After diagnosis of Chronic Exertional Compartment Syndrome (CECS), the participants will be referred to both physical therapy and Botox injection. In physical therapy, the therapist will perform strength measurements of the lower leg (ankle plantarflexion and dorsiflexion) which will be repeated 2 months following the injection. An ultrasound-guided injection of 50 units of Botox will be administered into the tibialis anterior. 25 units will be injected into two different spots in the muscle one being more proximal and the other distal. This will be a one-time injection and will be observed as to how it effects participant symptoms over the next 6 months at either a clinic visit (at 2 months) or telephone call (at 4 and 6 months after injection) via the University of Wisconsin Running Index. Two months following the injection, the participant will undergo repeat measurements of strength using the Kiio Force Sensor.

Should potential participants of childbearing potential wish to enroll in the study, a urine pregnancy test will be performed prior to enrollment; participants will not be enrolled if test is positive.

Chronic exertional compartment syndrome (CECS) is an overuse injury first described by Mavor in 1956 that typically affects young endurance athletes, classically distance runners. CECS occurs primarily in the lower leg, predominantly in the anterior compartment, although it has been reported elsewhere in the body.

The pathophysiology of CECS is not completely understood. Similar to acute compartment syndrome, it is thought to result from increased pressure within the restrictions of the fascial planes of a muscle compartment. Exercise increases blood flow to active muscles causing them to expand. If constricted by surrounding noncompliant fascia, such swelling increases pressure within the muscle compartment. Ultimately, pressure within the compartment reduces blood flow leading to muscle ischemia and pain when metabolic demands cannot be met. Several studies have demonstrated decreased blood flow and oxygenation in the legs of symptomatic patients with CECS.

Cessation of inciting activities resolves symptoms in most cases of CECS. Without this cessation, the prognosis for CECS is poor if treated non-operatively. Should symptoms continue, patients are referred for possible muscle compartment release, currently the most widely accepted treatment approach despite a significant number of treatment failures. To date, no alternative non-operative approach has successfully treated refractory symptoms.

Recently, it has been hypothesized that botulinum toxin could reduce intramuscular pressure in CECS . Isner-Horoboti et al, performed abobotulinum toxin A injections into the anterior and anterior/lateral compartments in 16 individuals with a mean follow up of 4.4 months (range 3-6 months). Fifteen (95%) patients were asymptomatic after intervention with fourteen (88%) exhibiting normalized post-exercise compartment pressures. Using manual muscle testing, they determined that 11 patients displayed decreased strength though did not produce noticeable subjective weakness. A later case report by Baria and Sellon presented the first long-term follow up (14 months) of a CECS case treated with botulinum toxin injections (Botox) in which the patient reported continued pain relief and had resumed her active lifestyle without adverse effects.

The proposed investigation will aim to build upon the results of existing studies. The novelty of this approach involves a differing dosage of the toxin (Botox) into a more targeted muscle group, specifically the tibialis anterior, while also utilizing a smaller dosage than in previous studies. Further, while previous studies have used manual muscle testing to test strength, many studies have found this method unreliable. As such, a Kiio force sensor will be used at multiple time points to determine weakness quantitatively. Lastly, the reliable and validated University of Wisconsin Running Index will be used to evaluate return to sport.

After diagnosis of CECS, the participants will be referred to both physical therapy and Botox injection. In physical therapy, the therapist will perform strength measurements of the lower leg (ankle plantarflexion and dorsiflexion) which will be repeated 2 months following the injection. An ultrasound-guided injection of 50 units of Botox into the tibialis anterior will be performed. 25 units will be injected into two different spots in the muscle, one being more proximal and the other distal. This will be a one-time injection that will be monitored to see how it effects participant symptoms over the next 6 months at either a clinic visit (at 2 months) or telephone call (at 4 and 6 months after injection) via the University of Wisconsin Running Index. Two months following the injection, the participant will undergo repeat measurements of strength using the Kiio Force Sensor.

Should potential participants be of childbearing potential wish to enroll in the study, a urine pregnancy test will be performed prior to enrollment; participants will not be enrolled if test is positive.

Inclusion Criteria:

• Willing to provide written informed consent
• Willing to comply with all study procedures and be available for the duration of the study including reliable use of telephone for communication
• Male or female, at least 18 years of age
• Documented diagnosis of CECS
• Females of childbearing potential must have a negative urine pregnancy test prior to enrollment and agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to enrollment and for the duration of study participation. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: Has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Be involved, either competitively or non-competitively, in an activity requiring significant running as determined by the PI

Exclusion Criteria:

• History of hypersensitivity or allergy to any of the study drugs or drugs of similar chemical classes
• Known neuromuscular disease
• Known pulmonary disease including but not limited to asthma, pneumonia, or upper respiratory tract infection
• Dysphagia
• Known cardiac disease including but not limited to congestive heart failure, arrhythmia, or history of myocardial infarction
• History of lower extremity fasciotomy
• Enrolled in another clinical trial or has used any investigational drugs, biologics, or devices within 30 days prior to enrollment
• Currently or have taken in the past medications that affect neuromuscular function: aminoglycosides, muscle relaxants, or other botulinum neurotoxin agents
• Women who are pregnant or breast-feeding
• Vulnerable populations
• Not suitable for study participation due to other reasons at the discretion of the investigator