Digesve Woes in Myotonic Dystrophy

Linda Nguyen, MD Director, Neurogastroenterology and Molity Clinical Assistant Professor Stanford University Overview

• GI symptoms in DM • Diagnosc tesng • Treatment opons – General disease specific therapies – DM specific treatments (if available) GI Symptoms in Muscular Dystrophy

• GI symptoms present in approximately 30-60% of paents • GI symptoms may precede diagnosis of muscular dystrophy – IBS like symptoms: abdominal pain/cramping • 25% felt GI symptoms most disabling

Ronnblom A et al. Scand J Gastroenterol 1996;31:654-647 Common GI Problems Symptoms Clinical Condions Difficulty Chewing, Swallowing or - Oropharyngeal dysphagia Coughing while eang (52-62%) - Esophageal dysmolity - Acid reflux and Voming - - Acid reflux Abdominal pain (45-62%) - Gastroparesis/Pseudoobstrucon - - Sphincter of Oddi dysfuncon Conspaon (55-62%) - Slow transit conspaon - Anal spasm - - Bacterial overgrowth - Bile salt malabsorpon Fecal inconnence - Weak anal sphincter Dysphagia

• Difficulty swallowing/choking • Most commonly reported symptom • No correlaon between peripheral muscle symptom severity and esophageal symptoms

Ronnblom A et al. Scand J Gastroenterol 1996;31:654-647 Symptoms

• Difficulty swallowing: Food geng stuck – Myotonia of the face, tongue, jaw – Pharyngeal weakness (Weak swallow) – /narrowing (Complicaon of acid reflux) – Muscle spasms of the lower • Aspiraon: Coughing/Pneumonia – Pharyngeal weakness (weak swallow) – Weak Upper esophageal sphincter – Acid Reflux • Chest pain Esophageal Tesng

• Video fluoroscopy • Esophageal Manometry (Swallow Study) Esophageal Tesng

• Endoscopy • Esophageal pH tesng Treatment of Swallowing Problems

• Speech therapy • Dietary changes: mechanical chopped, so, thick liquids • Feeding tube (especially if aspirang, weight loss) Treatment of GERD

• Dietary changes – Avoid: acidic foods, spicy foods, fay foods, caffeine, alcohol – Remain upright 3 hours aer eang • Elevate the head of the bed • Acid suppression therapy • Reglan Gastroparesis

• Slow stomach emptying • DM paent have slower gastric emptying compared to healthy controls – Even without symptoms • Symptoms: Nausea, voming and/or abdominal pain (aer eang) • May be worsening acid reflux Diagnosing Gastroparesis: Gastric Emptying Study

Delayed Gastric Emptying Normal Gastric Emptying Treatment of Gastroparesis

• Dietary changes – Low fat diet (fat slower to digest) – Low fiber (avoid “roughage”) – Small frequent meals • Stay hydrated with electrolytes – Gatorade – Pedialyte Available Treatment Opons for Gastroparesis

• Dopamine antagonists (D2-receptor): reglan, domperidone

• Serotonin agonist 5-HT4 (i.e. tegaserod, cisapride) • Cholinergic agonists (i.e. Neosgmine, bethanechol) • Macrolides-molin agonist: erythromycin, azithromycin – Improves gastric emptying with minimal affect on symptoms Meganty et. al. Am J Gastroenterol 2003 • Intrapyloric • Jejunal feeding tube • Gastric electrical smulaon Treatment of Gastroparesis

• Therapies reported/studied in DM – Metoclopramide (N=16): increases gastric emptying – Erythromycin (N=10): did not improve gastric emptying or symptoms except diarrhea – Cisapride (no longer available) Intesnal Pseudoobstrucon Chronic Intesnal Pseudoobstrucon

• Disordered small bowel molity (neuropathic or myopathic) leading to obstrucve-like symptoms and dilated bowel – Distension – 75% – Abdominal pain – 58% – Nausea - 49% – Conspaon - 48% – Heartburn/regurgitaon – 46% – Fullness – 44% – Epigastric pain/burning – 34% – Early saety – 37% – Voming – 36% Stanghellini V et al. Gut 1987 Diagnosing CIP

• Imaging (Xray, CT) • Small bowel – Avoid barium studies manometry Treatment of CIP

• AVOID UNNECESSARY SURGERY • Nutrional support, IV hydraon, decompression • Evaluate and treat small intesnal bacterial overgrowth (if present) • Promolity agents – Erythromycin/Azithromycin – Domperidone or metoclopramide – Octreode – Cholinergic agonist: Neosgmine, pyridosgmine, bethanechol Conspaon Conspaon Impairs Quality of Life

• HRQoL is impaired in paents with DM • GI Factors associated with decreased QOL – Conspaon – Gallstones

Peric S et al. Clinical Neurology and Neurosurgery 2013;115:270 Defining

Chronic constipation must include 2 or more of the following:

During at least 25% of

Sensation of Manual Sensation of < 3 Lumpy or anorectal maneuvers to Straining incomplete defecations hard stools obstruction/ facilitate evacuation per week blockage defecations

• Loose stools are rarely present without the use of • Insufficient criteria for

*Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis Longstreth GF et al. . 2006;130:1480-1491.

Causes of Conspaon in DM

• Slow colon transit – Altered colonic smooth muscle acvity – Abnormal enteric nervous system funcon – Autonomic dysfuncon – Decreased mobility • Anal sphincter dysfuncon (up to 90%) – Inability to relax anal sphincter with straining – Difficulty with defecaon/excessive straining Diagnosc Tesng

• Sitz marker study • Pelvic floor funcon in DM

• Low to Normal resng sphincter pressure • Weaker squeeze pressure • Myotonic contracon of the anal sphincter following the rectoanal inhibitory reflex (RAIR) • Pelvic (Anismus)

Lecointe-Besancon et al. Dig Dis Sci 1999;44:1090 Treatment of Conspaon

• Non-medical Therapy – Exercise – Diet • Medical Therapy – Fiber – Laxaves/Stool soeners – Promolity or prosecretory agents • Surgery Soluble vs. Insoluble Fiber

• Total Fiber intake 20-30 grams per day – Too much fiber can cause excessive bloang and gas • Soluble Fiber = aracts water and forms a gel slowing gastric emptying – Dried beans, oats, oat bran, rice bran, barley, citrus fruits, apples, strawberries, peas, potatoes • Insoluble Fiber = adds bulk to stool increasing colonic transit – Wheat bran, whole grains, cereals, seeds, skins on fruits and vegetables Medical Therapies

• Fiber (if diet insufficient) • Osmoc laxaves (lactulose, magnesium citrate, Miralax) • Smulant laxave (bisacodyl, senna, glycerin) • Prosecretory agents (lubiprostone, linaclode) • Suppositories/Enema- help with rectal evacuaon

Treatment of Defecatory Disorders

• Pelvic floor dysfuncon – therapy • Teach relaxaon of pelvic floor • Colostomy • or – Surgery Principles of Biofeedback

• Push with <50% of maximal force • Kegel exercises – Helps develop awareness of pelvic floor muscles • Abdominal exercises • Timing BMs aer meals and when urge present • Forward leaning or Squang posion – Facilitates whole body relaxaon • Stop trying aer 10-15 minutes Diarrhea

• Malabsorpon – Bacterial overgrowth • Treatment: Anbiocs and probiocs – Bile salt malabsorpon • Treatment: cholestyramine • Fecal impacon with overflow – Treatment: fiber, laxaves • Medicaons Gallstones

• Present in 25-50% of DM paents • Results from poor gallbladder funcon • Causes abdominal pain aer eang • Treatment – Surgery (cholecystectomy) – Ursodeoxycholic acid (Ursodiol): 8-10 mg/kg/d • Dissolves small gallstones at a rate of 1 mm/month • Prevents complicaons i.e. cholecyss Summary

• GI symptoms are common in paents with DM • GI symptoms can precede the diagnosis of DM • Symptoms can present gradually • DM can affect the GI tract from the mouth to the • Treatment opons are limited but available Take Home Points

• GI symptoms affect quality of life (QOL) • Symptomac treatment can improve symptoms and QOL • Targeted tesng can help guide therapy • Roune GI quesonnaires/assessments should be a part of regular DM care