Abstract
Background
Patients with foot drop due to peroneal nerve entrapment are treated with either conservative or surgical approaches, yet the optimal strategy remains unclear due to limited evidence. We aim to investigate whether neurolysis of the peroneal nerve is superior to conservative treatment.
Methods
This multicenter randomized controlled trial aimed to compare maximal conservative treatment with peroneal nerve neurolysis in patients with persistent foot drop (6 to 14 weeks post-onset). The primary endpoint was the change in distance covered during the 6-min walk test (6MWD) between randomization and 9 months. Secondary outcomes including time to recovery, gait, muscle strength, surgical complications, electrodiagnostics, and quality of life, were assessed at 6 weeks, 3 months, 6 months, 9 months and 18 months.
Results
The study ended prematurely due to recruitment challenges, with only 26 patients were randomized across 7 centers (12 to conservative treatment, 14 to surgery). No significant difference in 6MWD was observed at 9 months (564 m in the conservative group vs. 480 in the surgical group). Time to recovery which was faster in the conservative group (p = 0.02). Both groups showed improvements in muscle strength, gait and quality of life.
Conclusion
Recruitment difficulties stemmed from the condition's low incidence, strict eligibility criteria and high spontaneous recovery rate. Despite the trial's termination, results suggest clinical equipoise and good outcome regardless of treatment choice. Further research is needed to determine the role and timing of neurolysis.
Keywords: Foot drop, Peroneal nerve entrapment, Randomized controlled trial, Neurolysis, Conservative treatment
HIGHLIGHTS
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Despite being the most frequent mononeuropathy of the lower limbs, the optimal treatment strategy of patients with foot drop due to peroneal neuropathy is unknown. There is a clinical equipoise between conservative and surgical treatment.
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This study reports findings of the first randomized controlled trial comparing a conservative treatment strategy with surgical decompression of the peroneal nerve at the level of the fibular head. A wide range of outcome parameters are reported.
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The study was prematurely terminated due to important recruitment issues.
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Good outcome is reported in both treatment groups with an increase in ankle dorsiflexion strength, walking distance, quality of life and other gait outcome measures.
1. Background
Peroneal neuropathy is a frequent cause of foot drop (Carolus et al., 2021), causing gait difficulties and increased fall risk (Poppler et al., 2020). Peroneal neuropathies can be classified as idiopathic, idiopathic with risk factors (e.g., weight loss), or non-idiopathic (e.g., trauma-related) (Oosterbos et al., 2022a, 2023). This study focuses on idiopathic cases, with or without risk factors, termed peroneal nerve entrapment.
Both surgical and non-surgical treatment strategies in patients with peroneal nerve entrapment are considered standard of care (Oosterbos et al., 2022a). Conservative management emphasizes gait rehabilitation, proprioceptive training, ankle dorsiflexion strengthening, passive mobilization of the ankle and foot and stretching of calf muscles to prevent contractures. Surgical treatment involves neurolysis to decompress the peroneal nerve (Oosterbos et al., 2022b). Recovery rates are high, approximately 85% for surgical and 79% for conservative treatment in the largest surgical and non-surgical patient series (Oosterbos et al., 2022a). However, treatment strategies and outcome vary widely (Oosterbos et al., 2022c) due to limited high-level evidence and the absence of guidelines (Oosterbos et al., 2022a).
Robust evidence to establish current best practice is therefore lacking. This randomized controlled trial (RCT) aimed to compare conservative and surgical treatment for foot drop due to peroneal nerve entrapment hypothesizing that neurolysis leads to better recovery within 9 months compared to conservative treatment.
2. Methods
We conducted a multicenter randomized controlled trial with a parallel group design across 12 centers, approved by each center's medical ethics committee. Written informed consent was obtained from all patients prior to inclusion. The study was registered at ClinicalTrials.gov (identifier NCT04695834) and followed a published protocol (Oosterbos et al., 2022b). The study was conducted after the successful completion of a feasibility pilot study in six centers (Oosterbos et al., 2023).
2.1. Eligibility and randomization
Patients were included by a multidisciplinary study team consisting of neurosurgeons, neurologists and rehabilitation physicians at the outpatient clinic of each center. Eligible patients were at least 18 years old, with electrodiagnostically confirmed entrapment of the peroneal nerve and persistent foot drop (MRC score ≤3 for ankle dorsiflexion) at the moment of randomization. Ultrasound or magnetic resonance imaging (MRI) ruled out compressive masses at the fibular head. Exclusion criteria included traumatic or iatrogenic nerve lesions, bilateral disease, recurrent foot drop, inability to participate in physiotherapy, or conditions affecting trial assessments (e.g., pregnancy, psychiatric illness, or being bedridden).
Patients were only randomized if foot drop persisted (MRC-score ankle dorsiflexion ≤3) 6 to 14 weeks, to account for early foot drop recovery. A web-based randomization/treatment allocation system (Randomization module, REDCap) randomly assigned the patients using a 1:1 allocation ratio to either conservative treatment or surgery. The randomization list was concealed to all investigators.
2.2. Treatment
Patients allocated to surgical treatment underwent neurolysis within 1 week of randomization. under local, locoregional or general anesthesia. A curvilinear incision just distal to the fibular head was used and the nerve was identified proximal to the peroneus longus muscle. The nerve was released from surrounding fibrous tissue and fascia and decompressed were it ran under the peroneus longus muscle. Surgery was usually performed in an ambulatory setting. Conservative treatment followed a standardized physiotherapy protocol tailored to individual needs, focusing on ankle mobilization, calf stretching, dorsiflexion and eversion strengthening, proprioceptive training, gait rehabilitation, and home exercises. Physiotherapy aimed to reduce muscle atrophy, preserve ankle mobility and improve gait in general.
2.3. Outcomes
The primary endpoint was the difference in distance covered during the 6-min walk test (6MWD) between randomization and 9 months after randomization. The key secondary endpoint (time to recovery) and other secondary outcomes were recorded at study visits 10 days (surgery group only), 6 weeks, 3 months, 6 months, 9 months and 18 months (Oosterbos et al., 2022b). Time to recovery was defined as the time necessary to cover the minimal age- and sex-specific normal 6MWD and MRC-score ≥4 for ankle dorsiflexion. During the study visits, a trained outcome assessor evaluated motor weakness (MRC-score, isometric dynamometry), gait (functional ambulation categories (FAC), Stanmore questionnaire, 6MWT, 10-m walk test (10MWT), sensory changes, surgical complications, quality of life (EQ5D) and health-economic aspects (return to work at 6 weeks after randomization and work productivity and activity impairment questionnaire (WPAI). Electrodiagnostics (EDX) were repeated at 3 months and 9 months (Oosterbos et al., 2022b).
2.4. Blinding
Most trial assessments were done by trained physiotherapists or study nurses, who were blinded for treatment strategies. Participants wore long trousers to conceal surgical scars and applied bandages at the fibular head. Participants were not allowed to discuss their treatment with the outcome assessor. Paper source documents ensured no access to electronic patient files.
2.5. Statistical analysis
Given that no reliable estimates of the 6MWD were available for the study population, the sample size calculation was performed assuming a moderate effect size. Based on an effect size of 0.5, 172 patients would have 90% power to show a significant difference at a two-sided significance level of 5% in the change in the 6MWD from baseline to 9 months after randomization using a t-test. To compensate for 5% dropout anticipated based on patient interviews and a RCT of similar design (Peul et al.), a total of 182 patients was to be included.
The 6MWD was evaluated at each visit. A constrained longitudinal data analysis (cLDA) was performed taking the correlation between these measurements into account. The value at baseline and all follow-up measurements were taken as responses. The mean difference between the two treatment groups with a 95% confidence interval and a two-sided p-value will be reported. Time to recovery was analyzed using a generalized log-rank test with constant weights over time for interval-censored data. In addition, the Turnbull estimator with 95% confidence intervals was produced. Due to the premature trial termination, all secondary endpoints were discussed descriptively and no sensitivity or subgroup analyses were performed. The EQ-5D 5L index score was calculated using the Belgian EQ-5D 5L value set (Bouckaert et al., 2022). All statistical analysis were programmed using the SAS system version 9.4 or higher.
3. Results
The trial began in April 2021 but was terminated early due to recruitment issues. From April 2021 the study was activated in 11 centers in Belgium and 1 center in the Netherlands. Until September 2024 seven centers were able to recruit patients. We included 32 of 52 potentially eligible patients. Ten patients recovered prior to informed consent and 10 refused to participate. In addition, another 5 patients recovered and 1 withdrew consent before randomization. Ultimately, 26 patients were randomized: 12 patients to conservative treatment and 14 patients to surgery. One patient refused surgery due to a COVID-19 infection. Due to significant recruitment problems, the study was prematurely terminated after all active participants were evaluated for the 9 months study visit. At that moment, 13 patients already completed the 18 months visit. No cross-over occurred during the 9 months following randomization which remained unaltered after the 9 months study visit. The trial flow is visualized in Fig. 1.
Fig. 1.
Trial flow.
Baseline characteristics are summarized in Table 1. Most entrapments were idiopathic (53.8%). Weight loss during the last six months was the most common risk factor, with a mean of 26.0 kg (SD 15.6) in the conservative group and 12.2 kg (SD 8.5) in the surgical group.
Table 1.
Baseline characteristics.
| Baseline characteristics | Conservative treatment (N = 12) | Surgical treatment (N = 14) |
|---|---|---|
| Male | 8/12 (66.7%) | 7/14 (50.0%) |
| Age (years) | (12) 53 (15) | (14) 57 (12) |
| BMI (kg/m2) | (10) 25 (2) | (14) 25 (6) |
| Entrapment of left peroneal nerve | 5/12 (41.7%) | 7/14 (50.0%) |
| Health economics | ||
| Currently employed/working | 6/12 (50.0%) | 5/14 (35.7%) |
| Continue to work | 3/6 (50.0%) | 2/5 (40.0%) |
| Medical history | ||
| Previous L4/L5 pathology | 0/11 (0.0%) | 2/14 (14.3%) |
| Oncological history | 0/12 (0.0%) | 3/14 (21.4%) |
| Diabetes mellitus | 0/12 (0.0%) | 2/14 (14.3%) |
| Thyroid disease | 1/12 (8.3%) | 2/14 (14.3%) |
| >10 units alcohol/week | 1/12 (8.3%) | 1/13 (7.7%) |
| Etiology/Risk factors | ||
| Idiopathic | 8/12 (66.7%) | 6/14 (42.9%) |
| Weight loss | 2/12 (16.7%) | 6/14 (42.9%) |
| Habitual leg crossing | 3/12 (25.0%) | 6/14 (42.9%) |
| Prolonged squatting | 1/12 (8.3%) | 1/14 (7.1%) |
| Frequent kneeling | 0/12 (0.0%) | 1/14 (7.1%) |
| Subacute footdrop onset (>2 days) | 8/12 (66.7%) | 6/14 (42.9%) |
| Clinical assessment | ||
| MRC-score ankle dorsiflexion 0 | 0/12 (0.0%) | 2/14 (14.3%) |
| MRC-score ankle dorsiflexion 1 | 1/12 (8.3%) | 4/14 (28.6%) |
| MRC-score ankle dorsiflexion 2 | 5/12 (41.7%) | 3/14 (21.4%) |
| MRC-score ankle dorsiflexion 3 | 6/12 (50.0%) | 5/14 (35.7%) |
| Tinel sign at fibular head present | 5/12 (41.7%) | 4/14 (28.6%) |
Table 1. Baseline characteristics. BMI = body mass index; MRC = medical research scale. Statistics were depicted as n/N (%) or (n) Mean (SD) when appropriate.
3.1. Primary endpoint
At 9 months the mean 6MWD in the conservative group was 563.9 m versus 479.7 m in the surgical group. The change from baseline was the largest in the surgical group which had also a lower mean baseline value. The difference in change in 6MWD at 9 months between the two groups was not statistically significant (p = 0.112) (Table 2).
Table 2.
Evaluation of the primary endpoint.
| Primary endpoint | Statistic | Conservative treatment | Surgical treatment |
|---|---|---|---|
| Baseline 6MWD (m) | (n) Mean (SD) | (12) 478.8 (88.3) | (13) 337.5 (121.0) |
| Median (Q1; Q3) | 482 (443; 532) | 318 (240; 445) | |
| 9 months visit 6MWD (m) | (n) Mean (SD) | (10) 563.9 (77.7) | (12) 479.7 (81.7) |
| Median (Q1; Q3) | 553 (536; 602) | 487 (417; 556) | |
| Change from baseline 6MWD (m) |
(n) Mean (SD) | (10) 58.4 (47.8) | (12) 155.1 (102.2) |
| Median (Q1; Q3) |
56 (26; 102) |
135 (73; 238) |
|
| cLDA at 9 months | Mean (95% CI) | 50.2 (−11.9; 112.3) | |
| Difference in 6MWD (m) | p-value | P = 0.112 | |
Table 2. Evaluation of the primary endpoint (difference in distance covered during the 6-min walk test (6MWD) between randomization and 9 months after randomization). cLDA = Constrained longitudinal data analysis; SD = standard deviation; CI = confidence interval.
3.2. Secondary endpoints
3.2.1. Time to recovery
Time to recovery was statistically significantly different (p = 0.020) with faster recovery in the conservative group (p = 0.02), with 60% of patients achieving recovery by 9 months, compared to 17% in the surgical group (Table 3).
Table 3.
– Time to recovery.
| Study visit | Percentage (95%CI) recovered |
|
|---|---|---|
| Conservative treatment | Surgical treatment | |
| 6 weeks | 8.3% (1.2%; 46%) | 0% |
| 3 months | 33% (14%; 66%) | 0% |
| 6 months | 50% (26%; 79%) | 8.3% (1.3%; 44%) |
| 9 months | 60% (35%; 86%) | 17% (4.7%; 50%) |
Table 3. Time to recovery. Generalized logrank test p = 0.02023. Time to recovery is defined as the time necessary to cover the minimal age- and sex-specific normal 6MWD and reach an MRC-score ≥4 for ankle dorsiflexion. CI = confidence interval.
3.2.2. Muscle strength analysis
Ankle dorsiflexion, ankle eversion and hallux extension strength as measured by the MRC-scale is visualized in Fig. 2A-C, respectively. The median change (Q1; Q3) from randomization to 9 months later was 2 points on the MRC scale for ankle dorsiflexion in both the conservative (2; 2) and surgical group (1; 3). At 9 months, all 10 conservative patients had an MRC score ≥4 for ankle dorsiflexion, with normal strength (MRC 5) in 60% of patients. 75% of surgical patients achieved an MRC score ≥4 for ankle dorsiflexion at 9 months. Normal strength (MRC 5) was observed in 41.7% of surgical patients. At the final follow-up visit, 5 of 6 surgical patients had a maximal MRC score for ankle dorsiflexion. After 9 months, an MRC score ≥4 for ankle eversion was documented in 100% (10/10) and 91.7% (11/12) of the conservative and surgical group, respectively. At the same moment, an MRC score ≥4 for hallux extension was documented in 100% (10/10) and 66.7% (8/12) of the conservative and surgical group, respectively. The evolution of the MRC-scores is summarized in Supplementary Tables 1–3. Mean ankle dorsiflexion strength as measured by isometric dynamometry after 9 months was 138 N (SD 52.4 N) and 92.8 N (SD 65.1 N) in the conservative and surgical group, respectively. On average, ankle dorsiflexion strength did increase with 119.3 N (SD 64.5 N) and 84.2 N (SD 68.4 N) in the conservative and surgical treatment group after 9 months, respectively. The evolution of ankle dorsiflexion strength is depicted in Fig. 2D.
Fig. 2.
Muscle strength assessment.
3.2.3. Sensory changes
At randomization, 10 of 12 patients in the conservative group (83.3%) and 12 out of 13 patients in the surgical group (92.3%) reported sensory disturbances in the skin area innervated by the peroneal nerve. Nine months later, all but one patient in the surgical group reported at least partial recovery of sensory symptoms. Recovery was complete in 6 out of 10 (60.0%) conservative patients and in 7 out of 12 surgical patients (58.3%). At 18 months, 5 of 7 conservative patients reported complete recovery (71.4%) versus 4 out of 6 surgical patients (66.7%).
3.2.4. Gait assessment
All but two patients randomized to the surgical group were FAC 4 or FAC 5 at randomization. Mean FAC in the conservative group was FAC 5, mean FAC in the surgical group was FAC 4. After six weeks, all patients were FAC 4 or higher (Fig. 3A). The mean total score on the Stanmore questionnaire after 9 months was 96.9 points (SD 4.0 points) in the conservative group versus 81.3 points in the surgical group (SD 27.9 points). Based on these scores, outcome is excellent in the conservative group and good in the surgical group (Fig. 3B). Gait speed at 9 months improved by 0.5 m/s on average in the conservative group (SD 0.63 m/s) and by 0.81 m/s in the surgical group (SD 1.41 m/s). Mean gait speed at 9 months was 1.86 m/s (SD 0.54 m/s) and 2.00 m/s (SD 1.60 m/s) in the conservative and surgical group, respectively (Fig. 4A). Per protocol, good outcome correlated to a gait speed ≥1.14 m/s. Mean 6MWD after 18 months was 600.7 m (SD 95.5 m) and 440.7 m (SD 263.7 m) in the conservative and surgical group, respectively. This corresponds to an average increase in 6MWD of 82.1 m (SD 70.9m) in the conservative group and 73.8 m (SD 221.8 m) in the surgical group (Fig. 4B). At randomization, 8.3% of patients in the conservative group reached the minimal age-en sex specific 6MWD. This percentage increased to 60% after 9 months. For the surgical group, these percentages were 0% at randomization and 16.7% after 9 months. These percentages increased 18 months after randomization to 71.4% and 33.3% in the conservative and surgical group, respectively.
Fig. 3.
Gait assessment questionnaires. A. Functional ambulation categories (FAC) (Holden et al., 1984). FAC 3: dependent ambulation, need for standby guarding of one person; FAC 4: independent ambulation, level surfaces only; FAC 5: Independent ambulation, level and non-level surfaces. B. The Stanmore questionnaire (Gatskiy et al.). Seven sections (pain, need for orthosis, normal shoes, functional outcome, muscle power, degree of active dorsiflexion and foot posture) add up to a sum score of 100 points. Excellent outcome: 85 to 100 points; good outcome: 70 to 84 points; fair outcome: 55 to 69 points, poor outcome: <55 points.
Fig. 4.
Outcome of the 10 m walk test and the 6 min walk test. In the upper panel, mean gait speed was visualized. In the lower panel, mean 6 min walking distance (6MWD) was shown.
3.2.5. Quality of life
Quality of life, measured by the EQ-5D 5L questionnaire, improved in both treatment groups. The mean EQ-5D 5L index score at 9 months for conservative patients was 0.96 (SD 0.06), corresponding to 0.18 (SD 0.25) points increase compared to baseline. Mean overall health score at 9 months was 90.4 (SD 11.2) in this group; compared to a mean score of 66.5 (SD 22.1) at baseline. At randomization, 1 of 11 patients reported no walking difficulties versus 7 of 9 (77.8%) and 7 of 7 (100%) at respectively 9 months and 18 months. The mean EQ-5D 5L index score 9 months after randomization for surgical treatment was 0.83 (SD 0.24), corresponding to 0.27 (SD 0.18) points increase compared to baseline measurements. The mean overall health score after 9 months was 73.4 (SD 16.3); compared to a mean score of 62.3 (SD 24.6) at baseline. At randomization, all surgical reported walking difficulties versus 8 of 12 (66.7%) and 4 of 6 (66.7%) at 9 months and 18 months respectively. The evolution of the mean EQ-5D index value is depicted in Fig. 5.
Fig. 5.
Evolution of the mean EQ-5D 5L index value in both treatment groups. Values are anchored at 1 (full health) and 0 (a state as bad as being dead). The number of patients that completed the EQ5D questionnaire was depicted as (n = number of patients in the conservative group/number of patients in the surgical group).
3.2.6. Health economics
No data from the WPAI questionnaires is presented due to the small sample size, additional exclusion of non-reliable data and the small professionally active patient sample. The collected data from the WPAI questionnaires is available in Supplementary Table 4.
3.2.7. Surgical complications and other adverse events
Relevant surgical complications occurred in 2 of 14 patients (14.3%). One patient had a wound infection treated with antibiotics. In another patient, a postoperative hematoma was diagnosed without the need for revision surgery.
3.2.8. Electrodiagnostics
A conduction block was defined as a drop in compound motor action potential (CMAP) across the fibular head of more than 30%. During the screening visit, a conduction block was documented in 75% of conservative patients (9/12) and 72.7% of surgical patients (8/11). Three months later, these percentages dropped to 0.0% in the conservative group and 18.2% (2/11) in the surgical group. At 9 months, a conduction block was still observed in 18.2% (2/11) of surgical patients. At diagnosis, mean motor nerve conduction velocity decrement across the fibular head was 16.7 m/s (SD 10.7 m/s) in the conservative group and 9.90 m/s (SD 30.5 m/s) in the surgical group. After 9 months, the mean decrement in motor nerve conduction velocity was 1.55 m/s (SD 20.6 m/s), corresponding to a mean change in motor nerve conduction decrement across the fibular head of 14.7 m/s (SD 19.5 m/s). In the surgical group, mean motor nerve conduction decrement after 9 months was 4.5 m/s (SD 7.8 m/s), mean change in velocity decrement across the fibular head was 2.0 m/s (SD 28.7 m/s). In the conservative group, electromyography (EMG) abnormalities at rest were seen in 72.7% of cases (8/11) at diagnosis and in 12.5% (1/8) 9 months later. EMG abnormalities during voluntary contractions were noted in 90.9% (10/11) of patients in the same group at diagnosis and in 25.0% (2/8) of patients 9 months later. In the surgical group, EMG abnormalities at rest were seen in 72.7% of patients (8/11) and at the screening visit. EMG abnormalities during voluntary contraction were found in all patients. After 9 months, 27.3% (3/11) had EMG abnormalities in rest and 9.1% (1/11) had EMG abnormalities during voluntary contractions. Data from the nerve conductions studies and electromyography is summarized in Supplementary Table 5.
4. Discussion
This RCT aimed to compare conservative and surgical treatment for foot drop due to peroneal nerve entrapment but was terminated early due to recruitment challenges. Only 26 of the planned 182 patients were randomized in seven of 12 active study sites, far below the 90 anticipated by 2024, and notwithstanding a successful multicenter feasibility study (Oosterbos et al., 2023).
Recruitment issues stemmed from diverse challenges and these issues were well discussed among the principal investigators and funder prior to study termination. Little is known about the epidemiology and natural course of peroneal entrapment (Oosterbos et al., 2022a). Eligible patients were less frequently encountered than anticipated. Of all 52 eligible patients, 15 patients (28.8%) recovered prior to randomization (Fig. 1). Furthermore, almost 1 out of 5 eligible patients refused trial participation. Reasons for non-participation were frequently related to bias toward a specific treatment strategy or an unwillingness to be randomized. Both are well known phenomena in surgical RCTs (McCulloch et al., 2002). Potentially, some eligible patients were lost due to physician bias in clinical decision making, since daily practice is known to vary substantially (Oosterbos et al., 2022c). All together, centers were very infrequently confronted with study patients and study procedures never became part of a routine. Throughout the pilot study, slow recruitment was largely attributed to the global COVID-19 pandemic (Oosterbos et al., 2023), a finding not unique to the FOOTDROP trial (McDonald et al., 2023). We potentially overestimated the influence of the COVID-19 pandemic on trial recruitment. Not all participating centers were equally equipped to perform the study or experienced with data collection, further contributing to recruitment issues (McCulloch et al., 2002). Finally, we were unable to recruit in 20 centers as anticipated. This was largely due to the high administrative burden of performing a multicenter RCT, which was often not compatible with the busy schedule of a daily neurosurgical/neurological practice. Prior to site initiation, a feasibility questionnaire was completed to address these concerns. In future trials, even more attention should be paid to the administrative capacity of the participating study sites.
Despite early termination, the trial provides valuable prospective data. Indeed, we were able to report prospective outcome of both surgical and non-surgical treatment strategies throughout a long and thorough follow-up. Good outcome was reported in both treatment groups, with improvement in muscle strength, sensory function, gait and quality of life. Surgical patients had an MRC score ≥4 for ankle dorsiflexion in 75.0% and 83.3% at 9 and 18 months, respectively. Median MRC at final follow-up was 5. These numbers are comparable to the good outcome reported in the larger surgical case series (Oosterbos et al., 2022a; Broekx and Weyns, 2018; Tarabay et al., 2019). All patients in the conservative group reached an MRC score ≥4 for ankle dorsiflexion at 9 months, with all 7 patients reaching a MRC score of 5 at 18 months. These findings are comparable to the available data on conservative management (Oosterbos et al., 2022a; Aprile et al., 2007; Cruz-Martinez et al., 2000; Sangwan et al., 2004). The lack of a significant 6MWD difference suggests clinical equipoise, questioning the necessity and timing of neurolysis. The good outcomes in the conservative group do challenge the timing and added value of surgery in patients with foot drop due to peroneal nerve entrapment. This finding further supports the presence of clinical equipoise and should serve as a strong impetus for future trials, with reduced potential for physician bias compared to the pre-FOOTDROP trial context. Further studies are required to determine the place and timing of neurolysis in foot drop due to peroneal nerve entrapment, potentially through comparative effectiveness research. Given the observed rates of early recovery in the absence of surgical intervention, future studies should aim to identify patient subgroups that may derive benefit from surgical treatment. However, the present data are insufficient to support the identification of such subgroups. The etiology of peroneal nerve entrapment is multifactorial, with numerous established risk factors. The presence or absence of these risk factors may influence postoperative outcomes and may also help determine whether a patient is an appropriate surgical candidate. Furthermore, patients often present with multiple concomitant risk factors (Carolus et al., 2021), further adding to the complexity of this patient population.
4.1. Strengths and limitations
This is the first randomized controlled trial on the role of surgery in patients presenting with foot drop due to peroneal entrapment. We provide data on various parameters collected during the recovery period which adds epidemiological data on the long term outcome of this condition. The data presented is important to reduce publication bias in future systematic reviews and meta-analysis. The main limitation of this study is the sample size which was too small to detect any meaningful differences between both groups. Furthermore, since only 26 patients were randomized, groups were probably too small to be truly equal due to the randomization effect. Therefore all reported findings can only be considered exploratory and hypothesis generating. Reported results therefore do not suggest superiority of non-surgical treatment. Even though the surgical procedure is considered a standard procedure that should be performed competently by any appropriately trained surgeon, not all participating centers had dedicated peripheral nerve surgeons. This could potentially influence postoperative outcomes. The data presented in this research paper however, can help future researchers to avoid similar mistakes. Study results do not apply to all patients with peroneal neuropathy given the strict in- and exclusion criteria.
5. Conclusion
We report on the results of a randomized trial in patients with foot drop due to peroneal nerve entrapment. In this study we were unable to recruit the required sample size hampering a robust analysis of the data. Even though good outcome is reported after both conservative and surgical treatment, more research is warranted. Comparative effectiveness research could aid in establishing the place and timing of neurolysis of the peroneal nerve.
Declaration of competing interest
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Christophe Oosterbos and Tom Theys reports financial support was provided by KCE (Belgian Healthcare Knowledge Center). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
The FOOT DROP trial is funded by the Belgian Knowledge Health Care Centre (KCE) under the KCE Trials funding program (KCE19-1232).
Handling Editor: Dr W Peul
Footnotes
Supplementary data to this article can be found online at https://doi.org/10.1016/j.bas.2026.106160.
Appendix A. Supplementary data
The following are the Supplementary data to this article:
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