Transcript Intramuscular Electrical Stimulation for Hemiplegic Shoulder Pain

Percutaneous Peripheral
Nerve Stimulation (PNS) for
Hemiplegic Shoulder Pain
John Chae, MD
Objectives
• Describe the development of percutaneous
PNS for the treatment of hemiplegic shoulder
pain
• Assess the efficacy of percutaneous PNS in
reducing hemiplegic shoulder pain
• Discuss potential mechanisms of action
Disclosures
Investigational device
SPR Therapeutics
• Consultant
• Chief Medical Advisor
• Received sponsored research support
Funding from NIH
Where did it all start?
• New Jersey Medical
School (Fall, 89)
• Elective rotation in PMR
at Kessler
• Senior resident: “John,
if you can find a
solution to hemiplegic
shoulder pain you will
change the field of pain
management!”
Hemiplegic Shoulder Pain
High incidence and prevalence:
• Among all new strokes: ~25%
(150,000) at 6-mo;
• Among all (old and new)
stroke survivors: ~10%
(600,000)
Associated with:
• Poor motor recovery
• Poor functional recovery
• Poor quality of life
Muscle Atrophy
Weakness
Mechanical
Instability
Stroke
Spasticity
Surface
ES
Periosteal
traction
Pain
Subluxation
Joint
malalignment
Reduced ROM
Scapular
malrotation
Micro and
macro trauma
Immobility
Capsulitis
Complex
Regional
Pain
Syndrome
Capsule
Inflammation/
degeneration
Tendonitis
Tendinosis
Muscle
tears
Bursitis
Sheffler and Chae, Muscle Nerve, 2007
Tendons
Muscles
Bursa
Surface Electrical Stimulation
Best Practice
Not the Standard of Care
• There is strong evidence that
“Functional electrical stimulation
improves muscle function, pain,
subluxation, and range of motion
of the hemiplegic shoulder.”
(Teasell et al., Top Stroke Rehabil
2003)
• Corroborated by:
– VA/DoD Practice Guidelines
(2005)
– Ottawa Panel Evidence-based
Clinical Practice Guidelines
for Post-stroke rehabilitation.
(2006)
• Unable to tolerate 6-hrs of
stimulation per day for 6-wks
• Need for skilled personnel for:
– Reliable electrode placement
– Adjustment of stimulation
parameters to facilitate
tolerance and minimize
fatigue
Percutaneous PNS using
Intramuscular Nerve (IMN™) therapy
1994:
Insertion Needle
with Electrode
in Lumen
Stimulating Insulated Lead
Tip
• Not painful
• Low frequency (12Hz)
• No daily electrode placement
• No adjustment of parameters
NIA P60A6104184
CAUTION: Investigational device. Limited by Federal law
to investigational use.
Percutaneous PNS
Case Report
59 YOM, 18.5 months post-onset of hemiplegia
Shoulder Subluxation
Shoulder Pain
AFFECTED SIDE PRE-TREATMENT
UNAFFECTED SIDE
19 mm
POST-6 WEEK
TREATMENT
5 mm
3-MONTH
FOLLOW-UP
Time
(weeks)
BPI – NRS
(0 -10)
Baseline
7
6 (post-treatment)
4
18 (3-mo FU)
0
52 (1-yr FU)
0
2 mm
Chae et al,, Am J Phys Med Rehabil 2001; 80: 296 - 301
Published Percutaneous PNS Studies
Demonstrate Clinical Feasibility
Case Report:
Case Series 1; N=8
(NIA P60A6104184)
Chae et al, Am J PMR
2001
(NICHD R43HD34996;
NICHD K12HD010973)
Yu et al., Arch PMR
2001; 82: 20-25
8
7
Stimulation “on”
Pain Rating
6
5
4
Case Series 2; N=15
3
(NeuroControl)
2
Renzenbrink and
Ijzerman, Clin Rehabil
2004; 18: 359-65
1
0
0
5
10
15
Weeks
20
25
30
4-lead, Percutaneous PNS
Multi-center RCT
Subjects
• N = 61 at 6 US sites
• Chronic stroke survivors
• Shoulder pain
• Subluxation
Treatment Protocol
• 4-lead PNS vs. conventional Tx
• 6h/day x 6-wks of PNS
• 12-mo FU
Endpoints
NeuroControl Corporation,
• Primary outcomes: Pain & Safety
R44HD34996, K12HD010973
• Secondary outcomes: QoL, Subluxation,
motor impairment, ADLs, spasticity, ROM
CAUTION: Investigational device. Limited by Federal law to investigational use.
Pain relief maintained for at least 12-months after
Stimulation Turned Off
Brief Pain Inventory
– Pain Intensity
BPI 12
Treatment
(Stim ON)
Post-treatment
(Stim OFF)
EOT
12-mo
8
7
6
5
4
3
2
1
0
*
0
3-mo
*
6-mo
F=21.2, p<0.001
F=21.2
*
5
P<0.001
10
*
15
Months from Treatment Onset
Months from Treatment Onset
ITT PNS
ITT Control
Yu et al, Arch PMR 2004; Chae et al, Am J Phys Rehabil 2005
PP PNS
PP Control
4-lead, Percutaneous PNS
Multi-center RCT
Safety & Efficacy
• No serious adverse events
• Significant pain reduction
• Maintained to at least 12-mo after stimulation turned off
• Significant improvement in pain related QOL
Mechanism – No Effect On:
• Subluxation
• Motor impairment
• ADLs
• Spasticity
• Pain free ROM
Clinical Implementation
• 4-lead procedure was challenging for some investigators
Uncertainty…
Uncertainty….
Back Together Again….
Do we need 4 leads?
Can we simplify the procedure?
• Supraspinatus rarely
produced strong contractions
• Trapezius did not cross the
glenohumeral joint
• Middle and posterior deltoids
consistently produced strong
contractions
• Can a single electrode
activate both posterior and
middle deltoid?
• No need for tunneling
• Shorter procedure time
Single-lead, Percutaneous PNS
SPR Therapeutics; NICHD K24HD045600
Subjects
• N = 8 at 1 US site
• Chronic (>6mos) stroke survivors
• Hemiplegic Shoulder pain (BPI3 > 4)
• With or without Subluxation
Treatment Protocol
• 1-lead PNS case series
• 6h/day x 3-wks of PNS
• 4-wk FU (protocol) & 12-wk FU (clinical)
Endpoints
• Primary outcomes: Pain (BPI) & Safety
• Secondary outcomes: QoL (SF-36), ROM
Pain interference (BPI), Patient global
impression of change (PGIC)
CAUTION: Investigational device. Limited by Federal law to investigational use.
Single-lead, Percutaneous PNS
SPR Therapeutics; NICHD K24HD045600
Implant
F=11.0, p<0.001
* Explant
*
*
Stimulation
*
Single-lead as Effective as 4-leads
Single-lead Case Series
Observations
 Safety: No significant adverse events, including no infection
 Efficacy:
 Significant post-stroke shoulder pain reduction
 Significant improvement in QOL
 Dosage: 3-wks of stimulation appears to be as effective as 6wks of stimulation in reducing pain at end of treatment
 3 subjects without subluxation experienced significant pain
reduction
 5 subjects exhibited clinical evidence of subacromial bursitis or
supraspinatus impingement at baseline based on positive
Neer’s sign and test
Single-lead, Percutaneous PNS System
Technology
Percutaneous Lead, External Stimulator & Patch
Lead Placement
Procedure
•
•
•
•
Therapy
Percutaneous, intramuscular placement near peripheral nerve
Short out-patient procedure (<30 min)
Placed by non-surgeon
Lead: Specifically designed to be anchored in muscle
Extensive clinical use with excellent safety profile
Easily removed after therapy
3-weeks of stimulation therapy
Commercially
available stimulator
used during Study
CAUTION: Investigational
device. Limited by Federal
law to investigational use.
SMARTPATCH™
System by
SPR Therapeutics
23
CNS Sensitization (-)
PNS
Muscle Atrophy
Weakness
Mechanical
Instability
Stroke
Spasticity
Subluxation
Joint
malalignment
Reduced ROM
Scapular
malrotation
Micro and
macro trauma
Immobility
Periosteal
traction
Pain
Capsulitis
Complex
Regional
Pain
Syndrome
Capsule
Inflammation/
degeneration
Tendonitis
Tendinosis
Muscle
tears
Bursitis
Tendons
Muscles
Bursa
Mechanism of PNS Therapy
• Percutaneous PNS will activate directly low threshold (large
diameter) primary afferents
-Ia – muscle spindle receptor afferents
-Ib – Golgi tendon organ afferents
-synchronous activation at stimulation frequency (12 Hz)
• Activity in large diameter afferents inhibits transmission of pain
signals at the spinal cord; Gate theory (Melzack & Wall 1962, 1965)
-
Spikes/Bin
In
Spinothalamic
Tract
Neurons
Noxious stimulation
Peripheral Nerve
Stimulation
Chung et al., 1984
Mechanism of PNS Therapy
• Percutaneous PNS will activate directly:
– Efferents: low thresholds (large diameter) α-motoneuron efferents
– Causing muscle contraction
• Muscle Contraction will activate indirectly:
– Ia and Ib primary afferents
– II joint capsule and cutaneous afferents
– asynchronous physiological activation
• Dis-Sensitization: Pain relief produced by PNS Therapy outlasts the
period of stimulation
– 3-wks of stimulation produced pain relief for at least 12-wks after EOT
– physiological activity in afferents reverses the processes and
consequences of sensitization
Summary
• Described the development of percutaneous
PNS for the treatment of hemiplegic shoulder
pain
• Assessed the efficacy of percutaneous PNS in
reducing hemiplegic shoulder pain
• Discussed potential mechanisms of action
Acknowledgements: Funding
Sponsor
Number
Start
End
NIH-NIA
P60A6104184
12-1-95
11-30-97
NIH-NICHD
R43HD34996
1-1-97
6-30-97
NIH-NICHD
K12HD010973
7-1-95
6-30-00
NIH-NICHD
R44HD34996
9-1-98
8-30-00
NeuroControl
Sponsored Clinical Trial
1-1-00
6-30-03
NIH-NICHD
K24HD045600
3-2-07
2-29-12
SPR Therapeutics
Sponsored Clinical Trial
4-1-09
3-30-10
NIH-NICHD
R01HD059777
9-1-09
8-30-11
Thank You!
Percutaneous PNS
Case Report
59 YOM, 18.5 months post-onset of hemiplegia
Shoulder Subluxation
Shoulder Pain
AFFECTED SIDE PRE-TREATMENT
UNAFFECTED SIDE
19 mm
POST-6 WEEK
TREATMENT
5 mm
3-MONTH
FOLLOW-UP
Time
(weeks)
BPI – NRS
(0 -10)
Baseline
7
6 (post-treatment)
4
18 (3-mo FU)
0
52 (1-yr FU)
0
2 mm
Chae et al,, Am J Phys Med Rehabil 2001; 80: 296 - 301
Percutaneous PNS
Case Series 1, n=8
Shoulder Subluxation (mm)
BPI Pain Intensity (0 -10)
12
6
5
10.3
10
4.8
8
4
6
3
1.9
2
1.9
2
0
0
Post-Tx
3-mo
0.01
3.3
4
1
Pre-Tx
5
Pre-Tx
Post-Tx
3-mo
0.01
0.01
NICHD R43HD34996; NICHD K12HD010973
0.01
Yu et al., Arch Phys Med Rehabil 2001; 82: 20-25
Percutaneous PNS
Case Series 2, n=15
Brief Pain Inventory (numeric rating scale)
10
Physical functioning
Social functioning
8
Bodily pain
Vitality
6
Role emotional
4
Mental Health
Role physical
2
General health
0
baseline
treatment
12 weeks
24 weeks
Renzenbrink and Ijzerman, Clin Rehabil 2004; 18: 359-65
Favors treatment
Improvement (baseline – 24 weeks follow-up)
Significant Pain Reduction with
4-Lead Percutaneous PNS
Chronic Post-stroke Shoulder Pain Subjects achieving Pain Reduction
4-lead, 6-wk Therapy (N=32)
6-wk Conventional Therapies (N=29)
100%
Subjects (%)
84%
80%
66%
59%
60%
40%
31%
34%
24%
17%
20%
3%
0%
> 2 points
> 3 points
> 4 points
Complete Reduction
(Became pain free)
Degree of Pain Reduction
(11-point scale, 0=no pain, 10=pain as bad as you can imagine)
Yu et al, Arch PMR 2004; Chae et al, Am J Phys Rehabil 2005
33
1-lead PNS approach as effective as
previously evaluated 4-lead PNS approach
After 3-weeks of therapy:
 1-lead approach resulted in 70% average pain reduction
 4-lead approach resulted in 51% average pain reduction
No pain
10
Worst pain intensity in last week (BPI Q3)
Pain as bad as
you can
imagine
9
8
7
6
1-lead
5
4-lead
4
3
2
1
0
Baseline
3-week stim ON
6-week stim ON
34
Percutaneous PNS System using IMN™ Therapy
for Hemiplegic Shoulder Pain
Clinical Feasibility Demonstrated
Chronic Hemiplegic Shoulder Pain Subjects achieving Pain Reduction
4-lead, 6-wk Therapy (N=32)
6-wk Conventional Therapies (N=29)
100%
100%
100%
100%
1-lead, 3-wk Therapy (N=8)
Subjects (%)
84%
80%
66%
59%
60%
40%
31%
34%
24%
20%
25%
17%
3%
0%
> 2 points
> 3 points
> 4 points
Complete Reduction
(Became pain free)
Degree of Pain Reduction
(11-point scale, 0=no pain, 10=pain as bad as you can imagine)
Yu et al, Arch PMR 2004; Chae et al, Am J Phys Rehabil 2005; Wilson et al., in-press; Chae et al., in-review
35
Single-lead Pilot RCT vs Usual Care
Stroke survivors with
shoulder pain, with or
without subluxation; n=24
IM ES
OP Therapy
Aim 1: BPI 3
Aim 2: SF-36
Aim 3: Arm Function
and EMG activation
patterns
NICHD R01HD059777
RCT
Treatment: 3-wks
“Usual Care”
OP Therapy
Follow-up: 3-mo
36
Single-lead, 2-stage PNS Pilot Study
IDE approved Pilot Study
N ~ 20 Subjects
~ 3 - 4 US sites
Case Series
Gather preliminary data
on the safety, clinical
efficacy including quality
of life, placebo effect and
performance of the SPR 2stage PNS system
SPR Therapeutics, LLC
Short-term,
Trial Stage
Percutaneous
Lead
External stimulator
mounted on surface
return electrode
Long-term,
Implant Stage
Implantable Pulse
Generator
Implantable
Lead
CAUTION: Investigational
device. Limited by Federal
law to investigational use.
37
Sensitization
• Loss of inhibitory interneurons (and efficacy) in the
dorsal horn of the spinal cord, such that inputs on nonnoxious afferents (A-beta) are not inhibited and result
in the perception of pain.
• Abnormal sprouting and growth of terminal axons of
non-noxious afferents (A-beta) to make inappropriate
connections such that activity in these fibers result in
the perception of pain.
• Changes in functional connectivity between brain
regions that can influence the perception of ascending
activity as well as the modulation, via descending
activity, of sensory signal processing in the spinal cord.