Laboratory tests

General background laboratory tests

Routine bloods and x-rays are not a lot of help and should be limited. Plain x-rays of the hand and wrist are not cost effective. In 1977 the cost of radiology was estimated at $5,869 to $20,115 for each finding of therapeutic signficance. (Bindra 1977) and X-rays should only be arranged if there is some other indication for doing them such as a suspicion of rheumatoid arthritis or fracture. Checking the blood glucose for diabetes is probably worthwhile as undiagnosed diabetes is common in the age group who tend to present with CTS. The value of screening for thyroid underactivity in CTS patients who are clinically euthyroid has not been established (Bland 2007).

Laboratory tests specifically for CTS

In clinically obvious cases specific tests are not needed to make the diagnosis with reasonable certainty but a variety of methods may be used to help confirm the diagnosis when it is less certain and to a lesser extent to help exclude it when it is considered unlikely. Some of these methods also provide information which is useful not just for diagnosis but for predicting the outcome of treatment (prognosis) and which may be of help in evaluating the subsequent progress of the disease.

Nerve Conduction Studies (Neurophysiology) - Historically, the fact that the syndrome of night time waking with paraesthesiae in the fingers is caused by a problem at the wrist was not widely accepted until it became possible to measure nerve function electrically. Prior to this the symptoms were often blamed on problems at shoulder or neck level. Neurophysiological methods include both Nerve Conduction Studies (NCS) and Electromyography (EMG). In NCS the principle is much like testing an electrical cable. A signal is started at one point, travels along the length of the nerve, and is recorded as it passes by at another point. A variety of methods can be used to trigger a signal in a human nerve but the commonly used one in routine practice is to administer a small electrical shock. This method is used because it is easy to measure the time at which the signal starts and one can be relatively certain about exactly where along the nerve the stimulation takes place. To record the signal further along the nerve a second pair of electrodes are used, placed as near to the nerve as possible and with a very sensitive amplifier one can then detect the electrical voltage change which is produced by a signal travelling along a human nerve. Alternatively, the recording electrodes can be placed over a muscle. When the volley of signals travelling along the nerve reaches the muscle, it will twitch, and again this generates an electrical signal which can be recorded. Muscles, being much larger structures, generate much more electricity than nerves and for this reason the earliest forms of electrical test for CTS used muscle recording because the amplifiers then available were not good enough to detect the smaller nerve signals.

Trapped and damaged nerves have a useful electrical property for diagnosis in that the speed of conduction along the nerve slows at the site of trouble. This is caused by damage to a substance called myelin which surrounds nerve fibres and acts as a form of electrical insulation which speeds up conduction. The pathological process which occurs where the nerve is trapped is therefore called demyelination. If you can identify which few centimetres of nerve are conducting slowly you can be confident that you have located a problem of some kind. It is important however, in making a diagnosis of a localised problem such as CTS, to also show that other sections of the same nerve or other nerves, are conducting at normal speeds. In more advanced nerve injuries, when nerve fibres have died off, there is not only slowing of conduction but also the recorded signals become smaller and in the worst cases of CTS it may not be possible to record anything from the median nerve.

In the UK there are effectively no restrictions on who can perform nerve conduction testing and if you are having these tests done it is worth checking what sort of person is doing them. A few tests for CTS are done by doctors who have been trained in these methods and have expertise in the kinds of disease they may detect. Many are done by physiological scientists who have an extensive training in this kind of test but will have less background knowledge of the possible underlying diseases. There is however nothing to stop anyone buying a suitable machine, being trained for a few hours in which buttons to press by the manfacturer and offering to perform the tests.

There are three reasons for doing nerve conduction studies in patients with suspected CTS:

1) Diagnosis - Curiously, this is usually the least important reason for the tests as most cases of CTS are easy to diagnose simply from listening to the patient. The tests are however widely regarded as 'diagnostic' and many small modifications to the technique of performing NCS for CTS have been introduced over the years with the aim of making the tests more sensitive and able to detect milder abnormalities of nerve conduction. With the latest methods the false negative rate is probably in the region of 5% but it is impossible to establish this figure with certainty in the absence of a more reliable test with which to compare. The down-side to the use of very sensitive neurophysiological methods is that it tends to push up the false positive rate and one has to take care in the interpretation of positive results on some of these modern tests if the patient’s symptoms are not wholly typical of CTS. The false positive rate of any one of these test methods should be 5% or less but the overall false positive rate can be much higher if many of them are used in combination. (Redmond 1988)

2) Detection of other nerve problems - in a proportion of patients there will be a more widespread nerve problem underlying the development of CTS, or the clinical diagnosis of CTS may be so wrong that another condition entirely is detected by the neurophysiology. Diseases from the differential diagnosis which can be picked up in this way include generalised peripheral neuropathies, other single nerve lesions such as ulnar nerve entrapment at the elbow, and degenerative disorders such as motor neurone disease. One study described 12 patients with a diagnosis of carpal tunnel syndrome in whom carpal tunnel surgery was unsuccessful and another neurological disorder was diagnosed subsequently. Final diagnoses included polyneuropathy, radiculopathy, motor neurone disease, spondylotic myelopathy, syringomyelia, and multiple sclerosis. (Witt 2000)

3) Measurement of severity - NCS provide one way of measuring the severity of nerve damage. When we use the term ‘severity’ in relation to a medical disorder it is not always clear what we are talking about. In some cases we are referring to what one might term the “patient’s view” of severity - a more severe case is one in which the patient experiences more intense or more prolonged symptoms and more disability. Although there is no absolute way of measuring the severity of an essentially subjective symptom like pain there are established methods of partially quantifying the subjective severity of diseases using symptom questionnaires and one of these, especially designed for CTS (Levine 1993) is incorporated in our symptom questionnaire.

NCS address another aspect of severity. We can measure severity in terms of how far away from the normal range a laboratory measurement is, thus a patient with a haemoglobin of 3 has a more severe anaemia than a patient with a haemoglobin of 8 - even though both are anaemic when the normal value should be above 12 or so. NCS allow us to measure the severity of median nerve dysfunction in CTS in this way but NCS measurements are a little more complex than a single blood test measure because we normally make several different measurements of the behaviour of the nerve including measurements of the conduction velocities of motor and sensory nerve fibres and measures of the size of the recorded potentials. Various ways of combining multiple measures into a single number giving some idea of overall severity have been proposed. We have used the same grading system in Canterbury since 1992 - a method which gives each hand an overall score ranging from 0 (normal) to 6 (the most severe CTS possible). This grading scheme is very similar to one that is used widely in Italy (Padua 1997). The Italian grading has one less subdivision such that Italian grade 4 includes Canterbury grades 4 and 5, while Italian grade 5 corresponds to Canterbury grade 6.

A third meaning of the the term severity might be that more severe cases are those with a poorer prognosis. These three meanings of severity may or may not be correlated with each other. It may or may not be the case for example that patients with more severe subjective symptoms have a poorer prognosis.

Medical imaging (CT scanning, MRI scanning, Ultrasound scanning)

Medical diagnostic imaging has played an enormous role in the advance of modern medicine and unsurprisingly it has been applied to the carpal tunnel. Plain x-rays have been available since before the diagnosis of CTS was recognised but mainly provide images of the bony structure of the hand without much detail of soft tissues and they portray a three dimensional structure as a single plane on which images of many structures are superimposed. They can occasionally show bony abnormalities relevant to the diagnosis of CTS and should be employed in wrist injuries with possible fractures and in patients with bony abnormalities secondary to diseases such as rheumatoid arthritis. They are not however a cost effective investigation in idiopathic CTS (Bindra 1977). The imaging methods which are useful in CTS are those which give three dimensional views of the carpal tunnel and surrounding structures:

CT-SCANNING (Computed tomography)

The oldest method able to produce detailed 3-dimensional images or cross sectional views of living tissue relies on the mathematical analysis of data obtained from the transmission of x-rays through tissue at many different angles. The earliest studies of carpal tunnel dimensions were done with CT-scanning but this has now largely been superseded by MRI which gives more detailed images of soft tissue.

MRI

An imaging method which uses the excitation of nuclei within a magnetic field by radio waves to obtain images. The nuclei which are excited by the scanner are predominantly those of hydrogen atoms in water in the tissue and all tissues contain water molecules so MRI is capable of producing remarkably detailed images of many different tissue types. Furthermore, as it does not use x-rays there is no exposure to ionising radiation. Pathological changes in tissue can produce signal changes on MRI so that abnormal tissues can be highlighted in some circumstances. MRI has been used extensively in CTS for scientific studies of carpal tunnel dimensions and to a limited extent as an ordinary diagnostic tool. However, MRI scanners are expensive and cumbersome and produce strong magentic fields which mean they cannot be used on some patients with implanted metallic devices.

Ultrasound scanning

Familiar to most people from obstetric ultrasound images of babies in the womb, it is possible to mathematically reconstruct surprisingly accurate images of the body from the echoes of high frequency sound waves sent into the tissues. The spatial resolution of the images obtained is ultimately dependent on the frequency of the sound waves used to construct the image with higher frequencies being able to resolve smaller structures. Higher frequency ultrasound however penetrates less deeply into tissue and very high frequencies can only be used for very superficial structures, nor does ultrasound penetrate bone so that some structures can be effectively ‘hidden’ behind bones. It does have many advantages as an imaging method however. Ultrasound scanners are relatively inexpensive. Portable scanners are available which can be taken easily to the patient. Images are instantly available in real time and tissues can be watched in motion. For superficial tissues where high frequency probes can be used the resolution of ultrasound in the vertical plane (along the line of transmission of the sound waves) is superior even to that of MRI. Ultrasound scanning of peripheral nerve is a particular interest of the Canterbury neurophysiology department and there is a dedicated section of this website with detailed information and some example images.

What does imaging reveal about CTS (any method)?

On some occasions, imaging methods will reveal some anatomical abnormality relevant to the causation of CTS in the individual patient. Examples include space occupying lesions in the carpal tunnel including, tumours, ganglia, aberrant muscles, tendonitis, gouty deposits, localised infections and anomalous arteries. Much is made of this by proponents of the use of imaging in diagnosis but in fact such findings are relatively rare and it is even rarer for the knowledge that one of them is present to alter the management of the patient’s CTS. There are however imaging findings which are useful in the diagnosis of CTS even when the anatomical structures seen are only the ‘normal’ ones of the carpal tunnel. MRI can show signal change in the median nerve in CTS patients but the most consistent finding from all imaging methods is that the median nerve itself is enlarged in CTS patients. The median nerve is a fairly complex 3-dimensional shape and there remains some uncertainty about exactly what is the best way to measure it for diagnostic purposes ( see the ultrasound pages) but the most widely studied measurement at present is the cross sectional area of the nerve at the level of the wrist crease. This roughly corresponds to the level of the pisiform bone anatomically. The precise measurement obtained depends to some extent not on the nerve itself but also on the imaging method used, the quality of the scanner, the way the measurement is taken and the operator so normal values for these studies, like those for NCS, vary somewhat from one institution to another. In my own laboratory 95% of the normal population have a median nerve measured by ultrasound at this site of between 4 and 9 square millimetres on one scanner and 4-10 square millimetres on the other one (we have two and they give slightly different results). A measurement of 10/11 square millimetres is thus suspicious of CTS and 11/12 or larger is almost diagnostic, depending on which scanner we are using. A substantial number of studies have now been performed trying to evaluate the sensitivity and specificity of ultrasound diagnosis of CTS though, as with NCS, there is the same problem of there being no absolute reference standard for the diagnosis. Estimates of sensitivity range from 60-100% and specificity from 60-95%. Many other measurements have been looked at including some which are not median nerve dimensions - for example the amount of palmar bowing of the transverse carpal ligament. There is much less data for MRI, probably because of the relative expense.

Quantitative Sensory Testing

One of the cardinal features of CTS is loss of sensitivity of the fingertips. In the clinic this can be semiquantitavely assessed by measuring 2-point discrimination (the ability to perceive whether one or two pinpricks are felt when they are close together) or by using von-Frey hairs or Semmes-Weinstein monofilaments - a set of carefully calibrated fibres which produce a known amount of pressure on the skin when applied so that they just begin to bend. Several mechanical devices have been produced which test the ability of the patient to detect subtle variation in sensory stimuli such such as touch/pressure, temperature, vibration, or texture. All suffer from the fact that the patient has to report whether or not they can feel the test stimulus and although methods are available for reducing the amount of subjectivity in such tests it cannot be eliminated entirely and none of these methods have gained widespread acceptance in the routine diagnosis of CTS. 

Revision date - 10th December 2016