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Effects of steroid with repetitive procaine HCl injection in the management of carpal tunnel syndrome: An ultrasonographic study
Journal of the Neurological Sciences 316 (2012) 76–78
Contents lists available at SciVerse ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Effects of steroid with repetitive procaine HCl injection in the management of carpal tunnel syndrome: An ultrasonographic study Ömer Karadaş a,⁎, Özlem Köroğlu Omaç b, Fatih Tok c, Ahmet Özgül b, Zeki Odabaşı d a
Neurology Service, Erzincan Military Hospital, Erzincan, Turkey Department of Physical Medicine and Rehabilitation, Gulhane Military Medical Academy, Ankara, Turkey Physical Medicine and Rehabilitation Service, İskenderun Military Hospital, Hatay, Turkey d Department of Neurology, Gulhane Military Medical Academy, Ankara, Turkey b c
a r t i c l e
i n f o
Article history: Received 6 October 2011 Received in revised form 17 January 2012 Accepted 24 January 2012 Available online 13 February 2012 Keywords: Carpal tunnel syndrome Local anesthetic Corticosteroid
a b s t r a c t Background and aim: With the use of musculoskeletal ultrasonography (MSUS), morphological changes in the median nerve have been recently reported in patients with carpal tunnel syndrome (CTS). On the other hand, the literature still lacks the information whether those changes are further altered with steroid and local anesthetic injection which is a widely used treatment in this group of patients. Therefore, the aim of our study was to explore in-vivo the effects of steroid with repetitive procaine HCl injection on the median nerve of patients with CTS. Materials and method: This prospective clinical trial followed-up patients for 2 months. 22 patients (37 median nerves) with clinical and electrophysiological evidence of CTS were included in the study. All patients received both 40 mg of triamcinolone acetonide once and 4 ml of 1% procaine HCl twice a week for 2 weeks with the same technique. Clinical, functional, electrophysiological and ultrasonographic evaluations were performed at the study onset, and 2 months after the last injection. Results: Electrophysiological, ultrasonographic findings (median nerve anterior–posterior diameter, transverse diameter and cross sectional area in the proximal carpal tunnel and volar bulging,) VAS scores, Boston carpal tunnel symptom and function assessment scale improved significantly (Pb 0.05). Conclusion: Steroid injection with repetitive procaine HCl injection effectively reduced the symptoms of CTS, improved the Boston carpal tunnel symptom and function assessment scale and also electrophysiological and ultrasonographic findings. Long term effects remain to be studied. Indisputably, the use of MSUS seems to be promising in this regard. © 2012 Elsevier B.V. All rights reserved.
1. Introduction With the use of musculoskeletal ultrasonography (MSUS), morphological changes in the architecture of median nerve and carpal tunnel have been reported in patients with CTS [1]. The ultrasonographic changes that occur within the median nerve of those undergoing steroid injection for CTS have recently been reported [2]. The most consistent finding in MSUS for CTS is a significant increase in the cross-sectional area (CSA) of the nerve at the pisiform bone level (equivalent to the carpal tunnel inlet) [3]. Various diagnostic criteria have been published, and the median nerve CSA at the pisiform level has been cited most often [4]. Retinacular bowing (RB) was measured as the maximal volar displacement of the flexor retinaculum from a line connecting its attachment to the hook of hamate and trapezoid [5]. In addition to diagnosis, MSUS has been used to follow up the carpal tunnel and median nerve status postoperatively. ⁎ Corresponding author. Tel.: + 90 505 780 5041. E-mail address: [email protected] (Ö. Karadaş). 0022-510X/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2012.01.023
Lee at al. found that the CSAs of both the carpal tunnel and median nerve were greater 8 months after surgery, but there was no significant change in the flexor retinaculum (FR) [6]. Steroid injection into the carpal tunnel is frequently used and is known to be safe and effective [7,8]. It aims to reduce the inflammation and swelling of the flexor tenosynovitis, and reduce the pressure exerted on the median nerve. Steroids are usually mixed with local anesthetics, such as lidocaine HCL or prilocaine HCL [9–11], which have positive effects that can aid the treatment of CTS by inhibiting the spontaneous discharge ability of excitable nerves [12]. Procaine HCl is one of the most common local anesthetics that have the highest pKa level; thus the ability of procaine HCl to ionize is the highest among the local anesthetics. Ionization ability is positively correlated with the efficacy of local anesthetics [9,12]. However, the literature still lacks the information whether those changes are further altered with steroid and local anesthetic injection which is a widely used treatment in this group of patients. Another unenlightened subject was the effects of repetitive procaine HCl injection which is widely used as a part of neural therapy.
Ö. Karadaş et al. / Journal of the Neurological Sciences 316 (2012) 76–78
Therefore, the aim of our study was to explore in-vivo the effects of steroid with repetitive procaine HCl injection on the median nerve of patients with CTS. 2. Materials and method Patients with clinically suspected primary CTS were referred to the electromyography (EMG) laboratory of our Neurology department. Patients with symptoms of CTS, including nocturnal paraesthesia, pain in the median nerve distribution during activity or numbness in the median nerve distribution and positive electrophysiology study results were asked to participate in the study if they were >18 years old, had symptoms for less than 1 year, had no evidence of inflammatory arthritis, hypothyroidism, previous wrist trauma, or pregnancy, and had not previously been injected with steroids or local anesthetics into the carpal tunnel, splinted or operated on at the carpal tunnel. Patients with median nerve distal motor latency (DML) and sensory nerve conduction velocity (SNCV) longer than the reference values, and median nerve sensory peak latency ≥0.4 ms longer than that of the ulnar nerve based on median-versus-ulnar digit IV antidromic sensory peak latency comparison underwent needle electromyography of the abductor pollicis brevis (APB) muscle. Patients with fibrillation potentials, positive sharp waves, or chronic neuropathic changes (decreased recruitment pattern, long duration or high amplitude of motor unit potentials) during needle electromyography were excluded. All of the patients were women. Both hands of 15 patients with bilateral symptoms and positive electrophysiology findings were included in the study while only one hand in the remaining 7 patients was included in the study. Among the extremities 27 were right and 10 were left. All the patients provided informed consent and the study was approved by the local Institutional Review Board. All the patients in the study were injected with a mixture of 40 mg of triamcinolone acetonide and 4 ml of 1% procaine HCl for the first injection. The same investigator performed all the injections. A 25 G needle was inserted 1 cm proximal to the distal wrist-flexion crease, between the palmaris longus and flexor carpi radialis tendons. The needle was introduced slowly and the injection was stopped if the patient experienced pain or the sensation of pins and needles in the median nerve distribution. Following appropriate needle placement, the injections were administered. Then each patient was injected twice a week for 2 weeks with 4 ml of 1% procaine HCl with the same technique. All the nerve conduction studies were performed by the same investigator. A Medelec Synergy (Viasys, Ireland, 2008) electromyograph was used for nerve conduction studies, which were performed at baseline and 2 months after the last injection. DML (ms), compound muscle action potential (CMAP) amplitude (mV, recorded in the APB muscle), sensory nerve action potential (SNAP) amplitude (μV), and SNCV (m/s) recordings from digit II, Sensorial latency, ultrasonographic findings (median nerve anterior–posterior and transverse diameter and cross sectional area in the proximal carpal tunnel and volar bulging) VAS scores, Boston carpal tunnel symptom and function assessment scale (BCTQ) were evaluated. Data were analyzed using SPSS v.16.0 for Windows. Descriptive statistics are given as mean ± SD and quantities. Parameters at baseline, and 2 months post treatment were compared using the paired samples t test. The level of significance was set at P b 0.05. The correlations were assessed by Pearson correlation analysis. 3. Results The study included 22 patients (37 median nerves: right hand, 27; left hand, 10). All the patients were women with a mean age 55.5 ± 12.8 (26–77) years. All the patients completed the study and
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side effects were not observed in any of the patients at the end of the study. DML, SNAP amplitude, SNCV, Sensorial latency, sensorial amplitude, ultrasonographic findings (median nerve anterior-posterior diameter, transverse diameter and CSA in the proximal carpal tunnel and volar bulging), VAS scores, BCTQ showed significant improvement in all patients 2 months after the treatment (P b 0.05). The results are showed in Table 1. No significant correlations were detected between the parameters. 4. Discussion Corticosteroid injections into the carpal tunnel have been used for more than 40 years and are reported to be effective in the treatment of CTS [13–15]. Steroids are usually mixed with local anesthetics before injection in order to reduce pain during injection or to ensure accurate localization. Local anesthetics are used in small amounts for these purposes. Local anesthetics decrease and prevent the large transient increase in the permeability of excitable membranes to Na + that is normally produced by slight depolarization of the membrane. This action of local anesthetics is due to their direct interaction with voltage-gated Na + channels. As the anesthetic action progressively develops in a nerve, the threshold for electrical excitability gradually increases, the rate of the increase in the action potential declines, and the safety factor for conduction decreases. These factors decrease the probability of propagation of the action potential. Thus, local anesthetics stabilize the sodium channel [9]. Sodium channel alterations have been reported following damage or insult to peripheral nerves, as well as injury to fibers in close proximity [16]. The change in neuronal excitability (spontaneous and ectopic discharge) contributes to and maintains the condition [9,17–20]. Procaine HCL, the most effective local anesthetic due to its high pKa level (the highest among local anesthetics), pharmacologically blocks these channels and the processes underlying this change may be the most efficient mode of treatment [9,12,20]. There are a limited number of studies on the efficacy of local anesthetics in the treatment of CTS. Nalamamachu et al. compared the efficacy of a local 5% lidocaine patch applied daily to that of a single injection of 0.5 cc of 1% lidocaine plus 40 mg of methylprednisolone acetate and reported that the lidocaine patch effectively reduced the pain associated with CTS [20]. Armstrong et al. administered 6 mg of betamethasone and 1 cc of 1% lidocaine to 43 patients, and 1 cc of saline placebo plus 1 cc of 1% lidocaine to 38 patients, and reported that the patients that received the steroid had significant improvement in median nerve conduction parameters and in treatment satisfaction [21]. In both studies lidocaine was administered in small Table 1 Clinical, functional, electrophysiological and ultrasonographic evaluations of patients.
BCQT symptoms BCQT function VAS Proximal AP diameter (mm) Proximal transverse diameter (mm) Proximal CSA (cm2) Volar bulging Distal motor latency (ms) CMAP amplitude (mV) Sensory latency (ms) Sensory amplitude (μV) SNCV (m/s)
Baseline
2 months posttreatment
Mean ± SD
Mean ± SD
P
32.72 ± 6.96 19.24 ± 5.13 9.67 ± .94 2.17 ± .49 6.67 ± 1.13
23.56 ± 8.37 13.81 ± 5.46 2.81 ± 2.10 2.08 ± .38 5.67 ± 1.49
b0.001 b0.001 b0.001 0.199 b0.001
.13 ± .02 6.18 ± .82 4.27 ± .75 9.32 ± 2.94 3.07 ± .50 27.44 ± 12.54 40.06 ± 5.49
.11 ± .02 5.42 ± .68 3.80 ± .49 9.23 ± 2.32 2.73 ± .45 32.54 ± 11.76 46.98 ± 5.96
b0.001 b0.001 b0.001 0.837 b0.001 0.006 b0.001
BCQT, Boston Carpal Tunnel Questionnaire; VAS, Visual Analog Scale; AP, antero posterior; CSA, cross-sectional area; DML, distal motor latency; CMAP, compound muscle action potential; SNCV, sensory nerve conduction velocity. P value for bold entries b 0.05.
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Ö. Karadaş et al. / Journal of the Neurological Sciences 316 (2012) 76–78
doses. We used 4 cc of 1% procaine HCl. Procaine HCl has a higher ionization level due its high level of pKa. Thus, procaine HCl is hypothesized to be more effective than lidocaine HCl. Karadaş et al. compared the efficacy of 40 mg of triamcinolone acetonide injection and 4 ml of 1% procaine HCl injection in treatment of CTS and reported that local procaine HCl injection was as effective in reducing the symptoms of CTS and improving electrophysiological findings as steroid injection. The authors mentioned that patients that received both steroid and procaine HCl had better symptomatology scores than those that received either the steroid or procaine HCl alone [9]. However, they did not use MSUS to monitor the morphologic changes in the median nerve and the carpal tunnel and they did not use BCTQ which is a patient-reported outcome measure for CTS and has been tested for validity, reliability and responsiveness. Also its psychometric properties have been described extensively [22]. Caputi et al. reported that the anesthetic blocks extinguished presumed foci of nociceptor discharges maintained by perivascular neurogenic inflammation, thereby reestablishing normal central neurone sensitivity. Thus, repetitive blockade of the peripheral nerves appears to be effective in the treatment of neurogenic diseases [23]. Our study is the first to evaluate the effect of local steroid with repetitive local procaine HCl injection. On the other hand, we used MSUS to follow up the efficacy of the treatment. Ultrasonography is very important to detect or exclude possible pathologic and morphologic changes in median nerve as well as the carpal tunnel size and shape. Buchberger et al. demonstrated the enlargement and deformation of the median nerve with ultrasonography for the first time and described the characteristic features that could be found in patients with CTS [24]. Cartwright et al. reported significant changes in median nerve CSA after steroid injection, and the nerve CSA correlated with symptom score and electrodiagnostic parameters [2]. Meys et al. reported that patients who did not need surgery within the 1 year after steroid injection had a lower median nerve ultrasonographic CSA, a lower swelling ratio, and a lower symptom severity score [3]. In our study, median nerve anterior–posterior diameter, transverse diameter and cross sectional area in the proximal carpal tunnel and volar bulging of our patients improved significantly. These ultrasonographic results are compatible with the previous study. Also electrophysiological and clinical outcomes (VAS, BCTQ) improved significantly in the present study. These results are also compatible with the literature. Improvement of median nerve anterior–posterior diameter, transverse diameter and cross sectional area in the proximal carpal tunnel and volar bulging of our patients may indicate a real amelioration of the condition. MSUS has the ability to show the soft tissues including nerves and their changes. If there is any block or compression of the nerve, this will cause it to enlarge proximally or change its route. We showed in this study, that nerves enlarged proximal to the carpal tunnel decreased their cross-sectional area after the antiphlogistic and neural therapy. The present study has some limitations because of the small patient group. Additionally, the lack of a control group receiving placebo saline and the lack of long term of follow-up are the other limitations. Another limitation of the present study is lack of the treatment group receiving single injection of procaine HCl. Nevertheless, the results appear to be significant. Most importantly, complications related to the injections were not observed. In conclusion, local steroid with repetitive local procaine HCl injection was effective in reducing the symptoms of CTS and improving the function, electrophysiological and ultrasonographic findings. Further studies comparing the efficacy of single with repetitive procaine
HCl injections are required. The role of MSUS in the screening of the efficacy of local injections in CTS seems promising. Conflict of interest Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article. References [1] Kamolz LP, Schrogendorfer KF, Rab M, Girsch W, Gruber H, Frey M. The precision of ultrasound imaging and its relevance for carpal tunnel syndrome. Surg Radiol Anat 2001;23:117–21. [2] Cartwright MS, White DL, Demar S, Wiesler ER, Sarlikiotis T, Chloros GD, et al. Median nerve changes following steroid injection for carpal tunnel syndrome. Muscle Nerve 2011;44:25–9. [3] Meys V, Thissen S, Rozeman S, Beekman R. Prognostic factors in carpal tunnel syndrome treated with a corticosteroid injection. Muscle Nerve 2011;44:763–8. [4] Beekman R, Visser LH. Sonography in the diagnosis of carpal tunnel syndrome: a critical review of the literature. Muscle Nerve 2003;27:26–33. [5] Jayaraman S, Naidich TP. The carpal tunnel: ultrasound display of normal imaging anatomy and pathology. Neuroimaging Clin N Am 2004;14:103–13. [6] Lee CH, Kim TK, Yoon ES, Dhong ES. Postoperative morphologic analysis of carpal tunnel syndrome using high-resolution ultrasonography. Ann Plast Surg 2005;54: 143–6. [7] Mishra S, Prabhakar S, Lal V, Modi M, Das CP, Khurana D. Efficacy of splinting and oral steroids in the treatment of carpal tunnel syndrome: a prospective randomized clinical and electrophysiological study. Neurol India 2006;54:286–90. [8] Racasan O, Dubert T. The safest location for steroid injection in the treatment of carpal tunnel sydrome. J Hand Surg Br 2005;30:412–4. [9] Karadaş O, Tok F, Ulaş UH, Odabaşi Z. The effectiveness of triamcinolone acetonide vs. procaine hydrochloride injection in the management of carpal tunnel syndrome: a double-blind randomized clinical trial. Am J Phys Med Rehabil 2011;90:287–92. [10] Hagebeuk EE, de Weerd AW. Clinical and electrophysiological follow-up after local steroid injection in the carpal tunnel syndrome. Clin Neurophysiol 2004;115: 1464–8. [11] Sevim S, Dogu O, Camdeviren H, Kaleagasi H, Aral M, Arslan E, et al. Long-term effectiveness of steroid injections and splinting in mild and moderate carpal tunnel syndrome. Neurol Sci 2004;25:48–52. [12] Catterall AW, Mackie K. Local anesthetics. In: Brunton LL, Lazo JS, Parker KKL, editors. Goodman & Gilman's the pharmacological basis of therapeutics. Texas: The Mcgraw-Hill Companies Inc.; 2006. p. 241–51. ed 11. [13] Karatay S, Aygul R, Melikoglu MA, Yildirim K, Ugur M, Erdal A, et al. The comparison of phonophoresis, iontophoresis and local steroid injection in carpal tunnel syndrome treatment. Joint Bone Spine 2009;76:719–21. [14] Lee JH, An JH, Lee SH, Hwang EY. Effectiveness of steroid injection in treating patients with moderate and severe degree of carpal tunnel syndrome measured by clinical and electrodiagnostic assessment. Clin J Pain 2009;25:111–5. [15] Boyer MI. Corticosteroid injection for carpal tunnel syndrome. J Hand Surg Am 2008;33:1414–6. [16] Devor M, Govrin-Lippmann R, Angelides K. Na+ channel immunolocalization in peripheral mammalian axons and changes following nerve injury and neuroma formation. J Neurosci 1993;13:1976–92. [17] Gold MS. Na+ channel blockers for the treatment of pain: context is everything, almost. Exp Neurol 2008;210:1–6. [18] Gold MS, Weinreich D, Kim CS, Wang R, Treanor J, Porreca F, et al. Redistribution of Na(V)1.8 in uninjured axons enables neuropathic pain. J Neurosci 2003;23: 158–66. [19] Lai J, Porreca F, Hunter JC, Gold MS. Voltage-gated sodium channels and hyperalgesia. Annu Rev Pharmacol Toxicol 2004;44:371–97. [20] Nalamachu S, Crockett RS, Gammaitoni AR, Gould EM. A comparison of the lidocaine patch 5% vs naproxen 500 mg twice daily for the relief of pain associated with carpal tunnel syndrome: a 6-week, randomized, parallel-group study. Med Gen Med 2006;8:33. [21] 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;29:82–8. [22] Leite JC, Jerosch-Herold C, Song F. A systematic review of the psychometric properties of the Boston Carpal Tunnel Questionnaire. BMC Musculoskelet Disord 2006;7:78. [23] Caputi CA, Firetto V. Therapeutic blockade of greater occipital and supraorbital nerves in migraine patients. Headache 1997;37:174–9. [24] Buchberger W, Schön G, Strasser K, Jungwirth W. High-resolution ultrasonography of the carpal tunnel. J Ultrasound Med 1991;10:531–7.
Contents lists available at SciVerse ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Effects of steroid with repetitive procaine HCl injection in the management of carpal tunnel syndrome: An ultrasonographic study Ömer Karadaş a,⁎, Özlem Köroğlu Omaç b, Fatih Tok c, Ahmet Özgül b, Zeki Odabaşı d a
Neurology Service, Erzincan Military Hospital, Erzincan, Turkey Department of Physical Medicine and Rehabilitation, Gulhane Military Medical Academy, Ankara, Turkey Physical Medicine and Rehabilitation Service, İskenderun Military Hospital, Hatay, Turkey d Department of Neurology, Gulhane Military Medical Academy, Ankara, Turkey b c
a r t i c l e
i n f o
Article history: Received 6 October 2011 Received in revised form 17 January 2012 Accepted 24 January 2012 Available online 13 February 2012 Keywords: Carpal tunnel syndrome Local anesthetic Corticosteroid
a b s t r a c t Background and aim: With the use of musculoskeletal ultrasonography (MSUS), morphological changes in the median nerve have been recently reported in patients with carpal tunnel syndrome (CTS). On the other hand, the literature still lacks the information whether those changes are further altered with steroid and local anesthetic injection which is a widely used treatment in this group of patients. Therefore, the aim of our study was to explore in-vivo the effects of steroid with repetitive procaine HCl injection on the median nerve of patients with CTS. Materials and method: This prospective clinical trial followed-up patients for 2 months. 22 patients (37 median nerves) with clinical and electrophysiological evidence of CTS were included in the study. All patients received both 40 mg of triamcinolone acetonide once and 4 ml of 1% procaine HCl twice a week for 2 weeks with the same technique. Clinical, functional, electrophysiological and ultrasonographic evaluations were performed at the study onset, and 2 months after the last injection. Results: Electrophysiological, ultrasonographic findings (median nerve anterior–posterior diameter, transverse diameter and cross sectional area in the proximal carpal tunnel and volar bulging,) VAS scores, Boston carpal tunnel symptom and function assessment scale improved significantly (Pb 0.05). Conclusion: Steroid injection with repetitive procaine HCl injection effectively reduced the symptoms of CTS, improved the Boston carpal tunnel symptom and function assessment scale and also electrophysiological and ultrasonographic findings. Long term effects remain to be studied. Indisputably, the use of MSUS seems to be promising in this regard. © 2012 Elsevier B.V. All rights reserved.
1. Introduction With the use of musculoskeletal ultrasonography (MSUS), morphological changes in the architecture of median nerve and carpal tunnel have been reported in patients with CTS [1]. The ultrasonographic changes that occur within the median nerve of those undergoing steroid injection for CTS have recently been reported [2]. The most consistent finding in MSUS for CTS is a significant increase in the cross-sectional area (CSA) of the nerve at the pisiform bone level (equivalent to the carpal tunnel inlet) [3]. Various diagnostic criteria have been published, and the median nerve CSA at the pisiform level has been cited most often [4]. Retinacular bowing (RB) was measured as the maximal volar displacement of the flexor retinaculum from a line connecting its attachment to the hook of hamate and trapezoid [5]. In addition to diagnosis, MSUS has been used to follow up the carpal tunnel and median nerve status postoperatively. ⁎ Corresponding author. Tel.: + 90 505 780 5041. E-mail address: [email protected] (Ö. Karadaş). 0022-510X/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2012.01.023
Lee at al. found that the CSAs of both the carpal tunnel and median nerve were greater 8 months after surgery, but there was no significant change in the flexor retinaculum (FR) [6]. Steroid injection into the carpal tunnel is frequently used and is known to be safe and effective [7,8]. It aims to reduce the inflammation and swelling of the flexor tenosynovitis, and reduce the pressure exerted on the median nerve. Steroids are usually mixed with local anesthetics, such as lidocaine HCL or prilocaine HCL [9–11], which have positive effects that can aid the treatment of CTS by inhibiting the spontaneous discharge ability of excitable nerves [12]. Procaine HCl is one of the most common local anesthetics that have the highest pKa level; thus the ability of procaine HCl to ionize is the highest among the local anesthetics. Ionization ability is positively correlated with the efficacy of local anesthetics [9,12]. However, the literature still lacks the information whether those changes are further altered with steroid and local anesthetic injection which is a widely used treatment in this group of patients. Another unenlightened subject was the effects of repetitive procaine HCl injection which is widely used as a part of neural therapy.
Ö. Karadaş et al. / Journal of the Neurological Sciences 316 (2012) 76–78
Therefore, the aim of our study was to explore in-vivo the effects of steroid with repetitive procaine HCl injection on the median nerve of patients with CTS. 2. Materials and method Patients with clinically suspected primary CTS were referred to the electromyography (EMG) laboratory of our Neurology department. Patients with symptoms of CTS, including nocturnal paraesthesia, pain in the median nerve distribution during activity or numbness in the median nerve distribution and positive electrophysiology study results were asked to participate in the study if they were >18 years old, had symptoms for less than 1 year, had no evidence of inflammatory arthritis, hypothyroidism, previous wrist trauma, or pregnancy, and had not previously been injected with steroids or local anesthetics into the carpal tunnel, splinted or operated on at the carpal tunnel. Patients with median nerve distal motor latency (DML) and sensory nerve conduction velocity (SNCV) longer than the reference values, and median nerve sensory peak latency ≥0.4 ms longer than that of the ulnar nerve based on median-versus-ulnar digit IV antidromic sensory peak latency comparison underwent needle electromyography of the abductor pollicis brevis (APB) muscle. Patients with fibrillation potentials, positive sharp waves, or chronic neuropathic changes (decreased recruitment pattern, long duration or high amplitude of motor unit potentials) during needle electromyography were excluded. All of the patients were women. Both hands of 15 patients with bilateral symptoms and positive electrophysiology findings were included in the study while only one hand in the remaining 7 patients was included in the study. Among the extremities 27 were right and 10 were left. All the patients provided informed consent and the study was approved by the local Institutional Review Board. All the patients in the study were injected with a mixture of 40 mg of triamcinolone acetonide and 4 ml of 1% procaine HCl for the first injection. The same investigator performed all the injections. A 25 G needle was inserted 1 cm proximal to the distal wrist-flexion crease, between the palmaris longus and flexor carpi radialis tendons. The needle was introduced slowly and the injection was stopped if the patient experienced pain or the sensation of pins and needles in the median nerve distribution. Following appropriate needle placement, the injections were administered. Then each patient was injected twice a week for 2 weeks with 4 ml of 1% procaine HCl with the same technique. All the nerve conduction studies were performed by the same investigator. A Medelec Synergy (Viasys, Ireland, 2008) electromyograph was used for nerve conduction studies, which were performed at baseline and 2 months after the last injection. DML (ms), compound muscle action potential (CMAP) amplitude (mV, recorded in the APB muscle), sensory nerve action potential (SNAP) amplitude (μV), and SNCV (m/s) recordings from digit II, Sensorial latency, ultrasonographic findings (median nerve anterior–posterior and transverse diameter and cross sectional area in the proximal carpal tunnel and volar bulging) VAS scores, Boston carpal tunnel symptom and function assessment scale (BCTQ) were evaluated. Data were analyzed using SPSS v.16.0 for Windows. Descriptive statistics are given as mean ± SD and quantities. Parameters at baseline, and 2 months post treatment were compared using the paired samples t test. The level of significance was set at P b 0.05. The correlations were assessed by Pearson correlation analysis. 3. Results The study included 22 patients (37 median nerves: right hand, 27; left hand, 10). All the patients were women with a mean age 55.5 ± 12.8 (26–77) years. All the patients completed the study and
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side effects were not observed in any of the patients at the end of the study. DML, SNAP amplitude, SNCV, Sensorial latency, sensorial amplitude, ultrasonographic findings (median nerve anterior-posterior diameter, transverse diameter and CSA in the proximal carpal tunnel and volar bulging), VAS scores, BCTQ showed significant improvement in all patients 2 months after the treatment (P b 0.05). The results are showed in Table 1. No significant correlations were detected between the parameters. 4. Discussion Corticosteroid injections into the carpal tunnel have been used for more than 40 years and are reported to be effective in the treatment of CTS [13–15]. Steroids are usually mixed with local anesthetics before injection in order to reduce pain during injection or to ensure accurate localization. Local anesthetics are used in small amounts for these purposes. Local anesthetics decrease and prevent the large transient increase in the permeability of excitable membranes to Na + that is normally produced by slight depolarization of the membrane. This action of local anesthetics is due to their direct interaction with voltage-gated Na + channels. As the anesthetic action progressively develops in a nerve, the threshold for electrical excitability gradually increases, the rate of the increase in the action potential declines, and the safety factor for conduction decreases. These factors decrease the probability of propagation of the action potential. Thus, local anesthetics stabilize the sodium channel [9]. Sodium channel alterations have been reported following damage or insult to peripheral nerves, as well as injury to fibers in close proximity [16]. The change in neuronal excitability (spontaneous and ectopic discharge) contributes to and maintains the condition [9,17–20]. Procaine HCL, the most effective local anesthetic due to its high pKa level (the highest among local anesthetics), pharmacologically blocks these channels and the processes underlying this change may be the most efficient mode of treatment [9,12,20]. There are a limited number of studies on the efficacy of local anesthetics in the treatment of CTS. Nalamamachu et al. compared the efficacy of a local 5% lidocaine patch applied daily to that of a single injection of 0.5 cc of 1% lidocaine plus 40 mg of methylprednisolone acetate and reported that the lidocaine patch effectively reduced the pain associated with CTS [20]. Armstrong et al. administered 6 mg of betamethasone and 1 cc of 1% lidocaine to 43 patients, and 1 cc of saline placebo plus 1 cc of 1% lidocaine to 38 patients, and reported that the patients that received the steroid had significant improvement in median nerve conduction parameters and in treatment satisfaction [21]. In both studies lidocaine was administered in small Table 1 Clinical, functional, electrophysiological and ultrasonographic evaluations of patients.
BCQT symptoms BCQT function VAS Proximal AP diameter (mm) Proximal transverse diameter (mm) Proximal CSA (cm2) Volar bulging Distal motor latency (ms) CMAP amplitude (mV) Sensory latency (ms) Sensory amplitude (μV) SNCV (m/s)
Baseline
2 months posttreatment
Mean ± SD
Mean ± SD
P
32.72 ± 6.96 19.24 ± 5.13 9.67 ± .94 2.17 ± .49 6.67 ± 1.13
23.56 ± 8.37 13.81 ± 5.46 2.81 ± 2.10 2.08 ± .38 5.67 ± 1.49
b0.001 b0.001 b0.001 0.199 b0.001
.13 ± .02 6.18 ± .82 4.27 ± .75 9.32 ± 2.94 3.07 ± .50 27.44 ± 12.54 40.06 ± 5.49
.11 ± .02 5.42 ± .68 3.80 ± .49 9.23 ± 2.32 2.73 ± .45 32.54 ± 11.76 46.98 ± 5.96
b0.001 b0.001 b0.001 0.837 b0.001 0.006 b0.001
BCQT, Boston Carpal Tunnel Questionnaire; VAS, Visual Analog Scale; AP, antero posterior; CSA, cross-sectional area; DML, distal motor latency; CMAP, compound muscle action potential; SNCV, sensory nerve conduction velocity. P value for bold entries b 0.05.
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doses. We used 4 cc of 1% procaine HCl. Procaine HCl has a higher ionization level due its high level of pKa. Thus, procaine HCl is hypothesized to be more effective than lidocaine HCl. Karadaş et al. compared the efficacy of 40 mg of triamcinolone acetonide injection and 4 ml of 1% procaine HCl injection in treatment of CTS and reported that local procaine HCl injection was as effective in reducing the symptoms of CTS and improving electrophysiological findings as steroid injection. The authors mentioned that patients that received both steroid and procaine HCl had better symptomatology scores than those that received either the steroid or procaine HCl alone [9]. However, they did not use MSUS to monitor the morphologic changes in the median nerve and the carpal tunnel and they did not use BCTQ which is a patient-reported outcome measure for CTS and has been tested for validity, reliability and responsiveness. Also its psychometric properties have been described extensively [22]. Caputi et al. reported that the anesthetic blocks extinguished presumed foci of nociceptor discharges maintained by perivascular neurogenic inflammation, thereby reestablishing normal central neurone sensitivity. Thus, repetitive blockade of the peripheral nerves appears to be effective in the treatment of neurogenic diseases [23]. Our study is the first to evaluate the effect of local steroid with repetitive local procaine HCl injection. On the other hand, we used MSUS to follow up the efficacy of the treatment. Ultrasonography is very important to detect or exclude possible pathologic and morphologic changes in median nerve as well as the carpal tunnel size and shape. Buchberger et al. demonstrated the enlargement and deformation of the median nerve with ultrasonography for the first time and described the characteristic features that could be found in patients with CTS [24]. Cartwright et al. reported significant changes in median nerve CSA after steroid injection, and the nerve CSA correlated with symptom score and electrodiagnostic parameters [2]. Meys et al. reported that patients who did not need surgery within the 1 year after steroid injection had a lower median nerve ultrasonographic CSA, a lower swelling ratio, and a lower symptom severity score [3]. In our study, median nerve anterior–posterior diameter, transverse diameter and cross sectional area in the proximal carpal tunnel and volar bulging of our patients improved significantly. These ultrasonographic results are compatible with the previous study. Also electrophysiological and clinical outcomes (VAS, BCTQ) improved significantly in the present study. These results are also compatible with the literature. Improvement of median nerve anterior–posterior diameter, transverse diameter and cross sectional area in the proximal carpal tunnel and volar bulging of our patients may indicate a real amelioration of the condition. MSUS has the ability to show the soft tissues including nerves and their changes. If there is any block or compression of the nerve, this will cause it to enlarge proximally or change its route. We showed in this study, that nerves enlarged proximal to the carpal tunnel decreased their cross-sectional area after the antiphlogistic and neural therapy. The present study has some limitations because of the small patient group. Additionally, the lack of a control group receiving placebo saline and the lack of long term of follow-up are the other limitations. Another limitation of the present study is lack of the treatment group receiving single injection of procaine HCl. Nevertheless, the results appear to be significant. Most importantly, complications related to the injections were not observed. In conclusion, local steroid with repetitive local procaine HCl injection was effective in reducing the symptoms of CTS and improving the function, electrophysiological and ultrasonographic findings. Further studies comparing the efficacy of single with repetitive procaine
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