Sacral Neuromodulation
Restoring Function by Targeting Bladder-Brain
Communication in Idiopathic OAB Patients
Leading Theories in Mechanism of Action
Overview of
Overactive Bladder (OAB)
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Sacral Neuromodulation
Mechanism of Action
Current 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 OAB
OAB 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 Multifactorial
The 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, ChartierKastler 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
•
•
•
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
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.
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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
• The goal of Sacral
Neuromodulation (SNM)
is to modulate the
abnormal involuntary
reflexes of the lower
urinary tract and
restore voluntary
control.1,2
Infection, inflammation,
anatomic abnormalities
Voluntary Micturition
Control
Involuntary Reflex
Mechanisms
Medtronic
SNM
Neurological
diseases
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.
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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 Afferent
Activity within CNS
•
•
•
The action potentials induced by electrical stimulation are thought to alter
abnormal 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 Activity
in OAB Patients1
Areas involved in micturition
Areas involved in awareness and urge
Reference: 1. Blok BFM, Goen J, Bosch JLHR, et al. BJU Int. 2006;98:1238-1243.
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Conclusions
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•
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
Sacral Neuromodulation
Mechanism of Action
Current 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 Information
InterStim® 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
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