Complex Regional Pain Syndrome PMR Refresher Course

1. Complex Regional Pain Syndrome
Dr Venugopal Kochiyil FAFRM(RACP), FFPMANZCA
Medical Head – Northern Adelaide Rehabilitation Service
Modbury Hospital
Pain Physician – Flinders Medical Centre, Adelaide,South Australia

2. CRPS
• Complex chronic pain, severe disability and reduced
QoL
• Perplexed and fascinated clinicians
• Symptom complex include pain, sensory, autonomic,
trophic and motor abnormalities
• Can occur following minor trauma (fractures, sprain
etc), elective surgeries, stroke etc
• Spontaneous 10%

3. CRPS
• CRPS Type 1 -Formerly known as RSD (1946),
Sudeck dystrophy (1900)
• CRPS Type 2 – Formerly known as causalgia
IASP 1994
Silas Weir Mitchell

4. CRPS Type 1- IASP criteria
• The presence of an initiating noxious event or a cause
of immobilization
• Continuing pain, allodynia or hyperalgesia
disproportionate to the inciting event
• Evidence at some time of edema, changes in skin
blood flow or abnormal sudomotor activity in the area
of pain
• The diagnosis is excluded by the existence of any
condition that would otherwise account for the degree
of pain and dysfunction
Sensitivity 1, Specificity 0.41

5. Budapest criteria 2003
• Continuing pain, which is disproportionate to any inciting event
• Must report at least one symptom in three of the four following categories:
Sensory: hyperesthesia and/or allodynia
Vasomotor: temperature asymmetry and/or skin color changes and/or skin color
asymmetry
Sudomotor/ Edema: edema and/or sweating changes and/or sweating
asymmetry
Motor/Trophic: decreased range of motion and/or motor dysfunction (weakness,
tremor, dystonia) and/or trophic changes (hair, nail, skin)
• Must display at least one sign at time of evaluation in two or more of the following
categories:
Sensory: hyperalgesia (to pinprick) and/or allodynia
Vasomotor:temperature asymmetry (>1°C) and/or skin color changes and/or
asymmetry
Sudomotor/Edema: edema and/or sweating changes and/or sweating asymmetry
Motor/Trophic: decreased range of motion and/or motor dysfunction (weakness,
tremor, dystonia) and/or trophic changes (hair, nail, skin)
• There is no other diagnosis that better explains the signs and symptoms

6. Budapest criteria 2003
• For research purposes - atleast a symptom in each of
the four symptom categories and atleast one observed
sign in two or more sign categories

7. Sensitivity and specificity
Decision rules Sensitivity Specificity
2+ symptoms and 2+ signs 0.94 0.36
3+ symptoms and 2+ signs 0.85 0.69
4+ symptoms and 2+ signs 0.70 0.94
2+ symptoms and 3+ signs 0.76 0.81
3+ symptoms and 3+ signs 0.70 0.83
4+ symptoms and 3+ signs 0.86 0.75
Bruehl S, Harden RN et al. Pain 1999;81:147–54.

8. Phases of CRPS
• Acute phase – painful,
red, warm, swelling,
allodynia, hyperalgesia
(mechanical, thermal),
nail and hair changes,
muscle weakness,
negative sensory signs
Marinus J, Moseley GL et al. Lancet Neurol 2011; 10: 637–48

9. Cold phase
Marinus J, Moseley GL et al. Lancet Neurol 2011; 10: 637–48

10. Dystonic phase
Marinus J, Moseley GL et al. Lancet Neurol 2011; 10: 637–48

11. Motor symptoms and signs
• Weakness, Tremor, Decreased ROM, Difficulty in
performing complex movement patterns, focal
dystonia and myoclonus
• Motor symptoms increase with duration of CRPS
• Contractures and fibrosis
• Probably associated with plastic changes in sensory
and motor cortex

12. Dystonic postures in CRPS
Munts et al. BMC Neurology2011,11:53

13. Spread of CRPS 1
• Contiguous spread: A gradual enlargement in the area
affected over time
• Independent spread (ipsilateral (32%)and diagonal
(15%)): Spread of the disease from upper to lower
limb, or vice versa
• Mirror Spread (contralateral – 53%): Spread of
pathology to the contra lateral lower limb
van Rijn MA, Marinus J et al. J Neural Transm 2011; 118:1301–1309

14. Epidemiology
• 5.5- 26.2 cases per 100 000 person-years
• Incidence increases with age (till 70 years)
• More common in women ( approx 3 times)
• Arm more than legs (in adults)

15. Pathophysiology
• Aberrant inflammatory mechanisms
• Nociceptive sensitization
• Vasomotor dysfunction
• Maladaptive neuroplasticity
Marinus J, Moseley GL et al. Lancet Neurol 2011; 10: 637–48

16. Inflammatory mechanisms
• Activation of cutaneous nociceptors
Retrograde depolarisation of primary afferents
Release of neuropeptides (substance P, CGRP)
• Increased Interleukins and TNFα
• ? Autoimmune mechanisms

17. Vasomotor dysfunction
• A common problem in CRPS
• Warm (4 months), intermediate (4-15 months) and
cold type
• Inhibition of cutaneous sympathetic vasoconstrictor
activity
• Increased sensitivity to circulating catecholamines
(SMP)
• Endothelial dysfunction

18. Central nervous system
• Central sensitization
• Structural changes to emotional centres
• Impaired motor control – dystonia (GABAergic
mechanisms)
• Descending facilitation > descending inhibition
• Distortion of mental image of affected area
• Cortical reorganisation (S1 and M1)

19. Risk factors in CRPS
• No definite evidence of psychological risk factors
• Immobilisation of injured limb
• Use of ACE inhibitors
• Asthma and migraine

20. Genetic factors in CRPS
• Familial form of CRPS
• Patients younger than 50 years has increased risk of
sibling with CRPS (de Rooij et al. J Pain 2009;10:1250–1255)
• Association with different HLA factors

21. Bruehl S. Anesthesiology 2010; 113:713–25

22. Models of CRPS
• Animal chronic post-ischemia pain (CPIP) model -
produced by prolonged hindpaw ischemia and
reperfusion in the rat
• Human forearm immobilisation model

23. Outcome of CRPS
• Issues with what is the definition of recovery in
CRPS
• Usually monophasic but 2% relapsing remitting
• 30% completely recovered, 53% stable
• 15% no improvement, 30% not gone back to work
de Mos M, Huygen FJ et al. Clin J Pain 2009;25: 590-7

24. Management
• Patient information and education
• Pain relief
• Physical Rehabilitation
• Psychological and Vocational rehabilitation

25. Medications
• Nifedipine in acute phase – Level 4
• Short course of steroids in acute phase – Level 1
• Intravenous bisphosphonates in acute phase – Level 1
• IVIg – no evidence
• Opioids
• Neuropathic pain medications
• Baclofen or clonazepam for dystonia
• Intravenous ketamine infusion
(continuous/intermittent – inpatient/outpatient)

26. Biologicals
• Infliximab study was withdrawn

27. Rehabilitation
• Aim at activating premotor and primary motor
cortices
• Functional restoration
• Desensitization
• Gradual weight bearing

28. Graded motor imagery
• Three stages
Left/Right discrimination
Explicit motor imagery
Mirror therapy
• Activate cortical networks involved in sensory motor
processing

29. Recognise online
www.gradedmotorimagery.com

30. Evidence in CRPS
• Limited data (all available data for upper limb)
• Decreased pain experience, improved grip force,
improved global impression of change but no change
in perception of upper extremity function (Laqueux E,
Charest J et al. Int J Rehabil Res. 2012 Jun;35(2):138-45)
• No improvement in pain scores but some partial
functional improvement. Real world response is
variable (Johnson S, Hall J et al. Eur J Pain. 2012;16(4):550-61)

31. In CRPS
• Three RCTs by Moseley – NNT for 50% reduction in
pain was 2, NNT for 4/10 improvement in function
was 3 (Pain 2004a;108:192–8, Pain 2005;114:54–61, Neurology
2006b;67:2129–34)

32. Invasive interventions
• Appropriately timed and selected interventional
therapy has an adjunctive role
• Measured steps

33. Nerve blocks/sympathetic block
• Patients with mechanical allodynia, burning pain,
temperature and colour changes might benefit
• Repeat block if there is benefit
• Stellate ganglion block and lumbar sympathetic block
• ? Benefit in differentiating SMP from SIP
• Limited evidence
• Continuous/intermittent spinal infusions
(epidural/intrathecal)

34. Sympathectomy
• Chemical and surgical
• Regeneration of sympathetic chain
• Post sympathectomy neuralgia (44%)
• Compensatory hyperhidrosis, phantom sweating and
pathologic gustatory sweating

35. Implantable pumps (IT)
• Case reports
• If no response to SCS
• Patient selection
• Trial
• Medications (opioids, clonidine, local anaesthetic,
baclofen)

36. Spinal cord stimulation
• SCS + Physio was better than PT alone (Kemler et al NEJM
2000, J Neurosurg 2008) but no difference in functional
outcome
• ? Long term benefit
• ? Benefit in allodynia and hyperalgesia
• Benefit with sympathetic block may indicate better
results
• Patient selection and trial
• Ideally within 12 to 16 weeks

37. Stanton-Hicks M et al. Cli J Pain
1998;14:155-66

38. Prevention

39. Vitamin C and CRPS
• 4 Studies – 3 after upper limb surgery and one after
foot and ankle surgery
• Atleast 500mg started immediately after surgery and
continued for 45 to 50 days
Shibuya N, Humpers JM. J Foot Ankle Surg. 2013;52(1):62-6

40. Other options
• Multimodal analgesia
• Nerve blocks
• Calcitonin 100 units a day for four weeks

41. Surgery in a patient with CRPS
• What is the risk?
• Avoid surgery till acute symptoms have subsided
• No evidence that any preventive methods actually
prevent re-initiation or aggravation of CRPS