Conditions Associated With Carpal 'funnel Syndrome
J. CLARKE STEVENS, M.D.,* Department ofNeurology; C. MARY BEARD, R.N., M.P.H., Section of Clinical Epidemiology; W. MICHAEL O'FALLON, Ph.D., Section ofBiostatistics; LEONARD T. KURLAND, M.D., Dr.P.H., Section of Clinical Epidemiology
With use of a compreheusive medical records-linkage system, we identified the comorbid conditions and risk factors in the residents of Rochester, Minnesota, who had a diagnosis of carpal tunnel syndrome during 1961 through 1980. In 43.2% of the 1,016 patients, no associated conditions were found on review ofthe medical records, whereas associated conditions were documented in 56.8 %. The most frequent of these conditions were Colles' fracture, rheumatoid arthritis, hormonal agents or oophorectomy (or both), diabetes mellitus, and, among men, occupations that involved excessive use of the hands. Rheumatoid arthritis, diabetes mellitus, and pregnancy were significantly more frequent among the study patients with carpal tunnel syndrome than in the general population of Rochester, Minnesota. The standardized morbidity ratio was 3.6 for rheumatoid arthritis, 2.3 for diabetes mellitus, and 2.5 for pregnancy. The population attributable risk for pregnancy among women 15 to 44 years old was 7.0%. The standardized morbidity ratio for polymyalgia rheumatica was not significantly increased.
PATIENTS AND METHODS Residents of Rochester, Minnesota, with CTS were identified by using the medical records-linkage system of the Mayo Clinic and the Rochester Epidemiology Program Project.? Patients were included in the study if CTS was diagnosed during the period from 1961 through 1980. The minimal basis for acceptance as a case was a history of paresthesias in the distribution of the median nerve that caused nocturnal awakening or occurred during certain daytime activities. Most patients had other symptoms, such as persistent numbness, loss of sensitivity, clumsiness and weakness of the hand, and extension of pain proximally. Confirmatory physical signs included sensory loss in fingers innervated by the median nerve, Tinel's and Phalen's signs, and weakness and wasting of the thenar muscles. Electro*Mayo ClinicScottsdale, Scottsdale, Arizona. myography, when performed, was useful as a confirmatory This study was supported in part by Grants AR 30582 and procedure, but an abnormal finding was not needed for incluNS 17750 from the National Institutes of Health, Public Health sion in the study. The electromyographic findings in these Service. study patients have been published previously.' The medical records of cases accepted for inclusion in the Address reprint requests to Dr. J. C. Stevens, Department of study were reviewed for conditions that were present before Neurology, Mayo Clinic Scottsdale, 13400 East Shea Boulevard, the onset of CTS and that may have been associated with Scottsdale, AZ 85259.
Many conditions have been considered risk factors for carpal tunnel syndrome (CTS), a commonly recognized entrapment peripheral neuropathy. Among these conditions are female gender, use of oral contraceptives, prior oophorectomy, pregnancy, myxedema, diabetes mellitus, rheumatoid arthritis, prior Colles' fracture, polymyalgia rheumatica, eosinophilic fasciitis, and occupations that necessitate certain repetitive motions of the wrist. In this report, we describe the associated conditions documented in the medical records of the members of an incidence cohort with CTS in Rochester, Minnesota,' and assess the risk attributable to some of these conditions in this population.
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542
CONDITIONS ASSOCIATED WITH CARPAL TUNNEL SYNDROME
CTS. For example, extensive use of the hands was accepted as a risk factor if such activity was present and seemed to be the sole factor. Because certain activities are known to aggravate symptoms of CTS rather than being associated with the syndrome, inclusion of some activities involved subjective judgment. Determination of the most important associated conditions was based on a review of the available clinical data by one of us (l.C.S.). Diabetes mellitus was considered a risk factor if the diagnosis was made before or as much as 6 months after the onset of symptoms of CTS. The minimal criterion for the diagnosis of diabetes mellitus was as follows: from 1961 through 1971, blood glucose value of 110 mg/dl or more or results of glucose tolerance test of 170 mg/dl or more; from 1972 through 1980, blood glucose value of 130 mg/dl or more or results of glucose tolerance test of 190 mg/dl or more. The degree to which an exposure or a condition is associated with a disease in a specific population may be quantified by estimating a variable called the "attributable risk." Essentially, it is the proportion of persons with the disease who have the exposure or condition under review, adjusted for the prevalence of the exposure or condition in the population from which the patients originate. If this prevalence is known, the population attributable risk can be estimated by the following formula: No. of new cases - no. of unexposed new cases/( I - prevalence) No. of new cases
The prevalence rates for diabetes mellitus, polymyalgia rheumatica, rheumatoid arthritis, and bilateral oophorectomy were known from previous studies of the Rochester population. Another measure of disease association, referred to as a standardized morbidity ratio, is defined as the ratio of the observed number of patients with the condition to the expected number. This ratio provides an index of the association of the condition with CTS. Typically, the expected number is obtained by multiplying age-specific and sexspecific prevalence rates by the number of patients with CTS in each age-sex category and summing over all categories. If no association is present between the condition or exposure and the disease (CTS), the standardized morbidity ratio is 1.0. We determined whether an observed standardized morbidity ratio differs from 1.0 by using the Poisson distribution to obtain confidence intervals for the true standardized morbidity ratio based on the estimates. RESULTS The criteria for CTS were fulfilled by 1,016 patients (78.5% of whom were female), with a total of 1,600 affected hands. Handedness was recorded for 711 patients; 93% were right-
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handed and 7% were left-handed. Among the 1,016 patients, CTS involved only the right hand in 29.2%, only the left hand in 13.3%, and both hands in 57.5% (involvement was equivalent in both hands in 122, greater in the right hand in 310, and greater in the left hand in 152). The age at diagnosis ranged from 14 to 95 years, and the peak frequency was at 45 to 54 years (Fig. 1). Electromyography was performed in 505 patients, and the results were abnormal in 73%. CTS was diagnosed on the basis of both clinical and electromyographic criteria in 650 hands and on the basis of only clinical criteria in 950 hands. Surgical decompression of the carpal tunnel was performed on 676 hands (403 right hands and 273 left hands) of 486 patients. Of the 126 occupations noted in the medical records, the most frequently listed were "homemaker" and "retired" (Table 1). Of the 1,016 patients, 439 (43.2%) had idiopathic CTS, and 577 (56.8%) had other conditions associated with the syndrome (Table 2). A single associated condition was documented in the medical records of 499 patients. More than one associated condition was present in 78 patients, 61 of whom were judged to have one condition most likely associated with symptoms. (In Table 2, these patients are listed only once under that condition.) For 17 patients, we were unable to determine which of several associated conditions might be most important. The most frequently associated condition was trauma that involved the distal forearm, wrist, or hand. Ninety-two (12 male and 80 female) patients had Colles' fracture, 81 before and 11 after the onset of CTS. (The 78 patients listed in Table 2 are those in whom Colles' fracture was the main condition associated with CTS.) In 79 of the 81 patients in whom the fracture preceded CTS, the time from fracture to onset of symptoms of CTS was known. CTS developed the same day as the fracture in 3 of these patients, from day 2 to 2 years in 56, and after more than 3 years in 20. The right upper extremity was involved in 48 patients, the left upper extremity in 40, and both upper extremities in 4. The age at diagnosis of CTS in patients with Colles' fracture ranged from 14 to 95 years. In 85 of the 92 patients, the age at time of fracture was recorded; the median age was 28.9 years for male patients and 59.5 years for female patients. The other types of trauma documented in the medical records are noted in Table 2. Rheumatoid arthritis, present in 62 patients (definite in 40 and suspected in 22), was the most common associated collagen vascular disease. Single instances of CTS associated with seronegative polyarthritis, lupus erythematosus, periarteritis nodosa, and scleroderma were also identified. Seventy patients had diabetes mellitus before or within 6 months after the diagnosis of CTS. In 62 of these patients, diabetes was the only or the major recognized associated condition; in the 8 others, another disorder such as Colles'
CONDITIONS ASSOCIATED WITH CARPAL TUNNEL SYNDROME
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543
Number of patients 20
40
60
80
100
140
120
Age: 0-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85-89 90-95
fa Males IEJ Females
Fig. 1. Age-group at time of diagnosis of carpal tunnel syndrome in male and female patients, Rochester, Minnesota, 1961 through 1980.
fracture immediately preceded the onset of symptoms of CTS. Thirty patients reported excessive use of the hands in occupations with some presumed risk, such as heavy manual labor, factory work, or repetitive hand motion, and 10 noted the use of vibrating power tools (the absence of such information for the general population makes it difficult to interpret these reports). In 16 patients, symptoms of CTS developed in association with projects around the home, hobbies, and recreational activities that involved unaccustomed strenuous use of the hands. Four patients had symptoms in conjunction with long-standing or recent-onset physical disabilities that imposed stress on the wrists and hands. In 12 of these patients, symptoms of CTS developed shortly after a new job was begun or various projects around the home were initiated. Twenty-two other patients also experienced symptoms soon after starting a new activity; however, the symptoms were transient and disappeared within 1 year (occasionally within weeks or months). CTS was diagnosed during pregnancy in 47 patients (4.6%), with onset in the first trimester in 10, second trimester in 7, and third trimester in 28. The trimester of onset was not recorded for two patients. Symptoms disappeared after parturition in 25 patients but persisted in 20; for 2 patients, this information was not recorded. Nine other patients with preexisting CTS reported more pronounced symptoms during pregnancy.
Ideally, baseline incidence rates should be available to determine whether an "associated" condition is noted in excess frequency. Unfortunately, for many conditions, no such "expected" frequencies could be computed; therefore, the following factors were noted, but no conclusions about association could be inferred. Seventeen patients had more than one associated condition of uncertain significance (Table 3). In 39 women, symptoms of CTS began months or years after bilateral oophorectomy. The number of patients known to have used oral contraceptives (36 patients), conjugated estrogens (23 patients), or androgens (3 patients) does
Table I.-Most Frequently Listed Occupations of Patients With Carpal Tunnel Syndrome, Rochester, Minnesota, 1961 Through 1980 Occupation Homemaker Retired Nurse Secretary Teacher Office clerk Technician Physician or optometrist Salesclerk Nurse's aide
Male patients (N = 218)
Female patients (N = 798)
1 37 1
302 92 79 40 29 26 22 6 16 13
o 4 3
6
15 2
o
544
CONDITIONS ASSOCIATED WITH CARPAL TUNNEL SYNDROME
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in 205 patients (20.2%), often occurring within 1 or 2 years of the development of symptoms of CTS (Table 4). Because these conditions did not involve the carpal tunnel itself and did. not necessarily begin concurrent with the Patients symptoms of CTS, they were not considered the cause of the % Condition No. syndrome. Among those patients with nonspecific tenosyn439 43.2 Idiopathic ovitis of the wrist, 17 (47%) also had one of these rheumatic Associated condition 56.8 577 Trauma 136 13.4 conditions. An attempt was made to evaluate the frequency with 78 7.7 Colles' fracture Other forearm fracture 0.2 2 which diabetes mellitus, rheumatoid arthritis, and polymyal0.3 Old "wrist" fracture 3 gia rheumatica occurred in patients with CTS. This evalu0.5 Carpal bone fracture 5 ation included calculating a standardized morbidity ratio, as Wrist sprain 27 2.7 described previously. Because polymyalgia rheumatica selBlunt trauma to wrist 8 0.8 dom occurs in persons younger than 50 years old, incidence Operative procedure or 1.3 trauma that involved hand 13 rates included only those for the population older than 50 Collagen vascular disease 66 6.5 years of age. Hormonal agents, oophorectomy 65 6.4 The standardized morbidity ratios (and 95% confidence Diabetes mellitus 62 6.1 intervals) were as follows: for diabetes mellitus, 2.5 (1.5 to Excessive use of hands 60 5.9 3.9) for men and 2.2 (1.6 to 2.9) for women; for rheumatoid 54 Degenerative arthritis of wrist 5.3 Pregnancy 47 4.6 arthritis, 3.5 (1.4 to 7.2) for men and 3.9 (3.0 to 5.1) for 31 3.1 Nonspecific tenosynovitis women; and for polymyalgia rheumatica, 0.7 (0.3 to 1.3) for Miscellaneous 25 2.5 men and women. The risk ratios were significantly in14 1.4 Myxedema 1.7 creased for diabetes mellitus and rheumatoid arthritis but not Several associated conditions 17 for polymyalgia rheumatica. The association between pregnancy and CTS was evaluated by estimating a prevalence of not seem excessive, but precise information on comparable pregnancy in the cohort of women 15 to 44 years old by ages and duration of use in the community population is using fertility rates for Minnesota women in 1983.4 The unavailable. standardized morbidity ratio was 2.5. Similarly, the stanMiscellaneous conditions were present in 25 patients. dardized morbidity ratio for bilateral oophorectomy calcuPolymyalgia rheumatica preceded the development of symp- lated by using prevalence rates for 1975 was 0.9 (95% confitoms of CTS in 10 patients, and eosinophilic fasciitis was dence interval, 0.7 to 1.3).5 associated with CTS in 1 patient. In eight patients who had Population attributable risk percentage, which is a meaundergone surgical treatment, pathologic examination of sure of the strength of the association between these various biopsy specimens revealed deposits of amyloid. None of risk factors and CTS, was calculated for specific conditions. these patients subsequently showed evidence of generalized The resultant values for men and women were 4.2% and amyloidosis. Although several patients had ganglion cysts 3.8%, respectively, for diabetes mellitus and 2.3% and 5.1%, in the area of the wrist, the location of the cyst seemed to be respectively, for rheumatoid arthritis. Among women 15 to related to the development of symptoms in only two patients. 44 years old, the attributable risk for pregnancy was 7.0%. In one patient, a lipoma in the carpal canal was discovered at The assumption of a rare event did not apply, and confidence operation. In three patients, CTS was associated with infec- intervals were not calculated. tion, including one with septic arthritis of the wrist, one with osteomyelitis of the wrist, and one with lymphangitis and DISCUSSION swelling of the hand after laceration of the forearm. No This study of patients with CTS in Rochester, Minnesota, patient had acromegaly, uremia, or a forearm vascular shunt. from 1961 through 1980 has attempted to catalog the mediOf the 589 patients who underwent thyroid function stud- cal conditions that may be associated with CTS. In a retroies at the time of diagnosis of CTS, 14 (2.4%) had hypothy- spective analysis, the perception of an association is limited roidism. Although 10 patients had a family history of CTS, by the information available in the medical records; thus, the the question was so rarely addressed in the medical records data presented herein must be viewed as an approximation. that no meaningful statement can be made about the impor- In addition, the fact that certain conditions occur in patients tance of familial aggregation in this incidence series. with CTS does not necessarily signify etiologic importance. Nonspecific "rheumatic" disorders of the upper extrem- For some of the conditions for which incidence rates are ities, proximal and distal to the carpal tunnel, were noted unavailable to calculate the standardized morbidity ratio, a Table 2.-Associated Conditions Among 1,016 Patients With Carpal Tunnel Syndrome, Rochester, Minnesota, 1961 Through 1980
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CONDITIONS ASSOCIATED WITH CARPAL TUNNEL SYNDROME
Table 3.-Concordant Conditions in Patients With Carpal Tunnel Syndrome Who Had More Than One Associated Condition of Uncertain Significance, Rochester, Minnesota, 1961 Through 1980 Concordant conditions
No. of patients
Oophorectomy + use of estrogens Oophorectomy + arthritis Use of estrogens + arthritis Use of estrogens + old wrist fracture Use of oral contraceptives + old wrist fracture Use of oral contraceptives + tenosynovitis Use of oral contraceptives + arthritis Arthritis + tenosynovitis Arthritis + tenosynovitis + carpal bone anomaly
5 2 3 1 1
2
1 1 1
case-control study will be necessary to assess the level of etiologic association. In our study, 78.5% of the overall group with CTS were female patients. This finding corresponds to the 77% of 250 consecutive patients in a series who underwent electromyography in Baltimore, Maryland," and 70.5% of 400 patients with surgically treated CTS in Lund, Sweden.' In almost half (43.2%) of the cases of CTS in our series, no obvious explanation was available for the condition. Comparisons with other series identify some of the difficulties of attempting to determine a cause. In some previously described large series, the proportion of "spontaneous" cases has not been reported."!' In a surgically treated and presumably more severely affected series of patients, Cseuz and colleagues" found that 83% had systemic disease and other associated conditions. Goodwill'? accepted a specific cause in only 18 of 114 patients. In a series of 1,215 patients described by Yamaguchi and co-workers" (primarily referral cases at the Mayo Clinic), an associated condition could not be identified in 897 (74%), whereas a cause was noted in 318 (26%), with more than half being rheumatoid arthritis or myxedema (or both). The notable difference between the results in the referral series at the Mayo Clinic and the current study is indicative of the substantial effect of referral bias observed in studies conducted at tertiary-care centers. For the cases of CTSwe categorized as spontaneous, no obvious associated condition was noted in the medical records. The increase in incidence in perimenopausal women suggests that hormonal factors could have a role in idiopathic CTS,9 but the mechanism is unknown. Some,I4·15 but not all," investigators have found a decrease in the crosssectional area of the carpal tunnel in patients with idiopathic CTS. A smaller carpal tunnel in association with mild tenosynovial and arthritic changes may be sufficient to cause compression of the median nerve in these patients. Many reports relate various conditions to the development of CTS.
545
None of these reports, however, indicates the frequency of occurrence of associated conditions in a population. Careful review of our cases reveals that a combination of factors may produce symptoms and that it may be difficult to know which of them may be the dominant factor. This situation was found in 17 patients in our series and involved combinations of old wrist fractures, arthritis, and, possibly, hormonal factors. The ages of our patients ranged from 14 to 95 years, similar to the ages of a series of 400 surgically treated patients with CTS described in the largely population-based study in Lund, Sweden (age range, 18 to 85 years).' Most patients in the Swedish study were 32 to 60 years old; the peak age-group in the Rochester patients was 45 to 54 years. Trauma was the most common factor (13.4%) associated with the development of CTS in our incidence cohort. In comparison, trauma constituted 7.5% to 13% of cases of CTS in other large series.v" In the current study, wrist sprain, usually due to a fallon an outstretched arm, was a frequent injury. In eight of our patients, symptoms developed after accidental direct blunt trauma to the wrist; such patients constituted 9 of 439 in a series described by Phalen? and 11 of 400 in a report by Hybbinette and Mannerfelt.? Rheumatoid arthritis was shown to occur significantly more often in patients with CTS than expected in the general population of the same age and sex.'? In large surgical series, rheumatoid arthritis is usually listed as one of the three most common causes of CTSY·ll.13 The standardized morbidity ratio in our series was 3.6. Diabetes mellitus has long been suspected of predisposing nerves to entrapment neuropathies, including CTS.18 The standardized morbidity ratio for diabetes for the development of CTS in our series was 2.3. 19 The reason CTS is common in patients with diabetes is unknown, but aggravation of ischemia in nerves already stressed by chronic endoneurial hypoxia may be a factor." Dyck and associates," in a study of acute nerve compression in rats with diabetes induced with streptozocin, found that their peroneal nerves
Table 4.-Rheumatic Conditions in Patients With Carpal Tunnel Syndrome, Rochester, Minnesota, 1961 Through 1980 Rheumatic condition
No. of patients*
Triggerfinger Tenniselbow De Quervain's tenosynovitis Dupuytren'scontracture Tenosynovitis of forearm or hand Nonspecific synovitis of fingerjoints
108
*Somepatientshad morethan one condition.
53 33 24 18 11
546
CONDmONS ASSOCIATED WITH CARPAL TUNNEL SYNDROME
were more resistant to axonal injury than those of control rats; thus, alterations in the connective tissue sheaths of the nerve or in the transverse carpal ligament may be responsible for CTS. A recent case-control study from the Netherlands failed to demonstrate a relationship between diabetes and CTS.22 In addition to the patients with onset of CTS during pregnancy, mild and transient CTS developed in 44 patients, but the symptoms disappeared in 12 months or less without treatment, other than use of wrist splints at night. The conditions associated with transient symptoms were excessive use of the hands in 20 patients, wrist sprains in 2, rheumatoid arthritis in 2, tenosynovitis in 2, Colles' fracture in 2, and diabetes mellitus and polymyalgia rheumatica in 1 patient each. The CTS was spontaneous and had no apparent cause in 14 of the 44 patients. The current study suggests that CTS occurs 2.5 times more often among pregnant women than among nonpregnant women 15 to 44 years old. Voitk and colleagues" interviewed 1,000 postpartum patients by questionnaire and found that 25% had had symptoms of CTS, whereas only 46% of those with any type of hand symptoms had mentioned this fact to their physicians. In our study, of the 47 patients with CTS during pregnancy, onset by trimester was known for 45-CTS was diagnosed in 22%,16%, and 62% in the first, second, and third trimesters, respectively. In the study by Voitk and co-workers.P symptoms of CTS began in the first trimester in 6%, in the second trimester in 38%, and in the third trimester in 56%. Among 58 unselected pregnant patients who underwent electrodiagnostic study, Melvin and associates" found that 18 (31%) had symptoms of CTS but only 4 had significant abnormal findings. The frequency of CTS during pregnancy in other studies ranged from 2.3% to 10%.25,26 Several reports have described an association between CTS and bilateral oophorectomy.F'P As mentioned previously, the high incidence of CTS in perimenopausal women suggests that changes in ovarian function or use of exogenous estrogensv-" may be important in the development of symptoms and that "iatrogenic menopause" (that is, oophorectomy), which was noted in 2.5% of our female patients, might provide a similar mechanism. The standardized morbidity ratio indicated that the prevalence of oophorectomy among our patients with CTS was no greater than that expected in the community population of Rochester, Minnesota. Anecdotal reports and case series suggest that CTS may have an occupational association, primarily with manual labor or the use of vibrating power tools:" however, casecontrol and prospective studies have been. inadequate for drawing that conclusion. In our study and in other series in which occupations were tabulated, "homemaker" was the
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most frequently listed occupation.vP'" The effect of activity on the development of symptoms is controversial because many activities may merely aggravate an underlying problem. In our series, only cases that involved considerable manual labor were presumed to be "occupational" CTS; however, a case-control study unaffected by potential worker's compensation is needed to determine whether certain occupations are overrepresented. Factors implicated as being associated with CTS in jobs that involve manual labor include repetitive hand motion,27.33,34 various biomechanical factors,8.35,36 and long-term exposure to vibration.F-":" Examples of occupations perceived by some investigators to be associated with CTS are production seamstresses," grocery checkers.t-? meat-packers.rr" and bakers." Because CTS is more common in the dominant hand of both right-handed and left-handed patients, the extra stress borne by the dominant hand may contribute to symptoms." In several reports, degenerative arthritis of the wrist has been mentioned in association with CTS,7.10 Although many patients in our cohort had arthritic changes, assessing the importance of these changes was difficult because the frequency of similar joint changes is uncertain in the general population, particularly in older persons. Myxedema has often been cited as a risk factor for CTS,48,49 but only 14 cases (1.4%) were identified at the time of diagnosis of CTS in our incidence cohort. In a study of a large referral series, Yamaguchi and colleagues13 found that the proportion of patients with myxedema was 6.3%; thus, referral bias may have influenced that assessment. The association of polymyalgia rheumatica and eosinophilic fasciitis with CTS has been noted previously.P" The finding of 10 cases of polymyalgia rheumatica in the current series, however, was not significantly more than that expected among residents of Rochester, Minnesota." Amyloidosis is infrequently reported in conjunction with CTS, which is associated with a family history in the Rukavina type" or may be associated with multiple myelomav-" and other diseases." None of the eight patients with deposits of amyloid in the current series had a recorded family history of CTS or evidence of involvement of other organ systems; these findings suggested that the amyloid was localized to the tenosynovium.s" Many of our patients had nonspecific "rheumatic" conditions-trigger finger, tennis elbow, de Quervain's tenosynovitis, Dupuytren's contracture, tenosynovitis of the forearm or hand, and synovitis of the finger joints within 1 or 2 years before the development of CTS. The occurrence of these disorders may reflect medical or occupational factors or may indicate that patients with CTS have a tendency for tenosynovial or fibrosing reactions of structures in the carpal tunnel. Nonspecific rheumatic conditions were frequently noted in prior series as well. 9,13,61-63
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CONDITIONS ASSOCIATED WITH CARPAL TUNNEL SYNDROME
CONCLUSION In this study, we cataloged conditions associated with CTS in the residents of Rochester, Minnesota, during the years 1961 through 1980. The prevalence rates for several associated conditions were known from previous studies of the population of this community. Rheumatoid arthritis, diabetes mellitus, and pregnancy were significantly more frequent among patients with CTS than in the general population. Determining the relationship of other conditions to the development of CTS must await a case-control study. The high incidence of CTS in perimenopausal women is of considerable interest. A study of the incidence of CTS in women who have undergone oophorectomy may help shed light on the contribution of endocrine factors in the pathogenesis of CTS. Assigning a causal relationship of certain conditions is difficult because some patients have multiple disorders. Future studies of incidence must recognize this fact and explain how decisions about possible associations are made.
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Dekel S, Coates R: Primary carpal stenosis as a cause of "idiopathic" carpal-tunnel syndrome (letter to the editor). Lancet 2:1024,1979 Bleecker ML, Bohlman M, Moreland R, Tipton A: Carpal tunnel syndrome: role of carpal canal size. Neurology 35:1599-1604, 1985 Winn FJ Jr, Habes DJ: Carpal tunnel area as a risk factor for carpal tunnel syndrome. Muscle Nerve 13:254-258, 1990 Linos A, Worthington JW, O'Fallon WM, Kurland LT: The epidemiology of rheumatoid arthritis in Rochester, Minnesota: a study of incidence, prevalence, and mortality. Am J Epidemiol 111:87-98,1980 Mulder DW, Lambert EH, Bastron JA, Sprague RG: The neuropathies associated with diabetes mellitus: a clinical and electromyographic study of 103 unselected diabetic patients. Neurology 11:275-284, 1961 Palumbo PJ, Elveback LR, Chu C-P, Connolly DC, Kurland LT: Diabetes mellitus: incidence, prevalence, survivorship, and causes of death in Rochester, Minnesota, 1945-1970. Diabetes 25:566-573, 1976 Low PA: Recent advances in the pathogenesis of diabetic neuropathy. Muscle Nerve 10:121-128,1987 Dyck PJ, Engelstad JK, Giannini C, Lais AC, Minnerath SR, Karnes JL: Resistance to axonal degeneration after nerve compression in experimental diabetes. Proc Nat! Acad Sci USA 86:2103-2106,1989 De Krom MCTFM, Kester ADM, Knipschild PG, Spaans F: Risk factors for carpal tunnel syndrome. Am J Epidemiol 132:1102-1110, 1990 Voitk AJ, Mueller JC, Farlinger DE, Johnston RU: Carpal tunnel syndrome in pregnancy. Can Med Assoc J 128:277279;281,1983 Melvin JL, Burnett CN, Johnson EW: Median nerve conduction in pregnancy. Arch Phys Med Rehabil 50:75-80, 1969 Massey EW: Carpal tunnel syndrome in pregnancy. Obstet Gynecol Surv 33:145-148,1978 Ekman-Ordeberg G, Salgeback S, Ordeberg G: Carpal tunnel syndrome in pregnancy: a prospective study. Acta Obstet Gynecol Scand 66:233-235,1987 Cannon LJ, Bernacki EJ, Walter SD: Personal and occupational factors associated with carpal tunnel syndrome. J Occup Med 23:255-258, 1981 Bjorkqvist S-E, Lang AH, Punnonen R, Rauramo L: Carpal tunnel syndrome in ovariectomized women. Acta Obstet Gynecol Scand 56:127-130,1977 Pascual E, Giner V, Arostegui A, Conill J, Ruiz MT, Pico A: Higher incidence of carpal tunnel syndrome in oophorectomized women. Br J Rheumatol 30:60-62, 1991 Vessey MP, Villard-Mackintosh L, Yeates D: Epidemiology of carpal tunnel syndrome in women of childbearing age: findings in a large cohort study. Int J Epidemiol 19:655-659, 1990 Sabour MS, Fadel HE: The carpal tunnel syndrome-a new complication ascribed to the "pill." Am J Obstet Gynecol 107:1265-1267, 1970 Carpal tunnel syndrome identified as an occupational health hazard. Neurol Alert 3:8, October 1984 Birkbeck MQ, Beer TC: Occupation in relation to the carpal tunnel syndrome. Rheumatol Rehabil 14:218-221,1975 Silverstein BA, Fine LJ, Armstrong TJ: Occupational factors and carpal tunnel syndrome. Am J Ind Moo 11:343-358, 1987
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35. 36.
37.
38. 39. 40. 41.
42. 43. 44. 45. 46. 47. 48. 49.
CONDITIONS ASSOCIATED WITH CARPAL TUNNEL SYNDROME
Armstrong TJ, Chaffin DB: Carpal tunnel syndrome and selected personal attributes. J Occup Med 21:481-486,1979 Rothfleisch S, Sherman D: Carpal tunnel syndrome: biomechanical aspects of occupational occurrence and implications regarding surgical management. Orthop Rev 7:107109, 1978 Ramsey JD, Beshir MY: Vibration diseases. In Clinical Medicine. Vol 12, Chapter 100. Edited by JA Spittell Jr, EB Brody, RD Stewart. Philadelphia, Harper & Row, Publishers, 1984, pp 1-10 Chatterjee DS, Barwick DD, Petrie A: Exploratory electromyography in the study of vibration-induced white finger in rock drillers. Br J Ind Med 39:89-97, 1982 Wener MH, Metzger WJ, Simon RA: Occupationally acquired vibratory angioedema with secondary carpal tunnel syndrome. Ann Intern Med 98:44-46, 1983 Boyle JC, Smith NJ, Burke FD: Vibration white finger. J Hand Surg [B) 13:171-176,1988 Wieslander G, Norback D, Gothe C-J, Juhlin L: Carpal tunnel syndrome (CTS) and exposure to vibration, repetitive wrist movements, and heavy manual work: a case-referent study. Br JInd Med 46:43-47,1989 Margolis W, Kraus JF: The prevalence of carpal tunnel syndrome symptoms in female supermarket checkers. J Occup Med 29:953-956, 1987 Barnhart S, Rosenstock L: Carpal tunnel syndrome in grocery checkers: a cluster of a work-related illness. West J Med 147:37-40, 1987 Greenhouse AH: The carpal tunnel syndrome in neurologic practice. Nebr Med J 66:75-76,1981 Masear VR, Hayes JM, Hyde AG: An industrial cause of carpal tunnel syndrome. J Hand Surg [A] 11:222-227, 1986 Falck B, Aamio P: Left-sided carpal tunnel syndrome in butchers. Scand J Work Environ Health 9:291-297,1983 Kopell HP, Thompson WAL: Peripheral Entrapment Neuropathies. Second edition. Huntington, New York, Robert E Kreiger Publishing Company, 1976, p 101 Murray IPC, Simpson JA: Acroparaesthesia in myxoedema: a clinical and electromyographic study. Lancet 1:1360-1363, 1958 Purnell DC, Daly DD, Lipscomb PR: Carpal-tunnel syndrome associated with myxedema. Arch Intern Med 108:751-756, 1961
50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60.
61. 62.
63.
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Ahmed T, Braun AI: Carpal tunnel syndrome with polyrnyalgia rheumatica. Arthritis Rheum 21:221-223,1978 O'Duffy JD, Hunder GG, Wahner HW: A follow-up study of polymyalgia rheumatica: evidence of chronic axial synovitis. J Rheumatol 7:685-693,1980 Wollheim FA, Lindstrom CG, Eiken 0: Eosinophilic fasciitis complicated by carpal tunnel syndrome. J Rheumatol 8:856860, 1981 Jones HR Jr, Beetham WP: Carpal tunnel syndrome secondary to eosinophilic fasciitis (abstract). Muscle Nerve 6:527528, 1983 Michet CJ Jr, Doyle JA, Ginsburg WW: Eosinophilic fasciitis: report of 15 cases. Mayo Clin Proc 56:27-34, 1981 Chuang T-Y, Hunder GG, Ilstrup DM, Kurland LT: Polymya1gia rheumatica: a lO-year epidemiologic and clinical study. Ann Intern Med 97:672-680,1982 Lambird PA, Hartmann WH: Hereditary amyloidosis, the flexor retinaculum, and the carpal tunnel syndrome. Am J Clin Pathol 52:714-719,1969 Akin RK, Barton K, Walters PJ: Amyloidosis, macroglossia, and carpal tunnel syndrome associated with myeloma. J Oral Surg 33:690-692, 1975 Chapman RH, Cotter F: The carpal tunnel syndrome and amyloidosis: a case report. Clin Orthop 169:159-162, 1982 Stein K, Sterkel S, Linke RP, Goebel HH: Chemical heterogeneity of amyloid in the carpal tunnel syndrome. Virchows Arch A Pathol Anat Histopathol 412:37-45, 1987 Kyle RA, Eilers SG, Linscheid RL, Gaffey TA: Amyloid localized to tenosynovium at carpal tunnel release: natural history of 124 cases. Am J Clin Pathol 91:393-397, 1989 Lipscomb PR: Tenosynovitis of the hand and the wrist: carpal tunnel syndrome, de Quervain's disease, trigger digit. Clin Orthop 13:164-180,1959 Murray-Leslie CF, Wright V: Carpal tunnel syndrome, humeral epicondylitis, and the cervical spine: a study of clinical and dimensional relations. Br Med J 1:1439-1442, 1976 McArthur RG, Hayles AB, Gomez MR, Bianco AJ Jr: Carpal tunnel syndrome and trigger finger in childhood. Am J Dis Child 117:463-469,1969
J. CLARKE STEVENS, M.D.,* Department ofNeurology; C. MARY BEARD, R.N., M.P.H., Section of Clinical Epidemiology; W. MICHAEL O'FALLON, Ph.D., Section ofBiostatistics; LEONARD T. KURLAND, M.D., Dr.P.H., Section of Clinical Epidemiology
With use of a compreheusive medical records-linkage system, we identified the comorbid conditions and risk factors in the residents of Rochester, Minnesota, who had a diagnosis of carpal tunnel syndrome during 1961 through 1980. In 43.2% of the 1,016 patients, no associated conditions were found on review ofthe medical records, whereas associated conditions were documented in 56.8 %. The most frequent of these conditions were Colles' fracture, rheumatoid arthritis, hormonal agents or oophorectomy (or both), diabetes mellitus, and, among men, occupations that involved excessive use of the hands. Rheumatoid arthritis, diabetes mellitus, and pregnancy were significantly more frequent among the study patients with carpal tunnel syndrome than in the general population of Rochester, Minnesota. The standardized morbidity ratio was 3.6 for rheumatoid arthritis, 2.3 for diabetes mellitus, and 2.5 for pregnancy. The population attributable risk for pregnancy among women 15 to 44 years old was 7.0%. The standardized morbidity ratio for polymyalgia rheumatica was not significantly increased.
PATIENTS AND METHODS Residents of Rochester, Minnesota, with CTS were identified by using the medical records-linkage system of the Mayo Clinic and the Rochester Epidemiology Program Project.? Patients were included in the study if CTS was diagnosed during the period from 1961 through 1980. The minimal basis for acceptance as a case was a history of paresthesias in the distribution of the median nerve that caused nocturnal awakening or occurred during certain daytime activities. Most patients had other symptoms, such as persistent numbness, loss of sensitivity, clumsiness and weakness of the hand, and extension of pain proximally. Confirmatory physical signs included sensory loss in fingers innervated by the median nerve, Tinel's and Phalen's signs, and weakness and wasting of the thenar muscles. Electro*Mayo ClinicScottsdale, Scottsdale, Arizona. myography, when performed, was useful as a confirmatory This study was supported in part by Grants AR 30582 and procedure, but an abnormal finding was not needed for incluNS 17750 from the National Institutes of Health, Public Health sion in the study. The electromyographic findings in these Service. study patients have been published previously.' The medical records of cases accepted for inclusion in the Address reprint requests to Dr. J. C. Stevens, Department of study were reviewed for conditions that were present before Neurology, Mayo Clinic Scottsdale, 13400 East Shea Boulevard, the onset of CTS and that may have been associated with Scottsdale, AZ 85259.
Many conditions have been considered risk factors for carpal tunnel syndrome (CTS), a commonly recognized entrapment peripheral neuropathy. Among these conditions are female gender, use of oral contraceptives, prior oophorectomy, pregnancy, myxedema, diabetes mellitus, rheumatoid arthritis, prior Colles' fracture, polymyalgia rheumatica, eosinophilic fasciitis, and occupations that necessitate certain repetitive motions of the wrist. In this report, we describe the associated conditions documented in the medical records of the members of an incidence cohort with CTS in Rochester, Minnesota,' and assess the risk attributable to some of these conditions in this population.
Mayo Clin Proc 67:541-548,1992
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542
CONDITIONS ASSOCIATED WITH CARPAL TUNNEL SYNDROME
CTS. For example, extensive use of the hands was accepted as a risk factor if such activity was present and seemed to be the sole factor. Because certain activities are known to aggravate symptoms of CTS rather than being associated with the syndrome, inclusion of some activities involved subjective judgment. Determination of the most important associated conditions was based on a review of the available clinical data by one of us (l.C.S.). Diabetes mellitus was considered a risk factor if the diagnosis was made before or as much as 6 months after the onset of symptoms of CTS. The minimal criterion for the diagnosis of diabetes mellitus was as follows: from 1961 through 1971, blood glucose value of 110 mg/dl or more or results of glucose tolerance test of 170 mg/dl or more; from 1972 through 1980, blood glucose value of 130 mg/dl or more or results of glucose tolerance test of 190 mg/dl or more. The degree to which an exposure or a condition is associated with a disease in a specific population may be quantified by estimating a variable called the "attributable risk." Essentially, it is the proportion of persons with the disease who have the exposure or condition under review, adjusted for the prevalence of the exposure or condition in the population from which the patients originate. If this prevalence is known, the population attributable risk can be estimated by the following formula: No. of new cases - no. of unexposed new cases/( I - prevalence) No. of new cases
The prevalence rates for diabetes mellitus, polymyalgia rheumatica, rheumatoid arthritis, and bilateral oophorectomy were known from previous studies of the Rochester population. Another measure of disease association, referred to as a standardized morbidity ratio, is defined as the ratio of the observed number of patients with the condition to the expected number. This ratio provides an index of the association of the condition with CTS. Typically, the expected number is obtained by multiplying age-specific and sexspecific prevalence rates by the number of patients with CTS in each age-sex category and summing over all categories. If no association is present between the condition or exposure and the disease (CTS), the standardized morbidity ratio is 1.0. We determined whether an observed standardized morbidity ratio differs from 1.0 by using the Poisson distribution to obtain confidence intervals for the true standardized morbidity ratio based on the estimates. RESULTS The criteria for CTS were fulfilled by 1,016 patients (78.5% of whom were female), with a total of 1,600 affected hands. Handedness was recorded for 711 patients; 93% were right-
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handed and 7% were left-handed. Among the 1,016 patients, CTS involved only the right hand in 29.2%, only the left hand in 13.3%, and both hands in 57.5% (involvement was equivalent in both hands in 122, greater in the right hand in 310, and greater in the left hand in 152). The age at diagnosis ranged from 14 to 95 years, and the peak frequency was at 45 to 54 years (Fig. 1). Electromyography was performed in 505 patients, and the results were abnormal in 73%. CTS was diagnosed on the basis of both clinical and electromyographic criteria in 650 hands and on the basis of only clinical criteria in 950 hands. Surgical decompression of the carpal tunnel was performed on 676 hands (403 right hands and 273 left hands) of 486 patients. Of the 126 occupations noted in the medical records, the most frequently listed were "homemaker" and "retired" (Table 1). Of the 1,016 patients, 439 (43.2%) had idiopathic CTS, and 577 (56.8%) had other conditions associated with the syndrome (Table 2). A single associated condition was documented in the medical records of 499 patients. More than one associated condition was present in 78 patients, 61 of whom were judged to have one condition most likely associated with symptoms. (In Table 2, these patients are listed only once under that condition.) For 17 patients, we were unable to determine which of several associated conditions might be most important. The most frequently associated condition was trauma that involved the distal forearm, wrist, or hand. Ninety-two (12 male and 80 female) patients had Colles' fracture, 81 before and 11 after the onset of CTS. (The 78 patients listed in Table 2 are those in whom Colles' fracture was the main condition associated with CTS.) In 79 of the 81 patients in whom the fracture preceded CTS, the time from fracture to onset of symptoms of CTS was known. CTS developed the same day as the fracture in 3 of these patients, from day 2 to 2 years in 56, and after more than 3 years in 20. The right upper extremity was involved in 48 patients, the left upper extremity in 40, and both upper extremities in 4. The age at diagnosis of CTS in patients with Colles' fracture ranged from 14 to 95 years. In 85 of the 92 patients, the age at time of fracture was recorded; the median age was 28.9 years for male patients and 59.5 years for female patients. The other types of trauma documented in the medical records are noted in Table 2. Rheumatoid arthritis, present in 62 patients (definite in 40 and suspected in 22), was the most common associated collagen vascular disease. Single instances of CTS associated with seronegative polyarthritis, lupus erythematosus, periarteritis nodosa, and scleroderma were also identified. Seventy patients had diabetes mellitus before or within 6 months after the diagnosis of CTS. In 62 of these patients, diabetes was the only or the major recognized associated condition; in the 8 others, another disorder such as Colles'
CONDITIONS ASSOCIATED WITH CARPAL TUNNEL SYNDROME
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543
Number of patients 20
40
60
80
100
140
120
Age: 0-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85-89 90-95
fa Males IEJ Females
Fig. 1. Age-group at time of diagnosis of carpal tunnel syndrome in male and female patients, Rochester, Minnesota, 1961 through 1980.
fracture immediately preceded the onset of symptoms of CTS. Thirty patients reported excessive use of the hands in occupations with some presumed risk, such as heavy manual labor, factory work, or repetitive hand motion, and 10 noted the use of vibrating power tools (the absence of such information for the general population makes it difficult to interpret these reports). In 16 patients, symptoms of CTS developed in association with projects around the home, hobbies, and recreational activities that involved unaccustomed strenuous use of the hands. Four patients had symptoms in conjunction with long-standing or recent-onset physical disabilities that imposed stress on the wrists and hands. In 12 of these patients, symptoms of CTS developed shortly after a new job was begun or various projects around the home were initiated. Twenty-two other patients also experienced symptoms soon after starting a new activity; however, the symptoms were transient and disappeared within 1 year (occasionally within weeks or months). CTS was diagnosed during pregnancy in 47 patients (4.6%), with onset in the first trimester in 10, second trimester in 7, and third trimester in 28. The trimester of onset was not recorded for two patients. Symptoms disappeared after parturition in 25 patients but persisted in 20; for 2 patients, this information was not recorded. Nine other patients with preexisting CTS reported more pronounced symptoms during pregnancy.
Ideally, baseline incidence rates should be available to determine whether an "associated" condition is noted in excess frequency. Unfortunately, for many conditions, no such "expected" frequencies could be computed; therefore, the following factors were noted, but no conclusions about association could be inferred. Seventeen patients had more than one associated condition of uncertain significance (Table 3). In 39 women, symptoms of CTS began months or years after bilateral oophorectomy. The number of patients known to have used oral contraceptives (36 patients), conjugated estrogens (23 patients), or androgens (3 patients) does
Table I.-Most Frequently Listed Occupations of Patients With Carpal Tunnel Syndrome, Rochester, Minnesota, 1961 Through 1980 Occupation Homemaker Retired Nurse Secretary Teacher Office clerk Technician Physician or optometrist Salesclerk Nurse's aide
Male patients (N = 218)
Female patients (N = 798)
1 37 1
302 92 79 40 29 26 22 6 16 13
o 4 3
6
15 2
o
544
CONDITIONS ASSOCIATED WITH CARPAL TUNNEL SYNDROME
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in 205 patients (20.2%), often occurring within 1 or 2 years of the development of symptoms of CTS (Table 4). Because these conditions did not involve the carpal tunnel itself and did. not necessarily begin concurrent with the Patients symptoms of CTS, they were not considered the cause of the % Condition No. syndrome. Among those patients with nonspecific tenosyn439 43.2 Idiopathic ovitis of the wrist, 17 (47%) also had one of these rheumatic Associated condition 56.8 577 Trauma 136 13.4 conditions. An attempt was made to evaluate the frequency with 78 7.7 Colles' fracture Other forearm fracture 0.2 2 which diabetes mellitus, rheumatoid arthritis, and polymyal0.3 Old "wrist" fracture 3 gia rheumatica occurred in patients with CTS. This evalu0.5 Carpal bone fracture 5 ation included calculating a standardized morbidity ratio, as Wrist sprain 27 2.7 described previously. Because polymyalgia rheumatica selBlunt trauma to wrist 8 0.8 dom occurs in persons younger than 50 years old, incidence Operative procedure or 1.3 trauma that involved hand 13 rates included only those for the population older than 50 Collagen vascular disease 66 6.5 years of age. Hormonal agents, oophorectomy 65 6.4 The standardized morbidity ratios (and 95% confidence Diabetes mellitus 62 6.1 intervals) were as follows: for diabetes mellitus, 2.5 (1.5 to Excessive use of hands 60 5.9 3.9) for men and 2.2 (1.6 to 2.9) for women; for rheumatoid 54 Degenerative arthritis of wrist 5.3 Pregnancy 47 4.6 arthritis, 3.5 (1.4 to 7.2) for men and 3.9 (3.0 to 5.1) for 31 3.1 Nonspecific tenosynovitis women; and for polymyalgia rheumatica, 0.7 (0.3 to 1.3) for Miscellaneous 25 2.5 men and women. The risk ratios were significantly in14 1.4 Myxedema 1.7 creased for diabetes mellitus and rheumatoid arthritis but not Several associated conditions 17 for polymyalgia rheumatica. The association between pregnancy and CTS was evaluated by estimating a prevalence of not seem excessive, but precise information on comparable pregnancy in the cohort of women 15 to 44 years old by ages and duration of use in the community population is using fertility rates for Minnesota women in 1983.4 The unavailable. standardized morbidity ratio was 2.5. Similarly, the stanMiscellaneous conditions were present in 25 patients. dardized morbidity ratio for bilateral oophorectomy calcuPolymyalgia rheumatica preceded the development of symp- lated by using prevalence rates for 1975 was 0.9 (95% confitoms of CTS in 10 patients, and eosinophilic fasciitis was dence interval, 0.7 to 1.3).5 associated with CTS in 1 patient. In eight patients who had Population attributable risk percentage, which is a meaundergone surgical treatment, pathologic examination of sure of the strength of the association between these various biopsy specimens revealed deposits of amyloid. None of risk factors and CTS, was calculated for specific conditions. these patients subsequently showed evidence of generalized The resultant values for men and women were 4.2% and amyloidosis. Although several patients had ganglion cysts 3.8%, respectively, for diabetes mellitus and 2.3% and 5.1%, in the area of the wrist, the location of the cyst seemed to be respectively, for rheumatoid arthritis. Among women 15 to related to the development of symptoms in only two patients. 44 years old, the attributable risk for pregnancy was 7.0%. In one patient, a lipoma in the carpal canal was discovered at The assumption of a rare event did not apply, and confidence operation. In three patients, CTS was associated with infec- intervals were not calculated. tion, including one with septic arthritis of the wrist, one with osteomyelitis of the wrist, and one with lymphangitis and DISCUSSION swelling of the hand after laceration of the forearm. No This study of patients with CTS in Rochester, Minnesota, patient had acromegaly, uremia, or a forearm vascular shunt. from 1961 through 1980 has attempted to catalog the mediOf the 589 patients who underwent thyroid function stud- cal conditions that may be associated with CTS. In a retroies at the time of diagnosis of CTS, 14 (2.4%) had hypothy- spective analysis, the perception of an association is limited roidism. Although 10 patients had a family history of CTS, by the information available in the medical records; thus, the the question was so rarely addressed in the medical records data presented herein must be viewed as an approximation. that no meaningful statement can be made about the impor- In addition, the fact that certain conditions occur in patients tance of familial aggregation in this incidence series. with CTS does not necessarily signify etiologic importance. Nonspecific "rheumatic" disorders of the upper extrem- For some of the conditions for which incidence rates are ities, proximal and distal to the carpal tunnel, were noted unavailable to calculate the standardized morbidity ratio, a Table 2.-Associated Conditions Among 1,016 Patients With Carpal Tunnel Syndrome, Rochester, Minnesota, 1961 Through 1980
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CONDITIONS ASSOCIATED WITH CARPAL TUNNEL SYNDROME
Table 3.-Concordant Conditions in Patients With Carpal Tunnel Syndrome Who Had More Than One Associated Condition of Uncertain Significance, Rochester, Minnesota, 1961 Through 1980 Concordant conditions
No. of patients
Oophorectomy + use of estrogens Oophorectomy + arthritis Use of estrogens + arthritis Use of estrogens + old wrist fracture Use of oral contraceptives + old wrist fracture Use of oral contraceptives + tenosynovitis Use of oral contraceptives + arthritis Arthritis + tenosynovitis Arthritis + tenosynovitis + carpal bone anomaly
5 2 3 1 1
2
1 1 1
case-control study will be necessary to assess the level of etiologic association. In our study, 78.5% of the overall group with CTS were female patients. This finding corresponds to the 77% of 250 consecutive patients in a series who underwent electromyography in Baltimore, Maryland," and 70.5% of 400 patients with surgically treated CTS in Lund, Sweden.' In almost half (43.2%) of the cases of CTS in our series, no obvious explanation was available for the condition. Comparisons with other series identify some of the difficulties of attempting to determine a cause. In some previously described large series, the proportion of "spontaneous" cases has not been reported."!' In a surgically treated and presumably more severely affected series of patients, Cseuz and colleagues" found that 83% had systemic disease and other associated conditions. Goodwill'? accepted a specific cause in only 18 of 114 patients. In a series of 1,215 patients described by Yamaguchi and co-workers" (primarily referral cases at the Mayo Clinic), an associated condition could not be identified in 897 (74%), whereas a cause was noted in 318 (26%), with more than half being rheumatoid arthritis or myxedema (or both). The notable difference between the results in the referral series at the Mayo Clinic and the current study is indicative of the substantial effect of referral bias observed in studies conducted at tertiary-care centers. For the cases of CTSwe categorized as spontaneous, no obvious associated condition was noted in the medical records. The increase in incidence in perimenopausal women suggests that hormonal factors could have a role in idiopathic CTS,9 but the mechanism is unknown. Some,I4·15 but not all," investigators have found a decrease in the crosssectional area of the carpal tunnel in patients with idiopathic CTS. A smaller carpal tunnel in association with mild tenosynovial and arthritic changes may be sufficient to cause compression of the median nerve in these patients. Many reports relate various conditions to the development of CTS.
545
None of these reports, however, indicates the frequency of occurrence of associated conditions in a population. Careful review of our cases reveals that a combination of factors may produce symptoms and that it may be difficult to know which of them may be the dominant factor. This situation was found in 17 patients in our series and involved combinations of old wrist fractures, arthritis, and, possibly, hormonal factors. The ages of our patients ranged from 14 to 95 years, similar to the ages of a series of 400 surgically treated patients with CTS described in the largely population-based study in Lund, Sweden (age range, 18 to 85 years).' Most patients in the Swedish study were 32 to 60 years old; the peak age-group in the Rochester patients was 45 to 54 years. Trauma was the most common factor (13.4%) associated with the development of CTS in our incidence cohort. In comparison, trauma constituted 7.5% to 13% of cases of CTS in other large series.v" In the current study, wrist sprain, usually due to a fallon an outstretched arm, was a frequent injury. In eight of our patients, symptoms developed after accidental direct blunt trauma to the wrist; such patients constituted 9 of 439 in a series described by Phalen? and 11 of 400 in a report by Hybbinette and Mannerfelt.? Rheumatoid arthritis was shown to occur significantly more often in patients with CTS than expected in the general population of the same age and sex.'? In large surgical series, rheumatoid arthritis is usually listed as one of the three most common causes of CTSY·ll.13 The standardized morbidity ratio in our series was 3.6. Diabetes mellitus has long been suspected of predisposing nerves to entrapment neuropathies, including CTS.18 The standardized morbidity ratio for diabetes for the development of CTS in our series was 2.3. 19 The reason CTS is common in patients with diabetes is unknown, but aggravation of ischemia in nerves already stressed by chronic endoneurial hypoxia may be a factor." Dyck and associates," in a study of acute nerve compression in rats with diabetes induced with streptozocin, found that their peroneal nerves
Table 4.-Rheumatic Conditions in Patients With Carpal Tunnel Syndrome, Rochester, Minnesota, 1961 Through 1980 Rheumatic condition
No. of patients*
Triggerfinger Tenniselbow De Quervain's tenosynovitis Dupuytren'scontracture Tenosynovitis of forearm or hand Nonspecific synovitis of fingerjoints
108
*Somepatientshad morethan one condition.
53 33 24 18 11
546
CONDmONS ASSOCIATED WITH CARPAL TUNNEL SYNDROME
were more resistant to axonal injury than those of control rats; thus, alterations in the connective tissue sheaths of the nerve or in the transverse carpal ligament may be responsible for CTS. A recent case-control study from the Netherlands failed to demonstrate a relationship between diabetes and CTS.22 In addition to the patients with onset of CTS during pregnancy, mild and transient CTS developed in 44 patients, but the symptoms disappeared in 12 months or less without treatment, other than use of wrist splints at night. The conditions associated with transient symptoms were excessive use of the hands in 20 patients, wrist sprains in 2, rheumatoid arthritis in 2, tenosynovitis in 2, Colles' fracture in 2, and diabetes mellitus and polymyalgia rheumatica in 1 patient each. The CTS was spontaneous and had no apparent cause in 14 of the 44 patients. The current study suggests that CTS occurs 2.5 times more often among pregnant women than among nonpregnant women 15 to 44 years old. Voitk and colleagues" interviewed 1,000 postpartum patients by questionnaire and found that 25% had had symptoms of CTS, whereas only 46% of those with any type of hand symptoms had mentioned this fact to their physicians. In our study, of the 47 patients with CTS during pregnancy, onset by trimester was known for 45-CTS was diagnosed in 22%,16%, and 62% in the first, second, and third trimesters, respectively. In the study by Voitk and co-workers.P symptoms of CTS began in the first trimester in 6%, in the second trimester in 38%, and in the third trimester in 56%. Among 58 unselected pregnant patients who underwent electrodiagnostic study, Melvin and associates" found that 18 (31%) had symptoms of CTS but only 4 had significant abnormal findings. The frequency of CTS during pregnancy in other studies ranged from 2.3% to 10%.25,26 Several reports have described an association between CTS and bilateral oophorectomy.F'P As mentioned previously, the high incidence of CTS in perimenopausal women suggests that changes in ovarian function or use of exogenous estrogensv-" may be important in the development of symptoms and that "iatrogenic menopause" (that is, oophorectomy), which was noted in 2.5% of our female patients, might provide a similar mechanism. The standardized morbidity ratio indicated that the prevalence of oophorectomy among our patients with CTS was no greater than that expected in the community population of Rochester, Minnesota. Anecdotal reports and case series suggest that CTS may have an occupational association, primarily with manual labor or the use of vibrating power tools:" however, casecontrol and prospective studies have been. inadequate for drawing that conclusion. In our study and in other series in which occupations were tabulated, "homemaker" was the
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most frequently listed occupation.vP'" The effect of activity on the development of symptoms is controversial because many activities may merely aggravate an underlying problem. In our series, only cases that involved considerable manual labor were presumed to be "occupational" CTS; however, a case-control study unaffected by potential worker's compensation is needed to determine whether certain occupations are overrepresented. Factors implicated as being associated with CTS in jobs that involve manual labor include repetitive hand motion,27.33,34 various biomechanical factors,8.35,36 and long-term exposure to vibration.F-":" Examples of occupations perceived by some investigators to be associated with CTS are production seamstresses," grocery checkers.t-? meat-packers.rr" and bakers." Because CTS is more common in the dominant hand of both right-handed and left-handed patients, the extra stress borne by the dominant hand may contribute to symptoms." In several reports, degenerative arthritis of the wrist has been mentioned in association with CTS,7.10 Although many patients in our cohort had arthritic changes, assessing the importance of these changes was difficult because the frequency of similar joint changes is uncertain in the general population, particularly in older persons. Myxedema has often been cited as a risk factor for CTS,48,49 but only 14 cases (1.4%) were identified at the time of diagnosis of CTS in our incidence cohort. In a study of a large referral series, Yamaguchi and colleagues13 found that the proportion of patients with myxedema was 6.3%; thus, referral bias may have influenced that assessment. The association of polymyalgia rheumatica and eosinophilic fasciitis with CTS has been noted previously.P" The finding of 10 cases of polymyalgia rheumatica in the current series, however, was not significantly more than that expected among residents of Rochester, Minnesota." Amyloidosis is infrequently reported in conjunction with CTS, which is associated with a family history in the Rukavina type" or may be associated with multiple myelomav-" and other diseases." None of the eight patients with deposits of amyloid in the current series had a recorded family history of CTS or evidence of involvement of other organ systems; these findings suggested that the amyloid was localized to the tenosynovium.s" Many of our patients had nonspecific "rheumatic" conditions-trigger finger, tennis elbow, de Quervain's tenosynovitis, Dupuytren's contracture, tenosynovitis of the forearm or hand, and synovitis of the finger joints within 1 or 2 years before the development of CTS. The occurrence of these disorders may reflect medical or occupational factors or may indicate that patients with CTS have a tendency for tenosynovial or fibrosing reactions of structures in the carpal tunnel. Nonspecific rheumatic conditions were frequently noted in prior series as well. 9,13,61-63
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CONDITIONS ASSOCIATED WITH CARPAL TUNNEL SYNDROME
CONCLUSION In this study, we cataloged conditions associated with CTS in the residents of Rochester, Minnesota, during the years 1961 through 1980. The prevalence rates for several associated conditions were known from previous studies of the population of this community. Rheumatoid arthritis, diabetes mellitus, and pregnancy were significantly more frequent among patients with CTS than in the general population. Determining the relationship of other conditions to the development of CTS must await a case-control study. The high incidence of CTS in perimenopausal women is of considerable interest. A study of the incidence of CTS in women who have undergone oophorectomy may help shed light on the contribution of endocrine factors in the pathogenesis of CTS. Assigning a causal relationship of certain conditions is difficult because some patients have multiple disorders. Future studies of incidence must recognize this fact and explain how decisions about possible associations are made.
REFERENCES 1. Stevens JC, Sun S, Beard CM, O'Fallon WM, Kurland LT: Carpal tunnel syndrome in Rochester, Minnesota, 1961 to 1980. Neurology 38:134-138,1988 2. Kurland LT, Molgaard CA: The patient record in epidemiology. Sci Am 245:54-63, October 1981 3. Stevens JC: AAEE minimonograph #26: the electrodiagnosis of carpal tunnel syndrome. Muscle Nerve 10:99-113, 1987 4. Minnesota Department of Health: Minnesota Health Statistics 1983. Minneapolis, Minnesota Center for Health Statistics, 1985, p 29 5. Melton LJ, Bergstralh EJ, Malkasian GD, O'Fallon WM: Bilateral oophorectomy trends in Olmsted County, Minnesota,1950-1987. Epidemiology 2:149-152,1991 6. Reinstein L: Hand dominance in carpal tunnel syndrome. Arch Phys Med Rehabil 62:202-203, 1981 7. Hybbinette C-H, Mannerfelt L: The carpal tunnel syndrome: a retrospective study of 400 operated patients. Acta Orthop Scand 46:610-620, 1975 8. Kendall D: Aetiology, diagnosis, and treatment of paraesthesiae in the hands. Br Med J 2:1633-1640, 1960 9. Phalen GS: The carpal-tunnel syndrome: seventeen years' experience in diagnosis and treatment of six hundred fifty-four hands. J Bone Joint Surg [Am] 48:211-228, 1966 10. Gainer JV Jr, Nugent GR: Carpal tunnel syndrome: report of 430 operations. South Med J 70:325-328, 1977 II. Cseuz KA, Thomas JE, Lambert EH, Love JG, Lipscomb PR: Long-term results of operation for carpal tunnel syndrome. Mayo Clin Proc 41:232-241,1966 12. Goodwill CJ: The carpal tunnel syndrome: long-term follow-up showing relation of latency measurements to response to treatment. Ann Phys Med 8:12-21, 1965 13. Yamaguchi DM, Lipscomb PR, Soule EH: Carpal tunnel syndrome. Minn Med 48:22-33, 1965
14. 15. 16. 17.
18.
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20. 21.
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