Download Complex Regional Pain Syndromes

CRPS: Epidemiology, Pathophysiology,
Assessment, and Management
Martin D. Cheatle, PhD
Learning Objectives
 Describe the differential diagnoses when a patient presents with
signs of possible CRPS
 Demonstrate effective pharmacologic and novel
nonpharmacologic strategies to manage pain and improve
functionality
 Examine the potential benefits and long term efficacy of
interventional pain procedures in CRPS
Silas Weir Mitchell
 Causalgia in soldiers suffering from bullet or shrapnel injuries
during the civil war in the 1860s
In combining the Greek terms for burning (“kausos”) and pain
(“algos”) they coined the term “causalgia”
"...a painful swelling of the joints....may attack any
or all articulations of a member. It is distinct from
the early swelling due to the inflammation about
the wound itself, although it may be masked by it
for a time:nor is it merely a part of the general
edema....Once fully established, it keeps the joint
stiff and sore for weeks or months. When the acute
stage has departed, the tissues become hard and
partial ankylosis results."
Mitchell et al 1864
Evolution of CRPS
 1900: Sudeck – variant of causalgia
with bone demineralization
 1940s: the term reflex sympathetic
syndrome (RSD) was coined by Evans
 “The true diagnostic features are those
disorders initiated by perversions of
reflex sympathetic stimulation, namely
increased rubor or pallor, sweating,
edema, atrophy of skin, and spotty or
even cystic atrophy of bone”
(Evans 1946)
Evolution of CRPS
 1993: IASP Diagnostic criteria
CRPS I (reflex sympathetic dystrophy)
-- The presence of an initiating noxious event or a cause of immobilization
-- Continuing pain, allodynia, or hyperalgesia with which the pain is disproportionate to any inciting event
-- Evidence at some time of edema, changes in skin blood flow, or abnormal sudomotor activity in the region of pain
-- This diagnosis is excluded by existence of conditions that would otherwise account for degree of pain, dysfunction
Note: Criteria 2 through 4 must be satisfied
CRPS II (causalgia)
-- Presence of continuing pain, allodynia, or hyperalgesia after a nerve injury, not necessarily limited to the
distribution of the injured nerve
-- Evidence at some time of edema, changes in skin blood flow, or abnormal sudomotor activity in the region of pain
-- This diagnosis is excluded by the existence of conditions that would otherwise account for the degree of pain and
dysfunction
Note: All 3 criteria must be satisfied.
CRPS
 2003 Budapest criteria
• Aimed to improve diagnosis
and validity
 Other diagnostic criteria have
been proposed but all of them are
lacking
– Unclear pathophysiology of CRPS
– No gold standard diagnostic test
for CRPS
CRPS Epidemiology
 2007 retrospective review in the
Netherlands
– Query of general practice database
between 1996-2005
– Incidence rate of CRPS was
26.2 per 100,000 person years
(95% CI: 23.0-29.7)
– Females affected 3 times more often
than males
• Highest incidence in females
ages 61-70
– Upper extremity affected more
frequently than lower extremity
• Fracture was most common inciting
event (44%)
de Mos, de Bruijn et al. The incidence of complex regional pain syndrome: a population-based study. Pain. 2007 May;129 (1-2): 12-20
Epidemiology Continued
 Population based study in Olmsted County Minnesota
–Medical records from 1989 to 1999 with diagnosis codes for CRPS
–74 cases of CRPS-1 identified
• Incidence rate of 5.46 per 100,000 person years at risk
–Female patients 4 times more likely to develop CRPS in comparison
to males
• Median age onset of 46 years
–Upper limb affected twice more than lower limb
• All cases reported antecedent event and fracture was most
common trigger (46%)
Sandroni et al. Complex regional pain syndrome type 1: incidence and prevalence in Olmsted county, a population-based study. Pain. 2003 May; 103(1-2): 199-207
Pathophysiology
Proposed Pathophysiology
 Still being elucidated
 Common prevailing thoughts
–Multifactorial routes all affecting CNS, PNS, and SNS
–Could be genetic predisposition as well
Putting it All Together
 A speculative mechanism currently postulated in the pathogenesis of CRPS
– Tissue injury in the periphery leads to nerve injury that causes the release of
cytokines that produce signs of inflammation and locally increased
nociceptive responsiveness (peripheral sensitization)
– These effects are maximized in patients who may be genetically susceptible
to the disease
 As peripheral and central sensitization occur, trophic changes begin to
appear in the periphery around the area of tissue injury
 After the inciting event, nociceptive fibers in the area begin to upregulate
expression of adrenergic receptors, after which sympathetic nervous
system activity and circulating catecholamines can directly trigger
nociceptive firing
– Reduced sympathetic outflow in the region after the initiating trauma
produces signs of vasodilation and impaired thermoregulatory
responsiveness
• Diminished sympathetic outflow also contributes to upregulated sensitivity of
local adrenergic receptors, leading to exaggerated vasoconstrictive
responsiveness in the affected region in the presence of circulating
catecholamines
Bruehl. An update on the pathophysiology of complex regional pain syndrome. Anesthesiology. 2010; 113: 713-25
Pathophysiology Conclusion
 Complex and multifactorial
–Enhanced peripheral sensitization
–Enhanced central sensitization
 Up regulation of pro inflammatory cytokines
 Altered sympathetic and catecholamine function
 Genetic susceptibility
 Psychophysiological interactions
Clinical Manifestations
Clinical Manifestations
 Pain out of proportion to what is expected
 Allodynia
 Hyperalgesia
Clinical Manifestations
 Temperature changes
 Skin changes
 Trophic changes
–Hair/nails
Clinical Manifestations
 Edema
 Sweating changes
Clinical Manifestations
 Bony changes
 Limb contractures
CRPS in a Nutshell
 Painful neuropathic condition
– Distinguishes itself from other neuropathies by sympathetic symptoms that accompany it
 Symptoms usually present after trauma
– Not always the case
 In addition to classic neuropathic complaints
–
–
–
–
–
Allodynia, hyperalgesia
Swelling/edema
Skin color changes, temperature differences
Trophic changes to hair/nails/skin
End stage-altered motor function
 Type 1—absence of nerve injury
 Type 2—nerve injury present
Stages of CRPS
3 Stages of CRPS
Acute Phase
 Stage-1 (days to weeks)
–Burning pain out of proportion to initial injury
–Pain increases with emotion and physical contact
–Temperature and color variations
–Edema usually present
– 3-Phase bone scan may show increased periarticular uptake
in late phase
–Also may start to see hair and nail changes
3 Stages of CRPS
Dystrophic Phase
 Stage II (several weeks to months)
–Affected limb becomes
• Indurated
• Hairless
• Cyanotic
• Mottled
• Nails can become cracked and brittle
3 Stages of CRPS
Atrophic
 Stage 3 (6 months to years)
 Defined as irreversible tissue damage
–Skin is thin and shinny
–Pain spreads proximal and can migrate to other extremities
–Anxiety leads to sympathetic discharge which can lead to
worsening pain
–Many patient develop emotional disorders 2ndary to intractable pain
Diagnosing CRPS
Diagnosis
 Long standing continued pain
 Pain that is disproportionate to any inciting event
 All other etiologies have been excluded
 Budapest Criteria-2010
–Categorizes various clinical markers
–Must report at least 1 sign/symptom in 3 of 4 categories
Diagnosis
Budapest Criteria-2010
Diagnosis
Signs and Symptoms
 Sensory: hyperalgesia and/or allodynia
 Vasomotor: temperature asymmetry and/or skin color changes
 Sudomotor/edema: symptoms of edema and/or sweating
changes and/or asymmetry
 Motor/trophic: decreased range of motion and/or
motor dysfunction
Radiological Imaging
 Three-phase bone scan
–Accelerated blood flow and/or increased periarticular uptake
–Non-specific and can occur late in disease progression
 X-ray and X-ray bone densitometry
– Not been shown to be helpful in early stages of CRPS
• Osteoporosis can be seen later in progression and may help clinical diagnosis
 MRI has not been shown to be useful in diagnosis
Radiological Imaging
 Quantitative Sensory Testing
–Provides information about the function of afferent nerve fibers
 Quantitative Sudomotor Axon Reflex Test
–Provides information about the sudomotor reflex loops
 Thermography
–Measures heat emissions from the body using special
infrared technology
Management of CRPS
Pharmacological Management of CRPS
 Evidence based medications are few and far between
–Due to rarity of diagnosis
 Most practitioners treat as a neuropathic pain condition
–Antiepileptic Ca channel blockers
–TCAs
–SNRIs
–Antiepileptic Na channel blockers
–Opioids
–NSAIDs
Management Continued
 Since the data is lacking regarding medication therapies for CRPS
–Expert panels agree that a multimodal treatment plan should be
incorporated into patient care
• Panels also believe that first line therapies should include trials of an
anticonvulsant (ie, gabapentin), TCA, NSAID and possibly opioids for
refractory pain
Stanton-Hicks MD, Burton AW et al. An updated interdisciplinary clinical pathway for CRPS: report of an expert panel. Pain Pract. 2002;2(1):1
Bisphosphonates
 3 RCTs on use of bisphosphonates
– Placebo controlled trials with intranasal calcitonin, iv clodronate,
and iv alendronate
– 118 patients total
 Primary outcomes were active movement and motor function
 All 3 studies showed statistically significant improvement with therapies
– Given paucity of data available, bisphosphonates have been only well
documented medications that work
Gobelet C, . The effect of adding calcitonin to physical treatment on reflex sympathetic dystrophy. Pain. 1992;48:171–175.
Varenna M,et al. Intravenous clodronate in the treatment of reflex sympathetic dystrophy syndrome. A randomized, double blind, placebo controlled study. J Rheumatol. 2000;27:1477–1483.
Adami S, et al. Bisphosphonate therapy of reflex sympathetic dystrophy syndrome. Ann Rheum Dis. 1997;56: 201–204
Tran, Duong et al. Treatment of complex regional pain syndrome: a review of the evidence. Can Journal of Anaesth. 2010 Feb;57(2):149-66
Ketamine
 To help prevent or reduce central sensitization medications that
target the NMDA receptor can be used
–Placebo controlled trials show iv ketamine lowers pain scores in
CRPS patients
–However a recent systematic review concluded that there is no high
quality evidence to support its use
–No studies evaluating methadone yet
Schwartzman, Alexander et al. Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo controlled study. Pain.
2009 Dec 15; 147 (1-3): 107-15
Connolly SB, Prager JP et al. A systematic review of ketamine for complex regional pain syndrome. Pain Med. 2015 Jan 13 (epub ahead of print)
Steroids
 Two small randomized trials showing beneficial effect
–23 patients with post traumatic CRPS-1
• 13 patients randomized to receive 10 mg of prednisone three times a day vs
a placebo group
– Study group had up to 75% clinical improvement within a 12-week study period
–36 patients with post stroke CRPS
• 31 patients were nearly symptom free after a 10-day period of treatment
with low dose steroids
Christensen K, Jensen EM, Noer I. The reflex dystrophy syndrome response to treatment with systemic corticosteroids. Acta Chir Scand. 1982;148(8):653
Braus DF, Krauss JK, Strobel J. The shoulder-hand syndrome after stroke: a prospective clinical trial. Ann Neurol. 1994;36(5):728
Interventional Approaches
Lidocaine Infusions
Lidocaine Infusions
 No numerical data provided in study
 Small n=16
 ? Overstated effect: may suggest small benefit
Interventional Approaches
 Epidural clonidine
–Clonidine- α2-adrenergic agonist
–May decrease sympathetic output when placed intraspinally
–Catheter placed at C7-T1 for UE or L2-L3 for LE
–Clonidine at 2 doses: 300 μg or 700 μg
–Studied for a 6 hour period
Rauch, R. et al., Epidural Clonidine treatment for refractory reflex symathetic dsytrophy, Anesthestiology 79;1163-69, 1994
Interventional Approaches
 Epidural clonidine
–Decrease in VAS scores
–+sedation, +hypotension, +decreased HR
–Low sample size – 26 pts
–No long term follow up after 6 hrs
–No functional evaluation
Interventional Approaches
 Intravenous regional blocks (Bier block) with:
–Atropine, bretylium, droperidol, ketanserin
 Bottom line:
–Low quality evidence of effectiveness
–Very small sample sizes
–Significant associated side effects
O’Connell NE, et al. Interventions for Treating pain and disability in adults with complex regional pain syndrome- an
overview of systematic reviews (Review), The Cochrane Collaboration, issue 4, 2013
Sympathetic Blocks
Sympathetic Blocks
 Two studies looking at stellate or lumbar sympathetic blocks w/
local anesthetic for CRPS – Price 1998 and Verdugo 1995
 Crossover study with saline
 Looking at >50% pain relief – no difference for immediate
pain. Possibly some long term relief (48 hrs) w/ LA
 Cepeda 2005 – statistical analysis: not significant
Sympathectomy
 Study looking at RFA of the lumbar sympathetic chain vs
chemical neurolysis (Manjuanth 2008)
–RFA- 80°C for 90 sec
–Phenol
–Both group reported pain relief
–No difference btn groups at four months
–“These techniques should be use cautiously in clinical practice in
carefully selected pts.”
Botulinum Toxic Type A
Botulinum Toxic Type A
 Inhibits release of Ach from nerve terminals
 This works at the preganglionic sympathetic nerves and can
prolong a sympathetic block
Botulinum Toxic Type A (cont’d)
 Carroll et al – Sympathetic blocks with botulinum
 Crossover study using bupivacaine + botulinum toxic type A
or bupivacaine
 Median return of pain time was 71 days in botulinum toxic
type A group vs 10 days in bupivacaine group
 Low quality study and small sample size
 Requires further investigation
Spinal Cord Stimulation
Spinal Cord Stimulation
 Kemler et al, 2008
 54 pts, randomized to SCS+PT or just PT
 Significant pain reduction in SCS+PT group
 At 2 yrs, no difference in QOL or function
 ? Diminishing effectiveness of SCS over time
 At 5 yrs, higher patient satisfaction in SCS group
Surgical Sympathectomy
 Bandyk 2002–reported good pain relief with high
patient satisfaction
 ~20-30% showed no improvement
 Very limited data or evidence
Dennis F. Bandyk et al, Surgical sympathectomy for reflex sympathetic dystrophy syndromes, Journal of Vascular Surgery Volume 35,
Issue 2, February 2002, Pages 269–277
Biopsychosocial Approach to CRPS
Management
Relieving Pain in America:
Institute of Medicine June 2011
 We believe pain arises in the nervous system but represents a
complex and evolving interplay of biological, behavioral,
environmental, and societal factors…
http://www.nap.edu/catalog.php?record_id=13172
Biopsychosocial Approach to CPS
Comprehensive pain management programs based on the
biopsychosocial model of pain, typically emphasizing cognitive
behavioral therapy, a graded exercise program and appropriate
medication management have been shown to significantly improve
treatment outcomes (return to work, pain reduction and increase
in activity).
Gallagher, 1999
Loeser & Turk, 2000
McCraken & Turk, 2002
Cheatle & Gallagher, 2006
Biopsychosocial Treatment Program for CRPS
 CBT
 Functional restoration
 Evidence-based rational pharmacotherapy
 Social support
 Graded motor imagery
Cognitive Behavioral Therapy
 CBT focuses on maladaptive thought patterns (catastrophizing) and
behaviors (kinesiophobia) that occur frequently in patients with CNCP
 The objective of CBT is to guide the patient in recognizing and
reconceptualizing his/her personal view of pain, identifying their role in
the process of healing and promoting the patient being proactive rather
than passive, and competent rather than incompetent
 CBT include specific skill acquisition (relaxation therapy, stress
management, cognitive restructuring) followed by skill consolidation and
rehearsal, and relapse training (Turk, Flor, 2006)
CBT (cont’d)
 CBT has been found to be efficacious for a number of chronic
pain disorders including:
–Arthritis (Keefe & Caldwell, 1997)
–Sickle cell disease (Chen et al, 2004)
–Chronic low back pain (Lamb et al, 2010; Glombiewski et al, 2010)
–TMJ (Turner et al, 2006)
–Lupus (Greco et al, 2004)
–Pain in breast cancer patients (Tatrow et al, 2006)
Functional Restoration
 Focus on improvement of
functional restoration
– Occupational and physical therapy
• The most effective treatment option
• Desensitization and resetting altered
central processes of the brain
– Aquatic therapy
• Hydrostatic principles and buoyancy
component
• Mild compressive force around
affective extremities
– Decreases edema
– Assist in weight bearing of the
extremity
Graded Motor Imagery (GMI)
Pain is a Disease of the Brain
 Theory of pain modulation based
on nociception
 Pain perception involves all areas
of the brain
Factors that Influence Nociceptive Inputs
to Pain Perception
Tracey, I. Neuron 55, August 2, 2007
CNS Plasticity in Pain
CNS reorganization in a variety of chronic pain states: review.
Henry, Chiodo, Yang. PM&R Vol 3 Dec 2011
 CNS reorganization in response to
sensory and emotional
experiences
 Both structural and functional
intrinsic changes are
demonstrated
 Changes occur in number/
location of synapses
Neuroplasticity changes in PLP
 Phantom limb pain
– Remapping of somatosensory
cortex
– Brain activity changes in ipsilateral
motor cortex, thalamus, insula,
forebrain, ACC
Pain catastrophizing and neural responses to pain among persons
with fibromyalgia.
Gracely et al. Brain (2004)
 Increased activity in brain areas related to:
–Anticipation of pain (FC)
–Attention to pain (ACC, PFC)
–Emotional aspects of pain (amygdala)
What is Graded Motor Imagery (GMI)?
 Therapeutic techniques
 Began approximately 20 years ago
 Developed by a group of professional staff at the Neuro Orthopaedic Institute (NOI)
group in Australia
 Lorimer Moseley credited with researching and progressing techniques
 Is progressively expanding and is taught internationally
 Research is ongoing
GMI continued…
 Based on research, the brain is adaptable and changes over the course of our lives
 The brain can be “retrained” to help reduce pain
 GMI uses “brain exercises” to retrain how the brain processes pain
 “Graded Motor Imagery is the most up to date rehabilitation program – based on the
latest science and clinical trials to treat many complex pain, and movement problems”
(noigroup.com)
How is GMI used in therapy?
Three Phases:
1. Laterality training
2. Explicit motor imagery
3. Mirror therapy
Laterality training
Explicit motor imagery
Mirror therapy
Improved function
Who is GMI used with?
People with:
 Chronic pain
 Chronic regional pain syndrome (CRPS)
 Brachial plexus injuries
 Amputations
 Stroke/CVA
 Arthritis
*GMI techniques can be individualized for any diagnosis, depending on the person’s needs*
View Video:
http://noijam.com/2014/10/31/what-is-graded-motor-imagery/
New Frontiers
Multimodal Approach
CBT
Functional
Restoration
Interventions
Pharmacotherapy
Social Support
CRPS
GMI
Thank you!!!
[email protected]