How we may be misdiagnosing peripheral entrapment neuropathies. (Part 2)

Hi All

I last posted Part 1 of my blog assignment June 2020 which can be found here.

I have since returned to Eastbourne for my Upper Limb Module and it has been great to get back into academia and catching up/meeting others from the course. It has also reminded me to post part 2 of my blog.

As part of the assignment, 2 of my peers were asked to read the blog and come up with questions that came to mind.

Zoe’s Question

“Hi Derrick, an interesting read, thank you. I wanted to ask how you might test for small fibre damage/loss of function and how confident you would be of a nerve entrapment diagnosis if the tests were positive?”

Response

Hi Zoe

There are different methods in identifying nerve function, and it falls under these different categories:

• Clinical: Bedside examination, questionnaires, quantitative sensory testing (QST).
• Lab-based: Skin Biopsies

• Investigations: Nerve conduction studies and functional neuroimaging (fMRI’s, PET scans)

For this response, I will focus on the clinical tests as this is the most relevant and available to our practice. QST is a battery of clinically valid tests which can assess all aspects of somatosensory function. Due to the heterogeneous way it was conducted, a consensus meeting in the late 1990s helped informed the clinical practice guideline of QST as described by Rolke et al. (2006).

The tests are categorised either in the detection of

• “Loss of function” which is a loss in the ability to detect mechanical, hot, cold and vibration stimulus.
• “Gain of function” which is a reduced threshold potential to cold, heat, and pressure pain stimulus.

To answer your question, to assess for loss of small nerve fibre function, I would use a combination of warm, cold and pinprick detection. With respects to the confidence of the tests, in the literature, it suggests that “Pinprick” detection has high specificity (88%) whilst hot or cold detection has high sensitivity (98%) for people with CTS (Ridehalgh., et al 2018).  In context, if a person is unable to detect pinprick and hot/cold stimulus, I can be quite certain they have small fibre nerve dysfunction.

Tests	Hot/Cold detected	Hot/Cold undetected
Pinprick detected	Highly Unlikely dysfunction	Likely dysfunction
Pinprick undetected	Unlikely dysfunction	Highly likely dysfunction

The biggest limitation and reason why QST is not widely used is due to its timely process (close to an hour), and the need for specialised equipment. However, there have been emerging studies validating the use of low-cost, accessible and time-efficient alternatives to QST to make it more clinically realistic for clinicians to utilise somatosensory testing (Ridehalgh., 2018, Zhu et al., 2019).

To answer the second part of your question about the confidence in the diagnosis of nerve entrapment neuropathy if tests were positive. I would say the test’s do not offer the ability to delineate why a person may present with small nerve fibre neuropathy. Small nerve fibre neuropathy can be as a result of a variety of diseases, including diabetes mellitus, autoimmune disorders, alcohol, chemotherapy, drugs, trauma exposure and HIV (Levine et al., 2018). What would make me confident that nerve entrapment neuropathy was the primary diagnosis, is the combined method of good subjective history taking, clinical presentation, objective/test findings and sound clinical reasoning.

To conclude, currently, QST appears to be the most clinically accurate way we as physiotherapists can assess for nerve somatosensory function. Our utilisation of the tool when we have a clinical suspicion of a certain condition can be useful in raising diagnostic certainty.

References

Levine, T. D. (2018). Small Fiber Neuropathy: Disease Classification Beyond Pain and Burning. Journal of Central Nervous System Disease, 10, 117957351877170. https://doi.org/10.1177/1179573518771703

Rolke, R., Magerl, W., Campbell, K. A., Schalber, C., Caspari, S., Birklein, F., & Treede, R. D. (2006). Quantitative sensory testing: A comprehensive protocol for clinical trials. European Journal of Pain, 10(1), 77–88. https://doi.org/10.1016/j.ejpain.2005.02.003

Ridehalgh, C., Sandy-Hindmarch, O. P., & Schmid, A. B. (2018). Validity of clinical small-fiber sensory testing to detect small-nerve fiber degeneration. Journal of Orthopaedic and Sports Physical Therapy, 48(10), 767–774. https://doi.org/10.2519/jospt.2018.8230

Zhu, G. C., Böttger, K., Slater, H., Cook, C., Farrell, S. F., Hailey, L., … Schmid, A. B. (2019). Concurrent validity of a low-cost and time-efficient clinical sensory test battery to evaluate somatosensory dysfunction. European Journal of Pain (United Kingdom), 23(10), 1826–1838. https://doi.org/10.1002/ejp.1456

 

Gautam Question

“Hi Derrick, I have enjoyed your blog. I would like to know, have you come across any study which discussed the location of pain in CTS patients when neurological tests are negative in constriction type nerve injuries affecting small fibres only?”

Response

Hi Gautam

From my knowledge, I have not come across any studies that have looked explicitly at this, but I can speculate from the literature and infer what a person with small nerve fibre dysfunction may present with.

I have two theories:

• A person presents with no pain at all

Within nerves are structures called the “Nervi nervorum” which acts as the intrinsic innervation of nerve sheaths. These structures are made up of small nerve fibres, and if we recall, one of the primary functions of small fibers is in pain detection and production. It may be plausible that people with constriction related nerve injuries, where small nerve fibre dysfunction is dominant, could have impaired Nervi nervorums and may reduce a person’s sensitivity and production of pain (Schmid et al., 2018).

The flaw with this theory is being too reductionist onto one biological structure and cannot explain people with central nervous system dysfunction, other co-morbidities, and/or psychological factors which can influence a person’s ability to perceive pain.

• A person presents with pain at the affected nerve and neighbouring dermatomes.

Small nerve fibres dysfunction may lead to a reduction of cold/hot and pressure pain threshold. This can result in people suffering from pain at the dermatomal distribution of the site of dysfunction. However as mentioned in the blog, a consensus of set dermatome distribution has its limitations which may be why clinical we see different locations of symptoms (Downs, 2011).

Looking beyond peripheral nerves, we need to consider other parts of the nervous system that can affect a person’s sensory experience.  The dorsal root ganglion (DRG) is a cluster of sensory neurons that carries sensory information from the peripheral nervous system to the central nervous system (Ahimsadasan et al., 2018).

There is a theory, that a remote immune response occurs at the DRG in reaction to a peripheral injury. The neuroimmune response theory is where a peripheral nerve injury can stimulate an immune response to the whole nervous system and can activate certain inflammatory mediators, neuropeptides, and hormones at different sites (Dantzer 2018).

It is, therefore, a plausible explanation that in response to a peripheral nerve injury, other nerves with no dysfunction that share a common DRG with a dysfunctional nerve could all display symptoms due to the neuroimmune response at the DRG. Clinically there may be people that demonstrate the multi-dermatomal spread of symptoms, despite only having mononeuropathy on examination (Schmid et al., 2018).

However plausible these may sound, it is still based on theories and many assumptions are made from an oversimplification of biological processes from studies completed in animal models. As mentioned in the blog, these studies are useful in building up a mechanistic explanation of what may be happening from a cellular level.  In context, we need to remember that it is only one of many possible interactions that occur, and their effect size is unknown. Therefore, cautions must be made when applying them to clinical practice.

To summarise, there does not seem to be a consensus on pain location in people with nerve dysfunction with or without clinical findings. Individual differences are to be expected in mononeuropathies and multi-segment distribution is to be expected in most people we see clinically.

References

Ahimsadasan N, Kumar A. Neuroanatomy, Dorsal Root Ganglion. [Updated 2018 Oct 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-.

Boyd, B. S., Wanek, L., Gray, A. T., & Topp, K. S. (2010). Mechanosensitivity during lower extremity neurodynamic testing is diminished in individuals with Type 2 Diabetes Mellitus and peripheral neuropathy : a cross sectional study, 5–8.

Dantzer, R., & Introduction, I. (2020). NEUROIMMUNE INTERACTIONS : FROM THE BRAIN TO THE IMMUNE SYSTEM AND VICE, 477–504. https://doi.org/10.1152/physrev.00039.2016

Downs, M. B. (2011). Conflicting Dermatome Maps: Educational and Clinical Implications, 41(6), 427–434. https://doi.org/10.2519/jospt.2011.3506

Schmid, A. B., Hailey, L., & Tampin, B. (2018). Entrapment Neuropathies: Challenging Common Beliefs With Novel Evidence. Journal of Orthopaedic and Sports Physical Therapy, 48(2), 58–62. https://doi.org/10.2519/jospt.2018.0603