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J Brachial Plex Peripher Nerve Inj 2010; 05(01): e124-e130
DOI: 10.1186/1749-7221-5-11
Methodology
Milani et al; licensee BioMed Central Ltd.

Progesterone - new therapy in mild carpal tunnel syndrome? Study design of a randomized clinical trial for local therapy[*]

Paolo Milani
1   Dept. Neurological, Neurosurgical and Behavioural Sciences, Neurophysiology Clinic Section, University of Siena, Siena, Italy
2   Service de Physiologie Explorations Fonctionnelles, Hôpital Lariboisière, AP-HP, 2 rue Ambroise-Paré, 75010 Paris, France
3   Université Paris 7 Denis-Diderot, 2 rue Ambroise-Paré, 75010 Paris, France
,
Mauro Mondelli
4   EMG Service, Local Health Unit 7, Siena, Italy
,
Federica Ginanneschi
1   Dept. Neurological, Neurosurgical and Behavioural Sciences, Neurophysiology Clinic Section, University of Siena, Siena, Italy
,
Riccardo Mazzocchio
1   Dept. Neurological, Neurosurgical and Behavioural Sciences, Neurophysiology Clinic Section, University of Siena, Siena, Italy
,
Alessandro Rossi
1   Dept. Neurological, Neurosurgical and Behavioural Sciences, Neurophysiology Clinic Section, University of Siena, Siena, Italy
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Publikationsverlauf

15. Dezember 2009

26. April 2010

Publikationsdatum:
19. September 2014 (online)

   Lizenzen und Reprints

Abstract

Background Local corticosteroid injection for carpal tunnel syndrome (CTS) provides greater clinical improvement in symptoms one month after injection compared to placebo but significant symptom relief beyond one month has not been demonstrated and the relapse of symptoms is possible.

Neuroprotection and myelin repair actions of the progesterone was demonstrated in vivo and in vitro study.

We report the design of a randomized controlled trial for the local injection of cortisone versus progesterone in “mild” idiopathic CTS.

Methods Sixty women with age between 18 and 60 years affected by “mild” idiopathic CTS, diagnosed on the basis of clinical and electrodiagnostic tests, will be enrolled in one centre. The clinical, electrophysiological and ultasonographic findings of the patients will be evaluate at baseline, 1, 6 and 12 months after injection.

The major outcome of this study is to determine whether locally-injected progesterone may be more beneficial than cortisone in CTS at clinical levels, tested with symptoms severity self-administered Boston Questionnaire and with visual analogue pain scale.

Secondary outcome measures are: duration of experimental therapy; improvement of electrodiagnostic and ultrasonographic anomalies at various follow-up; comparison of the beneficial and harmful effects of the cortisone versus progesterone.

Conclusion We have designed a randomized controlled study to show the clinical effectiveness of local progesterone in the most frequent human focal peripheral mononeuropathy and to demonstrate the neuroprotective effects of the progesterone at the level of the peripheral nervous system in humans.

*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 Bland JD. Treatment of carpal tunnel syndrome. Muscle Nerve 2007; 36: 167-171 10.1002/mus.20802 17534984
    CrossrefPubMedGoogle Scholar
  • 2 Louis DS, Greene TL, Noellert RC. Complications of carpal tunnel surgery. J Neurosurg 1985; 62: 352-356 10.3171/jns.1985.62.3.0352 3973703
    CrossrefPubMedGoogle Scholar
  • 3 Cobb TK, Amadio PC. Reoperation for carpal tunnel syndrome. Hand Clin 1996; 12: 313-323 8724583
    Google Scholar
  • 4 Witt JC, Stevens JC. Neurologic disorders masquerading as carpal tunnel syndrome: 12 cases of failed carpal tunnel release. Mayo Clin Proc 2000; 75: 409-413 10.4065/75.4.409 10761498
    CrossrefPubMedGoogle Scholar
  • 5 Benson LS, Bare AA, Nagle DJ, Harder VS, Williams CS, Visotsky JL. Complications of endoscopic and open carpal tunnel release. Arthroscopy 2006; 22: 919-924 10.1016/j.arthro.2006.05.008 16952718
    CrossrefPubMedGoogle Scholar
  • 6 Braun RM, Rechnic M, Fowler E. Complications related to carpal tunnel release. Hand Clin 2002; 18: 347-357 10.1016/S0749-0712(01)00013-0 12371038
    CrossrefPubMedGoogle Scholar
  • 7 Urbaniak JR, Desai SS. Complications of nonoperative and operative treatment of carpal tunnel syndrome. Hand Clin 1996; 12: 325-335 8724584
    PubMedGoogle Scholar
  • 8 Boya H, Ozcan O, Oztekin HH. Long-term complications of open carpal tunnel release. Muscle Nerve 2008; 38: 1443-1446 10.1002/mus.21068 18949783
    CrossrefPubMedGoogle Scholar
  • 9 Abrams R. Endoscopic versus open carpal tunnel release. J Hand Surg Am 2009; 34: 535-539 10.1016/j.jhsa.2009.01.013 19258154
    CrossrefPubMedGoogle Scholar
  • 10 Vasiliadis HS, Xenakis TA, Mitsionis G, Paschos N, Georgoulis A. Endoscopic versus open carpal tunnel release. Arthroscopy 2010; 26: 26-33 10.1016/j.arthro.2009.06.027 20117624
    CrossrefPubMedGoogle Scholar
  • 11 Marshall S, Tardif G, Ashworth N. Local corticosteroid injection for carpal tunnel syndrome. Cochrane Database Syst Rev 2007; CD001554 17443508
    PubMedGoogle Scholar
  • 12 de Krom MC, Knipschild PG, Kester AD, Thijs CT, Boekkooi PF, Spaans F. Carpal tunnel syndrome: prevalence in the general population. J Clin Epidemiol 1992; 45: 373-376 10.1016/0895-4356(92)90038-O 1569433
    CrossrefPubMedGoogle Scholar
  • 13 Mondelli M, Giannini F, Giacchi M. Carpal tunnel syndrome incidence in a general population. Neurology 2002; 58: 289-294 11805259
    CrossrefPubMedGoogle Scholar
  • 14 Werner RA, Andary M. Carpal tunnel syndrome: pathophysiology and clinical neurophysiology. Clin Neurophysiol 2002; 113: 1373-1381 10.1016/S1388-2457(02)00169-4 12169318
    CrossrefPubMedGoogle Scholar
  • 15 Wilson JR, Sumner AJ. Immediate surgery is the treatment of choice for carpal tunnel syndrome. Muscle Nerve 1995; 18: 660-662 10.1002/mus.880180614 7538629
    CrossrefPubMedGoogle Scholar
  • 16 Gilliat RW. Acute compression block. In: AJ S. The Physiology of Peripheral Nerve Disease. WE Saunders; Philadelphia: 1980: 316-339
    Google Scholar
  • 17 Ochoa J, Marotte L. The nature of the nerve lesion caused by chronic entrapment in the guinea-pig. J Neurol Sci 1973; 19: 491-495 10.1016/0022-510X(73)90045-2 4724822
    CrossrefPubMedGoogle Scholar
  • 18 Marshall S, Tardif G, Ashworth N. Local corticosteroid injection for carpal tunnel syndrome. Cochrane Database Syst Rev 2002; CD001554 12519560
    PubMedGoogle Scholar
  • 19 Piazzini DB, Aprile I, Ferrara PE, Bertolini C, Tonali P, Maggi L, Rabini A, Piantelli S, Padua L. A systematic review of conservative treatment of carpal tunnel syndrome. Clin Rehabil 2007; 21: 299-314 10.1177/0269215507077294 17613571
    CrossrefPubMedGoogle Scholar
  • 20 Wong SM, Hui AC, Tang A, Ho PC, Hung LK, Wong KS, Kay R, Li E. Local vs systemic corticosteroids in the treatment of carpal tunnel syndrome. Neurology 2001; 56: 1565-1567 11402116
    CrossrefPubMedGoogle Scholar
  • 21 Ly-Pen D, Andreu JL, de Blas G, Sanchez-Olaso A, Millan I. Surgical decompression versus local steroid injection in carpal tunnel syndrome: a one-year, prospective, randomized, open, controlled clinical trial. Arthritis Rheum 2005; 52: 612-619 10.1002/art.20767 15692981
    CrossrefPubMedGoogle Scholar
  • 22 Hagebeuk EE, de Weerd AW. Clinical and electrophysiological follow-up after local steroid injection in the carpal tunnel syndrome. Clin Neurophysiol 2004; 115: 1464-1468 10.1016/j.clinph.2004.01.005 15134716
    CrossrefPubMedGoogle Scholar
  • 23 Padua L, Padua R, Aprile I, Pasqualetti P, Tonali P. Multiperspective follow-up of untreated carpal tunnel syndrome: a multicenter study. Neurology 2001; 56: 1459-1466 11402101
    CrossrefPubMedGoogle Scholar
  • 24 Baulieu EE. Neurosteroids: a novel function of the brain. Psychoneuroendocrinology 1998; 23: 963-987 10.1016/S0306-4530(98)00071-7 9924747
    CrossrefPubMedGoogle Scholar
  • 25 Melcangi RC, Cavarretta IT, Ballabio M, Leonelli E, Schenone A, Azcoitia I, Miguel Garcia-Segura L, Magnaghi V. Peripheral nerves: a target for the action of neuroactive steroids. Brain Res Brain Res Rev 2005; 48: 328-338 10.1016/j.brainresrev.2004.12.021 15850671
    CrossrefPubMedGoogle Scholar
  • 26 Schumacher M, Guennoun R, Mercier G, Desarnaud F, Lacor P, Benavides J, Ferzaz B, Robert F, Baulieu EE. Progesterone synthesis and myelin formation in peripheral nerves. Brain Res Brain Res Rev 2001; 37: 343-359 10.1016/S0165-0173(01)00139-4 11744099
    CrossrefPubMedGoogle Scholar
  • 27 Schumacher M, Guennoun R, Robert F, Carelli C, Gago N, Ghoumari A, Gonzalez Deniselle MC, Gonzalez SL, Ibanez C, Labombarda F. Local synthesis and dual actions of progesterone in the nervous system: neuroprotection and myelination. Growth Horm IGF Res 2004; 14 (Suppl A) S18-33 10.1016/j.ghir.2004.03.007 15135772
    CrossrefPubMedGoogle Scholar
  • 28 Wright DW, Kellermann AL, Hertzberg VS, Clark PL, Frankel M, Goldstein FC, Salomone JP, Dent LL, Harris OA, Ander DS et al.: ProTECT: a randomized clinical trial of progesterone for acute traumatic brain injury. Ann Emerg Med 2007; 49: 391-402 10.1016/j.annemergmed.2006.07.932 17011666
    CrossrefPubMedGoogle Scholar
  • 29 Jiang N, Chopp M, Stein D, Feit H. Progesterone is neuroprotective after transient middle cerebral artery occlusion in male rats. Brain Res 1996; 735: 101-107 10.1016/0006-8993(96)00605-1 8905174
    CrossrefPubMedGoogle Scholar
  • 30 Gonzalez SL, Labombarda F, Deniselle MC, Mougel A, Guennoun R, Schumacher M, De Nicola AF. Progesterone neuroprotection in spinal cord trauma involves up-regulation of brain-derived neurotrophic factor in motoneurons. J Steroid Biochem Mol Biol 2005; 94: 143-149 10.1016/j.jsbmb.2005.01.016 15862959
    CrossrefPubMedGoogle Scholar
  • 31 Kovacic U, Zele T, Osredkar J, Sketelj J, Bajrovic FF. Sex-related differences in the regeneration of sensory axons and recovery of nociception after peripheral nerve crush in the rat. Exp Neurol 2004; 189: 94-104 10.1016/j.expneurol.2004.05.015 15296839
    CrossrefPubMedGoogle Scholar
  • 32 Leonelli E, Bianchi R, Cavaletti G, Caruso D, Crippa D, Garcia-Segura LM, Lauria G, Magnaghi V, Roglio I, Melcangi RC. Progesterone and its derivatives are neuroprotective agents in experimental diabetic neuropathy: a multimodal analysis. Neuroscience 2007; 144: 1293-1304 10.1016/j.neuroscience.2006.11.014 17187935
    CrossrefPubMedGoogle Scholar
  • 33 Veiga S, Leonelli E, Beelke M, Garcia-Segura LM, Melcangi RC. Neuroactive steroids prevent peripheral myelin alterations induced by diabetes. Neurosci Lett 2006; 402: 150-153 10.1016/j.neulet.2006.03.058 16626861
    CrossrefPubMedGoogle Scholar
  • 34 Schumacher M, Weill-Engerer S, Liere P, Robert F, Franklin RJ, Garcia-Segura LM, Lambert JJ, Mayo W, Melcangi RC, Parducz A et al.: Steroid hormones and neurosteroids in normal and pathological aging of the nervous system. Prog Neurobiol 2003; 71: 3-29 10.1016/j.pneurobio.2003.09.004 14611864
    CrossrefPubMedGoogle Scholar
  • 35 Melcangi RC, Azcoitia I, Ballabio M, Cavarretta I, Gonzalez LC, Leonelli E, Magnaghi V, Veiga S, Garcia-Segura LM. Neuroactive steroids influence peripheral myelination: a promising opportunity for preventing or treating age-dependent dysfunctions of peripheral nerves. Prog Neurobiol 2003; 71: 57-66 10.1016/j.pneurobio.2003.09.003 14611868
    CrossrefPubMedGoogle Scholar
  • 36 Martini L, Magnaghi V, Melcangi RC. Actions of progesterone and its 5alpha-reduced metabolites on the major proteins of the myelin of the peripheral nervous system. Steroids 2003; 68: 825-829 10.1016/S0039-128X(03)00134-X 14667974
    CrossrefPubMedGoogle Scholar
  • 37 Melcangi RC, Ballabio M, Cavarretta I, Gonzalez LC, Leonelli E, Veiga S, Martini L, Magnaghi V. Effects of neuroactive steroids on myelin of peripheral nervous system. J Steroid Biochem Mol Biol 2003; 85: 323-327 10.1016/S0960-0760(03)00228-0 12943718
    CrossrefPubMedGoogle Scholar
  • 38 Melcangi RC, Leonelli E, Magnaghi V, Gherardi G, Nobbio L, Schenone A. Mifepristone (RU 38486) influences expression of glycoprotein Po and morphological parameters at the level of rat sciatic nerve: in vivo observations. Exp Neurol 2003; 184: 930-938 10.1016/S0014-4886(03)00338-8 14769385
    CrossrefPubMedGoogle Scholar
  • 39 Melcangi RC, Magnaghi V, Galbiati M, Martini L. Formation and effects of neuroactive steroids in the central and peripheral nervous system. Int Rev Neurobiol 2001; 46: 145-176 full_text 11599299
    PubMedGoogle Scholar
  • 40 Melcangi RC, Magnaghi V, Galbiati M, Martini L. Glial cells: a target for steroid hormones. Prog Brain Res 2001; 132: 31-40 full_text 11544999
    PubMedGoogle Scholar
  • 41 He J, Evans CO, Hoffman SW, Oyesiku NM, Stein DG. Progesterone and allopregnanolone reduce inflammatory cytokines after traumatic brain injury. Exp Neurol 2004; 189: 404-412 10.1016/j.expneurol.2004.06.008 15380490
    CrossrefPubMedGoogle Scholar
  • 42 Roof RL, Hoffman SW, Stein DG. Progesterone protects against lipid peroxidation following traumatic brain injury in rats. Mol Chem Neuropathol 1997; 31: 1-11 10.1007/BF02815156 9271001
    CrossrefPubMedGoogle Scholar
  • 43 O’Connor CA, Cernak I, Vink R. Both estrogen and progesterone attenuate edema formation following diffuse traumatic brain injury in rats. Brain Res 2005; 1062: 171-174 10.1016/j.brainres.2005.09.011 16256079
    CrossrefPubMedGoogle Scholar
  • 44 Peng HY, Chen GD, Lee SD, Lai CY, Chiu CH, Cheng CL, Chang YS, Hsieh MC, Tung KC, Lin TB. Neuroactive steroids inhibit spinal reflex potentiation by selectively enhancing specific spinal GABA(A) receptor subtypes. Pain 2009; 143: 12-20 10.1016/j.pain.2008.12.023 19250751
    CrossrefPubMedGoogle Scholar
  • 45 van Wingen G, van Broekhoven F, Verkes RJ, Petersson KM, Backstrom T, Buitelaar J, Fernandez G. How progesterone impairs memory for biologically salient stimuli in healthy young women. J Neurosci 2007; 27: 11416-11423 10.1523/JNEUROSCI.1715-07.2007 17942736
    CrossrefPubMedGoogle Scholar
  • 46 Roglio I, Giatti S, Pesaresi M, Bianchi R, Cavaletti G, Lauria G, Garcia-Segura LM, Melcangi RC. Neuroactive steroids and peripheral neuropathy. Brain Res Rev 2008; 57: 460-469 10.1016/j.brainresrev.2007.04.010 17543391
    CrossrefPubMedGoogle Scholar
  • 47 Katz JN, Stirrat CR, Larson MG, Fossel AH, Eaton HM, Liang MH. A self-administered hand symptom diagram for the diagnosis and epidemiologic study of carpal tunnel syndrome. J Rheumatol 1990; 17: 1495-1498 2273490
    PubMedGoogle Scholar
  • 48 Rempel D, Evanoff B, Amadio PC, de Krom M, Franklin G, Franzblau A, Gray R, Gerr F, Hagberg M, Hales T et al.: Consensus criteria for the classification of carpal tunnel syndrome in epidemiologic studies. Am J Public Health 1998; 88: 1447-1451 10.2105/AJPH.88.10.1447 1508472 9772842
    CrossrefPubMedGoogle Scholar
  • 49 Giannini F, Cioni R, Mondelli M, Padua R, Gregori B, D’Amico P, Padua L. A new clinical scale of carpal tunnel syndrome: validation of the measurement and clinical-neurophysiological assessment. Clin Neurophysiol 2002; 113: 71-77 10.1016/S1388-2457(01)00704-0 11801427
    CrossrefPubMedGoogle Scholar
  • 50 Levine DW, Simmons BP, Koris MJ, Daltroy LH, Hohl GG, Fossel AH, Katz JN. A self-administered questionnaire for the assessment of severity of symptoms and functional status in carpal tunnel syndrome. J Bone Joint Surg Am 1993; 75: 1585-1592 8245050
    CrossrefPubMedGoogle Scholar
  • 51 Padua L, Padua R, Lo Monaco M, Aprile I, Paciello N, Nazzaro M, Tonali P. Natural history of carpal tunnel syndrome according to the neurophysiological classification. Ital J Neurol Sci 1998; 19: 357-361 10.1007/BF02341782 10935830
    CrossrefPubMedGoogle Scholar
  • 52 American Association of Electrodiagnostic Medicine AAoN, and American Academy of Physical Medicine and Rehabilitation. Practice parameter for electrodiagnostic studies in carpal tunnel syndrome: summary statement. Muscle Nerve 2002; 25: 918-922 10.1002/mus.10185 12115985
    CrossrefPubMedGoogle Scholar
  • 53 Padua L, LoMonaco M, Gregori B, Valente EM, Padua R, Tonali P. Neurophysiological classification and sensitivity in 500 carpal tunnel syndrome hands. Acta Neurol Scand 1997; 96: 211-217 10.1111/j.1600-0404.1997.tb00271.x 9325471
    PubMedGoogle Scholar
  • 54 Ginanneschi F, Milani P, Reale F, Rossi A. Short-term electrophysiological conduction change in median nerve fibres after carpal tunnel release. Clin Neurol Neurosurg 2008; 110: 1025-1030 10.1016/j.clineuro.2008.07.006 18845386
    CrossrefPubMedGoogle Scholar
  • 55 Ginanneschi F, Mondelli M, Dominici F, Rossi A. Changes in motor axon recruitment in the median nerve in mild carpal tunnel syndrome. Clin Neurophysiol 2006; 117: 2467-2472 10.1016/j.clinph.2006.08.002 16987705
    CrossrefPubMedGoogle Scholar
  • 56 Press WH, Flannery BP, Teukolsky SA, Vetterling WT. Numerical Recipes. Cambridge Univ. Press; Cambridge, UK: 1986
    Google Scholar
  • 57 Hobson-Webb LD, Padua L. Median nerve ultrasonography in carpal tunnel syndrome: findings from two laboratories. Muscle Nerve 2009; 40: 94-97 10.1002/mus.21286 19533635
    CrossrefPubMedGoogle Scholar
  • 58 Mondelli M, Filippou G, Gallo A, Frediani B. Diagnostic utility of ultrasonography versus nerve conduction studies in mild carpal tunnel syndrome. Arthritis Rheum 2008; 59: 357-366 10.1002/art.23317 18311762
    CrossrefPubMedGoogle Scholar
  • 59 Mondelli M, Filippou G, Aretini A, Frediani B, Reale F. Ultrasonography before and after surgery in carpal tunnel syndrome and relationship with clinical and electrophysiological findings. A new outcome predictor?. Scand J Rheumatol 2008; 37: 219-224 10.1080/03009740801914850 18465458
    CrossrefPubMedGoogle Scholar