Rasha S. Jabri , MD

Dubai Anesthesia March 2012Tawam Hospital-JHMI Al Ain Abu Dhabi, UAE

When is it Reasonable to Speak about CRPS?

History

• American Civil War: GSW near neves

• 1864 : term “causalgia” long years final reminder of the battle-field

• Dr. Sudeck: trivial injuries result in osteoporotic changes near the site of injury (Sudeck’s atrophy)

History

• Rene Leriche : sympathetic nervous system as a mediating factor in the condition

• “Reflex sympathetic dystrophy” (RSD)

• Since the early descriptions of this painful condition many names have been applied to the syndrome

Terms for CRPS

• •Algodystrophy • •Algoneurodystrophy • •Causalgia • •Post-traumatic pain syndrome • •Post-traumatic dystrophy • •Post-traumatic osteoporosis • •Reflex sympathetic dystrophy • •Shoulder-hand syndrome • •Sudeck’s atrophy

Classification

• 1986 (IASP) formal description and classification of RSD but NO clear diagnostic criteria, NO specific underlying mechanisms.

• Many neuropathic pain conditions were included in the diagnosis of RSD, specifically those resistant to traditional treatments

Classification

• 1994 IASP new taxonomy of complex regional pain syndrome (CRPS), which would more accurately describe RSD and causalgia.

• New diagnostic criteria for CRPS which focused on clinical diagnosis from patient history, symptom description, physical signs and pain.

Classification

• CRPS : inciting events:– type I =RSD, follows a soft tissue injury – CRPS II= (causalgia) follows a well-defined

nerve injury

CPRS

• syndrome including,– complexity of the varied presentations– regionally, symptoms, which are typically non-

dermatomal– pain, usually out of proportion to the inciting trauma– syndrome, denoting the constellation of signs and

symptoms

• varied contribution of the sympathetic nervous system

Epidemiology•Overall incidence of CRPS to be 26.2 per 100,000 person

•CRPS I to be 5.46 per 100,000 person years at risk and a prevalence of 20.57 per 100,000.

• The incidence of CRPS II has been reported at 0.82 per 100,000 person years at risk and prevalence of 4.2 per 100,000 person years.

Risk Factors

• Extremities trauma/MVA↑

• Surgeries/Orthopedic↑( Knee, Ankle, CTS)

• Stroke, or unknown cause very rare

• Most cases between 50 and 70 years of age

• CRPS female predominance: 2.0-3.5:1.13

• Mainly Caucasian

Pathophysiology

• Theories peripheral mechanisms as well as central mechanisms for CRPS.

• In CRPS II biochemical, morphological (structural) and physiological changes of the injured and adjacent intact primary afferent neurons may occur

CPRS II

• The loss of DRG cells degeneration of the centrally projecting afferent axons and to denervation of dorsal horn neurons

• Secondary changes in the central representations changes in central representations (in the spinal cord, brain stem, thalamus and forebrain)

CPRS I• CRPS I central representations of the sensory,

autonomic, and somatomotor systems account for the clinical presentation in CRPS

• CRPS, particularly type I, is a systemic disease of neuronal systems: somatosensory, sympathetic, somatomotor, and peripheral (vascular, inflammatory) systems

Pathophysiology• Marked increase in alpha 1 adrenoreceptors which

appears in the injured extremity: skin muscle and nerve tissue

• Augment depolarization in nerve and muscle tissue resulting in an amplification effect of any stimuli

• Increase in pain w increase in either endogenous or exogenous catecholamines.

.

Tissue damage initiates a number of alterations of the peripheral and the

central pain pathways

Dahl, J. B. et al. Br Med Bull 2004 71:13-27; doi:10.1093/bmb/ldh030

Bruehl S. An Update on the Pathophysiology of CRPS Anesthesiology .September 2010;113(3):713-725

Bruehl S. An Update on the Pathophysiology of CRPS Anesthesiology .September

2010;113(3):713-725

Speculative Model of InteractingPathophysiologic Mechanisms in CRPS

Clinical Stages

• Classically: three distinct sequential progressive stages

• Disputes the traditional staging of CRPS

• Subtypes/subgroups exist in CRPS

Clinical Stages (Bonica)

I warm acute CRPS pain, sensory abnormalities, hyperalgesia, allodynia, vasomotor dysfunction, edema and sudomotor disturbance.

II (dystrophic stage) 3 to 6 mons more pain/sensory dysfunction and vasomotor dysfunction, with significant motor/trophic changes.

III (atrophic stage) cold extremity with decreased pain/sensory disturbance, continued vasomotor disturbance, increased motor/trophic changes.

General definition

• An array of painful conditions regional pain disproportionate in time or degree to the usual course of any known dz

• Regional: not in a specific nerve territory or dermatome usually has a distal predominance of abnormal sensory, motor, sudomotor, vasomotor, and/or trophic findings.

IASP CRPS subgroups NOT Sequential stages

(1) Relatively limited syndrome with vasomotor signs predominating

(2) Relatively limited syndrome with neuropathic pain/sensory abnormalities predominating

(3) Florid CRPS syndrome similar to ‘‘classic RSD’’ descriptions

Pattern and Spread

32. IE, et al. Signs and symptoms of reflex sympathetic dystrophy: prospective study of 829 patients. Lancet 1993;342:1012-1016.

Veldman PH.Signs and symptoms of RSD: prospective study of 829 patients. Lancet 1993;342:1012-1016.

Clinical Features

• CPRS is a painful and debilitating disorder primarily affecting one or more extremities.

key features

• Spontaneous pain, allodynia, hyperalgesia, edema, temperature change, abnormal vasomotor and sudomotor activity, trophic changes, and motor dysfunction

IASP

Diagnostic criteria to establish the diagnosis of CRPS (type I):

(1) initiating noxious event or immobilization

(2) continuing pain, allodynia, or hyperalgesia with pain disproportionate

(3) Edema, changes in skin blood flow, or abnormal sudomotor activity

• (4) the exclusion other medical conditions

CPRS II IASP

(1) continuing pain, allodynia, or hyperalgesia after an nerve injury

(2) Edema, changes in skin blood flow, or abnormal sudomotor activity

• (3) the exclusion other medical conditions

Sudomotor Changes & Edema

Trophic Changes

Trophic Changes

Conclusions and Clinical Implications

• IASP standardized, common methodology for making DX of CRPS or not

• Treatment for two distinct conditions

• CRPS and non-CRPS neuropathic

pain groups

IASP_

• Controversy about the value of consensus-based

dx criteria

• Absence of evidence-based information

• Necessity of validating in light of systematic validation research

Harden RN. Proposed new diagnostic criteria for CRPS. Pain Med. May-Jun2007;8(4):326-331

CRPS DX ?????

• “looser” vs “tighter” criteria?!!

• Validity dx of the criteria ?

• Sensitivity vs Specificity?

Harden RN. Proposed new diagnostic criteria for CRPS. Pain Med. May-Jun2007;8(4):326-331

IASP/CRPS dx Criteria

Adequately Sensitive

(rarely miss a case of actual CRPS)

Problems of overdiagnosis due to Poor Specificity

Harden RN. CRPS : Are the IASP diagnostic criteria valid and sufficiently comprehensive? Pain 1999;83:211–9

Harden RN. Proposed new diagnostic criteria for CRPS. Pain Med. May-Jun2007;8(4):326-331

• The modified criteria requires the presence of both for CRPS diagnosis

Objective Objective signs on PE signs on PE

Subjective Subjective symptomsymptom

Clinical DiagnosticCriteria by the Budapest group

• 2/4 sign categories and ¾ symptom categories for diagnosis

• Sensitivity of 0.85

• Specificity of 0.69

• Clinical vs research purposes2/4+4/4 more sensitivity and specificity around 80, 90%

Diagnostic Examination

• No single objective test for diagnosis

• Diagnostic tests may assist in determining the likelihood of the syndrome

Diagnostic Examination

• Sympathetic Blockade – sympathetically maintained pain or sympathetic

independent pain

• Skin Temperature Measurement – Infrared thermography– Difference of more than 2.2°C has a sensitivity

of 76% and a specificity of 93% for diagnosis of CRPS

Quantitative Autonomic Function Testing

– The quantitative sudomotor axon reflex test (QSART)

– difference in sweat production between an affected extremity and an unaffected extremity

– QSART test may help predict response to sympathetic block

– Research needs to be conducted to further assess the utility of the test

Vasomotor Testing

– Acute CRPS increase in vascular flow to the affected extremity secondary to neurogenic inflammation

– Decrease in sympathetic activity at the extremity

– Measured by doppler flowmetry – Additional studies to assess the utility in the

diagnosis of CRPS

Trophic Change Measurement

• Chronic CRPS present with changes in skin, nails or bone

• Evaluation of trophic changes to the bone by triple-phase bone scintigraphy has been used to substantiate the diagnosis of CRPS, although distinguishing between CRPS and acute trauma may difficult

Therapy

Pharmacological Therapy

– Antidepressants (tricyclic & dual inhibitors) are effective agents for treating a variety of neuropathic pain condition

– SSRI + DPNP, PHN? CRPS

• Anticonvulsants (Antiepileptics) – The gabapentinoid group of drugs, gabapentin

(GBP) and pregabalin (PGB), are the most commonly used antiepileptics drugs (AEDs) for CRPS

• Opioids – There are no long-term studies– Considered in CRPS if pain limits the patient’s

participation in physical restorative therapies– Fent Patch VAS↓, fx (Agarwal, Pain Med 2007)

• Calcium Regulating Medications (Bisphosphonates)

• Effective agents for the treatment of CRPS– Mechanism of action is unknown– (alendronate, pamidronate, clodronate)– May inhibit bone resorption and their

effectiveness have been confirmed in randomized controlled studies

– Manicourt (Arthritis Rheum 2004)

• Calcitonin– Thyroid gland, inhibit osteoclastic bone

resorption – Gobelet ( Pain 1992)– Intranasal calcitonin in 63 pts with CRPS in a

double-blind randomized study – Significant reduction in pain at rest and with

motion and increased mobility – Meta-analysis_Perez concluded that calcitonin

could provide effective pain relief in CRPS patients (J Pain Symptom Manage 2001)

Free Radical Scavenger

• Dimethylsulfoxide (DSMO)

• N-acetylcysteine (NAC)

• Effective in treating CRPS• Perez (Pain 2003)

Interventional Procedures

• Sympathetic Nerve Blockade – Diagnosis and treatment for CRPS

• Epidural Infusion – local anesthetic and opioid – fluoroscopic guidance catheter tip on the

affected side at the appropriate spinal segmental level

– Tunneled 5 days to 12 wks physiotherapy

Neuromodulation

• Only one in five CRPS patients is capable of returning to a normal level of functioning

• Spinal cord stimulation (SCS) is an intervention modality that may be used in patients with refractory pain

• Symptoms of CRPS have been ranked the second most frequent indicator for SCS therapy in the USA after post-laminectomy pain syndrome

SCS

• Pain relief as high as 70%

• when conservative therapies fail

• Kemler (J Neurosurg 2008)

• -------------------long term effect

• Harke (Eur J Pain 2005)

Intrathecal Drug Delivery

• Data citing the benefits is limited

• Case reports/series

• Viable consideration for patients that do not respond to SCS or w multiple sites of pain

• Alternatively ziconitide a nonopioid analgesic, has shown some promise in the treatment of severe chronic nonmalignant pain, including CRPS

Summary

• CRPS is a painful and debilitating disorder primarily affecting one or more extremities

• No specific etiology identified

• ? underlying pathophysiology

• Difficulties in diagnosis and treatment

• No single diagnostic test or a single or combination of therapies that are universally effective for CRPS

Conclusions

• Treatment of CRPS focuses on an early aggressive multimodal approach targets pain reduction and functional restoration

• Medications CRPS are approved for the treatment of other pain conditions

• Continued research may reveal additional mechanisms of the disease leading to preventive measures and additional targets for drug activity