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Evaluation of Upper Extremity Nerve Conduction Velocities and the Relationship Between Fibromyalgia and Carpal Tunnel Syndrome
Archives of Medical Research 43 (2012) 369e374
ORIGINAL ARTICLE
Evaluation of Upper Extremity Nerve Conduction Velocities and the Relationship Between Fibromyalgia and Carpal Tunnel Syndrome Baris Nacir, Hakan Genc, Burcu Duyur Cakit, Aynur Karagoz, and Hatice R. Erdem Department of Physical Medicine and Rehabilitation, Ministry of Health, Ankara Training and Research Hospital, Ankara, Turkey Received for publication March 14, 2012; accepted July 4, 2012 (ARCMED-D-12-00143).
Background and Aims. We undertook this study to evaluate upper extremity nerve conduction velocities (NCVs) in fibromyalgia syndrome (FS) and the relationship of the electrophysiological findings between carpal tunnel syndrome (CTS) and FS. Methods. Sixty three right-handed female patients diagnosed with FS and 52 righthanded age- and gender-matched healthy controls were enrolled in the study. Conduction studies of the median and ulnar nerves and median nerve F-wave latencies were assessed in both upper extremities using standard methods. CTS was diagnosed electrophysiologically if the median nerve sensory NCV was decreased and/or motor distal latency (DL) was prolonged. Results. CTS was detected electrophysiologically in 26 (20.63%) of 126 extremities of 63 patients and in three (2.82%) of 104 extremities of 52 individuals of the control group. Statistically significant differences were detected between groups with respect to rate of carpal tunnel syndrome ( p !0.05). There were no differences between results of NCVs of patients in FS group and healthy controls except the prolongation of the right median nerve motor DL ( p 5 0.019), decrease of the sensory NCV ( p 5 0.003) in the right median nerve, in the left median nerve ( p 5 0.011) and in the left ulnar nerve ( p 5 0.015). Conclusions. We determined an increased rate of CTS and decreased NCVs in the upper extremities in patients with FS. We should consider that complaints of paresthesia and pain in hands, increasing especially at nights, observed in FS may mask that CTS can be an associated illness. Ó 2012 IMSS. Published by Elsevier Inc. Key Words: Fibromyalgia, Carpal tunnel syndrome, Nerve conduction studies.
Introduction Fibromyalgia syndrome (FS) is a soft tissue rheumatism etiology of which is not exactly known. It is characterized by widespread musculoskeletal pain and tender points, sleep disturbance, morning stiffness, fatigue, irritable bowel syndrome, complaints of paresthesia, pain and a subjective sense of swelling in hands, as well as frequent psychological distress (1). According to the criteria of the American College of Rheumatology (ACR), paresthesia and sensory alterations, which are also frequently observed symptoms of focal neuropathies, are seen in O80% of patients diagnosed with FS (2,3). The symptom of paresthesia in hands has been reported to be Address reprint requests to: Baris Nacir, Ministry of Health Ankara Research and Education Hospital, 2nd Department of Physical Medicine and Rehabilitation, Ulucanlar Caddesi, Ankara 06340, Turkey; Phone: þ903124303857; FAX: þ903124681335; E-mail: [email protected]
a distinctly problematic complaint in some FS patients. Paresthesia has been stated to be capable of showing dissemination patterns confused with entrapment neuropathies and radiculopathies. The appearance mechanism of paresthesia in FS is not exactly known. However, paresthesia is considered to be a result of an abnormal sensory perception occurring due to central sensitization (4,5). Carpal tunnel syndrome (CTS) occurring as a consequence of the compression of the median nerve at the wrist is seen more frequently in women and is the most commonly seen entrapment neuropathy in the upper extremity. Although CTS may develop during the course of numerous diseases, in most cases the etiological cause cannot be detected (6,7). FS is a disease affecting |2% of the population 18 years of age and older and is more frequently seen in women than men (8). CTS prevalence in the community is estimated to be 9.2% (7). Epidemiological studies show that CTS, like
0188-4409/$ - see front matter. Copyright Ó 2012 IMSS. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.arcmed.2012.07.004
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FS, is a disease more frequently seen in women (6). Paresthesia and pain in hands, increasing especially at night, and morning stiffness can be seen in FS as is also seen in CTS. The similarity between the symptoms both in FS and CTS and incidence of both entities in women may lead to confusion and thus may make one disease mask the other (9). The aim of this study was to evaluate upper extremity nerve conduction velocities (NCVs) to detect prevalence of electrophysiological CTS and to compare the results with healthy individuals. Materials and Methods Sixty three right-handed consecutive female patients attending our clinic with complaints of paresthesia in hands between March 2006 and October 2007 and diagnosed with FS according to the ACR 1990 diagnostic criteria (1) and 52 right-handed, age- and gender-matched healthy controls were enrolled in study. All patients were homemakers. Control subjects were selected from the healthy hospital staff. The local ethics committee approved the study and written informed consent was obtained from each study participant. Patients !18 years and O65 years of age and with a history of hypo-hyperthyroidism, diabetes mellitus, rheumatoid arthritis, obesity, malignant disease, and distal radius fracture were excluded from the study. Patients with a history of medication use leading to neuropathy and patients treated with antiepileptic drugs for neuropathic pain were also excluded. None of the patients or controls performed repetitive wrist activities. Neurophysiological tests were performed at room temperature with a Nihon-Kohden Neuropack M1 (Tokyo, Japan) electroneuromyography equipment. Skin temperature was 32 C on the dorsum of the hand. Conduction studies of the median and ulnar nerves and median nerve F-wave latencies were assessed in both upper extremities using standard methods (10). Motor conduction studies were performed using an orthodromic method and superficial disc electrodes. Sensory conduction studies were performed using antidromic method and ring electrodes. Digit2-wrist segment was used for median sensory nerve conduction studies and digit5-wrist segment was used for ulnar sensory nerve conduction studies. Sensory NCVs were calculated from the beginning of the stimulus artifact to the onset of the sensory nerve action potential (SNAP). Peak-to-peak amplitudes were measured. In the motor nerve conduction studies, electrodes were placed over the abductor pollicis brevis muscle for the median nerve and the adductor digiti minimi muscle for the ulnar nerve. The active recording electrode was placed on the belly of the examined muscle and the reference electrode was placed on the tendon insertion. Compound muscle action potential (CMAP) was obtained by stimulating the median nerve at the wrist (5 cm proximal to the active recording electrode placed on the abductor pollicis brevis muscle) and antecubital fossa and the ulnar nerve
at the wrist (5 cm proximal to the active recording electrode placed on the adductor digiti minimi muscle) and at the ulnar sulcus. Motor distal latency (DL) was measured from the beginning of the stimulus artifact to the onset of the action potential. Peak-to-peak CMAP amplitude was measured. Fwave study was performed for the median nerve by recording from the same muscle using the electrode placement mentioned above. Active stimulating electrode was placed proximally and at least 10 successive supramaximal stimulations were given. Minimum F-wave latency (Fmin) was recorded. CTS was diagnosed electrophysiologically if the median nerve sensory NCV was decreased and/or motor DL was prolonged. According to the criteria of Padua et al., the severity of CTS was evaluated as negative (normal findings), minimal or very mild (abnormal sensory nerve conduction study of the palmewrist segment), mild (abnormal sensory nerve conduction study of any of the fingerewrist (digits IeIII) segments and normal motor DL), moderate (abnormal sensory nerve conduction study of any of the fingerewrist (digits IeIII) segments and prolonged motor DL), severe (absence of the compound nerve action potential of any fingerewrist segment and prolonged motor DL), extreme (absence of compound nerve action potential of any fingerewrist segment and CMAP) CTSs (11). SPSS 13.0 was used for statistical analysis. To evaluate the mean values of the groups, Student t test was used. The percentages between groups were compared using chi square test; p !0.05 was accepted as statistically significant. Results Mean age of 63 FS patients was 39.12 8.7 years (between 20 and 60 years) and mean age of the control group was 39.6 8.7 years (between 25 and 61 years). Demographic features of the groups are shown in Table 1. There were no statistically significant differences between groups with respect to mean age, weight and height ( p O0.05 for all parameters). Electrophysiological examination was performed in 126 extremities of 63 patients with FS and in 104 extremities of 52 control group individuals. CTS was detected electrophysiologically in 26 (20.63%) of 126 extremities of 63 patients and in 3 (2.82%) of 104 extremities of 52 control group individuals ( p !0.001). CTS was detected electrophysiologically in 16 (25.39%) of the 63 patients with FS; however, CTS was detected electrophysiologically in only two (3.84%) patients in the control group ( p !0.01). One Table 1. Demographic characteristics of FS patients and healthy control subjects
Age (years) Height (cm) Weight (kg)
FS (n 5 63)
Control (n 5 52)
p
39.1 8.7 160.0 5.3 70.1 7.2
39.6 8.7 160.1 4.4 69.40 10.3
0.895 0.781 0.269
FS, fibromyalgia syndrome.
Nerve Conduction Velocities Between Fibromyalgia and Carpal Tunnel Syndrome
hundred of the examined 126 extremities of 63 patients with FS were assessed as normal. Of the CTS detected in 26 extremities in the patient group with FS, 19 were mild and seven were moderate. Electrophysiologically mild CTS was present in three of the control group cases diagnosed with CTS. CTS was detected in the right upper extremities of 15 patients and in the left upper extremities of 11 patients with FS. CTS was detected in the right upper extremities of three individuals in the control group. Ten patients with FS had bilateral (bilateral mild in seven cases, moderate in three cases) and six patients had unilateral CTS (mild in five cases, moderate in one case). Bilateral mild CTS was detected in one individual and unilateral mild CTS was detected in one individual in the control group. There was a statistically significant difference between FS and control groups with respect to the frequency ( p !0.001) and severity of CTS ( p !0.01) and right/left extremity involvement ( p !0.01). The median and ulnar nerve sensory nerve conduction results of the patients and control groups are presented in Table 2. The median and ulnar nerve motor nerve conduction and median nerve Fmin results are presented in Table 3. When the results of the patient group with FS were compared to healthy controls, statistically significant prolongation of the right median motor DL ( p 5 0.019) and statistically significant slowing of the right median sensory NCV ( p 5 0.003), left median nerve sensory NCV ( p 5 0.011) and left ulnar nerve sensory NCV ( p 5 0.015) were determined. There were no statistically significant differences between groups with respect to the left median nerve motor DL, right and left ulnar nerve motor DL, left ulnar nerve sensory NCV, right and left median and ulnar nerve motor NCV, and right and left median mean F-latencies ( p O0.05). Discussion Fibromyalgia syndrome is a soft tissue rheumatism with unknown etiology. It is characterized by widespread musculoskeletal pain and tender points (1). Stiffness, skin sensitivity, irritable bowel syndrome, cognitive impairment,
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interstitial cystitis, tension and migraine headaches, dizziness, fluid retention, morning stiffness, pain in hands, paresthesia, restless leg syndrome, Raynaud’s phenomenon, mood disorder and sleep disorder frequently accompany FS. FS may also be associated with many other conditions and the frequent association of a secondary disease with FS may lead other diseases to be overlooked, misdiagnosed or confused with each other. Thus, a disease may lead to masking of another disease. This situation usually appears as a factor complicating effective treatment in FS (8). Of patients diagnosed with FS according to ACR classification criteria, 26e84% were reported to have paresthesia and other sensory symptoms (2,4,5,12). Because paresthesias are frequently seen in generalized and/or focal neuropathies as well as other neurological diseases, they may cause generalized and/or focal neuropathies to be overlooked or to be misdiagnosed in FS patients (5,13). Although there is no similarity between the studies with respect to the methodology and study population, there are few reported studies in the literature on the increase in the prevalence of CTS in patients with FS. The prevalence of CTS in FS patients has been reported to range between 6.7 and 35.1% in various studies (9,14e19). Tosun et al. (9) and Sarmer et al. (18) stated that the prevalence of CTS in patients with FS was increased; however, they did not find a statistically significant difference when compared to the control group. Ersoz detected CTS in five (15%) of 33 female patients with FS and one (5.9%) of 17 healthy controls. He reported that increased prevalence of CTS in comparison to the previous studies may be due to the detailed electrophysiological examination (17). PerezRuiz et al. reported CTS prevalence rate of 16% in 206 patients with FS and stated that CTS symptoms progressed more rigorously in patients with FS (14,15). Implementing the questionnaire method and provocative tests, Cimmino et al. reported CTS prevalence as 28% and FS prevalence as 21% in the general population and suggested an association with CTS in 9.7% of patients with FS (16). Cimmino et al. did not perform electrophysiological examinations in this study and the diagnosis relied only on anamnesis and
Table 2. Mean values of sensory nerve conduction studies in FS and healthy control subjects, and normal limits FS (n 5 63) mean SD Median nerve R Digit2-wrist L Digit2-wrist Ulnar nerve R Digit5-wrist L Digit5-wrist
Control (n 5 52) mean SD
p
Normal limits*
Vsens (m/s) SNAPamp (mV) Vsens (m/s) SNAPamp (mV)
52.8 20.2 53.5 19.6
6.2 8.7 5.2 7.2
56.1 22.4 56.2 19.3
4.9 4.4 4.5 9.6
0.003 0.487 0.011 0.896
49.4 10.0
Vsens (m/s) SNAPamp (mV) Vsens (m/s) SNAPamp (mV)
51.9 22.4 54.4 21.9
4.0 9.7 5.3 9.8
54.6 24.2 53.4 23.8
5.2 8.9 3.5 8.8
0.015 0.544 0.507 0.678
47.3 7.0
FS, fibromyalgia syndrome; R, right; L, left; Vsens, sensory nerve conduction velocity; SNAPamp, sensory nerve action potential amplitude. *Normal limits of our electroneuromyography laboratory for both sides. Lower limits for Vsens and SNAPamp.
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Table 3. Mean values of motor nerve conduction studies and median nerve F wave latencies (Fmin) in FS and normal control subjects, and normal limits FS (n 5 63) mean SD Median nerve Right
Left
Ulnar nerve Right
Left
Fmin Median nerve Median nerve
Control (n 5 52) mean SD
p
Normal limits*
DL (ms) Vmotor (m/s) CMAPamp (mV) DL (ms) Vmotor (m/s) CMAPamp (mV)
3.3 58.6 9.6 3.3 57.9 8.7
0.5 3.5 3.0 0.7 4.5 2.7
3.0 57.8 9.1 3.0 57.9 8.2
0.4 4.5 2.7 0.3 3.3 2.8
0.019 0.446 0.618 0.153 0.827 0.596
3.8 49.7 4.3
DL (ms) Vmotor (m/s) CMAPamp (mV) DL (ms) Vmotor (m/s) CMAPamp (mV)
2.7 59.4 9.8 2.6 60.0 9.6
0.4 5.0 1.7 0.4 5.3 1.8
2.6 60.9 9.5 2.7 60.8 9.3
0.4 4.3 1.9 0.5 4.5 1.7
0.814 0.51 0.895 0.967 0.342 0.624
3.3 49.9 7.0
Right Left
25.5 2.10 25.2 2.2
25.2 2.3 24.9 1.6
0.132 0.607
32
FS, fibromyalgia syndrome; DL, distal latency; Vmotor, motor nerve conduction velocity; CMAPamp, compound muscle action potential amplitude. *Normal limits of our electroneuromyography laboratory for both sides. Upper limits for DL and lower limits for Vmotor, CMAPamp.
provocative tests. We detected CTS electrophysiologically in 16 (25.39%) of 63 patients in the FS group, whereas we detected CTS electrophysiologically in two (3.84%) of 52 subjects in the healthy control group. The results of our study suggest that CTS is observed more frequently in the patient group with FS. The cause of this high rate detected in our study may be due to performing detailed and intensive electrophysiological examination as previously reported by Ersoz (17). Compression neuropathies are frequently observed findings in patients with FS and the differential diagnosis of polyneuropathies should be made (13). There is no study explaining the etiopathogenetic mechanisms of why compression neuropathies are frequently observed in patients with FS. Observance of compression neuropathies in FS in increased frequency with respect to normal population may be connected with weight gain, musculoskeletal pain, biomechanical factors secondary to hypermobility and increased sensitization appearing as a result of central sensitization (4,5). Pain observed in FS is considered to be due to nociceptive, neuropathic, and dysregulation in the central nervous system and psychopathic mechanisms (20e27). Prolongation of the duration of pain and differences in the temporal summation of pain following the repeating thermal and mechanical applications in patients with FS was detected and the importance of peripheral tissues in the appearance and permanence of the pain in FS was emphasized (21,24). Persistent and intensive nociceptive stimulation originating from joints, muscles and ligaments may cause central sensitization and pain by leading to transcriptional and translational differences in the spinal cord and the brain. What is important at this point is the requirement
for only minimal nociceptive stimulation for the permanence of chronic pain state after central sensitization (21). Consequently, we believe that peripheral sources of pain such as CTS overlapping with FS should be taken into consideration as pain-sustaining sources. Rowbotham expressed that FS should be evaluated as neuropathic pain due to the changes occurring in the function of the central nervous system despite being an anatomically undetectable nervous system lesion (28). Nerve regenerations or compression neuropathies (CTS or vertebral disc degeneration) resulting in ectopic impulse discharge or impairment of axonal transport eventuate in neuropathic pain (20). Actually, neuropathic pain characteristics are observed in FS due to the occurrence of chronic pain independent of stimulus, accompaniment of hyperalgesia, allodynia and paresthesia and manifestation of paroxysmal features (28e30). A clear diurnal variation may be observed in symptoms of median-nerve compression in some patients with FS. Deodhar et al. reported that this diurnal variation observed due to symptoms of mediannerve compression may be related to cyclic liquid retention seen in patients with FS (31). As seen in CTS, symptoms of pain and paresthesia in hands, increasing especially at night, can be observed in FS. The similarity between the symptoms of fibromyalgia and CTS and more often occurrence of both entities in females may lead to the easy confusion of both diseases and, thus, one disease may mask the other (9). The rate of undiagnosed CTS in patients with FS was reported to be higher than the general population prevalence rates (14e17). The differentiation of paresthesia and other sensory complaints from other compression neuropathies requiring
Nerve Conduction Velocities Between Fibromyalgia and Carpal Tunnel Syndrome
specific treatment is needed in patients with FS (13). Simms and Goldenberg reported the rate of paresthesia in patients with FS as quite remarkable (2). Electroneuromyography and nerve conduction studies may be helpful to distinguish paresthesia and other sensory symptoms frequently seen in patients with FS from entrapment neuropathies (13). However, the rare presence of objective abnormality in EMG, nerve conduction studies and other electrodiagnostic tests are indicated though clinical complaints and symptoms imitating CTS (2). Although no adequate studies exist on the role of the peripheral nervous system in the pathogenesis of FS, results obtained from our study may suggest the probable role of the peripheral nervous system. We believe that the detection of objective abnormality in the electrodiagnostic tests performed in our study is an issue to be dwelled on. Therefore, the abnormalities that we detected using electrodiagnostic tests in patients with FS require broader investigation in patient series with the inclusion of etiopathogenic mechanisms occurring in the peripheral nervous system. Nora et al. state that clinical presentation is quite variable in subjects with CTS diagnosed electrophysiologically. They even note the possibility of the presence of asymptomatic subjects as well (32). Variations in clinical presentation are reported to be due to the presence of tendonitis and fibromyalgia frequently accompanying CTS and personal factors such as perception of subjective pain (14,15,32,33). Straub et al. reported the presence of FS in patients with CTS as a factor causing failure of endoscopic carpal tunnel release operation (34). Akkus et al. emphasized that FS accompaniment in patients nonresponsive to local steroid injection should be kept in mind. Thus, they pointed out the requirements for the variations in the clinical presentations necessary for the correct diagnosis and effective treatment of CTS (19). Our study has some limitations such as the absence of lower extremity nerve conduction studies and conducting of F wave studies only in median nerves. The small sample size may be another limitation of our study. Detailed conduction studies in both upper and lower extremities in a larger study population may offer more information about the peripheral nervous system in FS patients. In conclusion, the most important finding of this study was significantly higher frequency of CTS in FS patients. Additionally, we detected that NCVs in FS slowed down and the prevalence of CTS increased in comparison to those of the controls. The presence of CTS may be masked by the symptoms of FS. Additionally, peripheral stimulus may be a source for persistent pain in FS. When all of these findings are considered, patients with FS should be assessed by electrophysiological tests in addition to anamnesis and provocative tests. Patients with FS should be examined carefully due to CTS accompaniment, and appropriate and effective therapeutic interventions should be applied.
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Thus, we believe that the quality of life of patients with FS will be improved. References 1. Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 1990;33:160e172. 2. Simms RW, Goldenberg DL. Symptoms mimicking neurologic disorders in fibromyalgia syndrome. J Rheumatol 1988;15:1271e1273. 3. Wolfe F, Anderson J, Harkness D, et al. A prospective, longitudinal, multicenter study of service utilization and costs in fibromyalgia. Arthritis Rheum 1997;40:1560e1570. 4. Yunus MB. Symptoms and signs of fibromyalgia syndrome: an overview. In: Wallace DJ, Clauw DJ, eds. Fibromyalgia & Other Central Pain Syndromes. Philadelphia: Lippincott, Williams & Wilkins; 2005. pp. 125e132. 5. Bennett R. Neurologic features of fibromyalgia. In: Wallace DJ, Clauw DJ, eds. Fibromyalgia & Other Central Pain Syndromes. Philadelphia: Lippincott, Williams & Wilkins; 2005. pp. 133e414. 6. de Krom MC, Kester AD, Knipschild PG, et al. Risk factors for carpal tunnel syndrome. Am J Epidemiol 1990;132:1102e1110. 7. de Krom MC, Knipschild PG, Kester AD, et al. Carpal tunnel syndrome: prevalence in the general population. J Clin Epidemiol 1992;45:373e376. 8. Mease P. Fibromyalgia syndrome: review of clinical presentation, pathogenesis, outcome measures, and treatment. J Rheumatol 2005; 75(suppl):6e21. 9. Tosun M, Cakırbay H, Boz C, et al. Carpal tunnel syndrome in patients with fibromyalgia syndrome. Turk J Rheumatol 2002;17:8e11. 10. Oh SJ. Clinical Electromyography: Nerve Conduction Studies. 2nd ed Baltimore: Williams & Wilkins; 1993. 11. Padua L, LoMonaco M, Gregori B, et al. Neurophysiological classification and sensitivity in 500 carpal tunnel syndrome hands. Acta Neurol Scand 1997;96:211e217. 12. Gurer G, S¸endur OF. Correlations of clinical features and findings in fibromyalgia patients. Turk J Rheumatol 2006;21:41e44. 13. Borg-Stein J. Management of peripheral pain generators in fibromyalgia. Rheum Dis Clin North Am 2002;28:305e317. 14. Perez-Ruiz F, Calabozo M, Alonso-Ruiz A, et al. High prevalence of undetected carpal tunnel syndrome in patients with fibromyalgia syndrome. J Rheumatol 1995;22:501e504. 15. Perez-Ruiz F, Calabozo M, Alonso-Ruiz A, et al. Fibromyalgia and carpal tunnel syndrome. Ann Rheum Dis 1997;56:438e439. 16. Cimmino MA, Parisi M, Moggiana G, et al. The association between fibromyalgia and carpal tunnel syndrome in the general population. Ann Rheum Dis 1996;55:780. 17. Ersoz M. Nerve conduction tests in patients with fibromyalgia: comparison with normal controls. Rheumatol Int 2003;23:166e170. 18. Sarmer S, Yavuzer G, K€uc¸€ukdeveci A, et al. Prevalence of carpal tunnel syndrome in patients with fibromyalgia. Rheumatol Int 2002; 22:68e70. 19. Akkus S, Kutluhan S, Akhan G, et al. Does fibromyalgia affect the outcomes of local steroid treatment in patients with carpal tunnel syndrome? Rheumatol Int 2002;22:112e115. 20. Zimmermann M. Pathophysiological mechanisms of fibromyalgia. Clin J Pain 1991;7(suppl 1):S8eS15. 21. Staud R, Rodriguez ME. Mechanisms of disease: pain in fibromyalgia syndrome. Nat Clin Pract Rheumatol 2006;2:90e98. 22. Staud R, Domingo M. Evidence for abnormal pain processing in fibromyalgia syndrome. Pain Med 2001;2:208e215. 23. Price DD, Staud R. Neurobiology of fibromyalgia syndrome. J Rheumatol 2005;75(suppl):22e28.
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24. Crofford LJ. The relationship of fibromyalgia to neuropathic pain syndromes. J Rheumatol Suppl 2005;75:41e45. 25. Nielsen LA, Henriksson KG. Pathophysiological mechanisms in chronic musculoskeletal pain (fibromyalgia): the role of central and peripheral sensitization and pain disinhibition. Best Pract Res Clin Rheumatol 2007;21:465e480. 26. Abrahams MJ. Neuropathic pain in soft tissue complaints. Best Pract Res Clin Rheumatol 2007;21:223e244. 27. Yunus MB. Role of central sensitization in symptoms beyond muscle pain, and the evaluation of a patient with widespread pain. Best Pract Res Clin Rheumatol 2007;21:481e497. 28. Rowbotham MC. Is fibromyalgia a neuropathic pain syndrome? J Rheumatol Suppl 2005;75:38e40.
29. Dworkin RH, Fields HL. Fibromyalgia from the perspective of neuropathic pain. J Rheumatol Suppl 2005;75:1e5. 30. Eyig€or S, Kirazlı Y. Fibromyalgia syndrome from the perspective of neuropathic pain. Agri 2008;20:8e12. 31. Deodhar AA, Fisher RA, Blacker CV, et al. Fluid retention syndrome and fibromyalgia. Br J Rheumatol 1994;33:576e582. 32. Nora DB, Becker J, Ehlers JA, et al. Clinical features of 1039 patients with neurophysiological diagnosis of carpal tunnel syndrome. Clin Neurol Neurosurg 2004;107:64e69. 33. Genc H, Saracoglu M, Duyur B, et al. The role of tendinitis in fibromyalgia syndrome. Yonsei Med J 2003;44:619e622. 34. Straub TA. Endoscopic carpal tunnel release: a prospective analysis of factors associated with unsatisfactory results. Arthroscopy 1999;15:269e274.
ORIGINAL ARTICLE
Evaluation of Upper Extremity Nerve Conduction Velocities and the Relationship Between Fibromyalgia and Carpal Tunnel Syndrome Baris Nacir, Hakan Genc, Burcu Duyur Cakit, Aynur Karagoz, and Hatice R. Erdem Department of Physical Medicine and Rehabilitation, Ministry of Health, Ankara Training and Research Hospital, Ankara, Turkey Received for publication March 14, 2012; accepted July 4, 2012 (ARCMED-D-12-00143).
Background and Aims. We undertook this study to evaluate upper extremity nerve conduction velocities (NCVs) in fibromyalgia syndrome (FS) and the relationship of the electrophysiological findings between carpal tunnel syndrome (CTS) and FS. Methods. Sixty three right-handed female patients diagnosed with FS and 52 righthanded age- and gender-matched healthy controls were enrolled in the study. Conduction studies of the median and ulnar nerves and median nerve F-wave latencies were assessed in both upper extremities using standard methods. CTS was diagnosed electrophysiologically if the median nerve sensory NCV was decreased and/or motor distal latency (DL) was prolonged. Results. CTS was detected electrophysiologically in 26 (20.63%) of 126 extremities of 63 patients and in three (2.82%) of 104 extremities of 52 individuals of the control group. Statistically significant differences were detected between groups with respect to rate of carpal tunnel syndrome ( p !0.05). There were no differences between results of NCVs of patients in FS group and healthy controls except the prolongation of the right median nerve motor DL ( p 5 0.019), decrease of the sensory NCV ( p 5 0.003) in the right median nerve, in the left median nerve ( p 5 0.011) and in the left ulnar nerve ( p 5 0.015). Conclusions. We determined an increased rate of CTS and decreased NCVs in the upper extremities in patients with FS. We should consider that complaints of paresthesia and pain in hands, increasing especially at nights, observed in FS may mask that CTS can be an associated illness. Ó 2012 IMSS. Published by Elsevier Inc. Key Words: Fibromyalgia, Carpal tunnel syndrome, Nerve conduction studies.
Introduction Fibromyalgia syndrome (FS) is a soft tissue rheumatism etiology of which is not exactly known. It is characterized by widespread musculoskeletal pain and tender points, sleep disturbance, morning stiffness, fatigue, irritable bowel syndrome, complaints of paresthesia, pain and a subjective sense of swelling in hands, as well as frequent psychological distress (1). According to the criteria of the American College of Rheumatology (ACR), paresthesia and sensory alterations, which are also frequently observed symptoms of focal neuropathies, are seen in O80% of patients diagnosed with FS (2,3). The symptom of paresthesia in hands has been reported to be Address reprint requests to: Baris Nacir, Ministry of Health Ankara Research and Education Hospital, 2nd Department of Physical Medicine and Rehabilitation, Ulucanlar Caddesi, Ankara 06340, Turkey; Phone: þ903124303857; FAX: þ903124681335; E-mail: [email protected]
a distinctly problematic complaint in some FS patients. Paresthesia has been stated to be capable of showing dissemination patterns confused with entrapment neuropathies and radiculopathies. The appearance mechanism of paresthesia in FS is not exactly known. However, paresthesia is considered to be a result of an abnormal sensory perception occurring due to central sensitization (4,5). Carpal tunnel syndrome (CTS) occurring as a consequence of the compression of the median nerve at the wrist is seen more frequently in women and is the most commonly seen entrapment neuropathy in the upper extremity. Although CTS may develop during the course of numerous diseases, in most cases the etiological cause cannot be detected (6,7). FS is a disease affecting |2% of the population 18 years of age and older and is more frequently seen in women than men (8). CTS prevalence in the community is estimated to be 9.2% (7). Epidemiological studies show that CTS, like
0188-4409/$ - see front matter. Copyright Ó 2012 IMSS. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.arcmed.2012.07.004
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Nacir et al./ Archives of Medical Research 43 (2012) 369e374
FS, is a disease more frequently seen in women (6). Paresthesia and pain in hands, increasing especially at night, and morning stiffness can be seen in FS as is also seen in CTS. The similarity between the symptoms both in FS and CTS and incidence of both entities in women may lead to confusion and thus may make one disease mask the other (9). The aim of this study was to evaluate upper extremity nerve conduction velocities (NCVs) to detect prevalence of electrophysiological CTS and to compare the results with healthy individuals. Materials and Methods Sixty three right-handed consecutive female patients attending our clinic with complaints of paresthesia in hands between March 2006 and October 2007 and diagnosed with FS according to the ACR 1990 diagnostic criteria (1) and 52 right-handed, age- and gender-matched healthy controls were enrolled in study. All patients were homemakers. Control subjects were selected from the healthy hospital staff. The local ethics committee approved the study and written informed consent was obtained from each study participant. Patients !18 years and O65 years of age and with a history of hypo-hyperthyroidism, diabetes mellitus, rheumatoid arthritis, obesity, malignant disease, and distal radius fracture were excluded from the study. Patients with a history of medication use leading to neuropathy and patients treated with antiepileptic drugs for neuropathic pain were also excluded. None of the patients or controls performed repetitive wrist activities. Neurophysiological tests were performed at room temperature with a Nihon-Kohden Neuropack M1 (Tokyo, Japan) electroneuromyography equipment. Skin temperature was 32 C on the dorsum of the hand. Conduction studies of the median and ulnar nerves and median nerve F-wave latencies were assessed in both upper extremities using standard methods (10). Motor conduction studies were performed using an orthodromic method and superficial disc electrodes. Sensory conduction studies were performed using antidromic method and ring electrodes. Digit2-wrist segment was used for median sensory nerve conduction studies and digit5-wrist segment was used for ulnar sensory nerve conduction studies. Sensory NCVs were calculated from the beginning of the stimulus artifact to the onset of the sensory nerve action potential (SNAP). Peak-to-peak amplitudes were measured. In the motor nerve conduction studies, electrodes were placed over the abductor pollicis brevis muscle for the median nerve and the adductor digiti minimi muscle for the ulnar nerve. The active recording electrode was placed on the belly of the examined muscle and the reference electrode was placed on the tendon insertion. Compound muscle action potential (CMAP) was obtained by stimulating the median nerve at the wrist (5 cm proximal to the active recording electrode placed on the abductor pollicis brevis muscle) and antecubital fossa and the ulnar nerve
at the wrist (5 cm proximal to the active recording electrode placed on the adductor digiti minimi muscle) and at the ulnar sulcus. Motor distal latency (DL) was measured from the beginning of the stimulus artifact to the onset of the action potential. Peak-to-peak CMAP amplitude was measured. Fwave study was performed for the median nerve by recording from the same muscle using the electrode placement mentioned above. Active stimulating electrode was placed proximally and at least 10 successive supramaximal stimulations were given. Minimum F-wave latency (Fmin) was recorded. CTS was diagnosed electrophysiologically if the median nerve sensory NCV was decreased and/or motor DL was prolonged. According to the criteria of Padua et al., the severity of CTS was evaluated as negative (normal findings), minimal or very mild (abnormal sensory nerve conduction study of the palmewrist segment), mild (abnormal sensory nerve conduction study of any of the fingerewrist (digits IeIII) segments and normal motor DL), moderate (abnormal sensory nerve conduction study of any of the fingerewrist (digits IeIII) segments and prolonged motor DL), severe (absence of the compound nerve action potential of any fingerewrist segment and prolonged motor DL), extreme (absence of compound nerve action potential of any fingerewrist segment and CMAP) CTSs (11). SPSS 13.0 was used for statistical analysis. To evaluate the mean values of the groups, Student t test was used. The percentages between groups were compared using chi square test; p !0.05 was accepted as statistically significant. Results Mean age of 63 FS patients was 39.12 8.7 years (between 20 and 60 years) and mean age of the control group was 39.6 8.7 years (between 25 and 61 years). Demographic features of the groups are shown in Table 1. There were no statistically significant differences between groups with respect to mean age, weight and height ( p O0.05 for all parameters). Electrophysiological examination was performed in 126 extremities of 63 patients with FS and in 104 extremities of 52 control group individuals. CTS was detected electrophysiologically in 26 (20.63%) of 126 extremities of 63 patients and in 3 (2.82%) of 104 extremities of 52 control group individuals ( p !0.001). CTS was detected electrophysiologically in 16 (25.39%) of the 63 patients with FS; however, CTS was detected electrophysiologically in only two (3.84%) patients in the control group ( p !0.01). One Table 1. Demographic characteristics of FS patients and healthy control subjects
Age (years) Height (cm) Weight (kg)
FS (n 5 63)
Control (n 5 52)
p
39.1 8.7 160.0 5.3 70.1 7.2
39.6 8.7 160.1 4.4 69.40 10.3
0.895 0.781 0.269
FS, fibromyalgia syndrome.
Nerve Conduction Velocities Between Fibromyalgia and Carpal Tunnel Syndrome
hundred of the examined 126 extremities of 63 patients with FS were assessed as normal. Of the CTS detected in 26 extremities in the patient group with FS, 19 were mild and seven were moderate. Electrophysiologically mild CTS was present in three of the control group cases diagnosed with CTS. CTS was detected in the right upper extremities of 15 patients and in the left upper extremities of 11 patients with FS. CTS was detected in the right upper extremities of three individuals in the control group. Ten patients with FS had bilateral (bilateral mild in seven cases, moderate in three cases) and six patients had unilateral CTS (mild in five cases, moderate in one case). Bilateral mild CTS was detected in one individual and unilateral mild CTS was detected in one individual in the control group. There was a statistically significant difference between FS and control groups with respect to the frequency ( p !0.001) and severity of CTS ( p !0.01) and right/left extremity involvement ( p !0.01). The median and ulnar nerve sensory nerve conduction results of the patients and control groups are presented in Table 2. The median and ulnar nerve motor nerve conduction and median nerve Fmin results are presented in Table 3. When the results of the patient group with FS were compared to healthy controls, statistically significant prolongation of the right median motor DL ( p 5 0.019) and statistically significant slowing of the right median sensory NCV ( p 5 0.003), left median nerve sensory NCV ( p 5 0.011) and left ulnar nerve sensory NCV ( p 5 0.015) were determined. There were no statistically significant differences between groups with respect to the left median nerve motor DL, right and left ulnar nerve motor DL, left ulnar nerve sensory NCV, right and left median and ulnar nerve motor NCV, and right and left median mean F-latencies ( p O0.05). Discussion Fibromyalgia syndrome is a soft tissue rheumatism with unknown etiology. It is characterized by widespread musculoskeletal pain and tender points (1). Stiffness, skin sensitivity, irritable bowel syndrome, cognitive impairment,
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interstitial cystitis, tension and migraine headaches, dizziness, fluid retention, morning stiffness, pain in hands, paresthesia, restless leg syndrome, Raynaud’s phenomenon, mood disorder and sleep disorder frequently accompany FS. FS may also be associated with many other conditions and the frequent association of a secondary disease with FS may lead other diseases to be overlooked, misdiagnosed or confused with each other. Thus, a disease may lead to masking of another disease. This situation usually appears as a factor complicating effective treatment in FS (8). Of patients diagnosed with FS according to ACR classification criteria, 26e84% were reported to have paresthesia and other sensory symptoms (2,4,5,12). Because paresthesias are frequently seen in generalized and/or focal neuropathies as well as other neurological diseases, they may cause generalized and/or focal neuropathies to be overlooked or to be misdiagnosed in FS patients (5,13). Although there is no similarity between the studies with respect to the methodology and study population, there are few reported studies in the literature on the increase in the prevalence of CTS in patients with FS. The prevalence of CTS in FS patients has been reported to range between 6.7 and 35.1% in various studies (9,14e19). Tosun et al. (9) and Sarmer et al. (18) stated that the prevalence of CTS in patients with FS was increased; however, they did not find a statistically significant difference when compared to the control group. Ersoz detected CTS in five (15%) of 33 female patients with FS and one (5.9%) of 17 healthy controls. He reported that increased prevalence of CTS in comparison to the previous studies may be due to the detailed electrophysiological examination (17). PerezRuiz et al. reported CTS prevalence rate of 16% in 206 patients with FS and stated that CTS symptoms progressed more rigorously in patients with FS (14,15). Implementing the questionnaire method and provocative tests, Cimmino et al. reported CTS prevalence as 28% and FS prevalence as 21% in the general population and suggested an association with CTS in 9.7% of patients with FS (16). Cimmino et al. did not perform electrophysiological examinations in this study and the diagnosis relied only on anamnesis and
Table 2. Mean values of sensory nerve conduction studies in FS and healthy control subjects, and normal limits FS (n 5 63) mean SD Median nerve R Digit2-wrist L Digit2-wrist Ulnar nerve R Digit5-wrist L Digit5-wrist
Control (n 5 52) mean SD
p
Normal limits*
Vsens (m/s) SNAPamp (mV) Vsens (m/s) SNAPamp (mV)
52.8 20.2 53.5 19.6
6.2 8.7 5.2 7.2
56.1 22.4 56.2 19.3
4.9 4.4 4.5 9.6
0.003 0.487 0.011 0.896
49.4 10.0
Vsens (m/s) SNAPamp (mV) Vsens (m/s) SNAPamp (mV)
51.9 22.4 54.4 21.9
4.0 9.7 5.3 9.8
54.6 24.2 53.4 23.8
5.2 8.9 3.5 8.8
0.015 0.544 0.507 0.678
47.3 7.0
FS, fibromyalgia syndrome; R, right; L, left; Vsens, sensory nerve conduction velocity; SNAPamp, sensory nerve action potential amplitude. *Normal limits of our electroneuromyography laboratory for both sides. Lower limits for Vsens and SNAPamp.
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Table 3. Mean values of motor nerve conduction studies and median nerve F wave latencies (Fmin) in FS and normal control subjects, and normal limits FS (n 5 63) mean SD Median nerve Right
Left
Ulnar nerve Right
Left
Fmin Median nerve Median nerve
Control (n 5 52) mean SD
p
Normal limits*
DL (ms) Vmotor (m/s) CMAPamp (mV) DL (ms) Vmotor (m/s) CMAPamp (mV)
3.3 58.6 9.6 3.3 57.9 8.7
0.5 3.5 3.0 0.7 4.5 2.7
3.0 57.8 9.1 3.0 57.9 8.2
0.4 4.5 2.7 0.3 3.3 2.8
0.019 0.446 0.618 0.153 0.827 0.596
3.8 49.7 4.3
DL (ms) Vmotor (m/s) CMAPamp (mV) DL (ms) Vmotor (m/s) CMAPamp (mV)
2.7 59.4 9.8 2.6 60.0 9.6
0.4 5.0 1.7 0.4 5.3 1.8
2.6 60.9 9.5 2.7 60.8 9.3
0.4 4.3 1.9 0.5 4.5 1.7
0.814 0.51 0.895 0.967 0.342 0.624
3.3 49.9 7.0
Right Left
25.5 2.10 25.2 2.2
25.2 2.3 24.9 1.6
0.132 0.607
32
FS, fibromyalgia syndrome; DL, distal latency; Vmotor, motor nerve conduction velocity; CMAPamp, compound muscle action potential amplitude. *Normal limits of our electroneuromyography laboratory for both sides. Upper limits for DL and lower limits for Vmotor, CMAPamp.
provocative tests. We detected CTS electrophysiologically in 16 (25.39%) of 63 patients in the FS group, whereas we detected CTS electrophysiologically in two (3.84%) of 52 subjects in the healthy control group. The results of our study suggest that CTS is observed more frequently in the patient group with FS. The cause of this high rate detected in our study may be due to performing detailed and intensive electrophysiological examination as previously reported by Ersoz (17). Compression neuropathies are frequently observed findings in patients with FS and the differential diagnosis of polyneuropathies should be made (13). There is no study explaining the etiopathogenetic mechanisms of why compression neuropathies are frequently observed in patients with FS. Observance of compression neuropathies in FS in increased frequency with respect to normal population may be connected with weight gain, musculoskeletal pain, biomechanical factors secondary to hypermobility and increased sensitization appearing as a result of central sensitization (4,5). Pain observed in FS is considered to be due to nociceptive, neuropathic, and dysregulation in the central nervous system and psychopathic mechanisms (20e27). Prolongation of the duration of pain and differences in the temporal summation of pain following the repeating thermal and mechanical applications in patients with FS was detected and the importance of peripheral tissues in the appearance and permanence of the pain in FS was emphasized (21,24). Persistent and intensive nociceptive stimulation originating from joints, muscles and ligaments may cause central sensitization and pain by leading to transcriptional and translational differences in the spinal cord and the brain. What is important at this point is the requirement
for only minimal nociceptive stimulation for the permanence of chronic pain state after central sensitization (21). Consequently, we believe that peripheral sources of pain such as CTS overlapping with FS should be taken into consideration as pain-sustaining sources. Rowbotham expressed that FS should be evaluated as neuropathic pain due to the changes occurring in the function of the central nervous system despite being an anatomically undetectable nervous system lesion (28). Nerve regenerations or compression neuropathies (CTS or vertebral disc degeneration) resulting in ectopic impulse discharge or impairment of axonal transport eventuate in neuropathic pain (20). Actually, neuropathic pain characteristics are observed in FS due to the occurrence of chronic pain independent of stimulus, accompaniment of hyperalgesia, allodynia and paresthesia and manifestation of paroxysmal features (28e30). A clear diurnal variation may be observed in symptoms of median-nerve compression in some patients with FS. Deodhar et al. reported that this diurnal variation observed due to symptoms of mediannerve compression may be related to cyclic liquid retention seen in patients with FS (31). As seen in CTS, symptoms of pain and paresthesia in hands, increasing especially at night, can be observed in FS. The similarity between the symptoms of fibromyalgia and CTS and more often occurrence of both entities in females may lead to the easy confusion of both diseases and, thus, one disease may mask the other (9). The rate of undiagnosed CTS in patients with FS was reported to be higher than the general population prevalence rates (14e17). The differentiation of paresthesia and other sensory complaints from other compression neuropathies requiring
Nerve Conduction Velocities Between Fibromyalgia and Carpal Tunnel Syndrome
specific treatment is needed in patients with FS (13). Simms and Goldenberg reported the rate of paresthesia in patients with FS as quite remarkable (2). Electroneuromyography and nerve conduction studies may be helpful to distinguish paresthesia and other sensory symptoms frequently seen in patients with FS from entrapment neuropathies (13). However, the rare presence of objective abnormality in EMG, nerve conduction studies and other electrodiagnostic tests are indicated though clinical complaints and symptoms imitating CTS (2). Although no adequate studies exist on the role of the peripheral nervous system in the pathogenesis of FS, results obtained from our study may suggest the probable role of the peripheral nervous system. We believe that the detection of objective abnormality in the electrodiagnostic tests performed in our study is an issue to be dwelled on. Therefore, the abnormalities that we detected using electrodiagnostic tests in patients with FS require broader investigation in patient series with the inclusion of etiopathogenic mechanisms occurring in the peripheral nervous system. Nora et al. state that clinical presentation is quite variable in subjects with CTS diagnosed electrophysiologically. They even note the possibility of the presence of asymptomatic subjects as well (32). Variations in clinical presentation are reported to be due to the presence of tendonitis and fibromyalgia frequently accompanying CTS and personal factors such as perception of subjective pain (14,15,32,33). Straub et al. reported the presence of FS in patients with CTS as a factor causing failure of endoscopic carpal tunnel release operation (34). Akkus et al. emphasized that FS accompaniment in patients nonresponsive to local steroid injection should be kept in mind. Thus, they pointed out the requirements for the variations in the clinical presentations necessary for the correct diagnosis and effective treatment of CTS (19). Our study has some limitations such as the absence of lower extremity nerve conduction studies and conducting of F wave studies only in median nerves. The small sample size may be another limitation of our study. Detailed conduction studies in both upper and lower extremities in a larger study population may offer more information about the peripheral nervous system in FS patients. In conclusion, the most important finding of this study was significantly higher frequency of CTS in FS patients. Additionally, we detected that NCVs in FS slowed down and the prevalence of CTS increased in comparison to those of the controls. The presence of CTS may be masked by the symptoms of FS. Additionally, peripheral stimulus may be a source for persistent pain in FS. When all of these findings are considered, patients with FS should be assessed by electrophysiological tests in addition to anamnesis and provocative tests. Patients with FS should be examined carefully due to CTS accompaniment, and appropriate and effective therapeutic interventions should be applied.
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