A 60-Year-Old Man with a 34-Year History of Chronic Exertional Compartment Syndrome and 3 Previous Surgical Fasciotomies, Successfully Treated with Injection of Botulinum Toxin

Background

Chronic compartment syndrome, often referred to as chronic exertional compartment syndrome (CECS), is a condition of pain following exercises of repeated motions. It usually presents as anterior leg pain in runners or in the arms of baseball pitchers. CECS is a diagnosis of exclusion, although intracompartmental pressure monitoring is the criterion standard [1–4]. Initial treatment is conservative with exercise reduction, physical therapy, limb taping, and gait retraining [5]. Classically, surgical decompression via fasciotomy is the next step if conservative measures fail; however, recent studies show botulinum toxin may be an effective alternative to surgery in this clinical context. Putatively regarded as definitive, surgery is rarely completely curative in practice, as CECS recurs in 50–80% of such patients in after a fasciotomy [6,7].

Patients with post-fasciotomy CECS recurrence have not been well-studied historically. A repeat fasciotomy is not ideal because the operation will be technically complicated, due to scar formation following the first operation; furthermore, they will have aged and potentially accrued more comorbidities after the initial operation [8,9]. If conservative measures fail, their post-fasciotomy recurrent CECS progresses until they develop significant baseline debilitation that warrants surgical intervention [9].

The absence of an evidence-based, non-surgical interventional therapy for post-fasciotomy CECS recurrence is responsible for the suffering and disease progression in these patients. Until 2 recent studies showed that intramuscular botulinum toxin injections provide symptom relief in surgically naïve patients, there has not been an evidence-based non-surgical therapy for CECS [10,11]. Both of those cohort studies focused only on the initial interventional CECS patients, who were all surgically naïve.

In this case report, we present the first known case of botulinum toxin being used to treat a patient with post-fasciotomy recurrent CECS. Our patient was a 60-year-old man with a 34-year history of CECS with 3 previous surgical fasciotomies (all were 4-compartment fasciotomies with fasciectomies) who presented with posterior calf pain (CECS typically affects the anterior and lateral leg compartments) and mobility issues that impacted his activities of daily living. Just 2 weeks after an intramuscular injection with onabotulinumtoxinA (BTX-A), his baseline mobility issues resolved and at 31-month follow-up he reported he was able to complete his activities of daily living without issues.

Case Report

A 60-year-old male former triathlete presented in 2020 to our clinic with a 2-month history of bilateral posterolateral calf pain at rest refractory to conservative measures, tingling, and a cold sensation in both feet. He also had a history of multiple near-falls when descending stairs, which in conjunction with his pain, limited his ability to walk. His symptoms occurred in the setting of a 34-year history of CECS, 33 years after his first fasciotomy.

The patient was first diagnosed with CECS in 1986, when he presented with bilateral calf pain at rest that markedly worsened on exertion and returned to baseline within 10–20 minutes of rest. His symptoms did not improve with rest, ice, and non-steroidal anti-inflammatories. His presentation was most consistent with CECS, and was further supported by a negative workup for competing etiologies, including multiple sclerosis and peripheral artery disease.

After minimally-invasive management strategies – dry needle nerve denervation and intramuscular steroid injections – failed to improve symptoms, a bilateral 4-compartment open fasciotomy was performed in 1987 [12]. As a post-op rehabilitation plan was not yet standard of care, he resumed his usual running regimen just 10 days later.

Six years later, his exertional symptoms returned (1993) and were attributed to post-fasciotomy CECS recurrence after intracompartmental pressures were found to be >15 mmHg at rest, per the Pedowitz criteria [1]. A repeat bilateral 4-compartment fasciotomy was performed but was complicated by intraoperative bleeding with hematoma formation that required each leg to be operated on separately. Following a post-operative rehabilitation plan, he returned to recreational running and was asymptomatic until his symptoms returned in 2003. Over the next 8 years, they progressed to lifestyle-limiting resting pain. Surgery was considered on multiple occasions but deferred due to his hematoma complications and expected degree of post-surgical scarring. When his resting pain became intolerable in 2010, intracompartmental pressures were again found to be elevated (>15 mmHg at rest in all compartments bilaterally) and confirmed post-fasciotomy recurrent CECS. In early 2011, he underwent bilateral 4-compartment fasciotomy with bilateral partial fasciectomies in the anterolateral and posteromedial planes, superficial peroneal neurolysis, and release of the soleus from the tibia. His surgery and post-surgical rehabilitation were uncomplicated, and he returned to his normal activities.

His chronic exertional pain recurred in 2019 and progressed over the year. He presented to our clinic in 2020 with tingling in the anterior leg bilaterally, difficulty walking, and a history of multiple near-falls when descending stairs due to his toes catching the steps. On examination at rest, he had a non-antalgic gait with bilaterally soft calf compartments and palpable posterior tibialis pulses. Sensation to light touch was intact in both of his lower extremities. He had normal, 5/5 strength throughout both legs; however, he had hypertrophy of the gastrocnemius and experienced posterior calf cramping upon plantar flexion.

Given the exertional nature of his symptoms with now-persistent pain at rest, we surmised that he had progressive recurrent CECS, for which he was interested in non-surgical intervention [10,11,13–16]. A total of 150 units of BTX-A in a concentration of 100 units: 1 mL was injected into each leg, in 50-unit aliquots into the medial gastrocnemius, lateral gastrocnemius, and lateral compartment.

At his 9-month virtual follow-up with us, he reported that he was symptom-free and had no mobility issues during his vacation that took place 2 weeks after the injections. Furthermore, he reported that he continued to be symptom-free at rest and had no issues descending stairs during this 9-month interval. He also noted that he would be pain-free at a walking pace of about 2 miles per hour but would have posterior calf pain when walking at a faster pace of 4 miles per hour.

At a 31-month virtual appointment with an orthopedic surgeon in December 2022, he was still able to comfortably complete his activities of daily living. However, he noted a recurrence of his rest pain and decrease in the range of motion in both ankles that began about 9 months after the botulinum toxin injections. A tentative surgical plan was made for a gastrocnemius muscle release either endoscopically or as part of a larger repeat fasciotomy, pending an in-person evaluation in early 2023.

Discussion

For post-fasciotomy CECS recurrence, onabotulinumtoxinA (BTX-A) is an effective treatment, as our case shows. Our patient’s presentation of posterior calf pain and mobility issues impacting activities of daily living are both atypical presentations of CECS but highlight the many ways this condition can present. The resolution of his mobility issues within 2 weeks, without the need for a complex post-procedural rehabilitation plan, shows that BTX-A injections have a rapid onset to symptom relief and can be an excellent treatment option for patients in need of immediate relief of debilitating symptoms. Furthermore, his mobility issues remain resolved 31 months after the injection, showing that this treatment modality provides long-term benefit of debilitating symptoms. However, the return of his rest and exertional pain at 9 months shows that BTX-A injections are not a permanent solution for recurrent CECS. Whether additional injections at the 9-month interval or a repeat fasciotomy would provide this patient greater benefit remains an open question, likely best answered by randomized clinical trials.

The approach to of CECS has changed little since the condition was first described in 1945 [17]. Surgical decompression remains the criterion standard treatment upon failing conservative measures, consisting of activity restrictions, physical therapy, and gait retraining. Putatively, surgery is regarded as definitive; however, the data on long-term outcomes is limited. There are just 10 longitudinal trials tracking patients for over 1 year: 2 trials have 2-year follow-up [18,19], 5 have 4-year [20–24], 2 have 5-year [25,26], and 1 has 10-year [27]. Across all those studies, the success rate of controlling all rest and exertional symptoms varies from 50% to 80% [6,7]. Surgery, therefore, is far from definitive management over a patient’s lifespan, particularly when patients are first diagnosed and operated on as young adults. Non-surgical alternatives are needed.

Botulinum toxin is one such treatment, and there is a limited but growing body of evidence to support its efficacy and safety. A PubMed search for “compartment syndrome botulinum toxin,” yielded 29 publications, only 5 of which were about chronic exertional compartment syndrome. Two were cohort studies which each had 16 patients [10,11], 5 were case reports of which 4 described leg injections [13–16], and 1 described a hand injection in a post-fasciotomy patient [28]. Collectively, these 5 papers described a total of 37 patients, of whom 33 had leg symptoms and 4 had hand symptoms. Except for the case report of hand injections [28], the other 36 patients were surgically naïve, and botulinum toxin injections were used for the initial management of their symptoms. The primary symptoms for all 36 patients were exertional with negligible symptoms when not exercising. No patient was reported to have had mobility issues with activities of daily living, only upon exercising.

In all of these studies of botulinum toxin for the initial treatment of CECS, all patients began to experience some symptom relief within 1 month. Some patients – particularly younger patients with mild symptoms—had no recurrence of symptoms at 6 months [10]. One case report showed complete symptom relief for up to 14 months – the longest follow-up interval recorded [13]. However, in patients who experienced recurrent symptoms, recurrence began to occur about 4–6 months after the injection [11]. Our patient’s experience – relief of his most debilitating symptoms within 2 weeks and return of exertional and resting pain symptoms at 9 months after injection – is similar to that reported in the literature. However, his symptoms of posterior calf pain and mobility issues at baseline make him truly unique, as none of the 36 patients previously studied had those symptoms. His positive response to BTX-A injections shows that this treatment modality suggests that BTX-A addresses the underlying pathophysiology of CECS, although the exact mechanism by which botulinum toxin alleviates CECS symptoms is not completely known [16].

To the best of our knowledge, this case report is the first to show the effectiveness of BTX-A in recurrent CECS of the legs many years after surgical treatment and may serve as a reference point for future physicians as a safe, alternative treatment between conservative and surgical intervention. Future work is needed to define optimal dosing strategies and timing of injections for a wider range of patients. While we caution against generalizing the results of a single case, our case highlights the potential for a safe, non-surgical treatment with long-term relief, warranting further investigation.

Currently, there are no published randomized controlled trials on the outcomes of botulinum toxin injections for CECS treatment. In the interim, while our institute is currently running such a trial with open enrollment, our case extends the literature by showing that BTX-A injections are therapeutic for patients with post-fasciotomy recurrent CECS.

Conclusions

For patients with post-fasciotomy recurrent CECS, botulinum toxin can treat debilitating mobility issues that impact a patient’s ability to perform activities of daily living. Symptom relief began just 2 weeks after the injection and persisted for over 31 months.