Whatever happened to RSD? Andrew Muir

History 1872 Mitchell described a syndrome of causalgia: Limbs of American Civil War soldiers who sustained nerve injuries Burning pain, hyperaesthesia, trophic changes with glossy skin The nomenclature relates to the Greek ‘kausis’ burning and ‘algos’ pain after a nerve injury 1901 Sudeck (bone changes after injury) 1940 Reflex Sympathetic Dystrophy (RSD) 1864 Mitchell described causalgia after treating casualties from American civil war. Pain often accompanied by including various sensory disturbances; temperature and sweating changes; glossy and other disturbances of the skin, subcutaneous tissues, muscles and joints; paralysis; and involuntary movements. 1940 Evans described the term RSD. Evans envisaged that prolonged bombardment of pain impulses set up a "vicious circle of reflexes" in the spinal cord that generated efferent activity in the sympathetic system leading to spasm in the peripheral blood vessels. As a consequence there was leakage of fluid from the capillaries which eventually caused dystrophic changes in peripheral tissues. The French surgeon Leriche had already noted that the limbs of patients with causalgia showed features that he thought reminiscent of vascular insufficiency. Because patients with ischaemic limbs were often treated by sympathectomy, Leriche argued by analogy that causalgia was due to an "irritation of the sympathetic" and might be alleviated by sympathectomy. These notions were later extended to RSD, although few noted that Leriche was later to retract his hypothesis.

CRPS: Nomenclature The nomenclature of CRPS Types I, II was adopted after a Consensus Conference in 1993 Standardised terminology Avoid unsustainable pathophysiological implications Take up has been patchy but increasing: 11% of articles between 1995 and 1999 used it but 3.5% 1995 & 27.5% in 1999 Type II refers to major nerve injury, Type I to the rest.

CRPS: Diagnostic Criteria A. Presence of an initiating noxious event or cause of immobilisation. B. Continuing pain, allodynia or hyperalgesia with which the pain is disproportionate to any inciting event. C. Evidence at some time of oedema, changes in skin blood flow, or abnormal sudomotor activity in the region of pain. D. This diagnosis is precluded by the existence of conditions that would otherwise account for the degree of pain or dysfunction.

CRPS: Diagnostic Criteria One group found that the criteria did not discriminate between CRPS I and Diabetic Peripheral neuropathy and positive predictive value between 40 and 60%. Criteria used in a check list can improve PPV to 0.91, sensitivity to 0.71 and specificity to 0.95 Baron suggests current presence of 3 symptoms and 2 signs.

Pathophysiology: It can be shown that cooling the body with affected limb isothermic causes pain associated with sympathetic tone. Controversial pharmacological challenge of Raja etc Some studies have demonstrated an overall decrease in sympathetic nervous system activity explaining the Acute ‘hot’, hypercirculation phase Chronic ‘denervation supersensitivity’ phase with the cold blue limb.

Pathophysiology: Most of the following have been demonstrated in animal models of nerve damage. Peripheral changes Expression of adrenoceptors on a subset of C-fibres, OR Noradrenaline mediated release of prostanoids Central changes ‘wind up’ Autonomic/somatic crosstalk & sprouting after nerve injury.

Pathophysiology: Sympathetic nervous system elaboration of noradrenalin can activate mast cells, inviting a immuno-inflammatory aspect to this.

Na+ Ca++ Ca++ Mao et al, Pain, 1995 AMPA-R NMDA-R mGluR G Mg++ IP3 SP Glu AMPA-R NMDA-R mGluR G Mg++ Na+ IP3 Ca++ Ca++ L-arg PKC activation Gene expression Nos NO

Practical Clinical Features: Pain Allodynia Temperature change Colour change Sweating Dystrophy Motor change Non dermatomal Should be marked Uncommon Non-specific

Practical Clinical Features: A continuum from: Icy cold, immobile, dripping with sweat, profound allodynia TO Hey! The X-ray looks OK … so how come it still hurts?

Practical Clinical Features: There exist a number of potential differential diagnoses, the most common and important one is DISUSE secondary to persistent pain, (where the clinical signs are likely to be less marked). Unrecognized local pathology(sprain, #, sepsis, cellulitis, allergy) Vascular insufficiency (Raynaud’s disease, thromboangiitis obliterans, thrombosis)

Practical Clinical Features: In all cases, the aims of treatment must be considered through the same process as any other patient with chronic pain. RESTORATION OF FUNCTION !

Treatment algorithms Guideline published in 1998 Functional restoration Physical and psychological methods To move through to another modality if no response in defined period Consensus report Complex Regional Pain Syndrome: Guidelines for therapy Stanton Hicks et al Clin J of Pain 14: 155-66 1998 (now more recent)

Response to Algorithm 100 experienced pain specialists Referral 32% orthopaedic specialist 12% neurologist, 12% GPs 9% self referred, 9% anaesthetist 8%neurosurgeon, 8%physiotherapist 6% lawyer/ case manager 4% podiatrist

Frequency of Treatments

Pharmacotherapy

Timing of treatment 97% believed better outcome if referred within 3 months of onset

Evidence based guidelines Don’t really exist Cochrane data base of RCTs Critical analysis of 22 RCTs Poor methodology Only looking at one modality Difficult to compare Calcitonin deceases pain of CRPS Perez et al Journ of Pain and Sympt Mgt 21, No6, June 2001

What do we know? Oral corticosteroids are effective (2 papers, 1 RCT) Bisphosphanates: Alendronate improved bone density with a trend to decrease in pain and swelling Clodronate improved pain substantially Spinal cord stimulation – moderate improvement Some support for: DMSO cream Epidural clonidine Intravenous bretyllium, ketanserin

What do we know? IVRB guanethidine is ineffective, bretyllium works (single trial) Ketanserin effective Ketorolac effective (1 paper)

A Reasonable Approach: Physiotherapy – (rest or mobilisation) Adequate analgesia Early pulse of corticosteroids Early referral to Pain Clinic for: Repeated temporary sympathectomies Epidural clonidine Bisphosphanates Long term management of chronic pain

Case study 1: History Mrs C Italian woman 70 years old History: 3mths ago gardening Stick pierced palm R hand Hot, swollen, dry, painful Treated antibiotics, sling deteriorated

Case 1: History Referred to orthopaedic hand surgeon ? Hysterical, ?CRPS type 1 unable to move arm, fingers unable to hold knife and fork unable to do washing, cooking

Case 1: History Investigations Referred to pain clinic x-ray, bone scan, ultrasound inflammatory markers Referred to pain clinic

Case 1: Examination Pain on light touch, Increased reaction to pain in most of arm viz palm, classic tender points Motor neglect. All upper limb movements impaired tissue swelling temperature cooler than other limb colour change

Case 1: Management Management: Initial TCA, oxycontin, physiotherapy cease sling, start hanging washing on clothes line Series of 3 stellate ganglion blocks Good response for some days with lasting improvement(SMP) Combined with physiotherapy: EMLA cream to palm, trigger point injections extensor origin

Case 1: Management Outcome good. Swelling gone, Movements substantially improved Function: returned to most activities Residual thickening of palmar flexion tendon middle finger Swelling substantially reduced Pain Medications ceased

Case 2: History Mr U Turkish man aged 48 Injured at work end 1999 conveyor belt fault results in open injury to R hand laceration palmar branch of digital nerve repair of digital nerve

Case 2: History Pain increased No progress with hand therapy burning, painful on light touch extending up arm No progress with hand therapy Referred to pain clinic for SGBs

Case 2 : Examination Wearing glove Holding arm up close to chest difficulty swinging arm/initiating movement decrease grip strength Hand cold blue sweaty, swollen

Case 2 : Management Diagnosis of CRPS type 2 Trial of oral medications neuorpathic agents, SR opioids, TCAs Trial of stellate ganglion blocks/ activation temporary improvement (SMP) poor compliance Multi-disciplinary pain assessment

Case 2 : Management Not suitable for pain management seeking cure unresolved anger/ litigation Referred for in-patient rehabilitation program (Plan: Cx epidural/ phys ther) Unsuccessful

Case 2 : Management further interventional Mx by pain specialist number 3 guanethidine blocks Spinal cord stimulation Unsuccessful

Case 2 : Management Further deterioration now back and leg pain, using stick not working/ low function at home depressed arm wasted, sweaty hand, no movement heavily involved with litigation, still focussed on cure and blame seeking multiple medical opinions

Case 2 : Management ASSESSED AS “NOT READY” for CBT based Pain Management Program

Case 3 : History Mr M.R. Aged 24, Australian born Had a venipuncture from R cubital fossa (lateral aspect) November 2000 Felt pain shoot up to shoulder/ felt faint 36hrs later woke up with clawed R hand Has not been able to open hand since Has not worked since

Case 3 : History Referred by GP for pain management 2 overdoses Had been working at previous job for 3 days prior to Venipunture No real indication for VP did not attend a doctor prior to VP Litigation in progress against pathology firm

Case 3 : History Now living with grandparents who are “looking after him” Has initiated referral to multiple specialists No reports available Difficulty contacting referring GP Using self prescribed splints at night

Case 3 : Examination Presentation agitated conflicting history with Mother Pain not a major complaint Both hands cool sweaty Holding R hand in tight claw Resistance to opening

Case 3 : Management No wasting in arm in general Increased forearm muscle bulk Possibly some wasting dorsum of hand No difference in temperature, swelling, sweating No allodynia No motor akinesia of arm in general Normal movements of shoulder and upper arm. Cannot move fingers

Case 3 : Management Diagnosis? Management ??????????Nerve injury ?????????CRPS ??Conversion disorder Management Full assessment (multi-disc) Counselling/ Reassurance No medications, general gym program

Case 3 : Management Participating in competitive manner in Gym program Enjoys being videoed Has taken up a correspondence course (sports psychology) Will have an EUA Unable to get any reports

Case 4 : History MRS B 58 year old woman (Australian born) Working as nurse in aged care MCA 1997: injured shoulder and ankle(soft tissue) Recovered, RTW Persistent swollen R leg Intermittent shoulder stiffness

Case 4 : History 1998 R leg gave way, fell fractured ankle POP/ int fixn pain and spasm swelling persistent problem when in POP prolonged rehabilitation 2X 3 mths IP persisting pain, swelling, spasm 2 further operations No progress, Referred to pain clinic

Case 4 : Examination Pleasant co-operative woman Wearing rigid ankle brace/ using wheelchair leg swollen, cool compared to L side intense allodynia, skin dry, discoloured multiple tender points over entire leg, back shoulder out of brace grossly abnormal gait and devel of spasm on light touch/ movet

Case 4 : Management Management initial Oxycontin/ gabapentin: Good analgesia No improvement in function/spasm Lumbar sympathetic block Excellent block with no change in symptoms (SIP)

Case 4 : Management Case conference Rehab/ Physio in-patient admission: epidural opiate/ clonidine/ Local Anaesthetic Allodynia/ spasm disappeared gait re-training, gym program ceased all analgesics returned to normal activities no splint/ no wheelchair skin/ temp/ swelling abated

Case 4 : Management 12 months later noted recurrence of spasm and pain skin changes/ allodynia trial hydrotherapy/ gym finding this difficult, further deterioration requested epidural treatment underwent multi-disc assessment

Case 4 : Management Cure focussed, not interested in CBT Program Admitted for epidural Similar response to previous Pt anxious that found walking difficult. Had persistent muscle cramp Referral to IP rehab (Not accepted by TAC) OP physio attempted: poor progress

Case 4 : Management became increasingly frustrated by TAC Frustrated that not cured Told that time to accept as chronic problem Reacted to this Now overall improvement, walking/ holidaying in USA

Role of Primary Care Physician (1) DIAGNOSIS early (2) Early Use of adequate analgesia to promote normal activity/ posture active physio/ not passive/ gentle reactivation. if physio cannot progress 1st step is increase in time based analgesia (3) Early referral to Multi disciplin PU urgent, not to go on long waiting list

Be Aware Some pain specialists unimodal approach diagnostician eg phentolamine infusion/ guanethidine block/ no response/ discharge interventionist: blocks/ more blocks/ spinal cord stimulation/ no rehab/ psych rehab/ no intervention/ pain relief psych/ no intervention/ rehab

Be Aware Adequate education/ counselling patients ill informed/ self help groups/ Internet: progressive disease explanation of the importance of return to normal function avoid surgery if possible/ only if appropriate and covered by analgesia Role of cognitions/ depression/ litigation as mediating factors