Complex regional pain syndromme

1. COMPLEX REGIONAL
PAIN SYNDROME
MODERATOR :DR SANDEEP
CONSULTANT
DEPARTMENT OF ORTHOPEDICS
RML HOSPITAL
PRESENTED BY: DR ABHISHEK RASTOGI

2. CASE STUDY:
 A 25-year-old woman presented with persistent pain and sclerotic and
oedematous skin lesions on her left hand. One year prior to her first visit,
she had accidentally sprained her left wrist. The initial pain subsided
quickly, but after a month, severe burning pain developed on her left thenar
eminence with marked swelling of the distal forearm and the hand. The pain
gradually intensified and spread to the entire left hand, accompanying
numbness, severe cold intolerance and muscle weakness. She underwent
physical therapy for several months at an orthopaedic clinic with no effect.
 On examination, pale-coloured, oedematous and indurated skin with a shiny
surface was observed over the patient’s left dorsal hand and fingers,
mimicking sclerodactyly (Fig.). The lateral 3 digits showed mild flexion
contracture. The dorsal skin over the left fingers could not be pinched. Hair
loss and hypohidrosis were also observed.

3.  Routine laboratory test results were unremarkable. Neurological examinations
revealed hyperalgesia, paresthesia, dysesthesia and muscle weakness in the left
forearm and the hand. Results of nerve conduction studies were normal.
Radiographic examination showed marked decalcification of her left lateral 3
fingers
 Eosinophilic fasciitis was excluded because this case showed unilateral
involvement. The absence of autoantibodies and presence of neurological
symptoms were inconsistent with scleroderma. Using the history of trauma,
symptoms and physical findings, CRPS I was diagnosed. Treatment with regular
stellate ganglion blockade and infra-red therapy was initiated

4. INTRODUCTION:
o DEFINITION: It is a chronic neuropathic painful condition which the patient
experiences, typically having a regional distibution(not limited to a typical nerve
distribution or dermatome) along with the following associated abnormal changes
o Sensory : allodynia , hypo/hyperaesthesia, hypo/hyperalgesia, hyperpathia
o Motor : weakness, dystonia, distal tremors, atrophy, contractures.
o Autonomic: swelling, edema, sweating
o Trophic changes: skin, hair and nails
o The magnitude and duration of the clinical course is always prolonged than
expected for the inciting event leading to a significant impairment of the motor
function.

5. o It most commonly occurs after a traumatic injury or iatrogenic insult like surgery, or
due to stroke or heart attack. Often the inciting event is unknown where no
evidence of neurological or physical damage is there to the affected area.
o According to the IASP the term CRPS or Complex Regional Pain Syndrome is of
specifc relevance and each word describes the disease:
• Complex: variable clinical presentation
• Regional: symptoms affecting a particular region
• Pain: disproportionate to the severity of the injury
• Syndrome: cluster of signs and symptoms
o It occurs more commonly in the upper limb, and is usually unilateral but may
sometimes be bilateral in presentation and rarely may spread from one limb to
another.

6. HISTORY:
 In 1864 during the American civil war, Silas Weir Mitchell with Morehouse and keen observed a chronic
burning pain in soldiers who suffered a traumatic nerve injury(gunshot injury) and used the term
causalgia, derived from two Greek words “kausis” meaning heat and “algos” meaning pain.
 later on the condition was also called reflex sympathetic dystrophy based on the hypothesis that it was
due to an overactivity of the sympathetic system, and finally in 1993 was termed “complex regional pain
syndrome” in a special consensus workshop held in Orlando, Florida.
 Other names of CRPS:
• Reflex sympathetic dystrophy
• Causalgia
• Sudecks atrophy
• Reflex neurovascular disorder
• Amplified musculoskeletal pain syndrome
• Algoneurodystrophy

7. EPIDEMIOLOGY:
 The incidence varies widely from study to study and is estimated to be between 5 and 26 per
100,000 per year. (Sandroni et al., 2003; de Mos et al., 2007; Elsharydah et al., 2017; Ott &
Maihofner, 2018)
 Female predisposition has been noted. Overall it is 4 times more common in women than men
according to the study of updated comprehensive review of complex regional pain syndrome done
by Allison Kesslera, Min Yoo and Randy Calisoff In 2020.
 The most commonly identified risk factors for CRPS include polytrauma, fractures, crush injuries,
and surgery, but up to 10 percent of patients may have no inciting events(Reinders et al., 2002;
Harden et al., 2007; Harden et al., 2010; Oh et al., 2019)
 Occurs in all age groups but peaks at age of 50-70 yrs.

8. TYPES:
It is divided into 3 types :
 Type 1: when there is a musculoskeltal injury with no evidence of nerve injury.
Includes RSD, Sudecks atrophy, RND or algoneurodystophy
 Type 2(causalgia): includes patients who fulfill the same criteria but with obvious
nerve damage , which might be partial or complete.
 Type 3 or CRPS-NOS*: when criteria are partially met and the condition is not
explained by any other disease.

9. CLINICAL PRESENTATION/ SYMPTOMS:
 The most evident clinical presentation in CRPS is avoidance behaviour and an
altered recovery pattern when the patient tries to use the area of the body that has
been injured.
 CRPS is a biphasic condition with early swelling and vasomotor instability(VMI)
giving way over a period of timescale to late contractures and joint stiffness.
 Symptoms and signs:
• Pain: described as simple aching/ burning/ throbbing/ shooting/ stabbing which has an
increased sensitivity(hyperalgesia), allodynia, hyperpathia.
• Vasomotor changes : swelling, edema, sweating, cold/warm skin,
• Motor changes: weakness, distal tremors, atrophy, contractures.

10.  Trophic changes:
• Skin texture: subcutaneous atrophy, waxy , thin and ulcerated.
• Nails brittle grooved and spotty, clubbing
• Hair loss
 Radiological features: sudecks atrophy or post traumatic osteoporosis maybe due
to disuse and include periarticular osteopenia.

11. Source: Rockwood and Green’s Fracture in adults 8th ed

12. STAGES OF CPRS:

13. STAGE 1(ACUTE):
• HYPEREMIA
• SWELLING
• GLOSSY SKIN

14. COLD TYPE CRPS
• Blue discolouration
of the skin
• Increased hair and
nail growth

15. STAGE 2(subacute/dystrophic):

16. STAGE 3(ATROPHIC):
• CONTRACTURES
• SKIN ULCERATION

17. EARLY PHASE OF CRPS:
 In this stage the vasomotor instability and edema dominate .
 Stage 1: vasodilated stage, dry hot and pink limb(warm red CRPS)
 Stage 2: vasoconstricted , blue, cold and sweaty.(cold bluish CRPS)
 Vasomotor instability is characterised by increase in temperature sensitivity with
variable amount of sweating.
 Edema marked in early phase involving distal part. Initially simple tissue swelling
which maybe overcome with physical therapy. With time ( stage 1 to stage 2) it
becomes fixed and indurated

18.  Joint mobility: In the early phase loss of joint mobility is due to swelling and pain
combined with the apparent inability to initiate movement or state of neglect or
denial with respect to the limb. As the early phase progresses, loss of joint mobility
is increasingly due to development of contractures.
 Only if the disease is halted before a fixed contracture has occurred can a complete
resolution occur.

20. LATE PHASE OF CRPS:
 Vasomotor instability receds, edema resolves and atrophy of the limb occurs
affecting every tissue.
 Skin thinned, joint creases and subcutaneous fat disappears, hair becomes fragile,
curled, nails pitted, ridged, brittle
 Palmar, plantar fascia thicken, tendon sheaths constricted, muscle contactures ,
joint capsules and collateral ligament become shortened, thickened leading to joint
contractures.

22. Bone changes:
 Universal involvement of the bone
Early phase : increased uptake on bone scan
Later phase: returns to normal
 Visible deminieralisation with patchy subchondral, or subperiosteal osteoporosis ;
metaphyseal banding and profound bone loss

23. DIAGNOSIS AND DIAGNOSTIC CRITERIA:
 Because the pathophysiological mechanisms of CRPS are not fully understood,
mechanism based diagnosis is not yet feasible. Therefore, the diagnosis of CRPS is
based solely on clinical signs and symptoms.
 During the diagnostic process, objective medical tests may be needed to rule out
other conditions that could account for the signs and symptoms that would
otherwise be used to support a diagnosis of CRPS, given that CRPS is explicitly a
diagnosis of exclusion
 1) International association for study of pain and diagnostic criteria(1994):
• high sensitivity and low specificity , therefore may lead to overdiagnose CRPS.
• Didn’t include motor and trophic signs and symptoms
• Permits diagnosis solely based on patient reported historical symptoms.

24. THE MODIFIED IASP DIAGNOSTIC CRITERIA FOR CRPS (2012):
 Modified by Bruehl and is also known as the Budapest diagnostic criteria.

25.  The important changes are :
 inclusion of clinical signs, their separation from symptoms
 Inclusion of features of motor abnormality and trophic changes
 Criteria provides a sensitivity of 0.7 and specificity of 0.94

26. INVESTIGATIONS:
1) SYMPATHETIC BLOCKADE:
• Stellate block in upper extremity
• Lumbar paravertebral block in lower extremity
 A successful block confirms a diagnosis of CRPS in the presence of other consistent
clinical findings.
 False positive results may occur due to somatic nerve block, systemic uptake of
local anaesthetic, or placebo affect of the invasive procedure itself.
2) OTHER DIAGNOSTIC TESTS:
• Thermography: efficacy doubtful
• Sweat test: 2 specific test
• Quantitative sudomotor axon reflex test
• Resting sweat output test.

27.  3) RADIOGRAPH: conventional radiographs maybe normal or show severe
osteopenia in 2-3 weeks after the onset of the disease. Neither sensitive nor
specific
 4)THREE PHASE BONE SCINTIGRAPHY: useful to make differentials and exclude
infections. Delayed images demonstrate diffuse and increased uptake throughout
hand and foot with juxta articular accentuation. Amount of tracer uptake do not
correlate with severity
 5)ELECTRODIAGNOSINTIC STUDIES: helps differentiate type 1 from type 2
• EMG
• NCV

28. DIFFERENTIAL DIAGNOSIS:
 INFLAMMATION
 Erysipelas
 Seronegative arthritis
 Rheumatological disease
 VASCULAR DISEASES
 Thrombosis
 Acrocyanosis
 Atherosclerosis’
 Raynauds disease
 NEUROPATHIC PAIN
 Nerve entrapment
 Radiculopathy
 Differential pain of CVA
 MYOFASCIAL PAIN
 Overuse or disuse of muscles
 Tennis elbow
 Injury due to repetitive strain
 PSYCHIATRIC PROBLEMS
 Malingering
 Somatoform pain disorders

29. ETIOLOGY:
 Since the exact mechanism for the causation of CRPS is not yet clearly understood,
various etiologies have been proposed which are:
• 1) Psychological abnormalities: there is evidence of association of the antecedent
psychological stress which probably exacerbate pain in CRPS.
• 2) Neuropathic pain: injured peripheral nerve fibres undergo cellular changes, non
harmful stimulus which wouldn’t activate the receptor normaly stimulate the dorsal horn
cells via Ab fibres causing allodynia in CRPS 2. C nociceptor dysfunction is also
postulated to cause causalgia
In CRPS 1, covert nerve lesions with artificial synapses have been postulated.
• 3) Sympathetic system abnormalities : features suggestive are abnormalities in skin blood
flow, temperature regulation , sweating and edema. On sympathetic manipulation like
stellate ganglion block, relief of symptoms confirms involvement of the sympathetic
system.

30.  SNS activity is usually not painful but is painful in CRPS termed Sympathetically
maintained pain(SMP), which is a body’s reaction to injury
 After nerve injury, the injured and unimjured nerve axons express alpha adrenergic
receptors and the sympathetic axons come to surround the sensory neuronal cell
bodies in dorsal root ganglion. This makes the sensory neurons sensitive to the
circulating catecholamines and nor adrenaline.
• 4)Abnormal inflammation:
 CRPS resembles an inflammatory state of the body and has features of
macromolecule extravastion and reduced oxygen concentration.
 Substance P and CGRP i.e the calcintonin related gene peptide are higher in CRPS
which causes augmented flare response and excessive protein extravasation.
 There is also evidence of overexposure of free radicals and is supported by the
evidence that free radical scanvenger vitamin C is an effective prophylaxis against
post traumatic CRPS.

31. • 5) Immobilisation and failure to use the affected limb:
 Earlier the term used was algodystrophy which means painful disuse.
 The patients are unable or unwilling to cooperate with the physical therapy to mobilise
the limb after trauma or surgery.
 Earlier the concept was that the patient didn’t move the immobile RSD limb due to the
inadvertent pain but now it is believed to be due to motor function deficits which was
often ignored as it was assumed to be hysterical.
 Motor impairments could range from spasms,dystonia , tremors, impaired grip force,
target reaching, grasping etc
 Mismatch between limb sensation and appearance with mental erasure of the affected
part., where authors suggested the term “body perception difference.” where the
patient ignore affected limb and find difficulty in initiating accurate direct movement
and mismatch between sensation perception and movement.

32. PATHOPHYSIOLOGY:
 It is now agreed that the syndrome is caused by a multifactorial process
involving both peripheral and central mechanisms.
 POSSIBLE MECHANISMS INVOLVED:
1. Nerve injury
2. Ischemic reperfusion injury or oxidative stress
3. Central sensitization
4. Peripheral sensitization
5. Altered sympathetic nervous system function or sympathoafferent coupling
6. Inflammatory and immune related factors
7. Brain changes
8. Genetic factors
9. Psychological factors and disuse

34. • Brain changes: reported with CRPS
There is a decreased representation of the affected limb in both the primary and the
secondary somatosensory cortices.
• Genetic factors: role poorly understood
Association with the HLA system (HLA DQ8 and HLA B62) have been reported.

35.  Recently a new hypothesis was formulated for the pathophysiology of CRPS in a
study conducted by Marc Russoa, Peter Georgius , Danielle M Santarelli in 2018 in
which they stated that the pathophysiology of CRPS may be better understood as
four components of altered function in terms of tissue trauma, abnormal pain
processing, autonomic imbalance and immune system alteration
 The condition may best be considered as an immune-neurological disorder, with a
combination of adaptive immune response and pathological pain processing.

37. TREATMENT:
 Treatment of the CRPS requires a multimodal approach and can be categorized
under two headings:
• Conservative management
• Interventional management
 The treatment should be initiated as early as possible, before the advent of
contractures which then give optimal results therefore high index of suspicion must
be maintained.
 Delay in diagnosis and treatment contribute to poor outcome

38.  INITIAL TREATMENT: Mainly conservative and includes multidisciplinary approach
• Includes reassurance, excellent analgesia
• Intensive careful physical therapy avoiding the exacerbation of the pain. It is the most
important factor in reversing the symptoms in the actue stage and helps imrove pain
function and prevent joint stiffness and contractures
• Pharmacotherapy with NSAIDS better pain relief as compared to opiates, centrally acting
analgesic like amitriptyline often useful.
• Immobilisation and splintage avoided
• Vit C administration: acts as an antioxidant and has increased tissue healing potential
• Goal directed therapy: specific modalitites are progressive weight bearing,
transcutaneous electric nerve stimulation, tactile desensitisation, massage, and contrast
bath therapy
• Graded motor imagery
• Mirror box therapy
• Psychotherapy

39. DRUGS:
 Many drugs have been succesfully tried for the management of CRPS and many are
still being investigated.
 Some Drugs include:
• Anti inflammatory drugs
• Analgesics
• Tricyclic antidepressants
• Caclitonin- osteoclasts inhibitor
• Bisphosphonates- Antinociceptic effect due to the effect on osteoclasts and control of
regional osteoporosis. It also inhibits PG E2, proteolytic enzymes, and lactic acid
contributing to the positive effects.
• SSRI( selective serotinergic reuptake inhibhitors)
• Anticonvulsants
• Antidepressants

40. SOURCE:Giovanni Iolascon & Antimo Moretti (2019) Pharmacotherapeutic options for complex regional pain syndrome, Expert
Opinion on Pharmacotherapy, 20:11, 1377-1386

41. INTERVENTION THERAPY:
 Intravenous regional sympathetic blockade : Guanethidine was the first drug used but
due to its side effect other drugs were subsequently used like reserpine, bretylium,
clonidine, local anaesthetic like lidocaine and prilocaine
 Local anaesthetic sympathetic blockade: these include block of the sympathetic
structures such as the stellate ganglion or the lumbar sympathetic chain(LASB) under
fluoroscopic or computed tomographic guidance.
1. Given when other forms of conservative treatment fail
2. In the early phase used for the diagnosis as well as management of the severe pain and
allodynia
3. Repeated blocks beneficial in selected patients to help participation in physiotherapy ,
especially when signs of improvement present
4. For prolonged block, radiofrequency ablation and phenol lysis are the options where
radiofrequency ablation is preferred.

42.  Spinal cord stimulation : Comprises of stimulating electrodes inserted in the
epidural space, which in turn is connected with a source which generates impulses
similar to pacemaker.
1. System shows effective reduction of the pain.
2. Intensity and nature of stimulation can be can be programmed
3. Mechanism by which it poorly understood but may involve restoring normal GABA levels
in the dorsal horn and affect release of adenosine which then reduce neuropathic pain
 Neuraxial techniques: Last resort measures which has shown some positive results.
1. Include epidural local anaesthetic, clonidine or opiods in management
2. Similarly, intrathecal delivery of morphine, bupivacaine, clonidine or baclofen can be tried
via implanted pumps.

43.  Sympathetic denervation: done only after an initial successful diagnostic
sympathetic block.
• Rare complications associated including post sympathectomy sympathalgia,
compensatory hyperhidrosis, Horner syndrome, spinal cord injury etc.
 Intramuscular botox injections: reduce the muscle spasm and also decrease the
inflammation. Cheap, safe and easy to administer only limitation being it may need
to be repeated after a few months and its reduced efficacy after repeated use
 Apmutation: Ultimate option for intractable symptoms of a debilitating limb
affected by CRPS. The treatment however have not shoen of much benefit.

44. TREATMENT ALGORITHM:

47. Pharmacotherapy guide. The following strategies are suggested for patients who
have been diagnosed with CRPS but who cannot begin or progress in the
functional restoration algorithm.

48. PROGNOSIS:
 Early treatment, usually within three months of the first symptom have a good
prognosis.
 Better in children although the recurrence rate is higher in children as compared to
adults.
 If the treatment is delayed, the disorder spreads quickly to the entire limb and
irreversible changes set in the bones, nerves and muscles.
 Cold CRPS has a worse prognosis than that of a patient with warm CRPS
 Until a definite pathophysiological mechanism is discovered and specific treatment
developed, interdisciplinary approach including pharmacologic and intervention
management in stepwise fashion will remain the best approach.

50. THANK YOU