Int Arch Occup Environ Health (2002) 75: 55±67 DOI 10.1007/s004200100278
O R I GI N A L A R T IC L E
Tohr Nilsson
Neurological diagnosis: aspects of bedside and electrodiagnostic examinations in relation to hand-arm vibration syndrome
Received: 11 September 2000 / Accepted: 9 May 2001 / Published online: 16 October 2001 Ó Springer-Verlag 2001
Abstract Objectives: The objective of this paper, was to direct attention to the diagnostic strategy and clinical approach necessary in the diagnosis of neuropathy in workers exposed to vibration. The purpose encompassed evaluation of selected aspects of bedside and electrodiagnostic examinations with respect to biological validity and the ability to distinguish between subjects with and without neuropathy. Methods: The neurological examinations viewed were restricted to those applicable to the upper extremity and neck system. A MEDLINE search was performed through the clinical queries service of PubMed searching for the following terms: nerve-conduction, Tinel's test, Phalen's test, tendon re¯ex, twopoint discrimination test, abduction external rotation test, and Spurling test. Retrieved articles were discussed both in relation to the test accuracy and the validity aspects of the tests. Results: The evidence in support of the view that neurological tests can accurately distinguish between subjects with and without neuropathy speci®cally addressing hand-arm vibration syndrome was sparse. The initial number of diagnostic hypotheses could be reduced by progressively ruling out diseases based on negative results of highly sensitive tests. As the possible diagnostic alternatives become fewer, the use of positive results from highly speci®c tests are more effective. The information value of the various diagnostic tests is determined by the change in pre-test to post-test probability of target disorder, which depends on the prevalence of the disorder and the likelihood ratios of the tests. The review showed that target disease charWork presented at the Southampton Workshop 2000: ``The diagnosis of disorders caused by hand-transmitted vibration'', 11±13 September 2000, ISVR, Southampton University, Southampton, UK. T. Nilsson Department of Occupational and Environmental Medicine, Sundsvall Hospital, 851 86 Sundsvall, Sweden E-mail:
[email protected] or
[email protected] Tel.: +46-60-181927 Fax: +46-60-181980
acteristics in¯uence the test outcome as well as the choice of ``gold standard'' and the population domain of the studies. Conclusions: The selection of various bedside examinations and diagnostic electrophysiological tests should be dependent on the clinical context, the history and results from the successive diagnostic tests. Keywords Hand-arm vibration á Diagnosis á Clinical examination á Electrodiagnostic
Background Extensive, long-lasting exposure to manual work involving the use of vibrating power machines has been associated, in epidemiological studies, with adverse effects on the peripheral nervous system. The neurological diagnosis of such a disorder comprises the collection of information on the functioning of the neurosensory system and an evaluation of the resulting data, in the setting of a clinical decision aimed primarily at therapeutic, medico-legal or prognostic outcomes. The diagnostic eort is associated with possible outcomes and treatments. It is conceivable that in the diagnostic process an observed pathophysiological event might both develop and be distorted in central sensory pathways even in the presence of organic peripheral nerve disease. In the hand-arm vibration syndrome (HAVS), the focus is on the health eects on the peripheral nervous system encompassing sensory and motor units. The sensory units (nerve ®bres with their endings, cell bodies and central processes) (Ochoa 1994) are characterised by their type of nerve ®bre, type of end organ, and their adequate stimuli. The motor unit is a corresponding anatomic entity of an anterior horn cell, its axon, the neuromuscular junctions, and all the muscle ®bres innervated by the nerve ®bre. Peripheral nerves react in a limited number of pathological ways to injury: Wallerian degeneration (the response to transection), segmental demyelination, axonal atrophy and degeneration, and primary disorders of the cell bodies (Asbury and Thomas 1995).
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The clinical manifestations of sensory neuropathy include: (1) positive symptoms (dysaesthesia; pain and paraesthesia), (2) negative symptoms (numbness, reduction or absence of sensitivity, loss of proprioception) and (3) provocative symptoms (dysaesthetic symptoms when the nerve is stressed by compression, tapping or stretching) (Lindblom and Ochoa 1992). The history and examination are the key to diagnosis in a person with neurological complaints (Bradley et al. 2000). From a detailed history, a skilled physician can derive clues that indicate the location as well as the pathology of the lesion. Therefore, the neurological examination and laboratory tests should be tailored to correspond to the hypothesis derived from the history. The decision to administer a given test or manoeuvre is made on the assumption that the results will signi®cantly change the pre-test probability for the diagnosis (Sackett et al. 2000). The purpose of each diagnostic test must also be considered when its applicability is evaluated. Especially in attempting early diagnosis of pre-symptomatic disease, single-screening, multiple screening or ``case-®nding'' among workers, any test used must have a high proven validity (Sackett et al. 2000). This was also a basic prerequisite already considered at the Stockholm Workshop ``Diagnostics and quantitative relationships to exposure'' (Gemne et al. 1995). At that workshop as well as in many studies, the interest has focused mainly on the value of separate tests rather than on the diagnostic process and the evaluation of clinical neurological examinations. The objective of this paper is to direct attention to the diagnostic strategy and the clinical approach necessary in the diagnosis of neuropathy in HAVS. The purpose encompasses evaluation of selected aspects of bedside and electrodiagnostic examinations in respect to biological validity and the ability to distinguish between subjects with and without neuropathy.
Methods The neurological examinations viewed were restricted to those applicable to the upper extremity and neck system. The background regarding how the value of various diagnostic tests should be interpreted and how to ®nd strategies for their use was searched for in the literature concerning evidence-based medicine (Black et al. 1999; Sackett et al. 2000). An overview of the bedside neurological examinations of the neck and the upper extremity, as presented in words in general medical textbooks (Wiebers et al. 1998), was complemented with the information in textbooks containing pictorial illustrations of the performance of the tests (Gross et al. 1996; Berryman Reese 1999). Sapira's Art and Science of Bedside Diagnosis (Orient 2000), which represents a combined approach containing a manual for the practical execution of the tests and the scienti®c evidence for its evaluation, was supplemented with a medical database search of the most recently presented analyses of the tests chosen. A MEDLINE search through the clinical queries service of PubMed searching for the following terms: nerveconduction, Tinel's test, Phalen's test, tendon re¯ex, two-point discrimination test, abduction external rotation test, and Spurling test, [search strategy = (Search term) AND (sensitivity and speci®city {MESH} OR sensitivity {WORD} OR diagnosis {SH} OR
diagnostic use {SH} OR speci®city {WORD})] produced 5,493, 110, 91, 17, 51, 10 and 12 references, respectively. For nerve conduction, the screening of the articles was restricted to the most recent 500. Based on a review of titles and abstracts, relevant publications were retrieved. All searches were supplemented with a selected screening of ``related articles'' in PubMed to compensate for possible inadequate search terms and a review of the bibliographies of the articles retrieved. In those cases where the literature was extensive, priority was given to reports from the past decade. Only those articles evaluating diagnostic methods of neuropathy were considered. There was no other criterion for rejection. The accuracy of the tests when given as sensitivity and speci®city was recalculated to ``likelihood ratios'' (LRs) for a positive and a negative test result according to the formulae: LR for a positive result = sensitivity/ (1±speci®city) and LR for a negative result = (1±sensitivity)/speci®city. The con®dence intervals were calculated according to the latest version of the diagnostic test StatCalc program by Glasziou (2000). By multiplying the likelihood with the pre-test probability, given as odds, the post-likelihood is reached, which can be transformed to a probability equal to the test's predictive value (Sackett et al. 2000). When provided, information on test-retest, and interexaminer reliability was also presented. Articles presenting insucient information for recalculation of LRs or only predictive values were not included in the tables, e.g. (Katz et al. 1990; AAEM quality assurance committee et al. 1993; Nathan et al. 1993; Gunnarsson et al. 1997; Werner et al. 1997b; Homan et al. 1999; Szabo et al. 1999; You et al. 1999) but were in most cases referred to in the text.
Neurological diagnosis History A thorough history with emphasis on symptom description (positive, negative and provocable symptom manifestations), information on qualitative, quantitative (hypo- and hyperaesthesia) and temporal sensory abnormalities, course, pattern, and symptom distribution speci®ed on a symptom drawing, forms the basis for the formulation of a tentative hypothesis (Asbury and Thomas 1995). Orient (2000) claims in her book on bedside diagnosis that generally, in medicine, the history is the most important source of information. She refers to studies where the history led to the ®nal diagnosis in 76%, bedside physical examination in 12% and laboratory tests in 11% of cases. The history is claimed to be especially important in the diagnosis of neurological disorders (Bradley et al. 2000). History and pain drawings have repeatedly proved to be important in diagnosis of neuropathy. Katz and colleagues (Katz et al. 1990) categorised hand diagrams into classical, probable, possible and unlikely carpal tunnel syndrome and found the hand drawing to be individually the best predictor, with a positive predictive value of 0.59. Symptoms Disturbances in hand function commonly reported as symptoms of numbness, paraesthesia (a concept that carries the implication that the abnormal sensation is perceived without apparent stimulus), as well as diculty in performing manipulative tasks, have been reported in workers handling vibrating power-machines
57
and among ordinary manual workers (Hagberg et al. 1992). If the pathological process occurs in large ®bre sensory nerves the character of the symptoms may be described as: tingling, pricking, buzzing, a constriction sensation, sense of swelling, or ``pins and needles''. Disorders aecting primarily small neurons give rise to painful dysaesthesia, burning, searing pains, and sensory loss (Asbury et al. 1994; Asbury and Thomas 1995; Asbury 2000). Injury can result in both hypaesthesia and hyperaesthesia. Hypaesthesia (a negative manifestation) re¯ects failure at any level along sensory channels and is characterised by diminution or absence of sensitivity. The person may or may not be aware of the de®cit. Negative sensory symptoms are late indicators of aerent dysfunction. If the rate of loss is slow and chronic, lack of cutaneous sensitivity may be unnoticed by the patient and dicult to demonstrate on examination (Asbury 2000). Positive manifestations also re¯ect dysfunction but are expressed mostly as symptoms (e.g. tingling, buzzing, pricking), without signs. Positive phenomena represent heightened activity in sensory pathways, and therefore they are not necessarily associated with any sensory de®cit at examination. The basis for positive phenomena is thought to be ectopic generation of volleys of impulses at a site of lowered neural threshold along the sensory pathways (Asbury 2000). Microelectrode recordings from the median nerve on human subjects exposed to vibration and to electric pulse trains, respectively, indicated that paraesthesia could be attributed to disturbances in aerent sensory ®bres (Burke and Applegate 1989). Long-time follow-ups of nerve injury have demonstrated cold sensitivity to be the most common sequela and with little or no decrease in symptoms over time (Collins et al. 1996). Cold intolerance in vibration-exposed workers has thus been discussed as a possible sequela of minor nerve injury, in addition to a possible increased vasospastic response to cold (StroÈmberg et al. 1999). The association between reported symptoms and vibrotactile acuity is not straightforward. The discrepancy between symptoms and signs may also entail sensory impairment without subjective recognition or symptoms. This applies for instance to thermal (Ekenvall et al. 1989) and tactile sensibility (Flodmark and Lundborg 1997). Such discrepancies may be illustrated by the results from Homan and co-workers (Homan et al. 1999) who found a relatively poor overlap between the reported symptoms, the physical examination ®ndings and the electrodiagnostic results. Such symptom-sign discrepancy is extensively reported and often clinical examination fails to distinguish between symptomatic and asymptomatic workers (Brammer et al. 1987; Kent et al. 1998). This problem was also observed by McGeoch and coworkers (McGeoch et al. 1994), who noticed that a number of workers reported no symptoms but had positive scores on one or more of the perception tests. Werner and co-workers performed nerve conduction
examinations among symptomatic and asymptomatic persons and found that some people with veri®ed neuropathy had symptoms and some did not (Werner et al. 1998). They reported a slowed sensory conduction velocity in the digital segment in 10% of the workers without symptoms and in 56% of those with symptoms. Nerve conduction studies by Cherniack, and co-workers (Cherniack et al. 1990) were neither signi®cantly dierent between more or less symptomatic groups nor correlated with clinical and quantitative tests. Another discrepancy between symptoms and signs arises when the subject reports symptoms of paraesthesia although there is an absence of pathological ®ndings in physical examination, neuro-electrodiagnostic testing, and quantitative sensory testing (QST). A provocation test may, in such cases, reveal a dysfunction, but such studies on vibration exposure are lacking, and only a few studies have been published, for instance, one on repetitive strain injuries (Greening and Lynn 1998). Coutu-Wakulczyk (Coutu-Wakulczyk et al. 1997) investigated the association between hand symptoms and quantitative measures of hand tactile acuity and found questions on functional de®ciencies (e.g. buttoning dif®culties) to be the best predictor while positive symptoms such as numbness had a predictive value of only 55%. Studies on symptom description and severity of symptoms in carpal tunnel syndrome, however, demonstrated numbness, tingling and nocturnal symptoms to be major manifestations, with a high correlation to nerve conduction measurements (You et al. 1999). They also found high correlation between symptom severity and nerve conduction abnormality. Physical examination Guided by hypotheses from the history, a careful bedside neurological examination is performed, including the test of somatosensory motor function, tendon re¯exes, and provocation manoeuvres. Such an examination is a prerequisite for an adequate interpretation of electrophysiological test results and QST. Interpretation of pain and sensory abnormalities calls for the examination of pain and referred pain in relation to the musculoskeletal system (Gross et al. 1996). StroÈmberg and colleagues (StroÈmberg et al. 1999) investigated the symptoms of vibration-exposed workers, and the results indicated two injuries that are easily confused: one at a receptor level in the ®ngertips and one in the carpal tunnel. Careful clinical assessment, neurophysiological testing and QST are therefore recommended in the diagnosis of subjects with hand-intensive work and exposure to vibration. Sensory function The bedside examination outlines the modality pro®le of the sensory dysfunction and the relative contribution
58
of negative and positive irritative symptoms. It is usually easy to document and to interpret the mechanism of threshold or suprathreshold ®ndings of hypo- or hyperaesthesia when the character of the evoked perception remains normal (Boivie et al. 1994). It becomes signi®cantly more dicult to decipher the pathophysiology when the sensation evoked is qualitatively abnormal. This is especially the case with lesions producing positive, irritative symptoms such as paraesthesia, dysaesthesia, pain, and allodynia (a concept that describes the situation in which an ordinarily non-painful stimulus, once perceived, is experienced as painful). An array of qualitative, spatial and temporal aberrations may further occur in one or more modalities. The cardinal signs of altered sensory unit function are an elevated threshold indicating a reduction of function, and a lowered threshold as a sign of increased sensitivity (Lindblom 1994) at QST. Numbness has been noticed (Lindblom and Ochoa 1992) without sensory loss. This may be due to positive phenomena, or to sensory dysfunction con®ned to suprathreshold stimuli. A signi®cant category of positive sensory phenomena involves inadequate subjective response to natural stimulation of receptors. StroÈmberg and co-workers (StroÈmberg et al. 1996), among other ®ndings, observed abnormal intolerance to cold in a case series of vibrationexposed patients. Altered sensory perception to vibration is also demonstrated in the study by Buch-Jaeger and Foucher (1994) who found a positive LR of 1.5 for increased sensitivity to vibration among carpal tunnel syndrome patients compared with 1.1 for reduced perception. Gap detection test Two-point discrimination is an innervation density test that measures overlapping receptive ®elds. The test is performed with a moving or a static stimulus. The static two-point examination is a simple bedside procedure performed with various devices, a two-point discrimination tester (Mackinnon and Dellon 1985), a DiskCriminator, a three-prong aesthesiometer, a folded paper clip (Crosby and Dellon 1989) or a pair of compasses. In normal patients no statistical dierence is found between the values obtained for either moving or static two-point discrimination, between any of the devices (Crosby and Dellon 1989). Interobserver reliability was increased when the tests were performed by surgeons and therapists, indicating that expertise in¯uences the results (Marx et al. 1998). Increased LRs have been demonstrated for the test when applied to workers exposed to hand-arm vibration (Bovenzi and Zadini 1989; Chatterjee 1994) (Table 1). One example of the lack of validity of static twopoint measurements has been highlighted in a study where of 24 people yielding no response to stimulation of median nerve 15 still revealed normal two-point discrimination test results (Marlowe et al. 1999). The stimulus intensity in the form of touch-pressure interacts
with one- and two-point application of the stimulus (Bell-Krotoski et al. 1993).
Provocative tests Neck Even a general physical examination of the neck can often reliably rule out signi®cant cervical spine injury (Gonzalez et al. 1999). In addition, special compression tests (eponyms are given within parentheses) can be performed to elicit and amplify radicular symptoms. The neural foramina become narrowed when the subject extends, turns, and rotates (laterally bends) the neck. Pressure measurements from the neural foramina in cadavers have revealed signi®cant pressure increase at each root level with increasing neck extension or rotation (Farmer and Wisneski 1994). The neck compression test The neck compression test (Spurling's test) is performed with the subject rotating the head to the aected side, laterally bending to the same side, while the examiner applies a compressive, axial force to the top of the subject's head (Farmer and Wisneski 1994). The interexaminer reliability was higher when the test was performed in a sitting position (Viikari-Juntura et al. 1989). The speci®city of the test is high, e.g. 98% (Uchihara et al. 1994) for the right-hand side, but the corresponding sensitivity is low (12%) and the estimates dier between the left and right sides (Table 2). Neck ¯exion test The neck ¯exion test (Lhermitte's sign) (Gutrecht 1989) is carried out with the subject sitting. The subject's head is passively ¯exed forward so that the chin approaches the chest. The ¯exion could also be extended to the hip. Provocation of radiating symptoms down the spine or into the extremities represents a positive test result. Although the test is well established (Gutrecht 1989) few studies have managed to demonstrate its usefulness. Uschihara and colleagues (Uchihara et al. 1994) found the test uninformative with an LR of 0.81 and 1.01 for a positive and negative test result, respectively. Nerve stretch test The nerve stretch test of the upper extremity (Elvey's test) is performed on a supine subject with the shoulder and scapula unobstructed. Speci®c manoeuvres to elongate the nerve trunk are performed by stretching the arm, extending the wrist and by contralateral rotation and bending (lateral ¯exion) of the head (Gross et al.
0.70±1.05 (Marlowe et al. 1999)
(Marx et al. 1998)
0.81±1.02 (Gerr and Letz 1998)
0.90±1.01 (Buch-Jaeger and Foucher 1994)
0.01±0.47 (Chatterjee 1994)
0.37±0.82 (Bovenzi and 0.37±0.70 Zandini1989)
0.86 0.69±6.23 2.0 Suspected CTS
0.91 0.99±4.87 CTS patients, 2.20 healthy controls Clinical symptoms
ENG ENG abnormal >5 mm 5 mm Static two-point
>6 mm >60 years
0.95 0.56±36.94 4.55 CTS Static two-point
>6 mm
ENG
CTS patients
0.55 0.51
0.07
2.69 9.91
1.08±6.50 1.44±68.14
17.73 HAVS controls
>2.5 mm >3.13 mm
Clinical symptoms HAVS
>0.25 mm
Moving two-point
HAVS
Throughout the body, peripheral nerves leave the spine and pass through small holes, long tunnels, and narrow spaces to reach their endpoints. Possible compression in the thoracic outlet forms the basis for arterial, venous and true neurological thoracic outlet syndrome (TOS), in addition to a subgroup entitled ``disputed neurologic TOS'' (Sanders 1991). The controversy between the proponents for under-diagnosis of disputed neurological TOS (Roos 1999) and the proponents for an over-diagnosis (Wilbourn 1999) is still not settled. Although many tests have been suggested (Oates and Daley 1996), the validity of the various examinations must be regarded as low due to lack of clarity in the de®nition of the disease entity. In a study by Toomingas and colleagues (Toomingas et al. 1999) exposure to vibration gave an odds ratio of 3.3 (95% CI 1.07±10.3) for a prevalent positive AER test irrespective of a de®nite TOS diagnosis.
Pronator compression test
Moving two-point
Clinical symptoms
Chain sawyers
2.62±120.06
(95% CI) Reference Likelihood ratio of ratio of negative result (95% CI) Likelihood ratio of ratio of positive result Population domain Diagnostic method
Thoracic outlet
Elbow
Cut-o criteria
Target disorder
1996). The validity of the nerve stretch test measured by tensile forces of the nerves showed that nerve tension is transmitted upward to the cords (Kleinrensink et al. 2000). These ®ndings do not support the selective use of the test to stress dierent nerve roots. Based on the tensile force distribution, the test was speci®c only for the median nerve. Interexaminer reliability (kappa) between two examiners was low (0.35) in the study by Viikari-Juntura (Viikari-Juntura 1988).
Thoracic outlet compression test, ``elevated arm stress test'' or ``abduction external rotation test'' (Roo's test)
Test
Table 1 Diagnostic accuracy of two-point discrimination test for various target disorders (HAVS hand-arm vibration syndrome, CTS carpal tunnel syndrome, ENG electroneurography)
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The pronator compression test is conducted by application of ®rm, but not painful, thumb pressure on the median nerve over the subject's pronator muscle in the volar forearm. A positive test result is considered if the symptomatic hand will elicit paraesthesia within 30 s (Gainor 1990). A wide range of physical ®ndings may occur with median nerve compressions. Experience indicates that these ®ndings often lack validity and are dicult to substantiate (Dawson et al. 1999). The referred case series (Gainor 1990) lack information on the discriminating power of the test compared with a diagnostic standard. Wrist Wrist ¯exion compression test In the wrist ¯exion compression test (Phalen's test) the subject actively places the wrists in complete, but
60
unforced, ¯exion for 60 s. The test is considered positive if numbness or paraesthesia is produced or exaggerated within the time limit (Phalen's sign). Reviews of the ability of Phalen's test to distinguish between subjects with and without carpal tunnel syndrome (CTS) (Kuhlman and Hennessey 1997) reveal a variation from 10% to 80%. Novak and colleagues (Novak et al. 1992) suggest a time course dependency for Phalen's sign in that it may be positive in the early stages of the CTS. Intracarpal canal ¯uid pressure (ICCFP) measurements have demonstrated that wrist extension and ¯exion result in the greater increase in ICCFP followed by forearm pronation and supination (Werner et al. 1997a). Radial and ulnar deviation also increase the pressure
(Werner et al. 1997a). Extension elicits the highest pressures. This is one rationale behind suggesting a ``reversed Phalen's manoeuvre (Werner et al. 1994b; Ghavanini and Haghighat 1998). According to the results from de Krom and colleagues (de Krom et al. 1990) the two tests are equally informative (Table 3). The tingling sign The mechanical stimulation test eliciting the tingling sign (Homan-Tinel sign a.k.a. Tinel test) of the median nerve is performed by gentle tapping over the distal wrist crease. A positive tingling sign is a sensation triggered by
Table 2 Diagnostic accuracy of neck compression test for axial disorders of the neck Test
Target disorder
Diagnostic method
Population domain
Likelihood ratio of positive result
(95% CI)
Likelihood (95% CI) ratio of negative result
Reference
X-ray, scan
Injured patients
5.10
4.39±5.93
0.12
0.04±0.35
(Gonzalez et al.1999)
Neck Cervical disc Myelography Myelography compression patients
Right: 5.83 Left: 10.5
1.31±25,99 1.42±77.40
Right: 0.63 Left: 0.59
0.38±1.03 0.38±0.91
(Viikari-Juntura et al. 1989)
Neck Cervical cord MRI compression deformity (right)
MRI patients
7.29
0.41±130.26 0.89
0.78±1.02
(Uchihara et al. 1994)
Neck Cervical cord MRI compression deformity (left)
MRI patients
0.81
0.05±12.33
0.92±1.1
(Uchihara et al. 1994)
General Spine injury examination
1.00
Table 3 Diagnostic accuracy of Phalen's test for carpal tunnel syndrome (CTS carpal tunnel syndrome, EMG electromyography, NC nerve conduction, DML distal motor latency) Test
Target disorder
Diagnostic Population method domain
Phalen
CTS
EMG
CTS patients
Phalen
CTS
NC
6.58±321.7
0.15
0.08±0.29
Phalen
CTS
NC
CTS patients, 46.0 controls Suspected CTS 2.11
1.41±3.16
0.64
0.52±0.79
Phalen
CTS
NC
3.3
1.76±6.18
0.43
0.33±0.54
Phalen
CTS
EMG
1.36
0.94±2.05
0.28
0.09±0.88
Phalen
CTS
NC
4.35
2.24±8.44
0.36
0.23±0.57
Phalen
CTS
DML
0.84
0.47±1.52
1.17
0.68±2.03
Reversed Phalen Phalen
CTS
DML
0.87
0.46±1.67
1.11
0.68±1.80
CTS
Clinical
8.65
5.69±13.16
0.15
0.10±0.21
Phalen Phalen
CTS CTS
NC NC
CTS patients, controls CTS patients, symptomatics CTS patients, controls Nocturnal paraesthesia Nocturnal paraesthesia CTS patients, controls CTS patients CTS patients
1.16 0.73
0.71±1.76 0.24±2.17
0.90 1.05
0.61±1.34 0.91±1.20
Phalen
CTS; mild, moderate, severe CTS; mild, moderate, severe
NC
CTS patients, controls
1.59
0.98±2.15
0.72
0.59±1.00
NC
CTS patients, controls
1.67
1.01±2.78
0.77
0.60±8.98
Reversed Phalen
Likelihood (95% CI) ratio of positive result 1.28
Likelihood (95% CI) ratio of negative result
0.94±1.73
Reference
(Buch-Jaeger and Foucher 1994) (Richter and Bruser 1999) (Kuhlman and Hennessey 1997) (Seror 1988) (De Smet et al. 1995) (Durkan 1991) (de Krom et al. 1990) (de Krom et al. 1990) (Gonzalez del Pino et al. 1997) (Burke et al. 1999) (Golding et al. 1986) (Ghavanini and Haghighat 1998) (Ghavanini and Haghighat 1998)
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the mechanical stimulus in the distal part of the peripheral nerve or at the site of the stimulus. The tingling sign may be classi®ed according to its location and to the magnitude threshold at which the response is triggered (Spicher et al. 1999). The sign should be considered positive only when localised sensitivity and marked tingling are obtained after gentle percussion (Alfonso and Dzwierzynski 1998) The use of the tingling sign has been extended to the performance of multiple Tinel's tests (Jabre et al. 1995) (Table 4). Proponents for the validity of the sign suggest it should be used with caution at early or mild compression and at advanced compression (Dellon 1984).
relation to the population domains studied (Table 5). An elaborated compression technique has been proposed by Tetro and colleagues (Tetro et al. 1998) who suggest the test be performed with the elbow extended, the forearm in supination, the wrist ¯exed to 60° and with constant digital pressure applied with one thumb over the median nerve at the carpal tunnel. The test is considered positive if symptoms occur within 30 s. Using the receiver operator characteristic curve technique the optimal cut-o time for the duration of the test was 20 s, giving a sensitivity of 82% (95% CI, 76±89) and a speci®city of 99% (95% CI, 97±100).
Motor function
Tethered median nerve stress test The tethered median nerve stress test ( LaBan test) is performed by passively hyperextending the supinated wrist, and the distal interphalangeal joint of the index ®nger for one minute (Raudino 2000). The test is classi®ed as positive if pain is perceived in the proximal forearm. In asymptomatic hands the likelihood of a positive test result was 0.37 (=0.03±3.55) and that of a negative was 1.14 (0.84±1.56). The test is therefore uninformative. Wrist compression test Compression test of the wrist (Durkan's test, McMurthry's test) is performed by applying a force corresponding to 150 mmHg over the carpal tunnel for 30 s (Durkan 1991). Resulting paraesthesia is a positive result. Thumb pressure without measurement of force is also used (de Krom et al. 1990). Resulting estimates vary mainly in
Grip strength The validity of motor function is related to the testing of speci®c muscles in relation to speci®c mono-neuropathies, e.g. testing of the abductor pollicis brevis muscle in median nerve neuropathy or the ``Froman's sign'' in ulnar neuropathy (Dawson et al. 1999). In the clinical setting of nerve compression neuropathies, motor weakness does not usually occur until sensory loss is marked (Lundborg 1988), but the weakness usually precedes atrophy. The simple clinical assessment of the small muscles embracing hand function is often a comparison with the strength of the examiner and is therefore unreliable. The hand power grip strength re¯ects the function of the ¯exor muscles of the lower part of the upper extremity, while ®nger strength re¯ects the function of the ®nger muscles. Grip strength assessed by dynamometer (Martin vigorimeter) measures air pressure in a bulb as a correlate to force. Normative values have been reported for healthy controls aged
Table 4 Diagnostic accuracy of Tinel's test for various neuropathies (CTS carpal tunnel syndrome, EMG electromyography, NC nerve conduction, DML distal motor latency) Test
Target disorder
Diagnostic method
Population domain
Likelihood (95%CI) ratio of positive result
Likelihood (95% CI) ratio of negative result
Reference
Tinel
CTS
EMG
CTS patients
1.15
0.78±1.68
0.92
0.72±1.17
Tinel
CTS
NC
Suspected CTS 1.82
0.97±3.40
0.88
0.78±0.99
Tinel
CTS
NC
CTS patients, controls Tinel CTS DML Nocturnal paraesthesia Tinel CTS EMG CTS patients, controls Force Neuropathy Pre-selection Patients, graded Tinel controls Tinel CTS NC CTS patients
2.83
1.53±5.20
0.54
0.38±0.78
(Buch-Jaeger and Foucher 1994) (Kuhlman and Hennessey 1997) (Durkan 1991)
0.84
0.36±1.96
1.08
0.74±1.57
1.66
0.90±3.06
0.77
0.57±1.09
5.0
2.73±9.15
0.56
0.42±0.74
1.3
0.64±2.65
0.93
0.75±1.15
Tinel multiple Neuropathy Clinical
1.17
0.93±1.46
0.58
0.28±1.22
2.09
1.05±4.15
0.8 ±
0.66±0.97
Wrist CTS; mild, compression moderate, severe
NC
Patients, controls CTS patients, controls
(de Krom et al. 1990) (Gelmers 1979) (Monsivais and Sun 1997) (Golding et al. 1986) (Jabre et al. 1995) (Ghavanini and Haghighat 1998)
62 Table 5 Diagnostic accuracy of wrist compression for carpal tunnel syndrome Test
Target disorder
Diagnostic method
Population domain
Wrist CTS compression
EMG
CTS patients
1.06
Wrist CTS compression Wrist CTS compression
NC
Wrist CTS compression Wrist CTS compression Wrist CTS compression
NC EMG NC Clinical
Likelihood (95% CI) ratio of positive result
Likelihood (95% CI) ratio of negative result
Reference
0.76±1.48
0.95
0.70±1.28
CTS patients, 23.5 controls Suspected CTS 1.01
6.01±91.9
0.14
0.07±0.27
0.71±1.72
0.97
0.82±1.13
CTS patients, symtomatics CTS patients, controls CTS patients, controls
0.94
0.07±1.48
1.11
0.46±2.66
8.67
3.76±20.12
0.15
0.07±0.31
(Buch-Jaeger and Foucher 1994) (Richter and Bruser 1999) (Kuhlman and Hennessey 1997) (De Smet et al. 1995) (Durkan 1991)
19.33
10.18±36.69
0.13
0.10±0.20
Wrist CTS compression
NC
CTS patients
0.83
0.59±1.17
1.28
0.72±2.20
Wrist CTS; mild, compression moderate, severe
NC
CTS patients, controls
1.28
0.86±1.92
0.83
0.61±1.12
from 5 to 93 years (Merkies et al. 2000). Results are not Gaussian distributed and are related to age. Low values are reported for the very young and the very old (Merkies et al. 2000). Hand circumference, height, gender (Desrosiers et al. 1995a) and body segment position at elbow, wrist (Desrosiers et al. 1995b), ®nger and sitting or standing position are other parameters associated with the outcome. The alternative static Jamar dynamometer gives results comparable to the Martin vigorimeter (Desrosiers et al. 1995c), but by some authors is claimed to elicit more discomfort for the subject. The mean of three trials has a 0.89 and 0.93 test-retest reliability for the right and left hands, respectively, compared with 0.79 and 0.86 for a corresponding single trial (Mathiowetz et al. 1984). Pain reduces handgrip strength. The choice between pinch grip or handgrip strength assessment in the examination of subjects with HAVS relates to the vibration frequency to which the subject has been exposed and the possible attenuation of vibration exposure in the hand or the forearm. Muscle stretch re¯exes Signi®cant loss or reduction of muscle stretch re¯exes is most often a result of disorders aecting a component of the re¯ex arc; that is, the peripheral aerent and eerent pathways or their segmental connection in the central nervous system. (Wiebers et al. 1998). An absent re¯ex has been described as a de®nite neurological sign, possibly indicating nerve-root compression (Bowditch et al. 1996). In patients over 40 years of age, the proportion with absent ankle re¯exes increases from 5% (41 to 50 years) to 37% (61 to 70 years) (Bowditch et al. 1996).
(Gonzalez del Pino et al. 1997) (Burke and Applegate 1999) (Ghavanini and Haghighat 1998)
The diagnostic speci®city of unequivocally abnormal re¯exes is reported as 70%±95%, decreasing with increasing age (Stam 1999), with a sensitivity of 50%±70%, for both peripheral and central lesions. Matsumoto and colleagues (Matsumoto et al. 1996) demonstrated, on a series of patients with cervical myelopathy, that the deep tendon re¯exes vary from diminished to exaggerated for similar disorders and in relation to the level of root injury. ''Stretch-shortening`` muscle activity has revealed reduced stretch re¯exes, possibly on the basis of in¯uence on the muscles, up to 4 days after exercise (Nicol et al. 1996). The validity of muscle stretch re¯exes on vibration-exposed persons with heavy manual work must therefore be questioned. Additional examinations With reference to possible systemic and musculoskeletal disorders, a general physical examination should be included in the bedside examination (Herbert et al. 2000). The aim is to identify other possible causes for the ®ndings, including systemic disease and musculoskeletal disorders possibly eliciting referred pain, numbness, and distorted sensory perception (Leer et al. 2000).
Electrodiagnostic tests In the diagnostic hypotheses testing process, electrodiagnostics gives guidance in cases with clinical uncertainty about whether weakness is neurogenic or myogenic, whether the neuropathy is axonal or demyelinating and, when the clinical localisation of the nerve
63
lesion is dicult, on how to obtain and to determine the distribution and the extent of the neuropathogenic process (Tucker and Bryer 1999). Over recent decades, advances in the techniques of electrophysiological evaluation have revolutionised the detection and characterisation of neuropathies (Kimura 1989). The range of electrodiagnostic studies that can be applied to the diagnosis and elucidation of peripheral neuropathies continues to increase (Amino 1999). Information about the possibilities, and also the pitfalls, of electrodiagnostics is repeatedly published (Kimura 1999; Krarup 1999). Pitfalls in the use of electrodiagnostic procedures are ®ndings that lead to erroneous conclusions regarding the nature of the underlying condition. It has become more important to avoid diagnostic errors, as disorders which until recently were beyond therapeutic reach, may now be treated by various procedures (Bradley et al. 2000). The diagnostic evolution and methodological acuity are necessarily connected with the possible therapeutic alternatives. The limited progress in the diagnosis of neurological HAVS could possibly be explained by the, until now, restricted number of therapeutic actions. Characteristics of conduction in motor and sensory nerves are represented as velocity, amplitude and distal latency. In nerve conduction studies, waveform analyses of compound action potentials help estimate the range of the functional units. The onset latency of the action potential relates only to the fastest conducting ®bres, and its waveform reveals the functional status of the remaining, slower conducting ®bres (Kimura 1999). The clinical validity of a slowing of conduction in itself leads to few, if any, clinical symptoms, as long as all the impulses arrive at the target organ. Conduction block, however, is often accompanied by symptoms of major loss of strength. Several requirements must be met concerning technique, clinical context and temporal development of the neuropathy in order for electrodiagnostic methods to produce valid results. Nerve conduction tests are in¯uenced by several measurement and host factor parameters, among which the most important is temperature of the body (Letz and Gerr 1994). Other covariates are height (Rivner et al. 1990), weight (Nathan et al. 1992), body mass index (Werner et al. 1994a), age, gender (Stetson et al. 1992), and examiner eect (Letz and Gerr 1994). Nerve conduction studies in normal subjects has generally revealed better reproducibility for conduction velocities than for amplitude measurements (Amino 1999). Test-retest variability in nerve conduction studies repeated twice with a time interval of 1±4 weeks showed that in both controls and patients amplitude varied more than terminal latency, motor conduction velocity and sensory conduction velocity (Kimura 1997). F-wave values showed the smallest range of variability (variation range), 10%, for the median nerve. Carefully designed protocols and training seem able to achieve a coecient of variation of about 10% (Amino 1999). Even a moderate test-retest correlation of 0.56 gave, for nerve conduction velocity, a
good performance concerning the smallest detectable statistical signi®cant dierence (3%) on group level standardised to the mean (Valk and Grootenhuis 2000). There are several studies which report that electrodiagnosis in¯uences the clinical evaluation in a large percentage of the patients. Electrodiagnostic testing substantially altered 42% of the diagnoses, con®rmed 37% and did not clarify 21% of the diagnostic decisions performed by a physician certi®ed in physical medicine, rehabilitation and electrodiagnostic medicine (Haig et al. 1999). Nevertheless, experienced neurophysiologists claim that despite certain limitations, nerve conduction studies can provide diagnostically pertinent information provided they are used judiciously in appropriate clinical contexts (Kimura 1997).
Discussion Possible in¯uence of target disease characteristics on test outcome In evaluating the evidence in support of the view that neurological tests can accurately distinguish between subjects with and without neuropathy, reports speci®cally addressing the HAVS are few. This is possibly attributable to the fact that there is no speci®c pathology or neuropathy characterising the neurosensory aspects of the HAVS [see reviews in, e.g. (StroÈmberg 1997; Nilsson 1998)]. Most studies demonstrating neuropathy among HAVS patients have investigated the association between vibration exposure and various tests, symptoms and physical signs. The majority of the studies reviewed in this paper cover tests for neuropathy due to entrapment at the carpal tunnel. The important studies are those that consider the severity of the disorder and where each test is applied to both early or mild cases and late cases of the target disorder. It has long been advocated that neuropathy, including CTS be classi®ed into stages of severity (Sunderland 1991). Few studies meet the prerequisite of including both mild and severe cases, e.g. (Ghavanini and Haghighat 1998). Nerve injury and repair are clearly related to time aspects of the pathophysiological process. Electrophysiological evaluation takes this course into consideration in its interpretation. It is suggested (Spicher et al. 1999) that the results from both Tinel's and Phalen's tests are confounded by the stage of the injury and the time aspect of nerve repair (Novak et al. 1992) and should be considered in the interpretation of these tests. Possible in¯uence of population domain on test outcome The observed variability in estimates of sensitivity, speci®city, and LRs for clinical tests raises the question of whether the tests have been evaluated in an
64
appropriate spectrum of patients. Studies encompassing healthy controls (Tables 1, 2, 3, 4, and 5) reveal high and low positive and negative LRs, respectively, while tests evaluated on uniform case series from primary to secondary or tertiary care groups produce values that successively border an indierent LR of 1. Gerr and colleagues demonstrated that the selection of comparison subjects (Gerr and Letz 1998) in¯uences the resulting estimates. When the clinical tests were evaluated using asymptomatic disease-free subjects, their performance was considerably better than when they were evaluated with symptomatic disease-free subjects. This result is compatible with that of de Krom et al. (1990). The great variety of new diagnostic tests revealing promising, high estimates tested on small groups of diseased and healthy controls therefore needs recon®rmation in an adequate patient spectrum. To be able to evaluate fully the complete nosographic picture, ®rm knowledge of pre-test probabilities on symptoms and signs is helpful. Populationbased information is needed on the prevalences of the most common dierential diagnoses, e.g. polyneuropathies. This calls for attention to individual signs of, for instance, diabetes, alcohol consumption, vitamin de®ciency, and medication, in addition to signs of focal neuropathy associated with ergonomic risk factors. Many clinicians are familiar with the fact that patients with musculoskeletal pain not infrequently report local and/or referred phenomena such as paraesthesia or numbness. Lately, common work-related musculoskeletal disorders such as epicondylitis, with pain, have been reported to result in reduced somatosensory perception (Leer et al. 2000). Possible in¯uence of the selected ``gold standard'' Normality, in most studies, is de®ned as the values within two standard deviations. The ``gold standard'' in neuropathy, however, is not settled in the literature establishing the usefulness of dierent diagnostic tests. Several attempts to relate clinical tests, sensitivity and speci®city to HAVS classi®cation (Cherniack et al. 1990; Kent et al. 1998) have been performed without any independently established, blind comparison with a reference or diagnosis.
Evaluation and interpretation of test descriptives The evaluation of diagnostic tests and manoeuvres has mainly relied on accuracy estimates obtained, irrespective of their validity and precision. When lists of estimates from dierent studies have been presented, the large variability has been most obvious (Kuschner et al. 1992; Buch-Jaeger and Foucher 1994; De Smet et al. 1995; Kuhlman and Hennessey 1997) (Tables 1, 2, 3, 4, and 5). The pooling of results from several studies (D'Arcy and McGee 2000) results in a larger number of cases on which to base the evaluation but it still does not address the question of validity because of lack of consideration of the particular characteristics of the population domain. The information value of a diagnostic test is determined by the change in pre-test to post-test probability of the target disorder, which is determined by the prevalence of the disorder (or pre-test probability), the test's LRs, and also by the clinical importance of passing the no-test, no-treatment, and the no-test, treatment thresholds. The diagnostic impact of a test result depends on whether the test is used to rule in or rule out a diagnosis (Table 6). A positive result in a test with very high speci®city and high LR eectively rules in the diagnosis, while a negative result for a test with high sensitivity rules out the diagnosis. The reason to rule in or rule out depends on treatment possibilities and treatment traditions. The treatment thresholds, therefore, vary between dierent physicians and countries, as well as over time. For Phalen's test, the positive predictive value changed from 3% to 39% when the prevalence of the target disorder increased from 1% to 20% (Szabo et al. 1999). The corresponding values at 15% and 40% prevalence was 0.21 and 0.50 in a study by Katz and collaborators (Katz et al. 1990). The value of each diagnostic test depends on its LR but also on the experience of the physician, which de®nes the pre-test probability. In a choice between competing tests, the one with the smallest negative LR is more eective in ruling out disease, and the test with the largest positive LR is preferred for ruling it in (Table 6). The sensitivity increases if several tests are administrated jointly. Fertl and colleagues (Fertl et al. 1998) demonstrated that the sensitivity increased from 0.79 for Phalen's test alone, to 0.92 when Phalen's test was evaluated jointly with the wrist compression test (0.83). Szabo and colleagues (Szabo
Table 6 Pre- to post-test probability change in relation to pre-test probability and test likelihood ratio. Recalculated after Sackett and collaborators (Sackett et al. 2000) Likelihood ratio
Pre-test 5%
Pre-test 10%
Pre-test 20%
Pre-test 30%
Pre-test 50%
Pre-test 70%
Diagnostic impact
10 ± Very positive 3 ± Moderately positive 1 ± Neutral 0.3 ± Moderately negative 0.1 ± Extremely negative
29 9 0 3.5 4.5
43 15 0 6.8 9
51 23 0 13 18.5
51 26 0 19 26
41 25 0 27 41
26 18 0 29 51
Rule-in
Rule-out
65
et al. 1999) demonstrated, in a study of various tests for CTS or a combination of tests, that the diagnostic power of a combination of four clinical tests did not increase with the addition of electrodiagnostic tests. In the diagnosis of neuropathies a sequential strategy facilitates clinical decision making. The initial number of diagnostic hypotheses should be reduced by progressively ruling out diseases based on the information retrieved. Negative results for highly sensitive tests are most eective in ruling out suspected diagnoses. As the possible diagnostic alternatives become fewer, the use of positive results from highly speci®c tests are more effective (Black et al. 1999). Once neuropathy is con®rmed, more than 100 possible associations (e.g. focal neuropathies from compression and entrapment, ischaemia, drugs, endocrine or metabolic disorders, infections, immune states, toxins, genetically determined disorders, pharmaceutical agents) have to be ruled out (Asbury et al. 1995). The selection of various bedside examinations and diagnostic electrophysiological tests should be dependent on the clinical context, the history and prior results from the successive diagnostic tests. Acknowledgements The author is indebted to the Institute of Sound and Vibration, Southampton, England, for his participation in the International Workshop: diagnosis of injuries caused by hand-transmitted vibration, 11th-12th September 2000, at which the paper was presented. Financial support from the Swedish Council for Working Life and Social Research (2001-0276) is gratefully acknowledged.
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