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J Brachial Plex Peripher Nerve Inj 2012; 07(01): e40-e52
DOI: 10.1186/1749-7221-7-7
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Maripuu et al.; licensee BioMed Central Ltd.

Reconstruction of sciatic nerve after traumatic injury in humans - factors influencing outcome as related to neurobiological knowledge from animal research[*]

Amanda Maripuu
1   Departments of Hand Surgery, Lund University, Lund, Sweden
,
Anders Björkman
1   Departments of Hand Surgery, Lund University, Lund, Sweden
,
Isabella M Björkman-Burtscher
2   Radiology, Lund University, Lund, Sweden
4   BioImaging Center and Department of Clinical Sciences Malmö, Lund University, Lund, Sweden
,
Peter Mannfolk
2   Radiology, Lund University, Lund, Sweden
,
Gert Andersson
3   Neurophysiology, Skåne University Hospital Malmö and Lund, Lund, Sweden
,
Lars B Dahlin
1   Departments of Hand Surgery, Lund University, Lund, Sweden
5   Department of Hand Surgery, Skåne University Hospital, SE-205 02, Malmö, Sweden
› Author Affiliations
Subject Editor:
Further Information

Publication History

07 June 2012

08 October 2012

Publication Date:
24 September 2014 (online)

Also available at
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Abstract

Background The aim was to evaluate what can be learned from rat models when treating patients suffering from a sciatic nerve injury.

Methods Two patients with traumatic sciatic nerve injury are presented with examination of motor and sensory function with a five-year follow-up. Reconstruction of the nerve injury was performed on the second and third day, respectively, after injury using sural nerve grafts taken from the injured leg. The patients were examined during follow-up by electromyography (EMG), MRI and functionalMRI (fMRI) to evaluate nerve reinnervation, cell death in dorsal root ganglia (DRG) and cortical activation; factors that were related to clinical history in the patients.

Results One patient regained good motor function of the lower leg and foot, confirmed by EMG showing good activation in the leg muscles and some reinnervation in the foot muscles, as well as some sensory function of the sole of the foot. The other patient regained no motor (confirmed by EMG) or sensory function in the leg or foot. Factors most influential on outcome in two cases were type of injury, nerve gap length and particularly type of reconstruction. A difference in follow-up and rehabilitation likely also influence outcome. MRI did not show any differences in DRG size of injured side compared to the uninjured side. fMRI showed normal activation in the primary somatosensory cortex as a response to cutaneous stimulation of the normal foot. However, none of the two patients showed any activation in the primary somatosensory cortex following cutaneous stimulation of the injured foot.

Conclusions In decision making of nerve repair and reconstruction data from animal experiments can be translated to clinical practice and to predict outcome in patients, although such data should be interpreted with caution and linked to clinical experience. Rat models may be useful to identify and study factors that influence outcome after peripheral nerve repair and reconstruction; procedures that should be done correctly and with a competent team. However, some factors, such as cognitive capacity and coping, known to influence outcome following nerve repair, are difficult to study in animal models. Future research has to find and develop new paths and techniques to study changes in the central nervous system after nerve injury and develop strategies to utilize brain plasticity during the rehabilitation.

Keywords

Sciatic nerve injury - Nerve regeneration - Reconstruction - Outcome - fMRI - Dorsal root ganglia

*This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


 

  • References

  • 1 Asplund M, Nilsson M, Jacobsson A, von Holst H. Incidence of traumatic peripheral nerve injuries and amputations in Sweden between 1998 and 2006. Neuroepidemiology 2009; 32: 217-228 10.1159/000197900 19174611
    CrossrefPubMedGoogle Scholar
  • 2 Lundborg G. A 25-year perspective of peripheral nerve surgery: Evolving neuroscientific concepts and clinical significance. J Hand Surg (Am) 2000; 25A: 391-414
    PubMedGoogle Scholar
  • 3 Kline DG, Kim D, Midha R, Harsh C, Tiel R. Management and results of sciatic nerve injuries: a 24-year experience. J Neurosurg 1998; 89: 13-23 10.3171/jns.1998.89.1.0013 9647167
    CrossrefPubMedGoogle Scholar
  • 4 Rosberg HE, Carlsson KS, Hojgard S, Lindgren B, Lundborg G, Dahlin LB. Injury to the human median and ulnar nerves in the forearm–analysis of costs for treatment and rehabilitation of 69 patients in southern Sweden. J Hand Surg (Br) 2005; 30: 35-39 10.1016/j.jhsb.2004.09.003
    PubMedGoogle Scholar
  • 5 Abrams M, Widenfalk J. Emerging strategies to promote improved functional outcome after peripheral nerve injury. Restor Neurol Neuros 2005; 23: 367-382
    PubMedGoogle Scholar
  • 6 Ruijs ACJ, Jaquet JB, Kalmijn S, Giele H, Hovius SER. Median and ulnar nerve injuries: a meta analysis of predictors of motor and sensory recovery after modern microsurgical nerve repair. Plast Reconstr Surg 2005; 116: 484-494 10.1097/01.prs.0000172896.86594.07 16079678
    CrossrefPubMedGoogle Scholar
  • 7 Lundborg G, Rosen B. Hand function after nerve repair. Acta Physiol (Oxf) 2007; 189: 207-217 10.1111/j.1748-1716.2006.01653.x
    CrossrefPubMedGoogle Scholar
  • 8 Dahlin LB. The nerve response to injury. In: Slutsky DJ. Upper Extremity Nerve Repair - Tips and Techniques: Master Skills Publication. American Society for Surgery of the Hand; Rosemont, Il, US: 2008: 15-28
    Google Scholar
  • 9 Raivich G, Makwana M. The making of successful axonal regeneration: genes, molecules and signal transduction pathways. Brain Res Rev 2007; 53: 287-311 10.1016/j.brainresrev.2006.09.005 17079020
    CrossrefPubMedGoogle Scholar
  • 10 Hanz S, Fainzilber M. Retrograde signaling in injured nerve–the axon reaction revisited. J Neurochem 2006; 99: 13-19 10.1111/j.1471-4159.2006.04089.x 16899067
    CrossrefPubMedGoogle Scholar
  • 11 Zhou FQ, Cohan CS. How actin filaments and microtubules steer growth cones to their targets. J Neurobiol 2004; 58: 84-91 10.1002/neu.10278 14598372
    CrossrefPubMedGoogle Scholar
  • 12 Hall SM. The biology of chronically denervated Schwann cells. Ann N Y Acad Sci 1999; 883: 215-233 10.1111/j.1749-6632.1999.tb08584.x 10586247
    CrossrefPubMedGoogle Scholar
  • 13 Stoll G, Jander S, Myers RR. Degeneration and regeneration of the peripheral nervous system: from Augustus Waller’s observations to neuroinflammation. J Peripher Nerv Syst 2002; 7: 13-27 10.1046/j.1529-8027.2002.02002.x 11939348
    CrossrefPubMedGoogle Scholar
  • 14 Saito H, Kanje M, Dahlin LB. Crossed over repair of the femoral sensory and motor branches influences N-CAM. Neuroreport 2010; 21: 841-845 10.1097/WNR.0b013e32833d40e2 20622691
    CrossrefPubMedGoogle Scholar
  • 15 Saito H, Kanje M, Dahlin LB. Delayed nerve repair increases number of caspase 3 stained Schwann cells. Neurosci Lett 2009; 456: 30-33 10.1016/j.neulet.2009.03.075 19429128
    CrossrefPubMedGoogle Scholar
  • 16 Li L, Houenou LJ, Wu W, Lei M, Prevette DM, Oppenheim RW. Characterization of spinal motoneuron degeneration following different types of peripheral nerve injury in neonatal and adult mice. J Comp Neurol 1998; 396: 158-168 10.1002/(SICI)1096-9861(19980629)396:2<158::AID-CNE2>3.0.CO;2-# 9634139
    CrossrefPubMedGoogle Scholar
  • 17 Tsuda Y, Kanje M, Dahlin LB. Axonal outgrowth is associated with increased ERK 1/2 activation but decreased caspase 3 linked cell death in Schwann cells after immediate nerve repair in rats. BMC Neurosci 2011; 12: 12 3031266 21251262
    CrossrefPubMedGoogle Scholar
  • 18 West CA, Davies KA, Hart AM, Wiberg M, Williams SR, Terenghi G. Volumetric magnetic resonance imaging of dorsal root ganglia for the objective quantitative assessment of neuron death after peripheral nerve injury. Exp Neurol 2007; 203: 22-33 10.1016/j.expneurol.2006.07.013 16950259
    CrossrefPubMedGoogle Scholar
  • 19 Rosen B, Lundborg G, Dahlin LB, Holmberg J, Karlson B. Nerve repair: correlation of restitution of functional sensibility with specific cognitive capacities. J Hand Surg (Br) 1994; 19: 452-458 10.1016/0266-7681(94)90209-7
    CrossrefPubMedGoogle Scholar
  • 20 Lundborg G, Rosen B. Sensory relearning after nerve repair. Lancet 2001; 358: 809-810 10.1016/S0140-6736(01)06001-9 11564490
    CrossrefPubMedGoogle Scholar
  • 21 Lundborg G. Nerve injury and repair: regeneration, reconstruction, and cortical remodeling. Elsevier/Churchill Livingstone; Philadelphia: 2004
    Google Scholar
  • 22 Jivan S, Kumar N, Wiberg M, Kay S. The influence of pre-surgical delay on functional outcome after reconstruction of brachial plexus injuries. J Plast Reconstr Aesthet Surg 2009; 62: 472-479 10.1016/j.bjps.2007.11.027 18485850
    CrossrefPubMedGoogle Scholar
  • 23 Jivan S, Novikova LN, Wiberg M, Novikov LN. The effects of delayed nerve repair on neuronal survival and axonal regeneration after seventh cervical spinal nerve axotomy in adult rats. Exp Brain Res 2006; 170: 245-254 10.1007/s00221-005-0207-7 16328277
    CrossrefPubMedGoogle Scholar
  • 24 Saito H, Dahlin LB. Expression of ATF3 and axonal outgrowth are impaired after delayed nerve repair. BMC Neurosci 2008; 9: 88 10.1186/1471-2202-9-88 2556676 18801180
    CrossrefPubMedGoogle Scholar
  • 25 Ray WZ, Mackinnon SE. Management of nerve gaps: autografts, allografts, nerve transfers, and end-to-side neurorrhaphy. Exp Neurol 2010; 223: 77-85 10.1016/j.expneurol.2009.03.031 2849924 19348799
    CrossrefPubMedGoogle Scholar
  • 26 Robert EG, Happel LT, Kline DG. Intraoperative nerve action potential recordings: technical considerations, problems, and pitfalls. Neurosurgery 2009; 65: A97-A104 10.1227/01.NEU.0000347473.67188.75 19927087
    CrossrefPubMedGoogle Scholar
  • 27 Kobayashi J, Mackinnon SE, Watanabe O, Ball DJ, Gu XM, Hunter DA, Kuzon Jr WM. The effect of duration of muscle denervation on functional recovery in the rat model. Muscle Nerve 1997; 20: 858-866 10.1002/(SICI)1097-4598(199707)20:7<858::AID-MUS10>3.0.CO;2-O 9179158
    CrossrefPubMedGoogle Scholar
  • 28 Aird RB, Naffziger HC. The pathology of human striated muscle following denervation. J Neurosurg 1953; 10: 216-227 10.3171/jns.1953.10.3.0216 13053251
    CrossrefPubMedGoogle Scholar
  • 29 Tung TH, Mackinnon SE. Nerve transfers: indications, techniques, and outcomes. J Hand Surg (Am) 2010; 35: 332-341 10.1016/j.jhsa.2009.12.002
    CrossrefPubMedGoogle Scholar
  • 30 Kim DH, Murovic JA, Tiel R, Kline DG. Management and outcomes in 353 surgically treated sciatic nerve lesions. J Neurosurg 2004; 101: 8-17 10.3171/jns.2004.101.1.0008 15255245
    CrossrefPubMedGoogle Scholar
  • 31 Yi C, Dahlin LB. Impaired nerve regeneration and Schwann cell activation after repair with tension. Neuroreport 2010; 21: 958-962 10.1097/WNR.0b013e32833e787f 20729767
    CrossrefPubMedGoogle Scholar
  • 32 Dahlin LB. Techniques of peripheral nerve repair. Scand J Surg 2008; 97: 310-316 19211385
    PubMedGoogle Scholar
  • 33 Moradzadeh A, Borschel GH, Luciano JP, Whitlock EL, Hayashi A, Hunter DA, Mackinnon SE. The impact of motor and sensory nerve architecture on nerve regeneration. Exp Neurol 2008; 212: 370-376 10.1016/j.expneurol.2008.04.012 2761727 18550053
    CrossrefPubMedGoogle Scholar
  • 34 Nichols CM, Brenner MJ, Fox IK, Tung TH, Hunter DA, Rickman SR, Mackinnon SE. Effect of motor versus sensory nerve grafts on peripheral nerve regeneration. Exp Neurol 2004; 190: 347-355 10.1016/j.expneurol.2004.08.003 15530874
    CrossrefPubMedGoogle Scholar
  • 35 Kvist M, Lemplesis V, Kanje M, Ekberg H, Corbascio M, Dahlin LB. Immunomodulation by costimulation blockade inhibits rejection of nerve allografts. J Peripher Nerv Syst 2007; 12: 83-90 10.1111/j.1529-8027.2007.00126.x 17565532
    CrossrefPubMedGoogle Scholar
  • 36 Kvist M, Kanje M, Ekberg H, Corbascio M, Dahlin LB. Costimulation blockade in transplantation of nerve allografts: long-term effects. J Peripher Nerv Syst 2008; 13: 200-207 10.1111/j.1529-8027.2008.00178.x 18844786
    CrossrefPubMedGoogle Scholar
  • 37 Sondell M, Lundborg G, Kanje M. Regeneration of the rat sciatic nerve into allografts made acellular through chemical extraction. Brain Res 1998; 795: 44-54 10.1016/S0006-8993(98)00251-0 9622591
    CrossrefPubMedGoogle Scholar
  • 38 Millesi H, Schmidhammer R. End-to-side coaptation–controversial research issue or important tool in human patients. Acta Neurochir Suppl 2007; 100: 103-106 10.1007/978-3-211-72958-8_22 17985556
    PubMedGoogle Scholar
  • 39 Oberlin C, Durand S, Belheyar Z, Shafi M, David E, Asfazadourian H. Nerve transfers in brachial plexus palsies. Chir Main 2009; 28: 1-9 10.1016/j.main.2008.11.010 19162520
    CrossrefPubMedGoogle Scholar
  • 40 Kerns JM, Danielsen N, Holmquist B, Kanje M, Lundborg G. The influence of predegeneration on regeneration through peripheral nerve grafts in the rat. Exp Neurol 1993; 122: 28-36 10.1006/exnr.1993.1104 8339787
    CrossrefPubMedGoogle Scholar
  • 41 Danielsen N, Kerns JM, Holmquist B, Zhao Q, Lundborg G, Kanje M. Pre-degenerated nerve grafts enhance regeneration by shortening the initial delay period. Brain Res 1994; 666: 250-254 10.1016/0006-8993(94)90779-X 7882035
    CrossrefPubMedGoogle Scholar
  • 42 Miloro M, Stoner JA. Subjective outcomes following sural nerve harvest. J Oral Maxil Surg 2005; 63: 1150-1154 10.1016/j.joms.2005.04.031
    CrossrefPubMedGoogle Scholar
  • 43 Ijpma FFA, Nicolai JPA, Meek MF. Sural nerve donor-site morbidity - Thirty-four years of follow-up. Ann Plas Surg 2006; 57: 391-395 10.1097/01.sap.0000221963.66229.b6
    CrossrefPubMedGoogle Scholar
  • 44 Hamilton SK, Hinkle ML, Nicolini J, Rambo LN, Rexwinkle AM, Rose SJ, Sabatier MJ, Backus D, English AW. Misdirection of regenerating axons and functional recovery following sciatic nerve injury in rats. J Comp Neurol 2011; 519: 21-33 10.1002/cne.22446 21120925
    CrossrefPubMedGoogle Scholar
  • 45 Kaas JH. Plasticity of sensory and motor maps in adult mammals. Annu Rev Neurosci 1991; 14: 137-167 10.1146/annurev.ne.14.030191.001033 2031570
    CrossrefPubMedGoogle Scholar
  • 46 Valero-Cabre A, Navarro X. Functional impact of axonal misdirection after peripheral nerve injuries followed by graft or tube repair. J Neurotrauma 2002; 19: 1475-1485 10.1089/089771502320914705 12490012
    CrossrefPubMedGoogle Scholar
  • 47 Ijkema-Paassen J, Meek MF, Gramsbergen A. Reinnervation of muscles after transection of the sciatic nerve in adult rats. Muscle Nerve 2002; 25: 891-897 10.1002/mus.10130 12115979
    CrossrefPubMedGoogle Scholar
  • 48 Wall JT, Kaas JH, Sur M, Nelson RJ, Felleman DJ, Merzenich MM. Functional reorganization in somatosensory cortical areas 3b and 1 of adult monkeys after median nerve repair: possible relationships to sensory recovery in humans. J Neurosci 1986; 6: 218-233 3944620
    PubMedGoogle Scholar
  • 49 Navarro X. Chapter 27: neural plasticity after nerve injury and regeneration. Int Rev Neurobiol 2009; 87: 483-505 19682656
    PubMedGoogle Scholar
  • 50 Lang EM, Borges J, Carlstedt T. Surgical treatment of lumbosacral plexus injuries. J Neurosurg Spine 2004; 1: 64-71 10.3171/spi.2004.1.1.0064 15291023
    CrossrefPubMedGoogle Scholar
  • 51 Wienbruch C, Candia V, Svensson J, Kleiser R, Kollias SS. A portable and low-cost fMRI compatible pneumatic system for the investigation of the somatosensensory system in clinical and research environments. Neurosci Lett 2006; 398: 183-188 10.1016/j.neulet.2006.01.025 16469438
    CrossrefPubMedGoogle Scholar
  • 52 Weibull A, Bjorkman A, Hall H, Rosen B, Lundborg G, Svensson J. Optimizing the mapping of finger areas in primary somatosensory cortex using functional MRI. Magn Reson Imaging 2008; 26: 1342-1351 10.1016/j.mri.2008.04.007 18550314
    CrossrefPubMedGoogle Scholar
  • 53 Miyauchi A, Kanje M, Danielsen N, Dahlin LB. Role of macrophages in the stimulation and regeneration of sensory nerves by transposed granulation tissue and temporal aspects of the response. Scand J Plast Reconstr Surg Hand Surg 1997; 31: 17-23 10.3109/02844319709010501 9075284
    CrossrefPubMedGoogle Scholar
  • 54 Brooks DN, Weber RV, Chao JD, Rinker BD, Zoldos J, Robichaux MR, Ruggeri SB, Anderson KA, Bonatz EE, Wisotsky SM, Cho MS, Wilson C, Cooper EO, Ingari JV, Safa B, Parrett BM, Buncke GM. Processed nerve allografts for peripheral nerve reconstruction: a multicenter study of utilization and outcomes in sensory, mixed, and motor nerve reconstructions. Microsurgery 2012; 32: 1-14 10.1002/micr.20975 22121093
    CrossrefPubMedGoogle Scholar
  • 55 Howe DW, Hansen ST. Immediate nailing of open fractures of the femoral shaft. J Bone Joint Surg (Am) 1988; 70: 812-820
    PubMedGoogle Scholar
  • 56 Terenghi G, Hart A, Wiberg M. The nerve injury and the dying neurons: diagnosis and prevention. J Hand Surg Eur Vol 2011; 36: 730-734 10.1177/1753193411422202 22058229
    CrossrefPubMedGoogle Scholar
  • 57 Castillo M, Mukherji SK. MRI of enlarged dorsal ganglia, lumbar nerve roots, and cranial nerves in polyradiculoneuropathies. Neuroradiology 1996; 38: 516-520 10.1007/BF00626085 8880708
    CrossrefPubMedGoogle Scholar
  • 58 West CA, McKay Hart A, Terenghi G, Wiberg M. Sensory neurons of the human brachial plexus: a quantitative study employing optical fractionation and in vivo volumetric magnetic resonance imaging. Neurosurgery 2012; 70: 1183-1194 discussion 1194 10.1227/NEU.0b013e318241ace1 22095219
    CrossrefPubMedGoogle Scholar
  • 59 Shen J, Wang HY, Chen JY, Liang BL. Morphologic analysis of normal human lumbar dorsal root ganglion by 3D MR imaging. AJNR Am J Neuroradiol 2006; 27: 2098-2103 17110675
    PubMedGoogle Scholar