Mechanisms of Action on Rectal Motricity of Intrarectal Botulinum Toxin Injections

Inclusion Criteria:

• Active or predominantly active fecal incontinence with failure of 1st-lineconservative treatments (normalization of transit, perineal re-education)

• Impairment of quality of life at investigator's discretion

• Patients at least 18 years of age

• Patients who have read and understood the information letter and signed the consentform

• Patients affiliated to the French Social Security system

• Women of childbearing age using effective contraception (Cf. CTFG) (estro-progestins or intrauterine device or tubal ligation) for at least 1 month and anegative B-HCG urine pregnancy test at inclusion and for the duration of the study.

• Postmenopausal women: confirmatory diagnosis (non-medically induced amenorrhea forat least 12 months prior to inclusion visit)

Exclusion Criteria:

General

• Pregnant women, women in labor, breastfeeding women, or women without provencontraception

• Patient deprived of liberty by administrative or judicial decision, or protectedadult (under guardianship or trusteeship)

• Exclusive passive fecal incontinence

• Patient suffering from constipation (Rome IV criteria)

• Patient with an evolving inflammatory or cancerous digestive pathology

• Previous rectal surgery

• Person participating in another research protocol or having participated in anotherresearch protocol in the 4 weeks preceding the inclusion visit

Linked to botulinum toxin injections

• Hypersensitivity to botulinum toxin or to one of the excipients (human albumin,sodium chloride)

• Neuromuscular junction pathology (myasthenia, Lambert-Eaton syndrome, etc.)

• Presence of infection at injection site(s)

• General anesthesia less than one month ago

• Association with aminoglycosides and anti-cholinesterase agents (risk of increasedtoxin effects)

• History of neurogenic damage such as polyradiculoneuritis

• History of dysphagia with esophageal or neurological stasis, swallowing disorders,inhalation pneumonitis

• Botulinum toxin injections in the 3 months preceding the study

• Clinical anal examination suggestive of anorectal abscess

• Recent history (<12 months) of myocardial infarction and/or rhythm disorders notreduced by appropriate treatment

• Peripheral motor neuropathies (such as amyotrophic lateral sclerosis or motorneuropathy) and underlying neurological disorders

• Current treatment with anticoagulants or anti-aggregants or haemostasis disordersaccording to recommendations (SFED). When patients are on anticoagulant oranti-aggregant therapy, the type of injections to be performed depends on the typeof anticoagulation and the patient's thrombo-embolic risk:

• Patients on anticoagulant or anti-aggregant therapy with a major thrombo-embolicrisk will not be included.

• Patients on anticoagulant or anti-aggregant therapy with a moderate or lowthrombo-embolic risk may be included. If patients are taking a vitamin K antagonist,treatment will be continued provided that the INR is within the usual range of 2 to 3 (GETED, HAS, 2008). If patients are taking anti-aggregants, these can be continued (SFED, HAS, 2012). If patients are taking new oral anticoagulants, they should takea short break and not take the AOD the evening before or the morning of theinjections (GIHP, 2015).

Linked to rectosigmoidoscopy

• Local pathology preventing colonoscopy (anal stenosis)

• Allergy or hypersensitivity to silicone and/or latex

Linked to laxatives

• Contraindication to DULCOLAX® 5 mg, gastro-resistant coated tablet

• Contraindication to XIMEPEG®, powder for oral solution

Linked to high-resolution manometry

• Clinically diagnosed intestinal obstruction

• Severe coagulopathy or oral anticoagulants

• Cardiac disorders for which vagal stimulation is poorly tolerated