Sacral Neuromodulation

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Restoring Function by Targeting Bladder-Brain Communication in Idiopathic OAB Patients Leading Theories in Mechanism of Action Sacral Neuromodulation

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Sacral Neuromodulation. Restoring Function by Targeting Bladder-Brain Communication in Idiopathic OAB Patients Leading Theories in Mechanism of Action. Overview of Overactive Bladder ( OAB). Sacral Neuromodulation Mechanism of Action. - PowerPoint PPT Presentation

Transcript of Sacral Neuromodulation

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Restoring Function by Targeting Bladder-Brain Communication in Idiopathic OAB Patients

Leading Theories in Mechanism of Action

Sacral Neuromodulation

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Overview of Overactive Bladder (OAB)

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Sacral 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 input• Modulation of abnormal afferent (sensory) activity• Normalization of brain activity• Restoration of bladder function

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The International Continence Society Definition of OABOAB is diagnosed and defined based on symptoms1

• Urgency with or without urge incontinence, usually with frequency and nocturia, in absence of pathologic or metabolic factors to explain symptoms

• Urgency is defined as the complaint of a sudden compelling desire to pass urine, which is difficult to defer

Reference: 1. Abrams P, Cardozo L, Fall M, et al. Urology. 2003;61:37-49.

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OAB is a Widespread Problem That is Expected to Increase• Approximately

37.4 million adults in the United States have symptoms of OAB1,2

• Epidemiologic 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. Alzheimer’s Association. Alzheimer’s facts and figures. www.alz.org/alzheimers_disease_facts_and_figures.asp. Accessed August 23, 2012.

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The Fundamental Cause of OAB May Be MultifactorialThe pathophysiology of OAB may depend on gender and age1

• Myogenic and neurogenic centric hypotheses have been proposed as causes of OAB1

• Functional MRI studies have shown diminished brain activity in certain regions, suggesting the central nervous system (CNS) plays a role in OAB1,2

• These 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.

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OAB Patients Have Altered Brain Responses

Abnormal response in areas processing urge and

social propriety1,2

Diminished 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.

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Neurophysiology of the Bladder

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The Lower Urinary Tract (LUT)

• Urine storage and micturition depend on the coordination of the bladder, bladder neck, urethra, and urethral sphincter1

• Coordination 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.

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A Healthy LUT Requires Neural Coordination with the Spinal Cord and Brain• Afferent pathways convey

sensory information on bladder fullness1,2

• Efferent motor pathways respond, resulting in voluntary urine control3,4

• Dysfunction 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.

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Urine Storage Reflex

• Low-level afferent signals are organized in the spinal cord and promote urine storage via efferent signals from the CNS1,2

References: 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.

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Urine Voiding Reflex –A Positive Feedback Loop

References: 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 brain1

• Descending efferent pathways then cause voluntary bladder contraction and the flow of urine2

• Normal voiding is, therefore, a function of a positive feedback mechanism3

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Dysfunction of Afferent Signaling in OAB

• OAB may be a result of increased, abnormal afferent activity, resulting in increased efferent signaling1

• Consequently, voluntary control of micturition is compromised1

Reference: 1. Leng WW, Morrisroe SN. Urol Clin N Am. 2006;33:491-501.

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Leading Theories in Mechanism of Action for Medtronic Sacral Neuromodulation

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Restoring Balance May Help OAB Patients

References: 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.1,2 Medtronic

SNM

Infection, inflammation, anatomic abnormalities

Involuntary Reflex Mechanisms

Voluntary Micturition Control

Neurologicaldiseases

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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 function1

• Activation of somatic afferent nerves alters bladder sensory pathways and inhibits reflex bladder hyperactivity1

Reference: 1. Leng WW, Morrisroe SN. Urol Clin N Am. 2006;33:491-501.

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Neurostimulator Implant Site

• Medtronic Sacral Neuromodulation sends electrical stimulation to the sacral nerve via the InterStim® System, which includes an implanted neurostimulator and lead

• The sacral nerve, in particular, influences pelvic floor behavior and is believed to modulate neural reflexes1

References: 1. Buback D. AORN J. 2001;73(1):176-190.

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Production of Action Potentials Modulate CNS Processing of Bladder Afferent Input• The neurostimulator provides

an electrical charge to an area near the sacral nerve, resulting in altered neural activity

• This stimulation likely depolarizes the nerve, causing an action potential1

• The signal propagates impulses along the axon as if the neuron had naturally fired an action potential1

Reference: 1. Johnson M. Watson T, ed. Electrotherapy: Evidence-Based Practice. 12th ed. Elsevier; 2008:259-286.

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Modulation of Abnormal AfferentActivity within CNS

• The action potentials induced by electrical stimulation are thought to alterabnormal sensory input from the bladder1,2

• Efferent pathways are uninhibited so as not to suppress voluntary voiding3

• Unlike other therapies that target the bladder, bladder regulation occurs without directly influencing the bladder or sphincter muscles4

References: 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.

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Normalization of Brain Activityin OAB Patients1

Reference: 1. Blok BFM, Goen J, Bosch JLHR, et al. BJU Int. 2006;98:1238-1243.

Areas involved in micturition Areas involved in awareness and urge

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Conclusions• OAB is a common problem with a prevalence that is expected to increase

• A healthy LUT is a result of a balance between sensory and motor signaling

• Sensory signals convey information on bladder fullness via the sacral nerve and may be altered in OAB patients

• Medtronic Sacral Neuromodulation delivers electrical stimulation to the sacral nerve which is thought to modulate abnormal sensory signaling

• Sacral Neuromodulation is correlated with more normal patterns of brain activation in OAB patients

• Further research into the mechanisms of action of SNM may provide insights into the pathophysiology of OAB and lead to future improvements in neuromodulation therapies

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Sacral 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 input• Modulation of abnormal afferent (sensory) activity• Normalization of brain activity• Restoration of bladder function

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Important 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 Control: Diathermy. Patients who have not demonstrated an appropriate response to test stimulation or are unable to operate the neurostimulator. Precautions/Adverse Events: For Urinary Control: Safety and effectiveness have not been established for bilateral stimulation; pregnancy, unborn fetus, and delivery; pediatric use under the age of 16; or for patients with neurological disease origins such as multiple sclerosis. For Bowel Control: Safety and effectiveness have not been established for bilateral stimulation; pregnancy, unborn fetus, and delivery; pediatric use under the age of 18; or for patients with progressive, systemic neurological diseases. For Urinary Control and for Bowel Control: The system may be affected by or adversely affect cardiac devices, electrocautery, defibrillators, ultrasonic equipment, radiation therapy, MRI, theft detectors/screening devices. Adverse events include pain at the implant sites, new pain, lead migration, infection, technical or device problems, adverse change in bowel or voiding function, and undesirable stimulation or sensations, including jolting or shock sensations. For full prescribing information, please call Medtronic at 1-800-328-0810 and/or consult Medtronic’s website at www.medtronic.com. Product technical manual must be reviewed prior to use for detailed disclosure. USA Rx Only. Rev 0409