Evaluating the Effectiveness of Perineural Nerve Block with Ropivacaine and Dexamethasone in Patients with Neurogenic Thoracic Outlet Syndrome—A Prospective Pilot Trial

Abstract

Objective: Neurogenic thoracic outlet syndrome (nTOS) is a rare compression neuropathy, and establishing a firm diagnosis can be challenging. Interscalene nerve blocks with Ropivacaine and Dexamethasone have been proposed in cases with typical symptoms and without evident pathology of the thoracic outlet (i.e., disputed nTOS) to establish the diagnosis. The aim of this study was to evaluate the effectiveness of interscalene nerve block for long-term pain relief in patients with true and disputed nTOS. Methods: Patients between 18 and 90 years of age with either true or disputed nTOS were prospectively included in the study. All patients received an interscalene nerve block with Ropivacaine and Dexamethasone. At baseline, 2, 6, 12, and 24 weeks after infiltration, minimum and maximum pain levels were assessed using the numeric rating scale (NRS 0–10). Furthermore, arm function was assessed using the Quick-DASH, and health-related quality of life was assessed by means of the SF-12 questionnaire. Statistical analysis was performed with SPSS version 29.0 using the Wilcoxon signed rank test and t-test for paired samples. A p-value below 0.05 was considered statistically significant. Results: A total of 21 patients were included in the study. There was a significant decrease in the minimum (Pmin) and maximum (Pmax) mean pain levels at 2 and 6 weeks after the baseline. Thereafter, 12 patients dropped out of the study due to surgery. In the remaining nine patients, pain levels remained significantly lower than baseline at 12 and 24 weeks after infiltration. Quick-DASH scores as well as the physical domain of the SF-12 showed significant improvement compared to baseline. Conclusions: In patients with true and disputed nTOS, long-term pain relief can be achieved with the interscalene nerve block with Ropivacaine and Dexamethasone. Additionally, the study indicated an improvement in arm function and health-related quality of life. In patients with disputed nTOS, the interscalene nerve block may be a useful tool to establish the diagnosis of clinically relevant true nTOS. Key points: Question: Does a scalene nerve block with Ropivacaine and Dexamethasone lead to long-term pain relief in patients with a neurogenic thoracic outlet syndrome (nTOS)? Findings: A scalene nerve block with Ropivacaine and Dexamethasone leads to significant pain relief, as well as an improvement in arm function and health-related quality of life for patients with a neurogenic TOS. Meaning: This study provides new insights into the diagnostic of neurogenic TOS and may be used as a short- and long-term pain therapy.

1. Introduction

Thoracic outlet syndrome (TOS) is defined by neurogenic upper extremity symptoms due to compression of the neurovascular bundle exiting the thoracic outlet [1]. Recent literature showed that the majority of TOS cases are primarily neurogenic (nTOS), produced by the impingement of the C5 to T1 nerve roots of the brachial plexus [2,3]. This impingement can occur at three distinct sites, namely the interscalene triangle, the costoclavicular space, and the sub thoracic minor space; however, the interscalene triangle, due to its closely intertwined anatomy, is most frequently affected [4]. A recent consensus paper published by Dengler et al. divided nTOS into three distinct subgroups: nTOS 1—weakness of the hand with concomitant muscular atrophy, with or without anatomic anomalies, or pain and sensory deficits; nTOS 2—anatomic anomalies with accompanying pain and sensory symptoms nTOS 3—only pain and sensory symptoms with radicular (3a), cervicoscapular (3b), or diffuse (3c) distribution of symptoms [5]. Types 1 and 2 were formerly classified as true nTOS, whereas Type 3 corresponds to the definition of disputed nTOS. In Types 1 and 2, surgical decompression of the thoracic outlet is advised; in type 3 nTOS, the consensus paper recommends a primarily conservative management consisting of physical therapy and local measures such as botulinum toxin or steroid injections. Surgery may be indicated, though, in patients with recurrent and severe pain. Surgical decompression usually consists of scalenotomy and circumferential neurolysis of the brachial plexus, with or without resection of the first rib [6].

Until now, there has been no agreed-upon conservative management for neurogenic TOS, and no technique with sufficient long-term pain relief has been described so far [7]. In 2017, the Cochrane Library postulated that Dexamethasone as a perineural adjunct for peripheral nerve block prolongs both sensory and motor block, and the injection of steroids around the brachial plexus has also been advocated in the consensus paper [8].

Dexamethasone is an anti-inflammatory glucocorticoid often used in clinics to treat peripheral nerve damage due to its capacity to reduce edema in neurological tissue and alleviate the consequences of neural inflammation [9]. However, its mechanisms of action are still not completely understood. It is tempting to associate the immunosuppressant and potential neurotrophic effects induced by Dexamethasone with its actions at the site of nerve compression or injury, which would lead to reduced infiltration of inflammatory cells and production of inflammatory mediators. This hypothesis was investigated in 2012 by Hongzhi et al., who found that Dexamethasone and vitamin B₁₂ promoted peripheral nerve repair in a rat model of sciatic nerve injury through the upregulation of brain-derived neurotrophic factor (BDNF) [10]. In 2015, Feng X. et al. [11] demonstrated that Dexamethasone enhanced sciatic nerve regeneration and functional recovery in a rat model of sciatic nerve injury through neuroprotection by restricting CD3-positive cell invasion. In addition, Dexamethasone upregulates the GAP-43 expression in the crushed/compressed or injured nerve after 21 days, which is mainly associated with the development and plasticity of the nervous system. H&E staining of sciatic nerves strongly supported the beneficial effect of Dexamethasone on axonal regeneration due to reduced edema as well as fewer degraded myelin sheets [11]. Previous studies also indicated that Dexamethasone did not only reduce the extent of demyelination but also had the potential to enhance remyelination [12,13,14,15,16].

The rationale for using Dexamethasone for TOS is based on its use in carpal tunnel syndrome (CTS) and its therapeutic successes in this application [17,18,19,20].

To further investigate Dexamethasone’s effect as a peripheral nerve block additive, this pilot trial was conducted to evaluate the effectiveness of scalene nerve block with Dexamethasone with regard to pain relief in nTOS. The primary aim was to assess the duration of significant pain reduction.

2. Methods

This study was questionnaire-based and was approved by the Institutional Review Board of the Medical University of Graz beforehand (with the registration number: EK 34-449 ex 21/22), and written informed consent was obtained from all subjects.

2.1. Definition of True and Disputed nTOS

Based on the definition proposed by Dengler et al. [5], patients that corresponded to nTOS 1 and 2 groups were defined as true nTOS, whereas patients corresponding to nTOS group 3 were defined as disputed nTOS.

2.2. Patient Selection

This pilot trial was carried out between October 2021 and January 2023 at the Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery of the Medical University of Graz, Austria.

Patients were deemed eligible for the study when they fulfilled the following criteria:

• Age between 18 and 90 years;
• Pain levels > 5 on the NRS for at least 6 months and no alleviation of symptoms through physical therapy and the following clinical features:
  • Clinical signs of nTOS (pain, sensory symptoms) without pathological findings in electroneurography or imaging studies (disputed nTOS) OR;
  • Established diagnosis of nTOS with pathologies in imaging studies (cervical rib, aberrant scalene muscle fibers, pathological flow profile of subclavian artery) as bridging therapy until surgery OR;
  • Recurrent nTOS symptoms (pain, sensory symptoms) after prior surgery in formerly diagnosed true nTOS.

In the first patient group, the interscalene nerve block, in addition to pain relief, was also utilized as a diagnostic tool to confirm the suspected diagnosis of nTOS, whereas in the other two groups, the nerve block was performed for pain therapy only. Patients with bilateral nTOS were further evaluated as two separate cases, with each limb corresponding to one case. Patients were not enrolled in the case of isolated vascular TOS or when there was known drug intolerance to Ropivacaine or Dexamethasone.

2.3. Prior Clinical Examination, Electroneurography, and Imaging Studies

Prior to enrolment, all patients underwent a mandatory set of clinical tests and imaging studies. Clinical examination encompassed evaluation for muscular atrophies, signs of vascular compression (diminished radial artery pulse during arm elevation), and the “TOS stress test” (90° shoulder abduction, elbow and wrist extended, head tilted to the contralateral side), which was deemed positive if this provoked the typical symptoms (pain exacerbation and numbness of the affected limb). Electroneurography of the median and ulnar nerves was performed in all patients to rule out additional nerve entrapment syndromes. A plain radiograph of the cervical spine was performed to detect any bony anomalies at the level of the thoracic outlet, such as a cervical rib or enlarged transverse processes. MRI of the cervical spine was performed to rule out foramen stenoses with root compression. Furthermore, all patients received a high-resolution ultrasound of the brachial plexus to detect any aberrant muscle fibers or fibrous strands surrounding the neurovascular structures. When clinically indicated, additional imaging studies were carried out, i.e., a CT scan to clarify the cervicothoracic junction.

2.4. Interscalene Nerve Block

The interscalene nerve block was carried out under ultrasound guidance and sterile conditions. For the intervention, the patient was placed in a lateral position with the affected side up and the head tilted to the contralateral side. Then, a 14-gauge needle was advanced into the interscalene triangle under continuous visualization, and 14 mL of 7.5 mg/mL Ropivacaine and 6 mg Dexamethasone were injected perineurally. The correct placement of the infiltration volume around the nerve roots was then visually confirmed with ultrasound. A transient paralysis of the affected arm, approximately 30 min after the intervention, including a complete sensory loss at the palm of the hand, served as clinical confirmation of the correct infiltration. In all patients, paralysis and sensory loss resolved 6 to 8 h after the intervention [21,22]. In patients with bilateral nTOS, the intervention was carried out over two consecutive days.

2.5. Assessment of Pain Levels, Paraesthesia, Numbness, and Weakness

Before the intervention, the patients underwent a detailed anamnesis as well as a clinical examination. The current pain level in a relaxed position (Pmin) and under stress (Pmax) was evaluated using the Numeric Pain Rating Scale (NRS—10 point Likert-scale) by asking, ‘What number would you rate your pain if zero is no pain and ten is the worst imaginable pain?’. In addition, patients were asked whether they experienced paraesthesia, numbness, or weakness (yes or no) of the affected upper limb.

2.6. Quick-DASH (Quick Disability of Arm, Shoulder, and Hand) Score

The Quick-DASH score is a questionnaire that assesses upper limb function in daily life. Higher scores are tantamount to higher disability. The score was assessed at baseline and at each follow-up visit. In patients with bilateral symptoms, the score was evaluated for each arm independently.

2.7. Short Form 12 Health Survey (SF12)

Health-related quality of life (HRQoL) was assessed using the Short-Form-12 Health Survey, which, in turn, is an abbreviated yet equally recognized and validated version of the original Short-Form-36 Health Survey [23]. The SF12 was used in its German version for this study and was evaluated at baseline and each follow-up visit. In patients with bilateral symptoms, only one SF12 was assessed to be used for both limbs.

2.8. Follow-Up Visits

All study parameters were assessed at baseline, as well as 2, 6, 12, and 24 weeks after the interscalene nerve block. Each follow-up visit also included a clinical examination to detect early signs of symptom recurrence. Patients dropped out of the follow-up regimen if they received surgery before completing the full follow-up period of 24 weeks.

2.9. Statistical Analysis

The data were expressed as medians with interquartile ranges and analyzed using the SPSS 29.0 (IBM Inc., Armonk, NY, USA) software. Descriptive statistics were calculated for all patient characteristics, results of minimum and maximum pain scores, as well as Quick-DASH and SF12 scores. Due to the small sample size, values were expressed as medians with minimums and maximums. For inductive analysis, the Wilcoxon signed-rank test and the t-test for paired samples were used, and baseline values were compared to values at each follow-up visit. A value of p < 0.05 was considered as statistically significant.

3. Results

In total, 21 upper limbs (18 female, 3 male) of 14 patients (2 men, 12 women: 7 bilateral, 7 unilateral) were included in the study. The median age was 37 years (22.5–42) and the median pain anamnesis was 29 (12–91) months. In 10 cases, the right arm was affected, and in 11 cases, the left arm was affected. According to the aforementioned definition, there were 12 cases of true nTOS and 9 cases of disputed nTOS. At baseline, weakness, paresthesia, and clumsiness were reported in all 21 examined arms. Between 6 and 12 weeks of follow-up, a total of 12 limbs dropped out of the study due to surgery. Of these, five patients had true nTOS, and infiltration served as a pain-bridging therapy. The remaining seven patients had a disputed nTOS with pain recurrence after 6 weeks and were therefore re-evaluated and ultimately scheduled for surgery.

Table 1. Patient collective and clinical data at baseline.

Parameter	Study Finishers	Drop-outs	Total
Gender f:m	6:3	12:0	18:3
Age, Median (min–max)	41 (19–53)	35 (21–45)	37 (19–45)
Pain anamnesis in months, Median (min–max)	18 (9–36)	84 (12–120)	29 (9–120)
True nTOS	2	6	8
Disputed nTOS	7	6	13
Bilateral	4	3	7

provides all relevant clinical data of the patient collective.

3.1. Pain Levels by NRS

At baseline, the reported mean Pmin and Pmax were 4.6 (3–6) and 8.1 (7–10).

Comparison of mean minimum pain levels at baseline and after infiltration showed a significant pain reduction after two weeks (Pmin 2.0 (1–3), p < 0.001, n = 21); six weeks (Pmin 2.1 (0–3.5), p < 0.001, n = 21); 12 weeks (Pmin 0.9 (0–1.5), p = 0.011, n = 9); and 24 weeks (Pmin 0.3 (0–0.5), p = 0.007, n = 9).

Accordingly, mean maximum pain levels compared to baseline had dropped significantly at two weeks (Pmax 4.3 (3–7), p < 0.001, n = 21); six weeks (Pmax 4.6 (3–6.5), p < 0.001, n = 21); 12 weeks (Pmax 3.0 (0–6), p = 0.028, n = 9) and 24 weeks (Pmax 1.4 (0–3), (p = 0.007, n = 9) (Figure 1—Pain levels by NRS).

3.2. Quick-DASH

At baseline, the reported mean Quick-DASH score was 52.7 (38.7–68.2).

Two weeks after the scalene nerve block, the mean Quick-DASH was 38.9 (26.1–47.6) (p < 0.001, n = 21); after six weeks it was 38.6 (23.9–56.8) (p < 0.001, n = 21); after 12 weeks it measured 22.5 (4.6–33.3) (p = 0.011, n = 9), and after 24 weeks it was 17.5 (3.4–29.4) (p = 0.008, n = 9). For detailed results, see Figure 2—Quick-DASH.

3.3. SF-12

At baseline, the reported mean physical SF-12 score was 34.4 (28.4–40.9), and the mean mental SF-12 score was 43.5 (34.1–54.4).

Two weeks after the scalene nerve block, the mean physical SF-12 score was 39.7 (34.1–43.2) (p = 0.019, n = 21); after six weeks it was 39.7 (33.6–48.2) (p = 0.039, n = 21); after 12 weeks it measured 48.2 (42.9–53.8) (p = 0.021, n = 9), and after 24 weeks it was 51.0 (40.4–56.2) (p = 0.034, n = 9). The control group in Figure 3 and Figure 4 is predefined from the SF-12 questionnaire and represents a random sample of a healthy German population.

See Figure 3—physical SF-12.

Figure 3. SF-12 physical scale.

Figure 3. SF-12 physical scale.

Two weeks after the scalene nerve block, the mean mental SF-12 score was 46.2 (36.8–56.7) (p = 0.258, n = 22); after six weeks, it was 45.1 (36.1–56.6) (p = 0.986, n = 22); after 12 weeks, it measured 58.0 (38.1–60.7) (p = 0.593, n = 9), and after 24 weeks, it was 55.9 (48.2–59.4) (p = 0.026, n = 9).

See Figure 4—mental SF-12.

Figure 4. SF-12 mental scale.

Figure 4. SF-12 mental scale.

4. Discussion

A scalene nerve block was performed in 21 upper limbs that were subject to true or disputed nTOS. A detailed examination of the pain level showed a significant reduction in the subjectively perceived minimum and maximum pain levels throughout the entire trial period (24 weeks), and this was evident at every follow-up interval. The initial mean value of the minimum pain (Pmin0) was reduced by 93.5% after 24 weeks (Pmin24). Reflecting that, the initial mean value of the maximum pain (Pmax0) was also reduced by 82.7% after 24 weeks (Pmax24). These results are in line with studies that suggest that interscalene brachial plexus blocks with Dexamethasone perineurally significantly decrease opioid consumption and the incidence of rebound pain after shoulder surgery [24,25]. Other authors, furthermore, found a significant pain reduction in patients with radiculopathy after selective nerve root blocks with Dexamethasone as an adjunct [26,27]. A case report by Sung Joon Chung et al. reported a patient who underwent deep tissue massage, which resulted in acute cervical radiculopathy due to C5 and C6 nerve root compression and inflammatory reactions around them. Hence, the patient received an ultrasound-guided C5 and C6 nerve root block twice, with 0.25% lidocaine and 20 mg Dexamethasone. After 24 weeks, the patient’s shoulder and wrist strength had recovered significantly [28]. Studies investigating CTS and local injections with Dexamethasone also demonstrated a significant pain reduction [17,18,19,20].

Another important finding of this study was the improvement of DASH scores over time after the nerve block. We were able to demonstrate that perceived impairment of the affected upper limb decreased significantly in patients with long-lasting effects greater than 12 weeks from the scalene nerve block. These observations are similar to those described in a study by Diner et al. who showed a significant re-gain of the function of the upper extremity and improvement of DASH scores after 12 weeks in patients who underwent surgery with decompression of the brachial plexus [29]. Similarly, a study by Ammi et al. evaluated the quality of life after TOS surgery with 3-, 6-, and 12-month follow-ups using the Quick-DASH and SF-12 questionnaire. The improvement of DASH became statistically significant at 3, 6, and 12 months, which is in line with the results of our study [30].

Health-related quality of life improved significantly on the SF-12 physical scale from two weeks after the nerve block and onwards. The effect was less evident on the mental scale of the SF-12, where significant results were only seen 24 weeks after the infiltration, and this occurred after more than half of the study population had already dropped out. A study by Al Rstum et al. demonstrated similar tendencies with the mental scale of the SF-12, which did not improve over time following surgical decompression of the brachial plexus. However, the physical scale of the SF-12 improved linearly with time from surgery, regardless of the etiology of TOS [31]. Another study by Chang et al. showed the same tendencies regarding the quality of life after TOS surgery, evaluated with the SF-12 questionnaire at 3, 6, 12, 18, and 24 months after the operation [32]. In 2012, Rochlin et al. investigated the quality of life after TOS surgery with a mean follow-up of 44.7 months and concluded that there is no significant difference in the SF-12 scores when comparing the long-term and short-term follow-ups. Regarding their results, patient factors, particularly comorbidities and opioid use, are more significantly relevant for the long-term quality of life than a preoperative scalene nerve block [33].

Since the drop-out group of 12 patients 6 weeks after infiltration constitutes more than half of the initial study population, we would like to provide more insight into this group. First of all, 6 of those 12 patients had a verified anatomical compression of the plexus brachialis (e.g., an accessory cervical rib or an enlarged transverse process) and were either way scheduled for surgery. Thus, the scalene nerve block was meant to be a pain bridge in the first place. The remaining six patients (without an objective finding) experienced a pain recurrence 6 weeks after the nerve block and were also scheduled for surgery. In these patients, anatomical abnormalities (e.g., strong ligaments) that could not be visualized beforehand became evident during surgery, likely causing brachial plexus compression. Another potential factor that distinguished these patients from the study finishers (n = 9) was the comparably long pain anamnesis, with a median of 84 months (12.6–117) (Table 1), and therefore, per definition, as proposed in the Budapest criteria, a CRPS II as a secondary diagnosis. Furthermore, the drop-out group had a minimum median pain level after 6 weeks of 3 (2–4) and a maximum pain level of 6 (4.3–7.8). In comparison, the study finishers had a median minimum pain level after 6 weeks of 0 (0–0.5) and a maximum pain level of 1 (0–3). These results show a significant difference between the drop-out group and the study finishers.

Taking all these findings into consideration, it seems that a scalene nerve block with Dexamethasone perineural can cause significant pain relief in patients with nTOS. While all patients experienced short-term pain relief, some patients even experienced a long-lasting effect after the scalene nerve block. Based on the findings of this pilot trial, it seems that the scalene nerve block could even represent a definitive therapy for some patients with nTOS—especially in cases with disputed nTOS—whereas some patients might only experience short-term symptom alleviation.

5. Strengths and Limitations

We assume that this is the first study that demonstrates the pain-reducing effect of perineural Dexamethasone as an adjunct in an interscalene brachial plexus block in patients with nTOS.

The strengths of this pilot trial are the prospectively collected data, a large patient collective (n = 21) for this rare peripheral neuropathy, as well as the significant results even after a drop-out of about 50% of the patients between the 6- and 12-week follow-up.

The limitation of this study is the absence of a control group and, hence, no randomization protocol. However, due to the many variations in symptomatic TOS, a much larger patient collective would be necessary. Furthermore, the number of drop-outs was fairly high. This was, on the one hand, due to patients being scheduled for surgery in the first place, and on the other, due to a recurrence of symptoms as early as six weeks of infiltration.

Last but not least, we have used the Dengler classification (nTOS 1, 2, 3, and 3a-c), developed by neurologists, which is not used by hand surgeons, for example. Therefore, our data contains an exceptionally high number of true-nTOS patients, while, according to generally accepted standards, true nTOS patients are less than 1% in all data.

6. Conclusions

The scalene nerve block with Ropivacaine and Dexamethasone seems to be an effective short-term pain therapy in patients with nTOS, irrespective of evident anatomic anomalies. In addition, the nerve block might constitute an effective long-term pain therapy in some patients with disputed nTOS. Furthermore, the scalene nerve block seems to be a feasible method to verify the diagnosis of nTOS in disputed cases, aiding in the decision-making for and against surgical decompression of the thoracic outlet.