google Scholar 

  • Nandedkar SD, Barkhaus PE (2007) Contribution of reference electrode to the compound muscle action potential. Muscle Nerve 36(1):87–92

    Google Scholar 

  • Nandedkar SD, Nandedkar DS, Barkhaus PE, Stalberg EV (2004) Motor unit number index (MUNIX). IEEE Trans Biomed Eng 51(12):2209–2211

    Google Scholar 

  • Navarro X (2016) Functional evaluation of peripheral nerve regeneration and target reinnervation in animal models: a critical overview. Eur J Neurosci 43(3):271–286

    Google Scholar 

  • Ohana M, Moser T, Moussaouï A, Kremer S, Carlier RY, Liverneaux P, Dietemann JL (2014) Current and future imaging of the peripheral nervous system. Diagn Interv Imaging 95(1):17–26

    Google Scholar 

  • Panegyres PK, Moore N, Gibson R, Rushworth G, Donaghy M (1993) Thoracic outlet syndromes and magnetic resonance imaging. Brain 116(4):823–841

    Google Scholar 

  • Parsons EC Jr, Does MD, Gore JC (2006) Temporal diffusion spectroscopy: theory and implementation in restricted systems using oscillating gradients. Magn Reson Med 55(1):75–84

    Google Scholar 

  • Pavlov S, Grosheva M, Streppel M, Guntinas-Lichius O, Irintchev A, Skouras E, Angelova S, Kuerten S, Sinis N, Dunlop S, Angelov D (2008) Manually-stimulated recovery of motor function after facial nerve injury requires intact sensory input. Experimental neurology 211:292–300

    Google Scholar 

  • Petrone PM, Casamitjana A, Falcon C, Artigues M, Operto G, Skouras S, Cacciaglia R, Molinuevo JL, Vilaplana V, Gispert JD, Salvadó G (2018) Characteristic brain volumetric changes in the AD preclinical signature. Alzheimers Dement 14(7):P1235

    Google Scholar 

  • Pette D, Vrbova G (1985) Neural control of phenotypic expression in mammalian muscle fibers. Muscle Nerve 8(8):676–689

    Google Scholar 

  • Polak JF, Jolesz FA, Adams DF (1988) Magnetic resonance imaging of skeletal muscle. Prolongation of T1 and T2 subsequent to denervation. Invest Radiol 23(5):365–369

    Google Scholar 

  • Power GA, Dalton BH, Behm DG, Doherty TJ, Vandervoort AA, Rice CL (2012) Motor unit survival in lifelong runners is muscle dependent. Med Sci Sports Exerc 44(7):1235–1242

    Google Scholar 

  • Quick TJ, Singh AK, Fox M, Sinisi M, MacQuillan A (2016) A quantitative assessment of the functional recovery of flexion of the elbow after nerve transfer in patients with a brachial plexus injury. Bone Joint J 98-B(11):1517–1520

    Google Scholar 

  • Rainey EE, Petrey LB, Reynolds M, Agtarap S, Warren AM (2014) Psychological factors predicting outcome after traumatic injury: the role of resilience. Am J Surg 208(4):517–523

    Google Scholar 

  • Rayner MLD, Brown HL, Wilcox M, Phillips JB, Quick TJ (2019) Quantifying regeneration in patients following peripheral nerve injury. J Plast Reconstr Aesthet Surg 73(2):201–208

    Google Scholar 

  • Robert MB, Peggy M, Jean MM, Frank PH (1995) Continuous intraoperative electromyographic recording during spinal surgery. J Neurosurg 82(3):401–405

    Google Scholar 

  • Ronchi G, Raimondo S (2017) Chronically denervated distal nerve stump inhibits peripheral nerve regeneration. Neural Regen Res 12(5):739–740

    Google Scholar 

  • Rose D, Kurtis IA, Cynthia TC, John WE, Philip RW (2010) Magnetic resonance neurography for the evaluation of peripheral nerve, brachial plexus, and nerve root disorders. J Neurosurg 112(2):362–371

    Google Scholar 

  • Rosen B, Lundborg G (2003) A new model instrument for outcome after nerve repair. Hand Clin 19(3):463–470

    Google Scholar 

  • Rotshenker S (2011) Wallerian degeneration: the innate-immune response to traumatic nerve injury. J Neuroinflammation 8:109–109

    Google Scholar 

  • Saadat S, Eslami V, Rahimi-Movaghar V (2011) The incidence of peripheral nerve injury in trauma patients in Iran. Ulusal travma ve acil cerrahi dergisi = Turk J Trauma Emerg Surg 17(6):539–544

    Google Scholar 

  • Saito H, Dahlin LB (2008) Expression of ATF3 and axonal outgrowth are impaired after delayed nerve repair. BMC Neurosci 9(1):88–88

    Google Scholar 

  • Scheib J, Hoke A (2013) Advances in peripheral nerve regeneration. Nat Rev Neurol 9(12):668–676

    Google Scholar 

  • Seddon HJB (1943) Three types of nerve injury. Brain 66(4):237–288

    Google Scholar 

  • Seddon HJ, Medawar PB, Smith H (1943) Rate of regeneration of peripheral nerves in man. J Physiol 102(2):191–215

    Google Scholar 

  • Seitz M, Grosheva M, Skouras E, Angelova SK, Ankerne J, Jungnickel J, Grothe C, Klimaschewski L, Hübbers C, Dunlop S, Angelov D (2011) Poor functional recovery and muscle polyinnervation after facial nerve injury in fibroblast growth factor-2−/− mice can be improved by manual stimulation of denervated vibrissal muscles. Neuroscience 182:241–247

    Google Scholar 

  • Seror P (2017) Neuralgic amyotrophy. An update. Joint Bone Spine 84(2):153–158

    Google Scholar 

  • Severinsen K, Jakobsen J (2009) Chromatolysis. In: Binder MD, Hirokawa N, Windhorst U (eds) Encyclopedia of neuroscience. Springer, Berlin/Heidelberg, pp 714–716

    Google Scholar 

  • Shemesh N, Alvarez GA, Frydman L (2015) Size distribution imaging by non-uniform oscillating-gradient spin echo (NOGSE) MRI. PLoS One 10(7):e0133201

    Google Scholar 

  • Shen Q, Loewenstein DA, Potter E, Zhao W, Appel J, Greig MT, Raj A, Acevedo A, Schofield E, Barker W, Wu Y, Potter H, Duara R (2011) Volumetric and visual rating of magnetic resonance imaging scans in the diagnosis of amnestic mild cognitive impairment and Alzheimer's disease. Alzheimers Dement 7(4):e101–e108

    Google Scholar 

  • Simon NG, Talbott J, Chin CT, Kliot M (2016) Chapter 40 – Peripheral nerve imaging. In: Masdeu JC, González RG (eds) Handbook of clinical neurology, vol 136. Elsevier, Amsterdam, pp 811–826

    Google Scholar 

  • Slimp JC (2000) Intraoperative monitoring of nerve repairs. Hand Clin 16(1):25–36

    Google Scholar 

  • Smith S, Knight R (2011) Clinical neurophysiology in peripheral nerve Injuries BT. In: Birch R (ed) Surgical disorders of the peripheral nerves. Springer, London, pp 191–229

    Google Scholar 

  • Smith JW, Thesleff S (1976) Spontaneous activity in denervated mouse diaphragm muscle. J Physiol 257(1):171–186

    Google Scholar 

  • Sobotka S, Mu L (2013) Force recovery and axonal regeneration of the sternomastoid muscle reinnervated with the end-to-end nerve anastomosis. J Surg Res 182(2):e51–e59

    Google Scholar 

  • Sollerman C, Ejeskar A (1995) Sollerman hand function test. A standardised method and its use in tetraplegic patients. Scand J Plast Reconstr Surg Hand Surg 29(2):167–176

    Google Scholar 

  • Stalberg E, Falck B (1997) The role of electromyography in neurology. Electroencephalogr Clin Neurophysiol 103(6):579–598

    Google Scholar 

  • Stanisz GJ, Midha R, Munro CA, Henkelman RM (2001) MR properties of rat sciatic nerve following trauma. Magn Reson Med 45(3):415–420

    Google Scholar 

  • Stassart RM, Möbius W, Nave K-A, Edgar JM (2018) The axon-myelin unit in development and degenerative disease. Front Neurosci 12:467

    Google Scholar 

  • Sulaiman W, Gordon T (2013) Neurobiology of peripheral nerve injury, regeneration, and functional recovery: from bench top research to bedside application. Ochsner J 13(1):100–108

    Google Scholar 

  • Sullivan R, Dailey T, Duncan K, Abel N, Borlongan CV (2016) Peripheral nerve injury: stem cell therapy and peripheral nerve transfer. Int J Mol Sci 17(12):2101

    Google Scholar 

  • Sunderland S (1951) A classification of peripheral nerve injuries producing loss of function. Brain 74(4):491–516

    Google Scholar 

  • Sutter M, Eggspuehler A, Muller A, Dvorak J (2007) Multimodal intraoperative monitoring: an overview and proposal of methodology based on 1,017 cases. Eur Spine J 2(Suppl 2):S153–S161

    Google Scholar 

  • Tagliafico A, Tagliafico G, Martinoli C (2010) Nerve density: a new parameter to evaluate peripheral nerve pathology on ultrasound. preliminary study. Ultrasound Med Biol 36(10):1588–1593

    Google Scholar 

  • Takehara I, Chu J, Schwartz I, Aye HH (2004) Motor unit action potential (MUAP) parameters affected by editing duration cursors. Electromyogr Clin Neurophysiol 44(5):265–269

    Google Scholar 

  • Timothy H (2014) Nerve injury: Classification, clinical assessment, investigation, and management. In: Handchirurgie Weltweit e.V (ed) Living textbook of hand surgery. GMS, Cologne

    Google Scholar 

  • Titelbaum DS, Frazier JL, Grossman RI, Joseph PM, Yu LT, Kassab EA, Hickey WF, LaRossa D, Brown MJ (1989) Wallerian degeneration and inflammation in rat peripheral nerve detected by in vivo MR imaging. AJNR Am J Neuroradiol 10(4):741–746

    Google Scholar 

  • Tung TH, Mackinnon SE (2010) Nerve transfers: indications, techniques, and outcomes. J Hand Surg 35(2):332–341

    Google Scholar 

  • Ultee J, Hundepool CA, Nijhuis TH, van Baar AL, Hovius SE (2013) Early posttraumatic psychological stress following peripheral nerve injury: a prospective study. J Plast Reconstr Aesthet Surg 66(10):1316–1321

    Google Scholar 

  • Valero-Cabré A, Navarro X (2001) H reflex restitution and facilitation after different types of peripheral nerve injury and repair. Brain Res 919(2):302–312

    Google Scholar 

  • van Rosmalen M, Lieba-Samal D, Pillen S, van Alfen N (2019) Ultrasound of peripheral nerves in neuralgic amyotrophy. Muscle Nerve 59(1):55–59

    Google Scholar 

  • Viddeleer AR, Sijens PE, van Ooyen PMA, Kuypers PDL, Hovius SER, Oudkerk M (2012) Sequential MR imaging of denervated and reinnervated skeletal muscle as correlated to functional outcome. Radiology 264(2):522–530

    Google Scholar 

  • Visser LH (2006) High-resolution sonography of the common peroneal nerve: detection of intraneural ganglia. Neurology 67(8):1473

    Google Scholar 

  • Voytik SL, Przyborski M, Badylak SF, Konieczny SF (1993) Differential expression of muscle regulatory factor genes in normal and denervated adult rat hindlimb muscles. Dev Dyn 198(3):214–224

    Google Scholar 

  • Waller Augustus V, Owen R (1851) Experiments on the section of the glossopharyngeal and hypoglossal nerves of the frog, and observations of the alterations produced thereby in the structure of their primitive fibres. Abstracts of the papers communicated to the Royal Society of London, vol 5, pp 924–925

    Google Scholar 

  • Wang FC, Delwaide PJ (1995) Number and relative size of thenar motor units estimated by an adapted multiple point stimulation method. Muscle Nerve 18(9):969–979

    Google Scholar 

  • Weinstein S (1993) Fifty years of somatosensory research: from the Semmes-Weinstein monofilaments to the Weinstein Enhanced Sensory Test. J Hand Ther 6(1):11–22; discussion 50

    Google Scholar 

  • Weis J, Kaussen M, Calvo S, Buonanno A (2000) Denervation induces a rapid nuclear accumulation of MRF4 in mature myofibers. Dev Dyn 218(3):438–451

    Google Scholar 

  • Weng LY, Hsieh CL, Tung KY, Wang TJ, Ou YC, Chen LR, Ban SL, Chen WW, Liu CF (2010) Excellent reliability of the Sollerman hand function test for patients with burned hands. J Burn Care Res 31(6):904–910

    Google Scholar 

  • Wessig C, Koltzenburg M, Reiners K, Solymosi L, Bendszus M (2004) Muscle magnetic resonance imaging of denervation and reinnervation: correlation with electrophysiology and histology. Exp Neurol 185(2):254–261

    Google Scholar 

  • Wilcox M, Gregory H, Powell R, Quick TJ, Phillips JB (2020) Strategies for peripheral nerve repair. Curr Tissue Microenviron Rep 1:49–59

    Google Scholar 

  • Willand MP, Chiang CD, Zhang JJ, Kemp SWP, Borschel GH, Gordon T (2015) Daily electrical muscle stimulation enhances functional recovery following nerve transection and repair in rats. Neurorehabil Neural Repair 29(7):690–700

    Google Scholar 

  • Windisch A, Gundersen K, Szabolcs MJ, Gruber H, Lømo T (1998) Fast to slow transformation of denervated and electrically stimulated rat muscle. J Physiol 510(2):623–632

    Google Scholar 

  • Wu P, Chawla A, Spinner RJ, Yu C, Yaszemski MJ, Windebank AJ, Wang H (2014) Key changes in denervated muscles and their impact on regeneration and reinnervation. Neural Regen Res 9(20):1796–1809

    Google Scholar 

  • Yarnitsky D, Sprecher E (1994) Thermal testing: normative data and repeatability for various test algorithms. J Neurol Sci 125(1):39–45

    Google Scholar 

  • Zhao S, Kim DH, Kline DG, Beuerman RW, Thompson HW (1993) Somatosensory evoked potentials induced by stimulating a variable number of nerve fibers in rat. Muscle Nerve 16(11):1220–1227

    Google Scholar 

  • Zivadinov R, Khan N, Medin J, Christoffersen P, Price J, Korn JR, Bonzani I, Dwyer MG, Bergsland N, Carl E, Silva D, Weinstock-Guttman B (2017) An observational study to assess brain MRI change and disease progression in multiple sclerosis clinical practice-the MS-MRIUS study. J Neuroimaging 27(3):339–347

    Google Scholar 

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Authors and Affiliations

  1. Peripheral Nerve Injury Research Unit, Royal National Orthopaedic Hospital, Stanmore, UK

    Matthew Wilcox, Hazel Brown & Tom Quick

  2. UCL Centre for Nerve Engineering, University College London, London, UK

    Matthew Wilcox, Hazel Brown & Tom Quick

  3. Department of Pharmacology, UCL School of Pharmacy, University College London, London, UK

    Matthew Wilcox

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  2. Hazel Brown
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  3. Tom Quick
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Correspondence to Matthew Wilcox .

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Editors and Affiliations

  1. Pharmacology, UCL School of Pharmacy, University College London Pharmacology, UCL School of Pharmacy, London, UK

    James Phillips

  2. Experimentelle u Klinische Traumatologie, Ludwig Boltzmann Institut für, Wien, Wien, Austria

    David Hercher

  3. Trauma Surgery, AUVA Unfallkrankenhaus Lorenz Böhler, Wien, Wien, Austria

    Thomas Hausner

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Wilcox, M., Brown, H., Quick, T. (2020). Clinical Outcome Measures Following Peripheral Nerve Repair. In: Phillips, J., Hercher, D., Hausner, T. (eds) Peripheral Nerve Tissue Engineering and Regeneration. Reference Series in Biomedical Engineering(). Springer, Cham. https://doi.org/10.1007/978-3-030-06217-0_11-1

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