1 INTRODUCTION

Nerve entrapment syndromes are peripheral neuropathies with structural changes in nerves due to microvascular disruption. Carpal tunnel syndrome or CTS is a common diagnosis that belongs to this category of diseases and must be differentiated from cervical radiculopathy or CR.¹ CR is mostly due to foraminal narrowing of the spinal nerve (70%–75%), and less frequently, a herniated nucleus pulposus is responsible for the presenting symptoms (20%–25%).² This includes pain, weakness (myotomal distribution), paresthesia, and sensory deficit (along the corresponding dermatome).³ Main differential diagnoses of CR include shoulder pathology, and other nerve entrapment syndromes (e.g., CTS or ulnar nerve entrapment).⁴

CTS is the most common nerve entrapment syndrome and it has an incidence of 1–3 persons per 1000 per year.⁵ Patients with CTS, initially complain of numbness and/or unpleasant sensation in fingers. Some of them experience pain and paresthesia in the forearm or shoulder.⁶ The diagnosis is based on characteristic symptoms and physical examination. Electromyography and/or nerve conduction velocity or EMG-NCV is used to confirm the diagnosis and exclude other conditions like polyneuropathy and radiculopathy as well.⁷ Similar to CR, treatment for CTS includes operative (nerve decompression) and nonoperative methods such as neutral-angle wrist splinting and steroid injection.⁸

Double crush syndrome (DCS) first was proposed by Upton et al. in 1973. They studied 115 patients with CTS, of which 81 (70%) had concomitant CR. This hypothesis stated that the proximal disruption of the axoplasmic flow might result in multiple injured sites alongside the peripheral nerve.⁹ This phenomenon may also be due to dorsal root ganglia inflammation, ion channel dysregulation, and neuroma in continuity.¹⁰ In addition, there are several animal studies that support DCS.^{11, 12} However, the accuracy of DCS has been questioned multiple times and remains controversial.^13-17

C6 and C7 nerve roots typically provide sensory innervation to digits 1–3 (the thumb, index, and middle finger), which are the same fingers affected in CTS, whereas C8 supplies digits 4 and 5. Thus, theoretically an isolated sensory deficit in digits 4 and 5 rules out the diagnosis of CTS. Accordingly, impairment in C6 and C7 nerve roots may result in overlapping symptoms and signs in these conditions and lead to misdiagnosis. CR and CTS require distinct treatment approaches at different sites along the upper extremities. In addition, there are many patients who are simultaneously affected by both conditions. These underscore the need to evaluate these patients with more scrutiny to differentiate between CR and CTS. In the present study, we aim to estimate the prevalence of CTS amongst patients with CR and explore the possibility of a positive correlation between the severity of CTS and CR.

2 METHODS

The current study is designed as a retrospective cross-sectional study. We enrolled patients with suspected CR who presented to our clinic between 2017 and 2020. The eligible patients for inclusion in the study were diagnosed with CR which was confirmed with EMG-NCV.¹⁸ Patients with overt diabetic neuropathy, prior spinal or hand surgery and/or fractures, and rheumatoid arthritis were not included. We used the following formula for sample size calculation: n = z²·p·q/d², where z = level of significance at 95% confidence interval (CI) (=1.96), p = proportion of patients who have coexisting CTS and CR in the study population (0.24), q = 1 – p (0.76), d = usually a constant set at 0.05. This formula yields 280 which is the minimum sample size for this study.

Patient history acquisition and physical examination (e.g., Tinel and Phalen tests) were carried out in all patients. Despite the clinical picture, all patients were assessed with electrodiagnostic studies or EDX, and an available EDX device (Medelec Premiere Plus) was used to record the results. The temperature of the hand was maintained at or above 32°C. Median Nerve conduction studies were done to assess the initial latency and baseline-to-peak amplitude. For this purpose, the abductor pollicis brevis muscle and third finger were used to record the motor and sensory response, respectively. The severity of CR was determined by assessing the reduction in amplitude and clinical manifestations. Furthermore, we categorized the CTS into mild, moderate, and severe based on EMG-NCV. Patients with CTS which was confirmed with most sensitive tests had mild disease. Moderate severity had normal terminal motor latency with slow sensory NCV, whereas, in the severe form of the disease, there was an overt increase in distal motor latency to abductor pollicis brevis.¹⁹

The analysis in this study was done via SPSS Statistics (version 19) and results were reported with a CI of 95%. A p value less than 0.05 was considered significant. Demographic data including age and sex were extracted from patients' records. The Kolmogorov–Smirnov test was run to assess the normality of distribution in quantitative data. Pearson's χ² test and paired T test were carried out to assess the correlation between the different variables. We acquired informed consent from each patient, and the data was anonymously codified. This study was approved by the Ethical Committee of the Tehran University of Medical Sciences and it is registered under IR.TUMS.IKHC.REC.1398.245.

3 RESULTS

4 DISCUSSION

Our study reported a relatively high prevalence of 62.2%, whereas in most studies, the frequency of DCS is low and ranges from 5% to 50%.^{17, 21, 22} This might be due to the fact that most patients were referred to our clinic from different provinces. Consistent with our findings, the increasing age was associated with DCS presence in most studies.^{17, 22-24} In our study, DCS was found at 10.6%, 17.5%, and 23% at C6, C7, and C8 levels, respectively. This higher frequency at the C8 level was congruent with Richardson's study (29.1%) and in contrast with Kwon's (3.9%).^{13, 21} In a similar study by Kwon et al. with a quantitative approach, 277 patients with CR were evaluated of which 39 (14%) had coexistent CTS. The frequencies of CTS were not statistically different according to nerve root level. They compared the latency and amplitude of motor and sensory responses between proximal nerve roots (C6 and C7) and C8 and found no significant difference. Theoretically, an association between CR and CTS is expected at proximal nerve roots (C6 and C7), but we found no correlation between the severity of CR and CTS at any nerve root level. This was in keeping with quantitative findings based on EDX in other studies as well.^{16, 20, 21}

We can attribute the development of DCS to the fact that CR and CTS may share some risk factors such as diabetes, medications, and some endocrinopathies.²⁵ Determining the order in which the DCS is treated is based on the extent of compression and the symptoms at each affected site. If a diagnosis of DCS is made, the surgeon will begin with standard nonsurgical management for each level of suspected nerve compression. Cervical nerve root compression can be treated initially with oral steroids, and avoiding movements that aggravate the condition. For distal lesions, common palliative treatments include steroid injections, splinting, and nonsteroidal anti-inflammatory drugs. If a patient with DCS does not experience clinical improvement with a carpal tunnel injection, this may indicate that they are unlikely to benefit from carpal tunnel release surgery alone.²⁶ According to Osterman's research, 33% of patients with DCS considered carpal tunnel release a failure, compared to only 7% of those with CTS alone.²⁷

This study had several limitations. First of all, it was a retrospective cross-sectional study that in comparison to prospective studies, has a lower ability to draw associations and causal relationships. It was conducted as a single-center study and the sample size was relatively small. In addition, we did not conduct a quantitative analysis based on latency and amplitude and did not design a regression model adjusting for potentially confounding variables. We recommend multiple-center prospective studies with quantitative data to clarify the correlation between the two conditions. Additionally, to the best of our knowledge, the pathologic processes that lead to DCS are still unknown and there is no existent standardized guideline for its treatment. Thus, we need translational research and protocol development for treating DCS.

5 CONCLUSION

In summary, the prevalence of DCS was relatively high in our study and involved the majority of patients. Increasing age was correlated with the development of DCS, and we found that women are more affected by DCS than men. CTS severity and CR severity were not correlated at the C6, C7, and C8 nerve roots. Thus, we could not demonstrate a causal relation between CR and CTS. Nevertheless, each of these conditions must be evaluated and treated with caution due to their high coexistence.

AUTHOR CONTRIBUTIONS

Alireza Teymouri: Data curation; formal analysis; writing—original draft; writing—review and editing. Seyede Zahra Emami Razavi: Conceptualization; data curation; investigation; methodology; validation; writing—review and editing. Mohaddeseh Azadvari: Data curation; investigation; project administration; writing—review and editing. Maryam Hosseini: Investigation; resources; supervision; validation.

CONFLICT OF INTEREST STATEMENT

The authors declare they have no conflict of interest.

TRANSPARENCY STATEMENT

The lead author Seyede Zahra Emami Razavi affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.