CC BY-NC-ND 4.0 · J Reconstr Microsurg Open 2023; 08(01): e23-e27
DOI: 10.1055/s-0042-1757323
Case Report

A Novel Technique Restores Function while Eliminating Intractable Neuropathic Pain in a 71-Year-Old Diabetic Patient under Challenging Injury Conditions

William F. Micheo
1   Department of Physical Medicine and Rehabilitation, University of Puerto Rico, San Juan, Puerto Rico
,
Christian A. Foy
2   Section of Orthopedic Surgery, University of Puerto Rico, San Juan, Puerto Rico
,
Damien P. Kuffler
3   Institute of Neurobiology, Medical School, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto Rico
› Author Affiliations
Funding None.

Abstract

Background The extent of functional recovery induced in healthy patients by sensory nerve grafts, the clinical “gold standard” technique for repairing peripheral nerves with a gap, is significantly limited by increasing gap length, time between trauma and repair, and patient age. When the values of any two, or all three, variables increase simultaneously, there is little to no recovery. For diabetic patients, even under the best of conditions and without any large variables, the extent of axon regeneration and functional recovery is significantly less, but generally none. Therefore, novel techniques are required that enhance recovery in diabetic patients.

Methods A 12-cm long median nerve gap in the wrist/palm of a 71-year-old male long-term diabetic patient was bridged 1.3 years post nerve injury with a sural nerve graft within a platelet-rich plasma-filled collagen tube.

Results By 2 months post-repair, the patient's level 6 chronic neuropathic pain was permanently eliminated. By 6.75 months, the palm had recovered good sensitivity to stimuli of all sensory modalities, including 4.56 g pressure and less than 15 mm two-point discrimination. Each finger had good motor function of M3–5, with partial to complete sensitivity to stimuli of all sensory modalities and an overall recovery of S3.

Conclusion This technique permanently eliminates severe chronic neuropathic pain while simultaneously inducing good motor and sensory recovery in a long-term diabetic patient, under conditions where recovery is rarely, if ever, seen, even in non-diabetic patients. This technique holds great promise of restoring function to diabetic patients, for whom it is otherwise not possible.



Publication History

Received: 16 October 2021

Accepted: 29 May 2022

Article published online:
28 February 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • References

  • 1 Saito H, Sango K, Horie H. et al. Enhanced neural regeneration from transected vagus nerve terminal in diabetic mice in vitro. Neuroreport 1999; 10 (05) 1025-1028
  • 2 Sango K, Horie H, Saito H. et al. Diabetes is not a potent inducer of neuronal cell death in mouse sensory ganglia, but it enhances neurite regeneration in vitro. Life Sci 2002; 71 (20) 2351-2368
  • 3 Nishida N, Yamagishi S, Mizukami H, Yagihashi S. Impaired nerve fiber regeneration in axotomized peripheral nerves in streptozotocin-diabetic rats. J Diabetes Investig 2013; 4 (06) 533-539
  • 4 Polydefkis M, Hauer P, Sheth S, Sirdofsky M, Griffin JW, McArthur JC. The time course of epidermal nerve fibre regeneration: studies in normal controls and in people with diabetes, with and without neuropathy. Brain 2004; 127 (Pt 7): 1606-1615
  • 5 Pan D, Mackinnon SE, Wood MD. Advances in the repair of segmental nerve injuries and trends in reconstruction. Muscle Nerve 2020; 61 (06) 726-739
  • 6 Hoben GM, Ee X, Schellhardt L. et al. Increasing nerve autograft length increases senescence and reduces regeneration. Plast Reconstr Surg 2018; 142 (04) 952-961
  • 7 Terzis JK, Kokkalis ZT. Outcomes of secondary reconstruction of ulnar nerve lesions: our experience. Plast Reconstr Surg 2008; 122 (04) 1100-1110
  • 8 Matejcík V, Pénzesová G. [Rare compression syndromes of the peripheral nerves of the forearm and distal leg]. Rozhl Chir 2006; 85 (03) 143-147
  • 9 Karabeg R, Jakirlic M, Dujso V. Sensory recovery after forearm median and ulnar nerve grafting. Med Arh 2009; 63 (02) 97-99
  • 10 Singh B, Singh V, Krishnan A. et al. Regeneration of diabetic axons is enhanced by selective knockdown of the PTEN gene. Brain 2014; 137 (Pt 4): 1051-1067
  • 11 Tu NH, Katano T, Matsumura S. et al. Role of c-Jun N-terminal kinase in late nerve regeneration monitored by in vivo imaging of thy1-yellow fluorescent protein transgenic mice. Eur J Neurosci 2016; 43 (04) 548-560
  • 12 Khoshnoodi M, Truelove S, Polydefkis M. Effect of diabetes type on long-term outcome of epidermal axon regeneration. Ann Clin Transl Neurol 2019; 6 (10) 2088-2096
  • 13 Ekström PA, Tomlinson DR. Impaired nerve regeneration in streptozotocin-diabetic rats is improved by treatment with gangliosides. Exp Neurol 1990; 109 (02) 200-203
  • 14 Kornfeld T, Vogt PM, Radtke C. Nerve grafting for peripheral nerve injuries with extended defect sizes. Wien Med Wochenschr 2019; 169 (9-10): 240-251
  • 15 Jonsson S, Wiberg R, McGrath AM. et al. Effect of delayed peripheral nerve repair on nerve regeneration, Schwann cell function and target muscle recovery. PLoS One 2013; 8 (02) e56484
  • 16 Kou Y, Zhang P, Yin X. et al. Influence of different distal nerve degeneration period on peripheral nerve collateral sprouts regeneration. Artif Cells Blood Substit Immobil Biotechnol 2011; 39 (04) 223-227
  • 17 Costales JR, Socolovsky M, Sánchez Lázaro JA, Álvarez García R. Peripheral nerve injuries in the pediatric population: a review of the literature. Part I: traumatic nerve injuries. Childs Nerv Syst 2019; 35 (01) 29-35
  • 18 Grinsell D, Keating CP. Peripheral nerve reconstruction after injury: a review of clinical and experimental therapies. BioMed Res Int 2014; 2014: 698256
  • 19 Fawcett JW, Verhaagen J. Intrinsic determinants of axon regeneration. Dev Neurobiol 2018; 78 (10) 890-897
  • 20 Pacheco A, Merianda TT, Twiss JL, Gallo G. Mechanism and role of the intra-axonal Calreticulin translation in response to axonal injury. Exp Neurol 2020; 323: 113072
  • 21 Painter MW, Brosius Lutz A, Cheng YC. et al. Diminished Schwann cell repair responses underlie age-associated impaired axonal regeneration. Neuron 2014; 83 (02) 331-343
  • 22 Kang H, Lichtman JW. Motor axon regeneration and muscle reinnervation in young adult and aged animals. J Neurosci 2013; 33 (50) 19480-19491
  • 23 Gunin AG, Petrov VV, Golubtzova NN, Vasilieva OV, Kornilova NK. Age-related changes in angiogenesis in human dermis. Exp Gerontol 2014; 55: 143-151
  • 24 Pola R, Aprahamian TR, Bosch-Marcé M. et al. Age-dependent VEGF expression and intraneural neovascularization during regeneration of peripheral nerves. Neurobiol Aging 2004; 25 (10) 1361-1368
  • 25 Kogawa S, Yasuda H, Terada M, Maeda K, Kikkawa R. Apoptosis and impaired axonal regeneration of sensory neurons after nerve crush in diabetic rats. Neuroreport 2000; 11 (04) 663-667
  • 26 Longo FM, Powell HC, Lebeau J, Gerrero MR, Heckman H, Myers RR. Delayed nerve regeneration in streptozotocin diabetic rats. Muscle Nerve 1986; 9 (05) 385-393
  • 27 Sango K, Mizukami H, Horie H, Yagihashi S. Impaired axonal regeneration in diabetes. perspective on the underlying mechanism from in vivo and in vitro experimental studies. Front Endocrinol (Lausanne) 2017; 8: 12
  • 28 Kobayashi M, Zochodne DW. Diabetic neuropathy and the sensory neuron: new aspects of pathogenesis and their treatment implications. J Diabetes Investig 2018; 9 (06) 1239-1254
  • 29 Zochodne DW. Diabetes mellitus and the peripheral nervous system: manifestations and mechanisms. Muscle Nerve 2007; 36 (02) 144-166
  • 30 Kennedy JM, Zochodne DW. The regenerative deficit of peripheral nerves in experimental diabetes: its extent, timing and possible mechanisms. Brain 2000; 123 (Pt 10): 2118-2129
  • 31 Ikeda M, Oka Y. The relationship between nerve conduction velocity and fiber morphology during peripheral nerve regeneration. Brain Behav 2012; 2 (04) 382-390
  • 32 Vakilinia SR, Vaghasloo MA, Aliasl F. et al. Evaluation of the efficacy of warm salt water foot-bath on patients with painful diabetic peripheral neuropathy: a randomized clinical trial. Complement Ther Med 2020; 49: 102325
  • 33 Schreiber AK, Nones CFM, Reis RC, Chichorro JG, Cunha JM. Diabetic neuropathic pain: physiopathology and treatment. World J Diabetes 2015; 6 (03) 432-444
  • 34 Ye F, Li H, Qiao G. et al. Platelet-rich plasma gel in combination with Schwann cells for repair of sciatic nerve injury. Neural Regen Res 2012; 7 (29) 2286-2292
  • 35 Ikumi A, Hara Y, Yoshioka T, Kanamori A, Yamazaki M. Effect of local administration of platelet-rich plasma (PRP) on peripheral nerve regeneration: an experimental study in the rabbit model. Microsurgery 2018; 38 (03) 300-309
  • 36 Sariguney Y, Yavuzer R, Elmas C, Yenicesu I, Bolay H, Atabay K. Effect of platelet-rich plasma on peripheral nerve regeneration. J Reconstr Microsurg 2008; 24 (03) 159-167
  • 37 Küçük L, Günay H, Erbaş O, Küçük Ü, Atamaz F, Coşkunol E. Effects of platelet-rich plasma on nerve regeneration in a rat model. Acta Orthop Traumatol Turc 2014; 48 (04) 449-454
  • 38 Foy C, Micheo W, Kuffler DP. Sensory and motor recovery following the repair of three long nerve gap in a senior patient 2.6 years post-trauma. Plast Reconstr Surg 2021;9(09): In press
  • 39 Kuffler DP, Reyes O, Sosa IJ, Santiago-Figueroa J. Neurological recovery across a 12-cm-long ulnar nerve gap repaired 3.25 years post trauma: case report. Neurosurgery 2011; 69 (06) E1321-E1326
  • 40 Santiago-Figueroa J, Sosa IJ, Reyes O, Guzman H, Hernandez R, Kuffler DP. A novel technique for reducing and eliminating peripheral neuropathic pain: a clinical study. J Pain Manag 2011; 4 (04) 387-394
  • 41 Hassanien M, Elawamy A, Kamel EZ. et al. Perineural platelet-rich plasma for diabetic neuropathic pain, could it make a difference?. Pain Med 2020; 21 (04) 757-765
  • 42 Ikumi A, Hara Y, Okano E. et al. Intraoperative local administration of platelet-rich plasma (prp) during neurolysis surgery for the treatment of digital nerve crush injury. Case Rep Orthop 2018; 2018: 1275713