Post on 28-Mar-2020
Interstitial Cystitis and Chronic Pelvic Pain: Interstitial Cystitis and Chronic Pelvic Pain: Case report and search for reliefCase report and search for relief
Chad Baxter, MDChad Baxter, MDPelvic Medicine and Reconstructive SurgeryPelvic Medicine and Reconstructive Surgery
Department of UrologyDepartment of UrologyDavid Geffen School of Medicine at UCLADavid Geffen School of Medicine at UCLA
Los Angeles, CaliforniaLos Angeles, California
Case of Refractory ICCase of Refractory IC
43 year old woman with 4 year history of43 year old woman with 4 year history of……Urinary frequency every 20 Urinary frequency every 20 –– 30 minutes, q130 minutes, q1--2hrs at night2hrs at nightPain with increasingly full bladderPain with increasingly full bladderIntermittentIntermittent dyspareuniadyspareuniaNo anatomic abnormality (urethralNo anatomic abnormality (urethral diverticulumdiverticulum, pelvic organ, pelvic organ prolapseprolapse, , pelvic mass, etc.)pelvic mass, etc.)No history of infection (HPV, STD, UTI)No history of infection (HPV, STD, UTI)CystoscopicCystoscopic evaluation normalevaluation normalUrodynamicsUrodynamics reveal sensory urgency, low capacity, no suggestion of reveal sensory urgency, low capacity, no suggestion of neuropathologyneuropathology
Case Study: Refractory ICCase Study: Refractory IC
Symptoms not alleviated bySymptoms not alleviated by……Diet modificationDiet modificationFluid and caffeine restrictionFluid and caffeine restriction
Physical therapy with biofeedbackPhysical therapy with biofeedback
AnticholinergicAnticholinergic therapytherapyAmitriptyleneAmitriptylene,, gabapentingabapentin,, ElmironElmironIntravesicalIntravesical anestheticsanestheticsNarcoticsNarcotics
Intravesical BotoxIntravesical BotoxCystoscopyCystoscopy withwith hydrodistentionhydrodistention
Defining the target:Defining the target:
Interstitial Cystitis (IC) and Chronic Pelvic Pain (CPP) are pooInterstitial Cystitis (IC) and Chronic Pelvic Pain (CPP) are poorly defined rly defined conditionsconditionsEstimated prevalence of 0.5 to 1.0%Estimated prevalence of 0.5 to 1.0%
Typically present withTypically present with……Poorly localized, but generallyPoorly localized, but generally suprapubicsuprapubic painpainIncreased pain with bladder fillingIncreased pain with bladder fillingUrinary urgency, frequencyUrinary urgency, frequencyNo identifiable etiologyNo identifiable etiology
Refractory to treatments, includingRefractory to treatments, including cystectomycystectomy with urinary diversionwith urinary diversionSignificantly diminished quality of lifeSignificantly diminished quality of life
Etiologic TheoriesEtiologic Theories
Primary bladder injuryPrimary bladder injury
IncreasedIncreased urothelialurothelial permeabilitypermeability
Increased inflammatory mediatorsIncreased inflammatory mediators
UpregulationUpregulation of neural pain pathwayof neural pain pathway
Increased CNS sympathetic activityIncreased CNS sympathetic activity
DysregulationDysregulation of HPA axisof HPA axis
Persistent pain beyond presence of inciting agentPersistent pain beyond presence of inciting agent
Etiologic TheoriesEtiologic Theories
Normal afferent input to CNS, no bladder pathologyNormal afferent input to CNS, no bladder pathology
Primary sensitization of central pathwaysPrimary sensitization of central pathwaysEmotional distress, prior trauma, other medical disease, etc.Emotional distress, prior trauma, other medical disease, etc.Normal pelvic sensation misinterpreted asNormal pelvic sensation misinterpreted as aberrentaberrent and painful (and painful (allodyniaallodynia))Evidence for centralEvidence for central hyperresponsivenesshyperresponsiveness to visceral related threat in IC to visceral related threat in IC patients.patients.
TwissTwiss
C, Kilpatrick L,C, Kilpatrick L,
CraskeCraske
M, et al: Increased startle responses in interstitial cystitis:M, et al: Increased startle responses in interstitial cystitis:
evidence for centralevidence for central
hyperresponsivenesshyperresponsiveness
to visceral related threat. Jto visceral related threat. J
UrolUrol. 181(5):2127. 181(5):2127--3333
Creation of rat modelCreation of rat model
Water avoidance distressing of ratsWater avoidance distressing of ratsPre and postPre and post--distressdistress urodynamicsurodynamics
IncreasedIncreased micturitionmicturition frequencyfrequencyDecreased latency to voidDecreased latency to voidDecresedDecresed voided volumevoided volume
HistologyHistologyIncreased bladderIncreased bladder vascularityvascularity in stressed animalsin stressed animalsDecreased brainDecreased brain--derivedderived neurotrophicneurotrophic factor (BDNF) expressionfactor (BDNF) expression
This novel stress model is the first nonThis novel stress model is the first non--invasive method to stimulate urinary invasive method to stimulate urinary frequency and urgencyfrequency and urgency
InterventionIntervention
EtiologyEtiology remainesremaines elusive and interventions empiric and ineffectiveelusive and interventions empiric and ineffective
Similar to other chronic pain conditions, allopathic treatment tSimilar to other chronic pain conditions, allopathic treatment targets the endargets the end--organ andorgan and dysregulateddysregulated nervous systemnervous system
Patients remain dissatisfied with treatment and seek alternativePatients remain dissatisfied with treatment and seek alternativess
Physicians frustrated by lack of efficacious treatment, exhaustiPhysicians frustrated by lack of efficacious treatment, exhausting patient ng patient interactionsinteractions
PROCAIMPROCAIM
UCLA School of Public Health and UCLA Center forUCLA School of Public Health and UCLA Center for NeurovisceralNeurovisceral Sciences Sciences and Womenand Women’’s Health database: s Health database:
People Reported Outcomes of Complimentary, Alternative, and IntePeople Reported Outcomes of Complimentary, Alternative, and Integrative grative Medicine (PROCAIM)Medicine (PROCAIM)
Patient recruitmentPatient recruitmentAlternative care providersAlternative care providersInternet support groups and society webInternet support groups and society web--sitessitesCraigCraig’’s List, major newsprint outlets, etc.s List, major newsprint outlets, etc.
Access PROCAIM website, complete onAccess PROCAIM website, complete on--line validated questionnaires line validated questionnaires www.www.procaimprocaim.org.org
PROCAIM and IC/CPP PatientsPROCAIM and IC/CPP Patients
Invited to analyze 275 patients with IC/CPPInvited to analyze 275 patients with IC/CPPTreated byTreated by
Prescription, OTCPrescription, OTCAllopathicAllopathicReikiReikiYogaYogaFrequency SpecificFrequency Specific MicrocurrentMicrocurrentMassageMassagePTPT
ChiropracticChiropracticMeditationMeditationAcupunctureAcupunctureHerbalistHerbalistPsychologyPsychologyPsychiatryPsychiatryHomeopathyHomeopathyAyurvedicAyurvedic
PROCAIM and IC/CPP PatientsPROCAIM and IC/CPP Patients
Completed treatment history, Early Trauma Inventory at enrollmenCompleted treatment history, Early Trauma Inventory at enrollmentt
Completed validated surveys at enrollment and q3monthsCompleted validated surveys at enrollment and q3months……..Health Survey SFHealth Survey SF--3636Patient Health QuestionnairePatient Health QuestionnaireHospital Anxiety and DepressionHospital Anxiety and DepressionPerceived Stress ScalePerceived Stress ScaleCoping Strategies/Coping Strategies/CatastrophizingCatastrophizingBrief Pain InventoryBrief Pain Inventory
PROCAIM and IC/CPP PatientsPROCAIM and IC/CPP Patients
Enrollment and analysis ongoingEnrollment and analysis ongoingNo clear beneficial treatment for IC/CPPNo clear beneficial treatment for IC/CPPDatabase an inadequate tool for this analysisDatabase an inadequate tool for this analysis
Convenience sampleConvenience samplePatientPatient--reported diagnosesreported diagnosesNo confirmatory interaction with patientsNo confirmatory interaction with patientsNot significantly powered to answer questions of efficacyNot significantly powered to answer questions of efficacy
Despite limitationsDespite limitations……..Early trauma increases symptom severity and diminishes quality oEarly trauma increases symptom severity and diminishes quality of life in f life in IC and CPP patientsIC and CPP patients
Excellent medium for honing skills of statistical analysis!Excellent medium for honing skills of statistical analysis!
Case Study: Refractory ICCase Study: Refractory IC
NeuromodulationNeuromodulation (NMS) successfully used for chronic pain conditions(NMS) successfully used for chronic pain conditions……Migraines, back pain, idiopathic angina pectorisMigraines, back pain, idiopathic angina pectoris
NMS via 3rd sacral foramina (S3) efficacious for refractory urinNMS via 3rd sacral foramina (S3) efficacious for refractory urinary urgency ary urgency and refractory urinary retention (mechanism unknown)and refractory urinary retention (mechanism unknown)Surreptitiously found S3 NMS to ameliorate some IC/CPP symptomsSurreptitiously found S3 NMS to ameliorate some IC/CPP symptoms
Alo
KM,
Holsheimer
J (2002) New trends in
neuromodulation
for the management of
neuropathic
pain. Neurosurgery 50:690–703.
Whitmore KE, Payne CK,
Diokno
AC,
Lukban
JC (2003) Sacral
neuromodulation
in patients with interstitial cystitis: a
multicenterclinical trial.
Int Urogynecol
J Pelvic Floor
Dysfunct
14:305–308, discussion 308–309
Peters KM,
Konstandt
D (2004) Sacral
neuromodulation
decreases narcotic requirements in refractory interstitial cystitis. BJU
Int
93:777–779
Case Study: Refractory ICCase Study: Refractory IC
Traditional placement of unilateral NMS via S3 foramen.
Indicated for refractory urgency/frequency syndromes and idiopathic urinary retention.
Novel caudalNovel caudal
neuromodulationneuromodulation
technique for technique for IC/CPPIC/CPP
Devised method of NMS overlying S2-S4 nerve roots bilaterally.
Rationale:
Pain transmitted via multiple spinal levels
Pain transmitted viaunmyelinated C-fibers, exacerbated viaupregulation of these fibers.
Does not address additional recruitement of sympathetic fibers in chronic pain (e.g.hypogastric plexus)
Novel caudalNovel caudal
neuromodulationneuromodulation
technique for IC/CPPtechnique for IC/CPP
Rationale (continued)
Inability to capture dysfunctional pain foci in unilateral, focal therapy
Modulation of several spinal levels likely to more effectively captureabherrent signaling
Each lead independently programmable
Bilateral leads allows for crossover electrical fields, bipolar stimulation, or unilateral as desired
May expand and contract electrical field, decrease motor and sensory side effects
Still cannot capture hypogastric plexus
Early Outcomes of CaudalEarly Outcomes of Caudal
NeuromodulationNeuromodulation
23 consecutive patients (16 female, 7 male)23 consecutive patients (16 female, 7 male)Average f/u 15 months (6 to 32)Average f/u 15 months (6 to 32)Average age 46.3Average age 46.3All refractory cases, exhausted pain All refractory cases, exhausted pain management servicesmanagement services57% on daily narcotics57% on daily narcotics
Zabihi
N,
Mourtzinos
A, Maher M,
Raz
S, Rodriguez R: Short-term results of bilateral S2-S4 sacral
neuromodulation
for treatment of refractory interstitial cystitis, painful bladder syndrome, and chronic pelvic pain. Int.
Urogyn. J (2008) 19: 553-557
Early Outcomes of CaudalEarly Outcomes of Caudal
NeuromodulationNeuromodulation
Validated outcomes questionnaires:
IC Symptom Index (ICSI)
IC Problem Index (ICPI)
Urogenital Distress Inventory (UCI-6)
RAND Health Survey SF-36
Visual analog pain scale
Improved 35% (p=0.005)
Improved 38% (p=0.007)
Improved 26% (p=0.05)
No significant change
Improved 40% (p=0.04)
Early Outcomes of CaudalEarly Outcomes of Caudal
NeuromodulationNeuromodulation
5 of 23 devices removed5 of 23 devices removed1 for infection1 for infection4 for loss of efficacy4 for loss of efficacy
Significant, durable effect in 18 of 23 (78%) and all off of narSignificant, durable effect in 18 of 23 (78%) and all off of narcoticscotics
Now performed more than 75 caudal NMS proceduresNow performed more than 75 caudal NMS procedures
Preparing longPreparing long--term f/u to assess efficacy, durability, plasticity of term f/u to assess efficacy, durability, plasticity of neural response, etc.neural response, etc.
Case of Refractory ICCase of Refractory IC
43 year old woman with 4 year history of43 year old woman with 4 year history of……Urinary frequency was every 20 Urinary frequency was every 20 –– 30 minutes, now q330 minutes, now q3--4 hours4 hoursResolution of pain with bladder fillingResolution of pain with bladder fillingRequired postRequired post--operative reoperative re--programming 3 timesprogramming 3 timesWill require battery change in approximately 6Will require battery change in approximately 6--8 years (outpatient surgery)8 years (outpatient surgery)
Future of CaudalFuture of Caudal
NeuromodulationNeuromodulation
Randomize to unilateral v. bilateral stimulationRandomize to unilateral v. bilateral stimulationRandomize to intermittent or continuousRandomize to intermittent or continuous stimstim..Obtain postoperative videoObtain postoperative video urodynamicsurodynamics ($)($)
Thank youThank you
Chad Baxter, MDChad Baxter, MDPelvic Medicine and Reconstructive SurgeryPelvic Medicine and Reconstructive Surgery
Department of UrologyDepartment of UrologyDavid Geffen School of Medicine at UCLADavid Geffen School of Medicine at UCLA
Los Angeles, CaliforniaLos Angeles, California