In this edition of Scandinavian Journal of Pain, Izadi and collaborators publish an interesting paper  showing the lack of relationship between clinical provocative tests of carpal tunnel syndrome (CTS) and results of nerve conduction studies (NCS), while they found significant associations between the results of NCS and clinical grading, Numeric Pain Rating Scale (NPRS) and the Boston carpal tunnel questionnaire (BCTQ).
CTS is due to a compression of the median nerve at the level of the wrist. It is by far the most common peripheral nerve entrapment syndrome, with a prevalence around 2–3% in a general population . CTS is associated with a number of risk factors, including pregnancy, hypothyroidism, diabetes, rheumatoid arthritis and obesity . The role of work-related factors is somehow controversial, but occupational biomechanical factors play a substantial role in the causation of CTS  and some recognize it as a work-related disorder caused by strain and repeated movements . The treatment of this entrapment mononeuropathy is either conservative (splinting, steroid injections) or surgical decompression of the carpal tunnel. Surgery has proved to be more efficient compared to non-surgical methods , , , but CTS may also improve spontaneously in some untreated patients , . Accordingly, while surgical decompression is the advised initial therapy for patients with severe CTS, milder forms of CTS without evidence of axonal loss can initially be treated conservatively .
It is important to bear in mind that several differential diagnoses may mimic CTS , including cervical radiculopathies (especially C6/C7), different types of peripheral polyneuropathies, other mononeuropathies including proximal median and ulnar neuropathy as well as local conditions of the wrist (arthrosis, tendinitis). Although CTS-surgery is regarded as efficient and relatively safe, it represents, as all surgical procedures, a potential risk of complications  including postoperative pain. A correct diagnosis is therefore mandatory before a surgical intervention, in order to avoid an unnecessary operation.
CTS is characterized by pain/paresthesia in the hand/wrist, typically localized to the radial fingers within the innervation territory of the median nerve. However, sensory complaints from non-median innervated hand/fingers  and pain in the arm/shoulder  are also common. The symptoms are typically worsened at night and may be reduced by shaking the hand. At daytime, the complaints may be provoked by repetitive activity or holding the hand/arm in sustained positions . Intermittent sensory complaints often dominate in the early stage, while more fixed sensory symptoms and motor complaints may appear if the compression of the nerve is sustained. A fixed sensory deficit and thenar wasting/weakness is associated with poorer prognosis . Thenar wasting is a sign of marked axonal loss and may represents a serious handicap for the patient since thumb opposition is important for the grip-function of the hand. The outcome of carpal tunnel surgery is better if the nerve is decompressed before a severe abnormality as marked axonal loss has occurred , , and it is accordingly important to identify early signs of axonal loss before the condition becomes so severe that thenar atrophy is clinically present. This is only possible via neurophysiological tests such as NCS and electromyography (EMG) (see e.g.  for an overview), methods with a notable impact on treatment plans both for CTS specifically and for neuromuscular disorders in general , .
2 Nerve conduction studies (NCS)
NCS combined with clinical assessment is by most regarded as the closest we come to a “gold standard” for CTS. NCS enables assessment of the thick myelinated sensory and motor fibers, and may be of importance in the workup of CTS for three main reasons: (1) to increase the diagnostic accuracy for CTS and assist the diagnosis of potentially mimicking disorders; (2) to assess the severity of CTS, enabling a more appropriate planning of treatment; and (3) to serve as a baseline that can be followed over time, being especially important for the evaluation of patients with unexpected persistent or new complaints after CTS-surgery.
By NCS, the first step of compression of the median nerve in the carpal tunnel is manifested by demyelinating features of the sensory fibers, typically reflected by increased latency/slowing of sensory conduction velocity across the wrist, between the distal part of the forearm and the palm/median-innervated fingers. Measurements comparing median nerve latencies/conduction velocities to the corresponding results from ulnar/radial nerves may reveal smaller abnormalities than absolute values, increasing the sensitivity of NCS , . The next step in a continued compression may involve motor fibers, as first shown by an increase in the distal motor latency (i.e. slowing of motor conduction velocity across the wrist from the median-innervated hand muscles). Eventually, a combined serious affection of the sensory nerve fibers which may include loss of sensory findings and more serious motor affection may be seen , . Decreased amplitudes, especially for motor recordings, represents a severe finding since this typically reflects axonal loss (although conduction block due to demyelination also may cause amplitude reductions , ).
NCS is reported to confirm a clinical CTS with a sensitivity above 85% and specificity above 95% . Importantly, a few patients with clinical CTS will have negative NCS findings (suggested to be around 5–10% , although the exact number may vary depending on how sensitive NCS techniques are being used). Conversely, some persons may have NCS signs of median nerve abnormalities at the wrist although they will not have and will not develop symptoms of CTS . In addition, patients with other nerve conditions, including a variety of different polyneuropathies, may show NCS signs of median neuropathy at the wrist even though their complaints not necessarily are related to these specific findings. In such circumstances, it is (as always) very important to evaluate the meaning of the NCS results within the clinical context and to be aware that NCS is not by itself “the gold standard” for the diagnosis of CTS.
3 NCS grading scales and severity of CTS
There exist different scales to grade the CTS-severity by NCS , ,  which may be used to assist in the choice of treatment (surgery vs non-surgery). Such grading scales may also add some prognostic information regarding CTS surgery, since preoperative NCS severity has been associated with the outcome after surgery , . In the actual paper by Izadi et al., mild CTS was characterized by a distal sensory latency >3.5 ms with a normal motor study, while a moderate CTS was characterized by abnormal sensory findings with a distal motor latency between 4.4 and 6.5. A severe CTS was defined by severe abnormal sensory findings and a distal motor latency >6.5 ms, with or without decreased motor amplitude .
Electromyography (EMG) is not required to diagnose a typical CTS, but may add valuable information in certain patients . If necessary, EMG can often be performed in the same session as NCS. Trained physicians can by EMG reveal subtle and early signs of axonal degeneration/loss of motor nerve fibers, information which may be of great value when evaluating the severity of CTS. Especially, significant denervation activity in median-innervated thenar muscles, reflecting ongoing axonal loss, will be an important indication for an early surgical intervention. In addition, EMG can be very helpful in the diagnosis of potentially mimicking disorders of CTS (cervical radiculopathies, plexopathies, polyneuropathies or other mononeuropathies of the arm), by demonstrating pathology in other muscles than the median-innervated thenar muscles.
4 NCS only reveal large fiber pathology
Although NCS is very useful as an objective nerve measurement, it is essential to remember that this method can only reveal loss-of-function (i.e. slowing/block of conduction, axonal loss) of the thick myelinated nerve fibers. In contrast, gain-of-function/increased excitability of large fibers, as well as the small nerve fibers per se (including the peripheral nociceptors), are not at all assessed by routine NCS. This may seem paradoxical since “positive” sensory symptoms (pain, paresthesia), as also shown by Izadi et al. , are common complaints in CTS. A variety of complex mechanisms may be involved in the generation of such subjective experiences, but there is no obvious direct mechanistic link between an objective large fiber “loss-of-function” at NCS (such as slowing of conduction velocity) and subjective “gain-of-function” symptoms (paresthesia/pain) of the patient. In contrast, it is well established that pain and paraesthesia may be mechanistically linked to small fiber pathology and changed nerve excitability , , .
The limitation that NCS only can reveal loss of large fiber function may, together with other factors including complex neuroplasticity changes and psychological/personality traits , probably explain some of the non-linear and complex relationship between NCS-severity and “positive” symptoms in CTS. Regarding neuropathic pain in general, there is no consistent relationship between the severity of nerve damage measured by routine methods and the subjective severity of pain experienced by the patient. It is commonly seen that a patient with a severe neuropathy does not suffer from neuropathic pain, and conversely, patients with severe neuropathic pain may only show minor signs of nerve damage on routine nerve testing, sometimes only limited to pathology of small nerve fibers. Accordingly, it is important to be aware that the report of pain does not follow the degree of nerve damage. Pain may actually be reported less commonly in advanced forms compared to more mild/moderate forms of CTS , and we will emphasize that a decreased pain rating will not automatically reflect an improvement of the condition of the nerve.
It has been claimed that CTS only/preferentially affects the large nerve fibers, but small fiber pathology is also convincingly demonstrated in patients with CTS , , . Although neither small fiber testing  nor methods which distinctly measure large nerve fiber excitability ,  play an important role in the routine workup of CTS today, even more refined methods for efficacious evaluation of these highly relevant variables for clinical use in the individual patient may hopefully become available in the future.
5 Provocative tests and clinical grading tools
As recommended by BMJ Best Practice , we share the opinion that all patients with suspected CTS ideally should be referred to NCS. At least, as also stated by UpToDate , NCS is essential if surgical treatment is being considered. However, this is a debated topic, and in contrast to the mentioned high-quality evidence-based medicine resources  some claim that the routine use of NCS is not required  (but see comments on this viewpoint in , ). Anyway, the local availability and waiting lists of NCS will differ, and the diagnosis of CTS is often based on a clinical evaluation only. This will often include the use of provocative tests such as the Tinel sign (gently tapping over the nerve at the wrist), Phalen’s test (pushing the dorsal surface of the hands together for 30–60 s) and the compression test (the examiner presses the thumb over the carpal tunnel), all evoking radiating sensory symptoms within the median-innervated fingers if being positive. In the present paper by Izadi and co-workers , there was no significant association between provocative tests and the results of NCS, implying that these tests are not accurate for assessing the severity of CTS. Regarding the diagnostic value, their sensitivity and specificity for CTS have been reported in a very wide range, being moderate at best , , . Although such provocative tests may assist in the clinical evaluation of CTS, they are by themselves insufficient to diagnose ,  or to assess the severity of CTS . Of note, BMJ best practice does not recommend Tinel’s or Phalen’s test as useful for CTS .
Clinical grading systems and validated questionnaires such as Boston Carpal Tunnel Questionnaire (BCTQ)  may be used for the evaluation of CTS. In the study by Izadi et al. , it was found that both the clinical grading, numerical pain ratings and BCTQ-scores (symptoms and functional status) correlated to NCS at group level, being in accordance with other reports , . In contrast, Mondelli et al. reported a lack of relationship between BQ and NCS in mild CTS .
6 Nerve ultrasound
Ultrasound is increasingly used as a complement to NCS for diagnosing neuromuscular disorders  and may be offered as a diagnostic test for CTS . A meta-analysis  reported the sensitivity and specificity in the diagnosis of CTS to be 77.6% and 86.8%, respectively, and it was recently reported that some patients with clinical CTS and normal NCS actually may have abnormal ultrasound findings . The most reliable and common finding in CTS is an enlargement of the median nerve at the wrist (increased cross-sectional area; CSA), but other findings such as changes in nerve echogenicity and bowing of the flexor retinaculum may also be seen . A disadvantage of nerve ultrasound is that it only enables assessment of morphological changes, not functional changes, and it could not directly reveal whether there is axonal loss or not. A relationship between ultrasound and NCS has been reported by some, for instance Mondelli et al. , while others found no clinical significant correlation between ultrasound parameters and NCS and concluded that ultrasound cannot be used to determine CTS severity . An advantage of ultrasound is the possibility to identify space-occupying lesions and anatomical variants. In that respect, MR of the wrist may also be of value in certain situations, but this is craving large resources .
Izadi et al.  found no correlation between commonly used clinical provocative tests (Tinel’s, Phalens’s, Reverse Phalen’s, manual carpal compression test) and the severity of NCS in patients with CTS. This is adding to the low usefulness of such provocative tests for diagnosing CTS , . Although they may be used as a part of the clinical evaluation of CTS, the diagnosis and assessment of severity should not depend on these tests. It is interesting that Izadi et al. found that pain ratings, clinical grading and Boston carpal tunnel questionnaire correlated with the severity of NCS at group levels, and these tools may obviously be helpful in the clinical workup of CTS. However, due to the interindividual variability and the complex link between the severity of nerve injury and subjective sensory symptoms, the use of these tools as the only indicators of nerve damage severity in the individual patient is questionable. In our opinion, NCS is to be recommended in all patients with suspected CTS for three reasons; (1) to assist in diagnosing CTS and mimicking disorders; (2) to assess CTS severity for optimal treatment planning; (3) to serve as a baseline for follow-up investigations. Although there are reasonable arguments that some patients with typical and mild CTS may be treated conservatively without the urgent need of NCS, the degree of nerve damage (e.g. is there axon loss or not?) can be difficult to evaluate on clinical basis only. When a severe damage with axonal loss of the median nerve becomes clinically obvious as thenar wasting, it may be too late for an optimal surgical outcome. In that respect, as commented by Bland , NCS is the only tool that can quantitatively reveal the deterioration in median nerve function that takes place as CTS evolves from a mild/moderate to a severe form. As advised by top rated evidence-based summaries like UpToDate  and BMJ Practice , a pre-surgery evaluation of a patient with suspected CTS should still include NCS.
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About the article
Published Online: 2018-06-12
Published in Print: 2018-07-26
Conflict of interest: None declared.
Citation Information: Scandinavian Journal of Pain, Volume 18, Issue 3, Pages 333–337, ISSN (Online) 1877-8879, ISSN (Print) 1877-8860, DOI: https://doi.org/10.1515/sjpain-2018-0089.