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Transcript of Sacral Neuromodulation
Restoring Function by Targeting Bladder-Brain Communication in Idiopathic OAB Patients
Leading Theories in Mechanism of ActionSacral NeuromodulationOverview of Overactive Bladder (OAB)2Sacral NeuromodulationMechanism of ActionCurrent scientific evidence supports the following concepts on the effect of SNM in OAB patients:Production of action potentials that modulate central nervous system (CNS) processing of bladder afferent inputModulation of abnormal afferent (sensory) activityNormalization of brain activityRestoration of bladder function3The International Continence Society Definition of OABOAB is diagnosed and defined based on symptoms1Urgency with or without urge incontinence, usually with frequency and nocturia, in absence of pathologic or metabolic factors to explain symptomsUrgency is defined as the complaint of a sudden compelling desire to pass urine, which is difficult to deferReference: 1. Abrams P, Cardozo L, Fall M, et al. Urology. 2003;61:37-49.4OAB is a Widespread Problem That is Expected to IncreaseApproximately 37.4 million adults in the United States have symptoms of OAB1,2Epidemiologic surveys suggest that the incidence of OAB rises as the population ages1
References: 1. Stewart WF, Van Rooyen JB, Cundiff GW, et al. World J Urol. 2003;20:327-336. 2. United Nations, Department of Economic and Social Affairs, Population Division (2011). World Population Prospects: The 2010 Revision, CD-ROM Edition. 3. Centers for Disease Control and Prevention (CDC). Air Pollution and Respiratory Health Branch, National Center for Environmental Health [asthma prevalence [asthma]. Atlanta, Georgia: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention; 2010. 4. National Diabetes Information Clearinghouse. National Diabetes Statistics, 2011. Atlanta, GA: U.S. Department of Health and Human Services. 5. Whitehead WE, Borrud L, Goode PS, et al. Gastroenterology. 2009;137:512-517. 6. National Osteoporosis Foundation. What is osteoporosis. www.nof.org/articles/7. Accessed October 25, 2012. 7. Alzheimers Association. Alzheimers facts and figures. www.alz.org/alzheimers_disease_facts_and_figures.asp. Accessed August 23, 2012. 5The Fundamental Cause of OAB May Be MultifactorialThe pathophysiology of OAB may depend on gender and age1Myogenic and neurogenic centric hypotheses have been proposed as causes of OAB1Functional MRI studies have shown diminished brain activity in certain regions, suggesting the central nervous system (CNS) plays a role in OAB1,2These hypotheses may not be mutually exclusive, and may vary across patient and disease types1
References: 1. Fowler CJ, Griffiths D, de Groat WC. Nat Rev Neurosci. 2008;9(6):453-466. 2. Griffiths D, Derbyshire S, Stenger A, Resnick N. J Urol. 2005;174:1862-1867. 6OAB Patients Have Altered Brain ResponsesAbnormal response in areas processing urge and social propriety1,2Diminished response in areas responsible for voluntary voiding1,2
References: 1. Griffiths D, Tadic SD. Neurourol Urodyn. 2008;27:466-474. 2. Griffiths D, Derbyshire S, Stenger A, Resnick N. J Urol. 2005;174:1862-1867.7Neurophysiology of the Bladder8The Lower Urinary Tract (LUT)Urine storage and micturition depend on the coordination of the bladder, bladder neck, urethra, and urethral sphincter1Coordination between the muscles of the LUT is mediated by neural pathways in the brain, spinal cord, and peripheral nerves1
Reference: 1. Fowler CJ, Griffiths D, de Groat WC. Nat Rev Neurosci. 2008;9(6):453-466.9
A Healthy LUT Requires Neural Coordination with the Spinal Cord and BrainAfferent pathways convey sensory information on bladder fullness1,2Efferent motor pathways respond, resulting in voluntary urine control3,4Dysfunction of the afferent neural pathways alters the balance of inhibitory and excitatory stimuli critical to voluntary bladder control5
References: 1. Andersson KE. Nat Clin Pract Urol. 2004;1(2):103-108. 2. Chancellor MB, Chartier-Kastler EJ. Neuromodulation. 2000;3(1):15-26. 3. Fowler CJ, Griffiths D, de Groat WC. Nat Rev Neurosci. 2008;9(6):453-466. 4. de Groat WC. Br J Pharmacol. 2006;147:S25-S40. 5. Leng WW, Morrisroe SN. Urol Clin N Am. 2006;33:491-501. 10Urine Storage Reflex11
Low-level afferent signals are organized in the spinal cord and promote urine storage via efferent signals from the CNS1,2References: 1. Fowler CJ, Griffiths D, de Groat WC. Nat Rev Neurosci. 2008;9(6):453-466. 2. de Groat WC. Br J Pharmacol. 2006;147:S25-S40. Urine Voiding Reflex A Positive Feedback Loop12References: 1. Andersson KE. Nat Clin Pract Urol. 2004;1(2):103-108. 2. Fowler CJ, Griffiths D, de Groat WC. Nat Rev Neurosci. 2008;9(6):453-466. 3. Leng WW, Morrisroe SN. Urol Clin N Am. 2006;33:491-501.High afferent signals are stimulated by intravesical pressure, resulting in increased activity to the brain1Descending efferent pathways then cause voluntary bladder contraction and the flow of urine2Normal voiding is, therefore, a function of a positive feedback mechanism3
Dysfunction of Afferent Signaling in OABOAB may be a result of increased, abnormal afferent activity, resulting in increased efferent signaling1Consequently, voluntary control of micturition is compromised113Reference: 1. Leng WW, Morrisroe SN. Urol Clin N Am. 2006;33:491-501.13Leading Theories in Mechanism of Action for Medtronic Sacral Neuromodulation1414Restoring Balance May Help OAB Patients15References: 1. Chancellor MB, Chartier-Kastler EJ. Neuromodulation. 2000;3(1):16-26. 2. Leng WW, Morrisroe SN. Urol Clin N Am. 2006;33:491-501. The goal of Sacral Neuromodulation (SNM) is to modulate the abnormal involuntary reflexes of the lower urinary tract and restore voluntary control.1,2MedtronicSNMInfection, inflammation, anatomic abnormalitiesInvoluntary Reflex MechanismsVoluntary Micturition ControlNeurologicaldiseases15
How Does Sacral Neuromodulation Work?Sacral Neuromodulation electrically stimulates somatic afferent nerves in a sacral spinal root and sends signals to the CNS that may restore normal bladder function1Activation of somatic afferent nerves alters bladder sensory pathways and inhibits reflex bladder hyperactivity116Reference: 1. Leng WW, Morrisroe SN. Urol Clin N Am. 2006;33:491-501.16Neurostimulator Implant SiteMedtronic Sacral Neuromodulation sends electrical stimulation to the sacral nerve via the InterStim System, which includes an implanted neurostimulator and leadThe sacral nerve, in particular, influences pelvic floor behavior and is believed to modulate neural reflexes117References: 1. Buback D. AORN J. 2001;73(1):176-190.
17Production of Action Potentials Modulate CNS Processing of Bladder Afferent InputThe neurostimulator provides an electrical charge to an area near the sacral nerve, resulting in altered neural activityThis stimulation likely depolarizes the nerve, causing an action potential1The signal propagates impulses along the axon as if the neuron had naturally fired an action potential1
18Reference: 1. Johnson M. Watson T, ed. Electrotherapy: Evidence-Based Practice. 12th ed. Elsevier; 2008:259-286.
Modulation of Abnormal AfferentActivity within CNSThe action potentials induced by electrical stimulation are thought to alterabnormal sensory input from the bladder1,2Efferent pathways are uninhibited so as not to suppress voluntary voiding3Unlike other therapies that target the bladder, bladder regulation occurs without directly influencing the bladder or sphincter muscles419References: 1. Johnson M. Evidence-Based Practice. 12th ed. Philadelphia, PA: Elsevier; 2008:259-286.2. Chancellor MB, Chartier-Kastler EJ. Neuromodulation. 2000;3(1):16-26. 3. Leng WW, Chancellor MB. Urol Clin N Am. 2005;32:11-18. 4. van der Pal F, Heesakkers JPFA, Bemelmans BLH. Curr Opin Urol. 2006;16:261-267. 19Normalization of Brain Activityin OAB Patients120Reference: 1. Blok BFM, Goen J, Bosch JLHR, et al. BJU Int. 2006;98:1238-1243. Areas involved in micturitionAreas involved in awareness and urge
20ConclusionsOAB is a common problem with a prevalence that is expected to increaseA healthy LUT is a result of a balance between sensory and motor signalingSensory signals convey information on bladder fullness via the sacral nerve and may be altered in OAB patientsMedtronic Sacral Neuromodulation delivers electrical stimulation to the sacral nerve which is thought to modulate abnormal sensory signalingSacral Neuromodulation is correlated with more normal patterns of brain activation in OAB patientsFurther research into the mechanisms of action of SNM may provide insights into the pathophysiology of OAB and lead to future improvements in neuromodulation therapies2121Sacral NeuromodulationMechanism of ActionCurrent scientific evidence supports the following concepts on the effect of SNM in OAB patients:Production of action potentials that modulate central nervous system (CNS) processing of bladder afferent inputModulation of abnormal afferent (sensory) activityNormalization of brain activityRestoration of bladder function
2222Important Safety InformationInterStim Therapy for Urinary Control is indicated for the treatment of urinary retention and the symptoms of overactive bladder, including urinary urge incontinence and significant symptoms of urgency-frequency alone or in combination, in patients who have failed or could not tolerate more conservative treatments. The following Warning applies only to InterStim Therapy for Urinary Control:Warning: This therapy is not intended for patients with mechanical obstruction such as benign prostatic hypertrophy, cancer, or urethral stricture.InterStim Therapy for Bowel Control is indicated for the treatment of chronic fecal incontinence in patients who have failed or are not candidates for more conservative treatments.
Contraindications for Urinary Control and for Bowel C