Oro-pharyngeal and Esophageal Motility and Dysmotility John E. Pandolfino, MD, MSci

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Oro-pharyngeal and Esophageal Department of Medicine Feinberg School of Medicine Northwestern University 1 Oro-pharyngeal and Esophageal Motility Function: Oropharynx Transfer food Prevent aspiration Breathing Speech Esophagus Transport food Prevent aspiration Prevent reflux 2 Stages of Swallow Oral Pharyngeal Esophageal Muscle type: Striated Striated Striated & smooth Nervous system: Cortex & medulla Medulla Medulla & ENS Volitional control: Complete Some Poor Sensation: Precise Good Poor 3 1

Disorders of Oro-pharyngeal and Esophageal Motility Histologic or pathologic descriptions of most of these disorders have been described These disorders are typically defined and diagnosed by motor patterns described on functional testing Fluoroscopy Manometry 4 Functional Imaging of Esophageal Peristalsis Flouroscopy 2.5 4.5 8.5 8.8 11. 5.6 7.1 13. 5 Functional Imaging of Esophageal Peristalsis Manometry 4 mmhg 4 mmhg 1 mmhg 1 mmhg Manometric port Manometric sleeve 4 mmhg mmhg 2 2.5 4.5 5.6 7.1 8.5 8.8 11. 13. 6 2

Functional Imaging of Esophageal Peristalsis High-Resolution Manometry 4 mmhg Manometric port 2.5 4.5 5.6 7.1 8.5 8.8 11. 13. 7 Functional Imaging of Esophageal Peristalsis Esophageal Pressure Topography Pressure mmhg Clouse Plot 11 9 7 5 3 Manometric port 1 2.5 4.5 5.6 7.1 8.5 8.8 11. 13. -1 8 Combined High-Resolution Manometry and Impedance HRIM: The Best of Both Worlds 3

High-Resolution Manometry Esophageal Pressure-Impedance Topography 1 Esophageal Pressure Topography of the UES Basal UES pressure Distance from nares (cm) 11 Upper Esophageal Sphincter Relaxation Fluoroscopy and Pressure Topography.5.7 1 2 Pharynx 1. 1.5 UES.5 1 1.5 2 2.5 3 Cm 4 5 6 7 Esophagus 2. Adapted Williams RB et al., Am J Physiol 21; 281: G129 12 4

Oro-pharyngeal Motility and Oro-pharyngeal Dysphagia 13 Functional Elements of a Swallow Oral and Pharyngeal Nasopharyngeal Laryngeal closure vestibule closure UES opening Bolus propulsion GI Motility online (May 26), doi:1.138/gimo2 Pharyngeal clearance Return to airway 14 Central Nervous System Control of Swallowing Cortex Brain stem Central Pattern Generator (CPG) Motor neurons Swallowing muscles Sensory receptors in oro-pharynx, larynx, esophagus MSP 37/12/4 PPvOM4 PJK Aziz & Thompson; Gastroenterology 1998; 114: 559 15 5

Oro-pharyngeal Dysphagia Impaired transit of food from the mouth to the esophagus Mechanical Propulsive Symptoms Aspiration Cough Nasopharyngeal regurgitation 16 Conditions Associated with Oro-pharyngeal Dysphagia Structural Strictures Osteophytes Tumors Post-surgical Trauma Caustic Congenital Propulsive Myopathy Peripheral neuropathy CNS (CVA, polio, ALS, etc.) Post-surgical 17 Patterns and Manifestations of Oro-pharyngeal Dysphagia Mechanical Element Tongue loading & Bolus propulsion Biomechanical Mechanism Lingual sensation and control Evidence of Dysfunction Sluggish, misdirected bolus Typical Diseases Parkinson's Surgical defects Cerebral palsy Nasopharyngeal closure Soft palate elevation Nasopharyngeal regurgitation Nasal voice Myasthenia Gravis Laryngeal closure Laryngeal elevation Arytenoid tilt Vocal fold closure Aspiration CVA Head Trauma UES opening UES relaxation Laryngeal elevation Anterior hyoid traction Sphincter distension Dysphagia Post-swallow residue Aspiration Diverticulum formation Cricopharyngeal Bar CVA Parkinson's Pharyngeal clearance Pharyngeal shortening Pharyngeal contraction Epiglottic flip Post-swallow residue Aspiration Polio Post-polio Oculopharyngeal dystrophy CVA 18 6

UES Obstruction / Cricopharyngeal Bar Cricopharyngeus Esophagus Trachea 19 mmhg UES Relaxation: CP Bar Increased Intrabolus Pressure Pharynx 35 1 3 25 2 2 15 1 UES 3 4 Cm 5 5-5 6 1 2 3 4 5 7 Esophagus 2 mmhg UES Relaxation: CP Bar After Dilation Pharynx 35 1 3 25 2 2 15 1 UES 3 4 Cm 5 5-5 6 1 2 3 4 5 7 Esophagus 21 7

Esophageal Motility and Esophageal Dysphagia 22 Pressure Topography of Esophageal Motility Clouse Plots: Anatomy 5 First Segment UES Proximal Esophagus 11 1 Transition Zone 9 Location along lumen (cm) 15 2 25 Second Segment Third Segment Distal Esophagus Fourth Segment 7 5 3 EGJ 1 3 s Deglutitive EGJ relaxation window 35 5 1 15 2 Time (s) -1 23 Peristalsis in Striated Muscle Portion of the Esophagus Nucleus ambiguus Striated muscle Smooth muscle Stimulus 24 8

Central Control of Peristalsis in the Smooth Muscle Portion of the Esophagus Dorsal motor nucleus of vagus Rostral Caudal Vagus nerve Preganglionic neuron LES Stimulus 25 5 Parallel Inhibitory and Excitatory Innervation of the Esophageal Smooth Muscle Dorsal motor nucleus of vagus Rostral Caudal Vagus nerve Preganglionic i neurons Ach (+) Ach (+) Postganglionic neuron NO/VIP/ATP (-) Smooth muscle Ach (+) 26 Gradient of Excitatory and Inhibitory Nerves in the Smooth Muscle Esophagus UES Striated muscle Cholinergic-Excitatory Smooth muscle Non-cholinergic-Inhibitory Cholinergic-Excitatory LES Stimulus Non-cholinergic-Inhibitory 27 9

Abnormal Gradient of Excitatory and Inhibitory Nerves Augmented Contractions UES Striated muscle Cholinergic-Excitatory Smooth muscle LES Stimulus Non-cholinergic-Inhibitory Cholinergic-Excitatory Non-cholinergic-Inhibitory 28 Abnormal Gradient of Excitatory and Inhibitory Nerves Simultaneous Contractions UES Striated muscle Cholinergic-Excitatory Smooth muscle Cholinergic-Excitatory LES Stimulus 29 Abnormal Gradient of Excitatory and Inhibitory Nerves Reduced Contractility UES Striated muscle Smooth muscle LES Stimulus 3 1

EGJ Anatomy and Pressure Morphology Excitatory Myogenic Inhibitory Inhibitory Excitatory GI Motility online (May 26) doi:1.138/gimo14 31 HRM EGJ Pressure Morphology Pressure (mmhg) Length along esophagus (cm) 4 2 Time (s) Pandolfino JE et al., Am J Gastroenterol 27; 12: 156 32 Sliding and Paraesophageal Hiatus Hernia Squamocolumnar Junction Phrenoesophageal Membrane Esophagus Herniated Stomach Esophagus Herniated Gastric Fundus Herniated Parietal Peritoneum Diaphragm Diaphragm Squamocolumnar Junction (normal position) 33 11

Pressure Topography of Esophageal Motility Anatomy (EGJ morphology) Len ngth along esophagus (cm) Length along esophagus (cm) 25 3 I 35 35 2 25 3 35 IIIa 35 3 6 9 12 3 6 9 12 time (sec) time (sec) Pressure (mmhg) 2 3 1 4 5 2 25 3 2 25 3 II IIIb RIP 34 35 Pressure Topography of Esophageal Motility Classification Scheme * may represent an Achalasia variant 36 12

Absent Peristalsis No continuous pressure domain > 3 mmhg isobaric contour EMD 7 8/15/7 PPvOM4 PJK Pandolfino JE, et al., Am J Gastroenterol 27; In Press 37 Peristaltic Dysfunction (Hypotensive) 3 cm defect in the 3 mmhg isobaric contour Normal Intact CFV CFV Pandolfino JE, et al., Am J Gastroenterol 28; 13: 27 38 High-Resolution Manometry Esophageal Pressure-Impedance Topography Defect size and IBT 39 13

Peristaltic Weakness Transition Zone Defect Ghosh SK; Neurogastroenterol Motil. 28 Dec; 2 (12): 1283-9 4 What Esophageal Manometry Can Do 41 Hypertensive Peristalsis (Amplitude >18mmHg) Spastic Nutcracker, DCI >8, mmhg s cm Pressure Topography Conventional line tracings Pandolfino JE, et al., Am J Gastroenterol 28; 13: 27 42 14

Pressure Topography of Esophageal Motility Spasm Diagnosis Distal esophageal spasm Normal EGJ relaxation and rapid CFV (spasm) with 2% of swallows Focal- Only one segment 43 Clinical Evolution of Achalasia Early Chronic Late Netter Atlas 44 Classic Achalasia Aperistalsis, impaired EGJR, dilated esophagus Pressure Topography Plot Landscape plot 3 4 6 1 5 7 8 1 2 9 11 time (sec) Pandolfino JE et al., Gastroenterology 28 Nov; 135 (5): 1526-33 45 15

Achalasia with Esophageal Compression Aperistalsis, impaired EGJR, Panesophageal pressurization Pressure Topography Plot Landscape plot 3 4 6 1 5 7 8 1 2 9 11 time (sec) Pandolfino JE et al., Gastroenterology 28 Nov; 135 (5): 1526-33 46 Spastic Achalasia Impaired EGJR, 2% Spastic contractions Pressure Topography Plot Landscape plot 3 4 6 1 5 7 8 1 2 9 11 time (sec) Pandolfino JE et al, Gastroenterology 28 Nov; 135 (5): 1526-33 47 Response Rates of Achalasia Treatments 83 patients categorized by pressure topography subtype Achalasia Intervention Type I Classic Type II Compression Type III Spasm All Types Botulinum toxin % (/2) 86% (6/7) 22% (2/9) 39% (7/18) Pneumatic dilation 38% (3/8) 73% (19/26) % (/11) 53% (24/45) Heller Myotomy 67% (4/6) 1% (13/13) % (/1) 85% (17/2) All (any) interventions 44% (7/16) 83% (38/46) 9% (2/21) 56% (47/83) Subsequent Intervention Number of interventions 1.3 1.5 1.2 ±.4* 2.4 ± 1. 1.8 ±.7 Successful last intervention 56% 96%* 29%* 71% Last intervention type B-,P-1,M-6 B-6,P-25,M-15 B-8,P-8,M-5 B-14,P-43,M-26 *P<.5 vs. Type I, p<.5 vs. Type III Pandolfino JE et al., Gastroenterology 28 Nov; 135 (5): 1526-33 48 16

Functional Obstruction PFV >8cm/s 2 trapped Intrabolus pressure 5 1 15 2 time (sec) 49 Pressure Topography of Esophageal Motility Classification Scheme * may represent an Achalasia variant 5 Summary Oro-pharyngeal and Esophageal Motor Disorders are defined using High-Resolution Manometry and/or Fluoroscopy Treatments focus on improving bolus clearance or reducing abnormal contractility in the body and lower esophageal sphincter of the esophagus Outside of Achalasia, treatment success is limited Future therapies are now focusing on reducing perception and altering sensitivity Medication Cognitive behavioral therapy 51 17

Thank You Peter Kahrilas Monika Kwiatek Sudip Ghosh Research Team at Northwestern Memorial Hospital Gastrointestinal Motility Online www.nature.com/gimo/index.html 52 53 18