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Neurophysiologic recovery after carpal tunnel release in diabetic patients
Clinical Neurophysiology 121 (2010) 1569–1573
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Neurophysiologic recovery after carpal tunnel release in diabetic patients Niels O.B. Thomsen a,*, Ingmar Rosén b, Lars B. Dahlin a a b
Department of Hand Surgery, Malmö University Hospital, Malmö, Sweden Department of Clinical Neurophysiology, Lund University Hospital, Lund, Sweden
a r t i c l e
i n f o
Article history: Accepted 15 March 2010 Available online 21 April 2010 Keywords: Carpal tunnel syndrome Diabetes Neuropathy Neurophysiology
a b s t r a c t Objective: To compare nerve conduction study results, before and after surgical carpal tunnel release, in diabetic and non-diabetic patients. Methods: In a prospective study (2004–2007), we included 35 consecutive diabetic patients with carpal tunnel syndrome (CTS), who were age and gender matched with 31 non-diabetic patients having idiopathic CTS. Preoperatively, and at the 1 year follow-up, nerve conduction studies were performed of the median and ulnar nerve. Presence of neuropathy was based on abnormal preoperative neurophysiologic values in both the sural and the peroneal nerve. Results: Diabetic patients demonstrated significantly impaired nerve conduction parameters, before as well as after surgical carpal tunnel release, compared to non-diabetic patients. However, neurophysiologic recovery after carpal tunnel release was not different between the two patient groups or between diabetic patients with or without peripheral neuropathy. In general, the largest neurophysiologic recovery was demonstrated for parameters with the greatest impairment, but normal values were seldom reached. Conclusions: Marked neurophysiologic impairment of the median nerve, or signs of peripheral neuropathy, does not preclude significant recovery after carpal tunnel release in diabetic patients. Significance: Diabetic patients with CTS should be offered the same opportunities for surgical carpal tunnel release as non-diabetic patients. Ó 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction Diabetic neuropathy is a common complication of both Type 1 and Type 2 diabetes which affects up to 50% of the patients. Length dependent, symmetric sensori-motor neuropathy represents its most frequent form, primarily affecting the feet and lower limbs, causing pain and paraesthesiae (Boulton et al., 2005). With progression of the neuropathy, symptoms spread proximally. Measurement of sensory and motor nerve conduction velocity is regarded important in the identification and quantification of neuropathy in diabetic patients, and to document the clinical course of treatment (Bril et al., 1998). In diabetes, impaired nerve conduction in non-compressed nerves develop early on in the disease, at which time it can still be reversed by strict metabolic control (Gregersen, 1968; Kikkawa et al., 2005; Rota et al., 2005). In the presence of diabetic neuropathy, structural nerve changes such as segmental and paranodal demyelination, may cause a decreased in nerve conduction velocity, as well as loss of axons in the nerve trunk might lead to decreased nerve action potential (Behse et al., 1977).
* Correspondence to: N.O.B. Thomsen, Department of Hand Surgery, Malmö University Hospital, SE-205 02 Malmö, Sweden. Tel.: +46 40 33 67 90; fax: +46 40 92 88 55. E-mail address: [email protected] (N.O.B. Thomsen).
Diabetic neuropathy also includes a group of focal entrapment mononeuropathies which are more common in diabetes, such as carpal tunnel syndrome (CTS). Nerve conduction studies are often used to confirm the clinical diagnosis of CTS and provide a high degree of sensitivity and specificity (Jablecki et al., 2002). However, its value as an additional diagnostic tool when compared to clinical history and examination has been questioned (Graham, 2008). In addition, it has not been possible to demonstrate a relationship between nerve conduction results and clinical outcome measures after carpal tunnel release (Mondelli et al., 2000; Schrijver et al., 2005). In spite of this, neurophysiology provides the most objective, noninvasive assessment of myelinated nerve fibre dysfunction, and has an important complimentary function in cases of atypical clinical presentation, or when other underlying causes such as neuropathy are suspected. Neurophysiologic evidence of asymptomatic CTS has been demonstrated in 20–30% of insulin and non-insulin dependent diabetic patients (Albers et al., 1996; Dyck et al., 1993). Paradoxical to increased susceptibility to focal nerve entrapment in diabetes, experimental and clinical nerve conduction studies have demonstrated increased resistance to ischaemic block (Lindstrom et al., 1997). While well documented for non-diabetic patients (Ginanneschi et al., 2008a; Naidu et al., 2003; Todnem and Lundemo, 2000), neurophysiologic results after carpal tunnel release in diabetic
1388-2457/$36.00 Ó 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.clinph.2010.03.014
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patients have only been sparsely investigated, and conclusions have been conflicting (Mondelli et al., 2004; Ozkul et al., 2002). The aim of this study, in which clinical results previously have been published (Thomsen et al., 2009a), was to compare nerve conduction study results before and after surgical carpal tunnel release, in a prospective series of age- and gender-matched diabetic and non-diabetic patients. 2. Methods 2.1. Patients From 2004 to 2007, consecutive patients with diabetes referred to our outpatient clinic with symptomatic CTS over at least six months, were invited to participate in the study. Eligibility criteria has previously been described in detail (Thomsen et al., 2009a). The study was approved by the Regional Ethical Review Board at Lund University. All patients gave informed consent to participate. We included 36 consecutive patients with diabetes and CTS and 36 age and gender matched non-diabetic patients with idiopathic CTS. The diagnosis of CTS was based on clinical history and symptoms, and confirmed by median nerve conduction studies (antidromic, wrist–palm, sensory conduction velocity [<44 m/s] and distal motor latency [>4.1 ms]). Exclusion criteria were: previous carpal tunnel release in the hand under study, clinical signs of focal nerve entrapment other than CTS, cervical radiculopathy, inflammatory joint disease, renal failure, thyroid disorders, previous wrist fracture on the affected side, daily long-term exposure to vibrating tools, pregnancy or age below 18 years. To ascertain that none of the non-diabetic patients has undiagnosed diabetes an oral glucose tolerance test was performed according to suggested guidelines (American Diabetes Association, 2006). Signs of peripheral neuropathy demonstrated in the nerve conduction study were an exclusion criterion for the non-diabetic patients with CTS, but not for the diabetic patients with CTS. After screening, we excluded one patient from the diabetic group due to the diagnosis of thyroid dysfunction. In the non-diabetic group, three patients we excluded because of diagnosed diabetes and two were excluded due to nerve conduction studies demonstrated signs of peripheral neuropathy of unknown origin. After screening there were no drop-outs and the follow-up rate was 100%. Thus, the patients under study consisted of 35 diabetic patients with CTS (15 Type 1 and 20 with Type 2 diabetes). The group included 22 females and 13 males with a mean age of 53 years (range 31–73). Mean duration of diabetes was 17 years (range 1–43) and mean duration of CTS symptoms was 27 months (range 8–96). Body mass index was 27.6 kg/m2 (SD ± 4.8) and glycosylated hemoglobin (HbA1c) level was 6.9% (SD ± 1.3). The diabetic patients were matched with 31 non-diabetic patients with CTS including 19 females and 12 males with a mean age of 52 years (range 35–77). Mean duration of CTS symptoms was 48 months (range 12–80). Body mass index was 27.0 kg/m2 (SD ± 4.1) and glycosylated hemoglobin level was 4.5% (SD ± 0.3).
(Viasys Inc., Madison, WI, USA). The investigations were conducted with surface electrodes (skin temperature kept above 30 °C); additional needle electromyography was not performed. All investigations were performed by the same technician and evaluated independently, by the same neurophysiologist. 2.3.1. Median motor nerve conduction studies We recorded distal motor latency (DML); (wrist to abductor pollicis brevis, distance between stimulation and recording electrodes 8 cm). Motor conduction velocity (MCV) was measured from elbow to wrist level. Compound muscle action potential (CMAP) was measured from onset to the peak of the initial monophasic negative muscle response. 2.3.2. Median sensory nerve conduction studies Orthodromic sensory nerve action potentials (SNAP) from digits I and III, were obtained with recording electrodes 2 cm proximal to distal wrist crease, inter-electrode distance 3 cm on stimulation at the proximal phalanx of digits I and III, respectively (Jablecki et al., 2002). Fractionated measurement of antidromic sensory conduction velocity (SCV) over the carpal tunnel segment (Rosen, 1993) was recorded by ring electrodes at digit III with stimulation of the median nerve in the palm, 2 cm proximal to the distal wrist crease, and at the elbow. 2.3.3. Ulnar motor and sensory nerve conduction studies Ulnar motor conduction was studied by recording CMAP from the abductor digiti minimi and stimulation at the wrist and at the elbow. Orthodromic sensory conduction was determined by stimulation of digit V and recording at the wrist. 2.3.4. Sural and peroneal nerve conduction studies To diagnose peripheral neuropathy, at the preoperative neurophysiologic session, all patients had measurement of sural nerve SCV, sural SNAP and peroneal nerve MCV. Sensory action potentials from the sural nerve were measured antidromic at the lateral malleolus with stimulation of the nerve at the posterolateral side of the calf (stimulation-recording distance standardized at 140 mm). Peroneal motor response was recorded from the extensor digiti brevis muscle with stimulation at the ankle and in the popliteal fossa. 2.4. Classification of neuropathy Criterion of peripheral neuropathy was detection of abnormal values in both the sural and the peroneal nerve (England et al., 2005). To classify the degree of neuropathy, we calculated Z-scores as standard deviation (SD) from mean of our non-diabetic patient group ([diabetic patient’s value – the mean of non-diabetic patients’ values]/SD of non-diabetic patients’ values). According to suggested guidelines by a group of European neurophysiologists, <±2SD were considered normal (Tankisi et al., 2005).
2.2. Surgical procedure The surgical procedure, previously described (Thomsen et al., 2009a), was performed by the same surgeon and consisted of a standardized open carpal tunnel release (short, palm only incision). No additional procedures were done. 2.3. Nerve conduction studies Preoperatively, and at a 1 year follow-up, nerve conduction studies were performed using a Viking Select electromyograph
2.5. Statistical analysis Differences in continuous data between groups and within groups were tested using non-parametric Mann–Whitney U-test and Wilcoxon signed rank test, respectively. Fisher’s exact test was used for categorical data. Correlations were performed using Spearman rank sum test and expressed as a coefficient (rs) with a level of significance. Statistical analysis was performed using SPSS 14.0 for Windows (SPSS Inc., Chicago, IL, USA). P < 0.05 was considered statistically significant.
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DML (ms) MCV (m/s) CMAP-wrist (mV) SCV I (m/s) SCV III (m/s) SNAP I (lV) SNAP III (lV) Elbow–wrist SCV (m/s) Wrist–palm SCV (m/s) Palm-digit III SCV (m/s)
52 weeks follow-up
Improvement
P-value
DM
Non-DM
DM
Non-DM
6.4 (5.8–7.1) 47.8 (44.4–51.1) [1] 5.0 (4.2–5.8) [1]
5.2 (4.8–5.7) 52.9 (51.2–54.6) 6.2 (5.4–7.1)
4.7 (4.5– 5.0) 49.2 (45.9–52.4) [1] 5.6 (4.9–6.3)
4.3 (4.0–4.5) 1.7 (1.2–2.2) 54.1 (52.3–55.9) 1.4 ( 0.1–2.9) 6.6 (5.9–7.3) 0.6 (0.1–1.1)
DM
Non-DM
Pre-op
52 weeks
Improv
1.0 (0.6–1.4) 1.2 ( 0.2–2.7) 0.3 ( 0.4–1.1)
0.003 0.002 0.05
0.002 0.001 0.05
0.07 0.8 0.5
21.3 (16.2–26.6) [10] 22.0 (16.0–28.0) [12]
29.5 (25.3–33.7) [3] 29.6 (23.8–35.4) [6]
36.0 (32.8–39.2) [1] 37.2 (33.1–41.2) [2]
42.3 (40.0–44.6) 14.6 (10.5–18.8) 12.8 (9.2–16.4) 44.2 (41.5–46.9) 15.2 (10.6–19.8) 14.5 (9.7–19.4)
0.02 0.04
0.001 0.005
0.7 0.9
4.7 (2.3–7.1) [10] 2.7 (1.2–4.2) [12] 36.0 (26.8–45.2) [12]
6.8 (4.3–9.3) [3] 3.9 (2.4–5.4) [6] 50.9 (43.3–58.5) [4]
8.1 (6.2–10.1) [2] 4.9 (3.5–6.2) [2] 53.6 (49.5–57.6) [1]
12.2 (9.6–14.8) 8.7 (6.6–10.8) 57.7 (56.0–59.5)
3.4 (1.7–5.1) 2.1 (1.3–2.9) 17.6 (9.6–25.6)
0.05 0.1 0.003
0.02 0.004 0.04
0.1 0.01 0.007
18.4 (14.0–22.8) [9]
24.1 (20.2–28.0) [4]
32.6 (29.6–35.6) [1]
40.1 (37.1–43.1)
14.2 (10.6–17.8) 16.0 (13.3–18.6)
0.03
0.001
0.2
34.2 (26.7–41.7) [9]
42.9 (35.9–49.9) [4]
46.9 (42.7–51.0) [1]
53.0 (49.8–56.2)
12.6 (6.6–18.7)
0.05
0.04
0.6
5.4 (2.9–7.9) 4.8 (3.2–6.5) 6.9 ( 0.7–14.2)
10.2 (4.6–15.8)
CMAP, compound muscle action potential; DML, distal motor latency; MCV, motor conduction velocity; SCV, sensory conduction velocity; SNAP, sensory nerve action potential. Results are reported as mean value (95% confidence interval) and [number with absent neurophysiologic response]. P-value <0.05 is indicated in bold.
3. Results
3.2. Ulnar nerve
The groups of diabetic and non-diabetic patients are comparable with the exception of the non-diabetic patients who had CTS symptoms for a significantly longer period (P < 0.008). The diabetic patients had excellent glycaemic control reflected by the glycosylated haemoglobin level (6.9 ± 1.3%).
The results reflect our exclusion of patients with clinical signs of focal nerve entrapment other than CTS (Table 2). However, the general finding, prior to and after carpal tunnel release, was that DML remained prolonged, and that both motor and sensory conduction velocities, as well as amplitudes, continued to be significantly reduced in diabetic compared to non-diabetic patients. No meaningful changes of conduction parameters were demonstrated at the follow-up of diabetic or non-diabetic patients.
3.1. Median nerve Results from the median nerve conduction studies on diabetic and non-diabetic patients before and after surgical carpal tunnel release are summarized in Table 1. Nearly all preoperative nerve conduction parameters were significantly impaired for the diabetic patients compared to the non-diabetic patients. At the 1 year follow-up, antidromic elbow–wrist SCV had improved to a significantly higher extent in the group of diabetic patients while SNAP III had improved considerably more in the non-diabetic patients. Otherwise, no differences in progress between the two patient groups were observed. The diabetic group included an increased number of patients with absent response on SCV I (10 vs. 3), SCV III (12 vs. 6), SNAP I (10 vs. 3) and SNAP III (12 vs. 6) compared to the non-diabetic patients. One year after surgery absent neurophysiologic response was observed only in a few diabetic patients, while response could be evoked in all non-diabetic patients. Preoperatively, the wrist–palm SCV over the carpal tunnel segment showed absent response in 9 and 4 of the diabetic and non-diabetic patients, respectively. After 1 year, absent response was only found in 1 of the diabetic patients while it had reappeared in all the nondiabetic patients.
3.3. Sural and peroneal nerve Fourteen diabetic patients (10 Type 1 and 4 Type 2) had abnormal values of both the sural and peroneal nerve, and thereby classified as having peripheral neuropathy. The degree of neuropathy, among the diabetic patients, was classified by standard deviation (SD) from mean of our non-diabetic patient group, i.e. Z -scores (sural nerve SCV [ 3.7 SD], sural nerve SNAP [ 1.2 SD], peroneal nerve MCV [ 2.3 SD]). We interpret our results as mild peripheral neuropathy (Tankisi et al., 2005). The 21 diabetic patients with no signs of neuropathy, all sural and peroneal nerve measurements were within ±0.5 SD of the values for the non-diabetic patient group. 3.4. Diabetic patients with and with out neuropathy Impairment of nerve conduction parameters in diabetic patients with neuropathy, were demonstrated for both the median and the ulnar nerve. Median nerve SCV III, Elbow–wrist SCV and Palm-digit
Table 2 Ulnar nerve neurophysiologic recovery after carpal tunnel release in diabetic (DM) and non-diabetic (Non-DM) patients. Preoperative
DML (ms) MCV (m/s) CMAP-wrist (mV) SCV V (m/s) SNAP V (lV)
52 weeks follow-up
Improvement
DM
Non-DM
DM
Non-DM
DM
3.2 (3.1–3.3) 53.6 (51.7–55.4) 6.9 (6.3–7.5)
3.0 (2.9–3.1) 58.6 (56.6–60.6) 7.2 (6.7–7.7)
3.3 (3.1–3.5) 53.8 (52.2–55.5) 7.1 (6.5–7.7)
2.9 (2.7–3.0) 59.6 (57.8–61.3) 7.9 (7.4–8.3)
0.09 ( 0.05–0.2) 0.3 ( 1.2–1.7) 0.2 ( 0.2–0.6)
50.1 (47.9–52.2) 4.9 (3.6–6.1)
53.2 (51.1–55.3) 6.9 (5.6–8.3)
49.4 (47.0–51.8) 4.6 (3.4–5.8)
53.0 (50.8–55.1) 7.2 (5.8–8.6)
0.7 ( 1.9–0.6) 0.3 ( 1.0–0.5)
P-value Non-DM
Pre-op
52 weeks
Improv
–0.09 ( 0.2–0.04) 1.0 ( 0.8–2.7) 0.7 (0.3–1.1)
0.005 0.001 0.6
0.001 0.001 0.03
0.06 0.3 0.09
0.2 ( 1.9–1.4) 0.3 ( 0.5–1.1)
0.04 0.02
0.06 0.002
0.8 0.3
CMAP, compound muscle action potential; DML, distal motor latency; MCV, motor conduction velocity; SCV, sensory conduction velocity; SNAP, sensory nerve action potential. Results are reported as mean value (95% confidence interval). P-value <0.05 is indicated in bold.
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III SCV, were significantly reduced before as well as after surgical carpal tunnel release in the diabetic patients with neuropathy compared to those without neuropathy. For the ulnar nerve this applied for SCV and SNAP V. No differences in post-surgical improvement were demonstrated between patient with and without neuropathy. 3.5. Correlations To explore the influence of preoperative nerve conduction values on the ability to achieve post-surgical nerve conduction improvement, we performed Spearman correlation tests. With the exception of SNAP values, all preoperative median nerve measurements were negatively correlated with the obtained improvement after 1 year. In other words, the largest improvement was demonstrated for those with greatest impairment. E.g. wrist–palm SCV; rs = 0.69, (P = 0.001) and rs = 0.45, (P = 0.01), DML; rs = 0.89, (P = 0.001) and rs = 0.85, (P = 0.001) for the diabetic and non-diabetic patients, respectively. However, despite large improvements normal nerve conduction values were seldom reached (Table 1). 4. Discussion In this study, diabetic patients demonstrated significantly impaired nerve conduction parameters prior to and after surgical carpal tunnel release compared to non-diabetic patients. Regarding neurophysiologic recovery after carpal tunnel release, no differences were found between the two patient groups. Even though the largest neurophysiologic recovery was demonstrated for parameters with the greatest impairment, normal values were not always reached. Ulnar nerve measurements point towards the existence of subclinical neuropathy in diabetic patients. Finally, we demonstrated that diabetic patients with neurophysiologic signs of peripheral neuropathy have significant nerve impairment, also in the upper limb, compared to diabetic patients with no signs of peripheral neuropathy. However, post-surgical improvement was the same regardless of the presence of neuropathy. In non-diabetic patients with idiopathic CTS, significant neurophysiologic recovery of DML and SCV occur early on after carpal tunnel release (Ginanneschi et al., 2008a; Lang et al., 1995), but normal values were only regained in patients with minor nerve conduction abnormalities (Mondelli et al., 2000; Padua et al., 1996). In comparison of the outcome after carpal tunnel release in diabetic and non-diabetic patients, Ozkul et al. (2002) found improvement for DML and SCV to be significantly lower in diabetic patients. They had included diabetic patients on diet treatment or oral medication, and patient with bilateral symptoms were allowed to participate twice. It was concluded that CTS in the diabetic group was not only due to external anatomical factors, but also dependent on internal metabolic and vascular factors which delayed recovery. From a larger cohort of patients with CTS, Mondelli et al. (2004) selected elderly (mean age 67 year) insulin and non-insulin dependent diabetic patients to compare with non-diabetic patients having idiopathic CTS. They found no differences in the electrophysiological outcome after release of the median nerve. Results from these two studies are contradictory, why the present state of knowledge concerning neurophysiologic outcome after carpal tunnel release in diabetic patients, is inconclusive. Furthermore, no previous studies allow a differentiation of results between diabetic patients with and without peripheral neuropathy. Abnormality of nerve conduction in non-compressed nerve trunks, are recognized to develop early in diabetes (Rota et al., 2005). We were therefore not surprised to find that the measured
nerve conduction parameters were significantly impaired in the diabetic patients. Recently, pathology of a non-compressed posterior interosseous nerve in the distal forearm of the same diabetic and non-diabetic patients as studied here, demonstrated a reduction in endoneurial capillary and myelinated nerve fibre densities, compared to control subjects without CTS or neuropathy (Thomsen et al., 2009b). It is therefore tempting to speculate that this mutual nerve pathology in diabetic and non-diabetic patients with CTS could in part explain the similarity in post-surgical recovery. Subsequently, the increased nerve conduction might be caused by improved intraneurial microcirculation, but normal values were not reached because of the reduction in myelinated nerve fibre density, which was further accentuated in the diabetic patient group. For nearly all neurophysiologic parameters, we found a significant inverse correlation between preoperative values and obtained improvement. This means that the largest improvement occurred in those who had the largest preoperative impairment. A similar pattern of improvement has been described in prior studies on patients with idiopathic CTS (Higgs et al., 1997; Rotman et al., 2004). However, it is worth noticing that it has not been possible to demonstrate any relationship between neurophysiologic recovery and patients’ self-reported symptom relief (Mondelli et al., 2000; Schrijver et al., 2005). Therefore, and in accordance with our clinical experience, patients even with mild neurophysiologic impairment may experience substantial symptomatic relief after carpal tunnel release. Our results indicate that carpal tunnel release is beneficial even for diabetic patients with severe neurophysiologic impairment. Reduced motor conduction velocity of the forearm median nerve, is not uncommon in idiopathic CTS. The pathogenesis has been ascribed to a selective slowing of large myelinated nerve fibres in the carpal tunnel (Stevens, 1997), retrograde conduction slowing and/or retrograde axonal atrophy (Chang et al., 2008). An experimental setting demonstrated that a partial peripheral nerve injury may induce a reactive slowing of motor conduction velocity in the axons proximal to the injury site (Havton et al., 2001). We found the reduction of elbow–wrist SCV significantly more pronounced in diabetic patients. Possible mechanisms for this difference might be the increased susceptibility to nerve compression and the noticeable impairment of fast axonal transport found in diabetes (Dahlin et al., 1986; Hansson, 1995). As recovery was marked, our results demonstrate that significantly reduced median nerve forearm conduction velocity is not a negative prognostic factor of neurophysiologic improvement after carpal tunnel release in diabetic patients. Abnormality in ulnar nerve conduction has previously been found in patients with mild CTS (Ginanneschi et al., 2008b). The mean changes that we observed in the ulnar nerve after surgery were less than what is considered clinically detectable and meaningful (Dyck and O’Brien, 1989), which probably reflects that we carefully excluded patients with signs of nerve entrapment other that CTS. Although within the normal range of our laboratory, we found ulnar nerve conduction parameters to be generally impaired in diabetic patients. This is supportive of subclinical neuropathy of the ulnar nerve, previously described in asymptomatic Type 2 diabetic patients using tactilometry (Dahlin et al., 2008). The influence of peripheral neuropathy on results after carpal tunnel release has only been sparsely investigated. So far, results have been obtained by chart review or telephone survey on patients with neuropathy of different origin (Clayburgh et al., 1987; Morgenlander et al., 1997). Or, the sample of diabetic patients with neuropathy has been too small to allow reliable comparison and conclusion (Capasso et al., 2009; Mondelli et al., 2004). Our study represents the first comparative evaluation of neurophysiologic recovery after carpal tunnel release in diabetic patients with and without peripheral neuropathy. An interesting finding is that the
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conduction velocity proximal and distal, but not at the carpal tunnel segment, was significantly reduced in diabetic patients with peripheral neuropathy. This implies a more homogeneous nerve dysfunction in neuropathy, compared to the reactive changes due to nerve compression, and may be used to indicate presence of peripheral neuropathy. However, in our diabetic patients carrying evidence of mild peripheral neuropathy, no differences in recovery could be demonstrated compared to diabetic patients without neuropathy. To evaluate, the influence of various degrees of neuropathy a much larger study group is required than included in the present study. Previously, we have demonstrated that the diabetic patients with CTS experience the same beneficial clinical outcome after carpal tunnel release as non-diabetic patients (Thomsen et al., 2009a). The clinical implication and conclusion of the present study is that even though diabetic patients with CTS have significantly impaired nerve conduction parameters compared to non-diabetic patients with CTS, they obtain the same degree of neurophysiologic recovery after surgical carpal tunnel release. This result even applies to diabetic patients with evidence of peripheral neuropathy. We therefore, recommend that diabetic patients with CTS are offered the same opportunities for surgical carpal tunnel release as non-diabetic patients.
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Neurology 2002;58:1589–92. Kikkawa Y, Kuwabara S, Misawa S, Tamura N, Kitano Y, Ogawara K, et al. The acute effects of glycemic control on nerve conduction in human diabetics. Clin Neurophysiol 2005;116:270–4. Lang E, Spitzer A, Pfannmuller D, Claus D, Handwerker HO, Neundorfer B. Function of thick and thin nerve fibers in carpal tunnel syndrome before and after surgical treatment. Muscle Nerve 1995;18:207–15. Lindstrom P, Lindblom U, Brismar T. Delayed recovery of nerve conduction and vibratory sensibility after ischaemic block in patients with diabetes mellitus. J Neurol Neurosurg Psychiatry 1997;63:346–50. Mondelli M, Padua L, Reale F, Signorini AM, Romano C. Outcome of surgical release among diabetics with carpal tunnel syndrome. Arch Phys Med Rehabil 2004;85:7–13. Mondelli M, Reale F, Sicurelli F, Padua L. Relationship between the selfadministered Boston questionnaire and electrophysiological findings in follow-up of surgically-treated carpal tunnel syndrome. J Hand Surg [Br] 2000;25:128–34. Morgenlander JC, Lynch JR, Sanders DB. Surgical treatment of carpal tunnel syndrome in patients with peripheral neuropathy. Neurology 1997;49: 1159–63. Naidu SH, Fisher J, Heistand M, Kothari MJ. Median nerve function in patients undergoing carpal tunnel release: pre- and post-op nerve conductions. Electromyogr Clin Neurophysiol 2003;43:393–7. Ozkul Y, Sabuncu T, Kocabey Y, Nazligul Y. Outcomes of carpal tunnel release in diabetic and non-diabetic patients. Acta Neurol Scand 2002;106:168–72. Padua L, LoMonaco M, Aulisa L, Tamburrelli F, Valente EM, Padua R, et al. Surgical prognosis in carpal tunnel syndrome: usefulness of a preoperative neurophysiological assessment. Acta Neurol Scand 1996;94:343–6. Rosen I. Neurophysiological diagnosis of the carpal tunnel syndrome: evaluation of neurographic techniques. Scand J Plast Reconstr Surg Hand Surg 1993;27:95–101. Rota E, Quadri R, Fanti E, Isoardo G, Poglio F, Tavella A, et al. Electrophysiological findings of peripheral neuropathy in newly diagnosed type II diabetes mellitus. J Peripher Nerv Syst 2005;10:348–53. Rotman MB, Enkvetchakul BV, Megerian JT, Gozani SN. Time course and predictors of median nerve conduction after carpal tunnel release. J Hand Surg [Am] 2004;29:367–72. Schrijver HM, Gerritsen AA, Strijers RL, Uitdehaag BM, Scholten RJ, de Vet HC, et al. Correlating nerve conduction studies and clinical outcome measures on carpal tunnel syndrome: lessons from a randomized controlled trial. J Clin Neurophysiol 2005;22:216–21. Stevens JC. AAEM minimonograph #26: the electrodiagnosis of carpal tunnel syndrome. American Association of Electrodiagnostic Medicine. Muscle Nerve 1997;20:1477–86. Tankisi H, Pugdahl K, Fuglsang-Frederiksen A, Johnsen B, de Carvalho M, Fawcett PR, et al. Pathophysiology inferred from electrodiagnostic nerve tests and classification of polyneuropathies. Suggested guidelines. Clin Neurophysiol 2005;116:1571–80. Thomsen NO, Cederlund R, Rosen I, Bjork J, Dahlin LB. Clinical outcomes of surgical release among diabetic patients with carpal tunnel syndrome: prospective follow-up with matched controls. J Hand Surg Am 2009a;34:1177–87. Thomsen NO, Mojaddidi M, Malik RA, Dahlin LB. Reduced myelinated nerve fibre and endoneurial capillary densities in the forearm of diabetic and non-diabetic patients with carpal tunnel syndrome. Acta Neuropathol 2009b;118:785–91. Todnem K, Lundemo G. Median nerve recovery in carpal tunnel syndrome. Muscle Nerve 2000;23:1555–60.
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Neurophysiologic recovery after carpal tunnel release in diabetic patients Niels O.B. Thomsen a,*, Ingmar Rosén b, Lars B. Dahlin a a b
Department of Hand Surgery, Malmö University Hospital, Malmö, Sweden Department of Clinical Neurophysiology, Lund University Hospital, Lund, Sweden
a r t i c l e
i n f o
Article history: Accepted 15 March 2010 Available online 21 April 2010 Keywords: Carpal tunnel syndrome Diabetes Neuropathy Neurophysiology
a b s t r a c t Objective: To compare nerve conduction study results, before and after surgical carpal tunnel release, in diabetic and non-diabetic patients. Methods: In a prospective study (2004–2007), we included 35 consecutive diabetic patients with carpal tunnel syndrome (CTS), who were age and gender matched with 31 non-diabetic patients having idiopathic CTS. Preoperatively, and at the 1 year follow-up, nerve conduction studies were performed of the median and ulnar nerve. Presence of neuropathy was based on abnormal preoperative neurophysiologic values in both the sural and the peroneal nerve. Results: Diabetic patients demonstrated significantly impaired nerve conduction parameters, before as well as after surgical carpal tunnel release, compared to non-diabetic patients. However, neurophysiologic recovery after carpal tunnel release was not different between the two patient groups or between diabetic patients with or without peripheral neuropathy. In general, the largest neurophysiologic recovery was demonstrated for parameters with the greatest impairment, but normal values were seldom reached. Conclusions: Marked neurophysiologic impairment of the median nerve, or signs of peripheral neuropathy, does not preclude significant recovery after carpal tunnel release in diabetic patients. Significance: Diabetic patients with CTS should be offered the same opportunities for surgical carpal tunnel release as non-diabetic patients. Ó 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction Diabetic neuropathy is a common complication of both Type 1 and Type 2 diabetes which affects up to 50% of the patients. Length dependent, symmetric sensori-motor neuropathy represents its most frequent form, primarily affecting the feet and lower limbs, causing pain and paraesthesiae (Boulton et al., 2005). With progression of the neuropathy, symptoms spread proximally. Measurement of sensory and motor nerve conduction velocity is regarded important in the identification and quantification of neuropathy in diabetic patients, and to document the clinical course of treatment (Bril et al., 1998). In diabetes, impaired nerve conduction in non-compressed nerves develop early on in the disease, at which time it can still be reversed by strict metabolic control (Gregersen, 1968; Kikkawa et al., 2005; Rota et al., 2005). In the presence of diabetic neuropathy, structural nerve changes such as segmental and paranodal demyelination, may cause a decreased in nerve conduction velocity, as well as loss of axons in the nerve trunk might lead to decreased nerve action potential (Behse et al., 1977).
* Correspondence to: N.O.B. Thomsen, Department of Hand Surgery, Malmö University Hospital, SE-205 02 Malmö, Sweden. Tel.: +46 40 33 67 90; fax: +46 40 92 88 55. E-mail address: [email protected] (N.O.B. Thomsen).
Diabetic neuropathy also includes a group of focal entrapment mononeuropathies which are more common in diabetes, such as carpal tunnel syndrome (CTS). Nerve conduction studies are often used to confirm the clinical diagnosis of CTS and provide a high degree of sensitivity and specificity (Jablecki et al., 2002). However, its value as an additional diagnostic tool when compared to clinical history and examination has been questioned (Graham, 2008). In addition, it has not been possible to demonstrate a relationship between nerve conduction results and clinical outcome measures after carpal tunnel release (Mondelli et al., 2000; Schrijver et al., 2005). In spite of this, neurophysiology provides the most objective, noninvasive assessment of myelinated nerve fibre dysfunction, and has an important complimentary function in cases of atypical clinical presentation, or when other underlying causes such as neuropathy are suspected. Neurophysiologic evidence of asymptomatic CTS has been demonstrated in 20–30% of insulin and non-insulin dependent diabetic patients (Albers et al., 1996; Dyck et al., 1993). Paradoxical to increased susceptibility to focal nerve entrapment in diabetes, experimental and clinical nerve conduction studies have demonstrated increased resistance to ischaemic block (Lindstrom et al., 1997). While well documented for non-diabetic patients (Ginanneschi et al., 2008a; Naidu et al., 2003; Todnem and Lundemo, 2000), neurophysiologic results after carpal tunnel release in diabetic
1388-2457/$36.00 Ó 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.clinph.2010.03.014
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patients have only been sparsely investigated, and conclusions have been conflicting (Mondelli et al., 2004; Ozkul et al., 2002). The aim of this study, in which clinical results previously have been published (Thomsen et al., 2009a), was to compare nerve conduction study results before and after surgical carpal tunnel release, in a prospective series of age- and gender-matched diabetic and non-diabetic patients. 2. Methods 2.1. Patients From 2004 to 2007, consecutive patients with diabetes referred to our outpatient clinic with symptomatic CTS over at least six months, were invited to participate in the study. Eligibility criteria has previously been described in detail (Thomsen et al., 2009a). The study was approved by the Regional Ethical Review Board at Lund University. All patients gave informed consent to participate. We included 36 consecutive patients with diabetes and CTS and 36 age and gender matched non-diabetic patients with idiopathic CTS. The diagnosis of CTS was based on clinical history and symptoms, and confirmed by median nerve conduction studies (antidromic, wrist–palm, sensory conduction velocity [<44 m/s] and distal motor latency [>4.1 ms]). Exclusion criteria were: previous carpal tunnel release in the hand under study, clinical signs of focal nerve entrapment other than CTS, cervical radiculopathy, inflammatory joint disease, renal failure, thyroid disorders, previous wrist fracture on the affected side, daily long-term exposure to vibrating tools, pregnancy or age below 18 years. To ascertain that none of the non-diabetic patients has undiagnosed diabetes an oral glucose tolerance test was performed according to suggested guidelines (American Diabetes Association, 2006). Signs of peripheral neuropathy demonstrated in the nerve conduction study were an exclusion criterion for the non-diabetic patients with CTS, but not for the diabetic patients with CTS. After screening, we excluded one patient from the diabetic group due to the diagnosis of thyroid dysfunction. In the non-diabetic group, three patients we excluded because of diagnosed diabetes and two were excluded due to nerve conduction studies demonstrated signs of peripheral neuropathy of unknown origin. After screening there were no drop-outs and the follow-up rate was 100%. Thus, the patients under study consisted of 35 diabetic patients with CTS (15 Type 1 and 20 with Type 2 diabetes). The group included 22 females and 13 males with a mean age of 53 years (range 31–73). Mean duration of diabetes was 17 years (range 1–43) and mean duration of CTS symptoms was 27 months (range 8–96). Body mass index was 27.6 kg/m2 (SD ± 4.8) and glycosylated hemoglobin (HbA1c) level was 6.9% (SD ± 1.3). The diabetic patients were matched with 31 non-diabetic patients with CTS including 19 females and 12 males with a mean age of 52 years (range 35–77). Mean duration of CTS symptoms was 48 months (range 12–80). Body mass index was 27.0 kg/m2 (SD ± 4.1) and glycosylated hemoglobin level was 4.5% (SD ± 0.3).
(Viasys Inc., Madison, WI, USA). The investigations were conducted with surface electrodes (skin temperature kept above 30 °C); additional needle electromyography was not performed. All investigations were performed by the same technician and evaluated independently, by the same neurophysiologist. 2.3.1. Median motor nerve conduction studies We recorded distal motor latency (DML); (wrist to abductor pollicis brevis, distance between stimulation and recording electrodes 8 cm). Motor conduction velocity (MCV) was measured from elbow to wrist level. Compound muscle action potential (CMAP) was measured from onset to the peak of the initial monophasic negative muscle response. 2.3.2. Median sensory nerve conduction studies Orthodromic sensory nerve action potentials (SNAP) from digits I and III, were obtained with recording electrodes 2 cm proximal to distal wrist crease, inter-electrode distance 3 cm on stimulation at the proximal phalanx of digits I and III, respectively (Jablecki et al., 2002). Fractionated measurement of antidromic sensory conduction velocity (SCV) over the carpal tunnel segment (Rosen, 1993) was recorded by ring electrodes at digit III with stimulation of the median nerve in the palm, 2 cm proximal to the distal wrist crease, and at the elbow. 2.3.3. Ulnar motor and sensory nerve conduction studies Ulnar motor conduction was studied by recording CMAP from the abductor digiti minimi and stimulation at the wrist and at the elbow. Orthodromic sensory conduction was determined by stimulation of digit V and recording at the wrist. 2.3.4. Sural and peroneal nerve conduction studies To diagnose peripheral neuropathy, at the preoperative neurophysiologic session, all patients had measurement of sural nerve SCV, sural SNAP and peroneal nerve MCV. Sensory action potentials from the sural nerve were measured antidromic at the lateral malleolus with stimulation of the nerve at the posterolateral side of the calf (stimulation-recording distance standardized at 140 mm). Peroneal motor response was recorded from the extensor digiti brevis muscle with stimulation at the ankle and in the popliteal fossa. 2.4. Classification of neuropathy Criterion of peripheral neuropathy was detection of abnormal values in both the sural and the peroneal nerve (England et al., 2005). To classify the degree of neuropathy, we calculated Z-scores as standard deviation (SD) from mean of our non-diabetic patient group ([diabetic patient’s value – the mean of non-diabetic patients’ values]/SD of non-diabetic patients’ values). According to suggested guidelines by a group of European neurophysiologists, <±2SD were considered normal (Tankisi et al., 2005).
2.2. Surgical procedure The surgical procedure, previously described (Thomsen et al., 2009a), was performed by the same surgeon and consisted of a standardized open carpal tunnel release (short, palm only incision). No additional procedures were done. 2.3. Nerve conduction studies Preoperatively, and at a 1 year follow-up, nerve conduction studies were performed using a Viking Select electromyograph
2.5. Statistical analysis Differences in continuous data between groups and within groups were tested using non-parametric Mann–Whitney U-test and Wilcoxon signed rank test, respectively. Fisher’s exact test was used for categorical data. Correlations were performed using Spearman rank sum test and expressed as a coefficient (rs) with a level of significance. Statistical analysis was performed using SPSS 14.0 for Windows (SPSS Inc., Chicago, IL, USA). P < 0.05 was considered statistically significant.
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DML (ms) MCV (m/s) CMAP-wrist (mV) SCV I (m/s) SCV III (m/s) SNAP I (lV) SNAP III (lV) Elbow–wrist SCV (m/s) Wrist–palm SCV (m/s) Palm-digit III SCV (m/s)
52 weeks follow-up
Improvement
P-value
DM
Non-DM
DM
Non-DM
6.4 (5.8–7.1) 47.8 (44.4–51.1) [1] 5.0 (4.2–5.8) [1]
5.2 (4.8–5.7) 52.9 (51.2–54.6) 6.2 (5.4–7.1)
4.7 (4.5– 5.0) 49.2 (45.9–52.4) [1] 5.6 (4.9–6.3)
4.3 (4.0–4.5) 1.7 (1.2–2.2) 54.1 (52.3–55.9) 1.4 ( 0.1–2.9) 6.6 (5.9–7.3) 0.6 (0.1–1.1)
DM
Non-DM
Pre-op
52 weeks
Improv
1.0 (0.6–1.4) 1.2 ( 0.2–2.7) 0.3 ( 0.4–1.1)
0.003 0.002 0.05
0.002 0.001 0.05
0.07 0.8 0.5
21.3 (16.2–26.6) [10] 22.0 (16.0–28.0) [12]
29.5 (25.3–33.7) [3] 29.6 (23.8–35.4) [6]
36.0 (32.8–39.2) [1] 37.2 (33.1–41.2) [2]
42.3 (40.0–44.6) 14.6 (10.5–18.8) 12.8 (9.2–16.4) 44.2 (41.5–46.9) 15.2 (10.6–19.8) 14.5 (9.7–19.4)
0.02 0.04
0.001 0.005
0.7 0.9
4.7 (2.3–7.1) [10] 2.7 (1.2–4.2) [12] 36.0 (26.8–45.2) [12]
6.8 (4.3–9.3) [3] 3.9 (2.4–5.4) [6] 50.9 (43.3–58.5) [4]
8.1 (6.2–10.1) [2] 4.9 (3.5–6.2) [2] 53.6 (49.5–57.6) [1]
12.2 (9.6–14.8) 8.7 (6.6–10.8) 57.7 (56.0–59.5)
3.4 (1.7–5.1) 2.1 (1.3–2.9) 17.6 (9.6–25.6)
0.05 0.1 0.003
0.02 0.004 0.04
0.1 0.01 0.007
18.4 (14.0–22.8) [9]
24.1 (20.2–28.0) [4]
32.6 (29.6–35.6) [1]
40.1 (37.1–43.1)
14.2 (10.6–17.8) 16.0 (13.3–18.6)
0.03
0.001
0.2
34.2 (26.7–41.7) [9]
42.9 (35.9–49.9) [4]
46.9 (42.7–51.0) [1]
53.0 (49.8–56.2)
12.6 (6.6–18.7)
0.05
0.04
0.6
5.4 (2.9–7.9) 4.8 (3.2–6.5) 6.9 ( 0.7–14.2)
10.2 (4.6–15.8)
CMAP, compound muscle action potential; DML, distal motor latency; MCV, motor conduction velocity; SCV, sensory conduction velocity; SNAP, sensory nerve action potential. Results are reported as mean value (95% confidence interval) and [number with absent neurophysiologic response]. P-value <0.05 is indicated in bold.
3. Results
3.2. Ulnar nerve
The groups of diabetic and non-diabetic patients are comparable with the exception of the non-diabetic patients who had CTS symptoms for a significantly longer period (P < 0.008). The diabetic patients had excellent glycaemic control reflected by the glycosylated haemoglobin level (6.9 ± 1.3%).
The results reflect our exclusion of patients with clinical signs of focal nerve entrapment other than CTS (Table 2). However, the general finding, prior to and after carpal tunnel release, was that DML remained prolonged, and that both motor and sensory conduction velocities, as well as amplitudes, continued to be significantly reduced in diabetic compared to non-diabetic patients. No meaningful changes of conduction parameters were demonstrated at the follow-up of diabetic or non-diabetic patients.
3.1. Median nerve Results from the median nerve conduction studies on diabetic and non-diabetic patients before and after surgical carpal tunnel release are summarized in Table 1. Nearly all preoperative nerve conduction parameters were significantly impaired for the diabetic patients compared to the non-diabetic patients. At the 1 year follow-up, antidromic elbow–wrist SCV had improved to a significantly higher extent in the group of diabetic patients while SNAP III had improved considerably more in the non-diabetic patients. Otherwise, no differences in progress between the two patient groups were observed. The diabetic group included an increased number of patients with absent response on SCV I (10 vs. 3), SCV III (12 vs. 6), SNAP I (10 vs. 3) and SNAP III (12 vs. 6) compared to the non-diabetic patients. One year after surgery absent neurophysiologic response was observed only in a few diabetic patients, while response could be evoked in all non-diabetic patients. Preoperatively, the wrist–palm SCV over the carpal tunnel segment showed absent response in 9 and 4 of the diabetic and non-diabetic patients, respectively. After 1 year, absent response was only found in 1 of the diabetic patients while it had reappeared in all the nondiabetic patients.
3.3. Sural and peroneal nerve Fourteen diabetic patients (10 Type 1 and 4 Type 2) had abnormal values of both the sural and peroneal nerve, and thereby classified as having peripheral neuropathy. The degree of neuropathy, among the diabetic patients, was classified by standard deviation (SD) from mean of our non-diabetic patient group, i.e. Z -scores (sural nerve SCV [ 3.7 SD], sural nerve SNAP [ 1.2 SD], peroneal nerve MCV [ 2.3 SD]). We interpret our results as mild peripheral neuropathy (Tankisi et al., 2005). The 21 diabetic patients with no signs of neuropathy, all sural and peroneal nerve measurements were within ±0.5 SD of the values for the non-diabetic patient group. 3.4. Diabetic patients with and with out neuropathy Impairment of nerve conduction parameters in diabetic patients with neuropathy, were demonstrated for both the median and the ulnar nerve. Median nerve SCV III, Elbow–wrist SCV and Palm-digit
Table 2 Ulnar nerve neurophysiologic recovery after carpal tunnel release in diabetic (DM) and non-diabetic (Non-DM) patients. Preoperative
DML (ms) MCV (m/s) CMAP-wrist (mV) SCV V (m/s) SNAP V (lV)
52 weeks follow-up
Improvement
DM
Non-DM
DM
Non-DM
DM
3.2 (3.1–3.3) 53.6 (51.7–55.4) 6.9 (6.3–7.5)
3.0 (2.9–3.1) 58.6 (56.6–60.6) 7.2 (6.7–7.7)
3.3 (3.1–3.5) 53.8 (52.2–55.5) 7.1 (6.5–7.7)
2.9 (2.7–3.0) 59.6 (57.8–61.3) 7.9 (7.4–8.3)
0.09 ( 0.05–0.2) 0.3 ( 1.2–1.7) 0.2 ( 0.2–0.6)
50.1 (47.9–52.2) 4.9 (3.6–6.1)
53.2 (51.1–55.3) 6.9 (5.6–8.3)
49.4 (47.0–51.8) 4.6 (3.4–5.8)
53.0 (50.8–55.1) 7.2 (5.8–8.6)
0.7 ( 1.9–0.6) 0.3 ( 1.0–0.5)
P-value Non-DM
Pre-op
52 weeks
Improv
–0.09 ( 0.2–0.04) 1.0 ( 0.8–2.7) 0.7 (0.3–1.1)
0.005 0.001 0.6
0.001 0.001 0.03
0.06 0.3 0.09
0.2 ( 1.9–1.4) 0.3 ( 0.5–1.1)
0.04 0.02
0.06 0.002
0.8 0.3
CMAP, compound muscle action potential; DML, distal motor latency; MCV, motor conduction velocity; SCV, sensory conduction velocity; SNAP, sensory nerve action potential. Results are reported as mean value (95% confidence interval). P-value <0.05 is indicated in bold.
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III SCV, were significantly reduced before as well as after surgical carpal tunnel release in the diabetic patients with neuropathy compared to those without neuropathy. For the ulnar nerve this applied for SCV and SNAP V. No differences in post-surgical improvement were demonstrated between patient with and without neuropathy. 3.5. Correlations To explore the influence of preoperative nerve conduction values on the ability to achieve post-surgical nerve conduction improvement, we performed Spearman correlation tests. With the exception of SNAP values, all preoperative median nerve measurements were negatively correlated with the obtained improvement after 1 year. In other words, the largest improvement was demonstrated for those with greatest impairment. E.g. wrist–palm SCV; rs = 0.69, (P = 0.001) and rs = 0.45, (P = 0.01), DML; rs = 0.89, (P = 0.001) and rs = 0.85, (P = 0.001) for the diabetic and non-diabetic patients, respectively. However, despite large improvements normal nerve conduction values were seldom reached (Table 1). 4. Discussion In this study, diabetic patients demonstrated significantly impaired nerve conduction parameters prior to and after surgical carpal tunnel release compared to non-diabetic patients. Regarding neurophysiologic recovery after carpal tunnel release, no differences were found between the two patient groups. Even though the largest neurophysiologic recovery was demonstrated for parameters with the greatest impairment, normal values were not always reached. Ulnar nerve measurements point towards the existence of subclinical neuropathy in diabetic patients. Finally, we demonstrated that diabetic patients with neurophysiologic signs of peripheral neuropathy have significant nerve impairment, also in the upper limb, compared to diabetic patients with no signs of peripheral neuropathy. However, post-surgical improvement was the same regardless of the presence of neuropathy. In non-diabetic patients with idiopathic CTS, significant neurophysiologic recovery of DML and SCV occur early on after carpal tunnel release (Ginanneschi et al., 2008a; Lang et al., 1995), but normal values were only regained in patients with minor nerve conduction abnormalities (Mondelli et al., 2000; Padua et al., 1996). In comparison of the outcome after carpal tunnel release in diabetic and non-diabetic patients, Ozkul et al. (2002) found improvement for DML and SCV to be significantly lower in diabetic patients. They had included diabetic patients on diet treatment or oral medication, and patient with bilateral symptoms were allowed to participate twice. It was concluded that CTS in the diabetic group was not only due to external anatomical factors, but also dependent on internal metabolic and vascular factors which delayed recovery. From a larger cohort of patients with CTS, Mondelli et al. (2004) selected elderly (mean age 67 year) insulin and non-insulin dependent diabetic patients to compare with non-diabetic patients having idiopathic CTS. They found no differences in the electrophysiological outcome after release of the median nerve. Results from these two studies are contradictory, why the present state of knowledge concerning neurophysiologic outcome after carpal tunnel release in diabetic patients, is inconclusive. Furthermore, no previous studies allow a differentiation of results between diabetic patients with and without peripheral neuropathy. Abnormality of nerve conduction in non-compressed nerve trunks, are recognized to develop early in diabetes (Rota et al., 2005). We were therefore not surprised to find that the measured
nerve conduction parameters were significantly impaired in the diabetic patients. Recently, pathology of a non-compressed posterior interosseous nerve in the distal forearm of the same diabetic and non-diabetic patients as studied here, demonstrated a reduction in endoneurial capillary and myelinated nerve fibre densities, compared to control subjects without CTS or neuropathy (Thomsen et al., 2009b). It is therefore tempting to speculate that this mutual nerve pathology in diabetic and non-diabetic patients with CTS could in part explain the similarity in post-surgical recovery. Subsequently, the increased nerve conduction might be caused by improved intraneurial microcirculation, but normal values were not reached because of the reduction in myelinated nerve fibre density, which was further accentuated in the diabetic patient group. For nearly all neurophysiologic parameters, we found a significant inverse correlation between preoperative values and obtained improvement. This means that the largest improvement occurred in those who had the largest preoperative impairment. A similar pattern of improvement has been described in prior studies on patients with idiopathic CTS (Higgs et al., 1997; Rotman et al., 2004). However, it is worth noticing that it has not been possible to demonstrate any relationship between neurophysiologic recovery and patients’ self-reported symptom relief (Mondelli et al., 2000; Schrijver et al., 2005). Therefore, and in accordance with our clinical experience, patients even with mild neurophysiologic impairment may experience substantial symptomatic relief after carpal tunnel release. Our results indicate that carpal tunnel release is beneficial even for diabetic patients with severe neurophysiologic impairment. Reduced motor conduction velocity of the forearm median nerve, is not uncommon in idiopathic CTS. The pathogenesis has been ascribed to a selective slowing of large myelinated nerve fibres in the carpal tunnel (Stevens, 1997), retrograde conduction slowing and/or retrograde axonal atrophy (Chang et al., 2008). An experimental setting demonstrated that a partial peripheral nerve injury may induce a reactive slowing of motor conduction velocity in the axons proximal to the injury site (Havton et al., 2001). We found the reduction of elbow–wrist SCV significantly more pronounced in diabetic patients. Possible mechanisms for this difference might be the increased susceptibility to nerve compression and the noticeable impairment of fast axonal transport found in diabetes (Dahlin et al., 1986; Hansson, 1995). As recovery was marked, our results demonstrate that significantly reduced median nerve forearm conduction velocity is not a negative prognostic factor of neurophysiologic improvement after carpal tunnel release in diabetic patients. Abnormality in ulnar nerve conduction has previously been found in patients with mild CTS (Ginanneschi et al., 2008b). The mean changes that we observed in the ulnar nerve after surgery were less than what is considered clinically detectable and meaningful (Dyck and O’Brien, 1989), which probably reflects that we carefully excluded patients with signs of nerve entrapment other that CTS. Although within the normal range of our laboratory, we found ulnar nerve conduction parameters to be generally impaired in diabetic patients. This is supportive of subclinical neuropathy of the ulnar nerve, previously described in asymptomatic Type 2 diabetic patients using tactilometry (Dahlin et al., 2008). The influence of peripheral neuropathy on results after carpal tunnel release has only been sparsely investigated. So far, results have been obtained by chart review or telephone survey on patients with neuropathy of different origin (Clayburgh et al., 1987; Morgenlander et al., 1997). Or, the sample of diabetic patients with neuropathy has been too small to allow reliable comparison and conclusion (Capasso et al., 2009; Mondelli et al., 2004). Our study represents the first comparative evaluation of neurophysiologic recovery after carpal tunnel release in diabetic patients with and without peripheral neuropathy. An interesting finding is that the
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conduction velocity proximal and distal, but not at the carpal tunnel segment, was significantly reduced in diabetic patients with peripheral neuropathy. This implies a more homogeneous nerve dysfunction in neuropathy, compared to the reactive changes due to nerve compression, and may be used to indicate presence of peripheral neuropathy. However, in our diabetic patients carrying evidence of mild peripheral neuropathy, no differences in recovery could be demonstrated compared to diabetic patients without neuropathy. To evaluate, the influence of various degrees of neuropathy a much larger study group is required than included in the present study. Previously, we have demonstrated that the diabetic patients with CTS experience the same beneficial clinical outcome after carpal tunnel release as non-diabetic patients (Thomsen et al., 2009a). The clinical implication and conclusion of the present study is that even though diabetic patients with CTS have significantly impaired nerve conduction parameters compared to non-diabetic patients with CTS, they obtain the same degree of neurophysiologic recovery after surgical carpal tunnel release. This result even applies to diabetic patients with evidence of peripheral neuropathy. We therefore, recommend that diabetic patients with CTS are offered the same opportunities for surgical carpal tunnel release as non-diabetic patients.
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