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A Novel Treatment for Carpal Tunnel Syndrome?

      Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy and is caused by chronic compression of the median nerve as it enters the carpal tunnel. Although the prevalence and incidence of CTS vary widely depending on the diagnostic criteria used, it is thought that, clinically, approximately 1 in 10 people have development of carpal tunnel syndrome.
      Practice parameter for carpal tunnel syndrome (summary statement): report of the Quality Standards Subcommittee of the American Academy of Neurology.
      • Padua L.
      • Coraci D.
      • Erra C.
      • et al.
      Carpal tunnel syndrome: clinical features, diagnosis, and management.
      At this time, there is no consensus for the treatment of mild to moderate carpal tunnel syndrome. The American Academy of Orthopedic Surgeons has stated that nonsurgical treatments, such as splinting of the wrist to a neutral position and local corticosteroid injections, are reasonable options for patients early in the course of symptoms when there is no evidence of median nerve denervation.
      • Keith M.W.
      • Masear V.
      • Amadio P.C.
      • et al.
      Treatment of carpal tunnel syndrome.
      A 2007 Cochrane review found that the duration of benefit of local corticosteroid injections and the effect on mild to moderate CTS are unknown, but the effects appear to be temporary with unclear benefit beyond 1 month.
      • Marshall S.
      • Tardif G.
      • Ashworth N.
      Local corticosteroid injection for carpal tunnel syndrome.
      This review also found that 2 injections of corticosteroid into the carpal tunnel did not provide further clinical benefit compared with 1. More recent studies have reported that the benefit may last up to 10 weeks and, in some studies, up to 1 year with reduced need for surgical treatment at 1 year.
      • Atroshi I.
      • Flondell M.
      • Hofer M.
      • Ranstam J.
      Methylprednisolone injections for the carpal tunnel syndrome: a randomized, placebo-controlled trial.
      • Karadaş Ö.
      • Tok F.
      • Akarsu S.
      • Tekin L.
      • Balaban B.
      Triamcinolone acetonide vs procaine hydrochloride injection in the management of carpal tunnel syndrome: randomized placebo-controlled study.
      • Ly-Pen D.
      • Andréu J.L.
      • Millán I.
      • de Blas G.
      • Sánchez-Olaso A.
      Comparison of surgical decompression and local steroid injection in the treatment of carpal tunnel syndrome: 2-year clinical results from a randomized trial.
      • Peters-Veluthamaningal C.
      • Winters J.C.
      • Groenier K.H.
      • Meyboom-de Jong B.
      Randomised controlled trial of local corticosteroid injections for carpal tunnel syndrome in general practice.
      An alternative treatment is presented in this issue of Mayo Clinic Proceedings by Wu et al.
      • Wu Y.-T.
      • Ho T.-Y.
      • Chou Y.-C.
      • et al.
      Six-month efficacy of perineural dextrose for carpal tunnel syndrome: a prospective, randomized, double-blind, controlled trial.
      The authors performed a prospective, randomized, placebo-controlled, double-blind study of ultrasound-guided perineural injection using 5% dextrose (D5W) in patients with electrophysiologically mild to moderate median neuropathies at the wrist. The authors report a significant reduction in pain and disability, improved electrophysiological responses, and a decreased cross-sectional area of the median nerve using ultrasonography, all of which persisted at 6 months. Also notable in the study by Wu et al is the significant improvement observed in the placebo group in pain and disability scores as well as cross-sectional area of the median nerve. This placebo effect is common in CTS studies, ranging from 20% to 34%, and may be due to the natural history of CTS, which can be characterized by spontaneous remissions.
      • Armstrong T.
      • Devor W.
      • Borschel L.
      • Contreras R.
      Intracarpal steroid injection is safe and effective for short-term management of carpal tunnel syndrome.
      • Dammers J.W.
      • Veering M.M.
      • Vermeulen M.
      Injection with methylprednisolone proximal to the carpal tunnel: randomised double blind trial.
      • Manente G.
      • Torrieri F.
      • Di Blasio F.
      • Staniscia T.
      • Romano F.
      • Uncini A.
      An innovative hand brace for carpal tunnel syndrome: a randomized controlled trial.
      As suggested by the authors, the improvement observed in both the treatment and placebo groups may reflect, at least in part, the effect of hydrodissection, whereby injectate (here D5W) placed around the nerve separates the nerve from the flexor retinaculum, underlying subsynovial connective tissue, and flexor tendons. Hydrodissection is commonly used in routine ultrasound-guided, pain-targeted, nonanesthesia nerve blocks. Its contribution to the effect in this study is uncertain, an issue the authors are planning to address in a follow-up study.
      Carpal tunnel syndrome is more common in diabetic patients, especially in those with coexisting diabetic polyneuropathy.
      • Perkins B.A.
      • Olaleye D.
      • Bril V.
      Carpal tunnel syndrome in patients with diabetic polyneuropathy.
      In fact, there is strong evidence that both type 1 and type 2 diabetes are risk factors for CTS.
      • Pourmemari M.H.
      • Shiri R.
      Diabetes as a risk factor for carpal tunnel syndrome: a systematic review and meta-analysis.
      The optimum treatment of CTS in this population is not established. The American Academy of Orthopedic Surgeons has made no recommendations for treatment of CTS in patients with coexisting diabetes mellitus.
      • Keith M.W.
      • Masear V.
      • Amadio P.C.
      • et al.
      Treatment of carpal tunnel syndrome.
      In the study by Wu et al,
      • Wu Y.-T.
      • Ho T.-Y.
      • Chou Y.-C.
      • et al.
      Six-month efficacy of perineural dextrose for carpal tunnel syndrome: a prospective, randomized, double-blind, controlled trial.
      only 6.67% of patients in the D5W group were diabetic. Given the small sample size, the applicability of the results in terms of safety and efficacy in this population cannot be addressed. Corticosteroid injections for CTS, as well as various other pain syndromes, have been used safely in diabetic patients. Several studies have found that the effects on blood glucose levels are transient (≤5 days) and manageable often without significant adverse effect.
      • Stepan J.G.
      • London D.A.
      • Boyer M.I.
      • Calfee R.P.
      Blood glucose levels in diabetic patients following corticosteroid injections into the hand and wrist.
      • Catalano III, L.W.
      • Glickel S.Z.
      • Barron O.A.
      • Harrison R.
      • Marshall A.
      • Purcelli-Lafer M.
      Effect of local corticosteroid injection of the hand and wrist on blood glucose in patients with diabetes mellitus.
      Those with hemoglobin A1c levels greater than 7% (to convert to proportion of total hemoglobin, multiply by 0.01) are more vulnerable.
      • Kim N.
      • Schroeder J.
      • Hoffler C.E.
      • Matzon J.L.
      • Lutsky K.F.
      • Beredjiklian P.K.
      Elevated hemoglobin A1C levels correlate with blood glucose elevation in diabetic patients following local corticosteroid injection in the hand: a prospective study.
      Evaluation of D5W injections in patients with CTS and coexisting diabetes mellitus is needed, especially in those with an elevated hemoglobin A1c level greater than 7%.
      The use of D5W by Wu et al is a unique approach to CTS. The authors note that D5W is the most common injectate for perineural injection in their experience. In the United States, however, local anesthetic with or without a corticosteroid is the most common injectate for nonanesthetic, pain-targeted perineural injections. Dextrose solutions may have a direct analgesic effect when injected perineurally.
      • Reeves K.D.
      • Sit R.W.
      • Rabago D.P.
      Dextrose prolotherapy: a narrative review of basic science, clinical research, and best treatment recommendations.
      Additionally, dextrose solutions (usually in hypertonic concentrations) are one of the most commonly utilized (and studied) injectates used with prolotherapy. Prolotherapy is the injection of an irritant solution into a joint, around a ligament, or at a tendinous insertion site to relieve pain and decrease laxity. Injections are usually repeated at regular intervals (usually every several weeks) over a period of time (usually a few months). Although the mechanism of prolotherapy is uncertain, it is no longer thought to equate to sclerotherapy (ie, induced sclerosis/scarring of tissue around the injection site). Prolotherapy may induce a low-grade inflammatory reaction at the injection site, mimicking injury, activating fibroblasts, and promoting collagen deposition and connective tissue repair. Although Wu et al note that D5W is not hypertonic and therefore is presumed safe, some studies have suggested that the induced connective tissue proliferation with prolotherapy is not dependent on an inflammatory response or on hypertonicity of the dextrose solution.
      • Reeves K.D.
      • Sit R.W.
      • Rabago D.P.
      Dextrose prolotherapy: a narrative review of basic science, clinical research, and best treatment recommendations.
      This factor is pertinent when considering the potential safety of repeated D5W injections perineurally in the carpal tunnel. Animal models have documented that the administration of 10% dextrose (a hypertonic solution) into the carpal tunnel equivalent in a rabbit induced a transverse carpal ligament equivalent (subsynovial connective tissue) proliferation and thickening after one injection; these effects increased with successive injections. This experiment caused median nerve compression and demyelination, and, indeed, such administration of 10% dextrose was proposed as an animal model of CTS.
      • Oh S.
      • Ettema A.M.
      • Zhao C.
      • et al.
      Dextrose-induced subsynovial connective tissue fibrosis in the rabbit carpal tunnel: a potential model to study carpal tunnel syndrome?.
      • Yoshii Y.
      • Zhao C.
      • Schmelzer J.D.
      • Low P.A.
      • An K.N.
      • Amadio P.C.
      Effects of multiple injections of hypertonic dextrose in the rabbit carpal tunnel: a potential model of carpal tunnel syndrome development.
      • Yoshii Y.
      • Zhao C.
      • Schmelzer J.D.
      • Low P.A.
      • An K.N.
      • Amadio P.C.
      Effects of hypertonic dextrose injections in the rabbit carpal tunnel.
      Ultrasonographic evaluations focused on the cross-sectional area of the median nerve in the study by Wu et al but not on possible proliferative effects on connective tissue surrounding structures such as the transverse carpal ligament. Future studies, especially with serial injections, should consider this variable.
      In summary, the trial by Wu et al
      • Wu Y.-T.
      • Ho T.-Y.
      • Chou Y.-C.
      • et al.
      Six-month efficacy of perineural dextrose for carpal tunnel syndrome: a prospective, randomized, double-blind, controlled trial.
      has proposed an interesting new treatment for CTS, but many questions still remain and further studies are needed. Further human studies are needed to replicate the response in this study and to gain understanding into the pathophysiologic mechanism of the benefits reported with D5W injections. Long-term follow-up of these patients would be helpful to determine how long these benefits persist and to see if repeated injections paradoxically increase the risk of recurrent CTS symptoms by inducing carpal tunnel connective tissue proliferation. Ultimately, a direct comparison with corticosteroid injections will be needed to determine which treatment is safer and more beneficial.

      References

      1. Practice parameter for carpal tunnel syndrome (summary statement): report of the Quality Standards Subcommittee of the American Academy of Neurology.
        Neurology. 1993; 43: 2406-2409
        • Padua L.
        • Coraci D.
        • Erra C.
        • et al.
        Carpal tunnel syndrome: clinical features, diagnosis, and management.
        Lancet Neurol. 2016; 15: 1273-1284
        • Keith M.W.
        • Masear V.
        • Amadio P.C.
        • et al.
        Treatment of carpal tunnel syndrome.
        J Am Acad Orthop Surg. 2009; 17: 397-405
        • Marshall S.
        • Tardif G.
        • Ashworth N.
        Local corticosteroid injection for carpal tunnel syndrome.
        Cochrane Database Syst Rev. 2007; : CD001554
        • Atroshi I.
        • Flondell M.
        • Hofer M.
        • Ranstam J.
        Methylprednisolone injections for the carpal tunnel syndrome: a randomized, placebo-controlled trial.
        Ann Intern Med. 2013; 159: 309-317
        • Karadaş Ö.
        • Tok F.
        • Akarsu S.
        • Tekin L.
        • Balaban B.
        Triamcinolone acetonide vs procaine hydrochloride injection in the management of carpal tunnel syndrome: randomized placebo-controlled study.
        J Rehabil Med. 2012; 44: 601-604
        • Ly-Pen D.
        • Andréu J.L.
        • Millán I.
        • de Blas G.
        • Sánchez-Olaso A.
        Comparison of surgical decompression and local steroid injection in the treatment of carpal tunnel syndrome: 2-year clinical results from a randomized trial.
        Rheumatology (Oxford). 2012; 51: 1447-1454
        • Peters-Veluthamaningal C.
        • Winters J.C.
        • Groenier K.H.
        • Meyboom-de Jong B.
        Randomised controlled trial of local corticosteroid injections for carpal tunnel syndrome in general practice.
        BMC Fam Pract. 2010; 11: 54
        • Wu Y.-T.
        • Ho T.-Y.
        • Chou Y.-C.
        • et al.
        Six-month efficacy of perineural dextrose for carpal tunnel syndrome: a prospective, randomized, double-blind, controlled trial.
        Mayo Clin Proc. 2017; 92: 1179-1189
        • Armstrong T.
        • Devor W.
        • Borschel L.
        • Contreras R.
        Intracarpal steroid injection is safe and effective for short-term management of carpal tunnel syndrome.
        Muscle Nerve. 2004; 29: 82-88
        • Dammers J.W.
        • Veering M.M.
        • Vermeulen M.
        Injection with methylprednisolone proximal to the carpal tunnel: randomised double blind trial.
        BMJ. 1999; 319: 884-886
        • Manente G.
        • Torrieri F.
        • Di Blasio F.
        • Staniscia T.
        • Romano F.
        • Uncini A.
        An innovative hand brace for carpal tunnel syndrome: a randomized controlled trial.
        Muscle Nerve. 2001; 24: 1020-1025
        • Perkins B.A.
        • Olaleye D.
        • Bril V.
        Carpal tunnel syndrome in patients with diabetic polyneuropathy.
        Diabetes Care. 2002; 25: 565-569
        • Pourmemari M.H.
        • Shiri R.
        Diabetes as a risk factor for carpal tunnel syndrome: a systematic review and meta-analysis.
        Diabet Med. 2016; 33: 10-16
        • Stepan J.G.
        • London D.A.
        • Boyer M.I.
        • Calfee R.P.
        Blood glucose levels in diabetic patients following corticosteroid injections into the hand and wrist.
        J Hand Surg Am. 2014; 39: 706-712
        • Catalano III, L.W.
        • Glickel S.Z.
        • Barron O.A.
        • Harrison R.
        • Marshall A.
        • Purcelli-Lafer M.
        Effect of local corticosteroid injection of the hand and wrist on blood glucose in patients with diabetes mellitus.
        Orthopedics. 2012; 35: e1754-e1758
        • Kim N.
        • Schroeder J.
        • Hoffler C.E.
        • Matzon J.L.
        • Lutsky K.F.
        • Beredjiklian P.K.
        Elevated hemoglobin A1C levels correlate with blood glucose elevation in diabetic patients following local corticosteroid injection in the hand: a prospective study.
        Plast Reconstr Surg. 2015; 136: 474e-479e
        • Reeves K.D.
        • Sit R.W.
        • Rabago D.P.
        Dextrose prolotherapy: a narrative review of basic science, clinical research, and best treatment recommendations.
        Phys Med Rehabil Clin N Am. 2016; 27: 783-823
        • Oh S.
        • Ettema A.M.
        • Zhao C.
        • et al.
        Dextrose-induced subsynovial connective tissue fibrosis in the rabbit carpal tunnel: a potential model to study carpal tunnel syndrome?.
        Hand (N Y). 2008; 3: 34-40
        • Yoshii Y.
        • Zhao C.
        • Schmelzer J.D.
        • Low P.A.
        • An K.N.
        • Amadio P.C.
        Effects of multiple injections of hypertonic dextrose in the rabbit carpal tunnel: a potential model of carpal tunnel syndrome development.
        Hand (N Y). 2014; 9: 52-57
        • Yoshii Y.
        • Zhao C.
        • Schmelzer J.D.
        • Low P.A.
        • An K.N.
        • Amadio P.C.
        Effects of hypertonic dextrose injections in the rabbit carpal tunnel.
        J Orthop Res. 2011; 29: 1022-1027

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