Complex Regional Pain Syndrome(CRPS)

Complex regional pain syndrome(CRPS)

Introduction

Abnormal post traumatic pain following any nerve injury
3 basic criteria for diagnosis (American Association for Hand Surgery)
Disproportionate pain
hyperpathia-prolonged pain after stimulation
allodynia-marked pain from a usually nonpainful simulation
pain is usually constant.
Interference with function
Autonomic-type abnormality (eg, skin discoloration, sweating, dryness, edema, temperature change, osteoporosis)
CRPS (International Pain Nomenclature Group task force 1996) - defined on purely clinical grounds
CRPS is a clinical diagnosis – there are no physiological markers
CRPS is initiated by trauma, compounded by post traumatic event(tight cast) , and exacerbated by pre-morbid physiological state
Early recognition and prompt treatment is the single most important predictor of recovery
80% pts with RSD diagnosed within 1 yr of injury show significant improvement
50 % pts diagnosed after 1 yr have significant impairment

Classification

2 major categories and three types

Sympathetically maintained pain syndrome (SMP)

pain that is maintained by sympathetic efferent innervation and or circulating catecholamines
responds to sympathetic blocks
seen in Types I and II

Sympathetically independent pain syndrome (SIP)

Does not respond to sympathetic block
Seen in Type III

Clinically patients may have varying components of SMP and SIP throughout the course of the disease

Type I (classically “reflex sympathetic dystrophy”) follows an initiating noxious event

Pain - Continuous pain or allodynia and hyperpathia is not limited to the territory of a single peripheral nerve and is disproportionate to the inciting event
Functional Impairment
Autonomic dysfunction - Edema, skin blood flow abnormality, abnormal sudomotor activity, and motor dysfunction are disproportionate to the inciting event
Exclusion - Diagnosis is excluded by the existence of conditions that would otherwise account for the degree of pain and dysfunction

Type II (classically described “major causalgia”) includes the following

Nerve injury - Major nerve injury, more regionally confined presentation (usually), principally involving the territory of the involved nerve
Pain - Spontaneous pain or allodynia and hyperpathia usually limited to the area involved but may spread distally or proximally
Functional impairment
Autonomic dysfunction -Edema, blood flow abnormality, or abnormal sudomotor activity is or has been shown in the region of pain subsequent to the inciting event, or there is motor dysfunction disproportionate to the inciting event
Exclusion -Diagnosis is excluded by conditions that otherwise account for the degree of pain and dysfunction

Type III (sympathetically independent pain)

classification identifies cases of disproportionate pain and sensory change with motor and tissue change that do not respond to sympathetic block.

Pathophysiology

Normally pain is felt in the presence of actual or impending cellular injury , in the absence of trauma persistent pain is pathological
Proinflammatory cells like lymphocytes and mast cells accumulate in the affected tissue, releasing cytokines and histamine, and activate inflammatory mediators, such as prostaglandins, which are responsible for sensitizing C nociceptor afferent nerve endings
This information is transmitted to the dorsal root ganglia where sensitization of a wide dynamic range of neurons (WDR) contributes to the central nociceptive discharge.
Within the dorsal horn, NMDA receptor transmitter interactions produce long lasting potentials , is refractory to stimulation and is theorized to play a role in CRPS I and II
The perception of pain is determined by complex interaction of afferent, descending modulatory pathways and peripheral and central factors
Vasomotor disturbances can result from a variety of mechanisms including antidromic vaso dilation, vasoparalytic dilatation, normal somatosensory reflexes and denervation supersensitivity
Abnormalities:

abnormal neurotransmitter release secondary to nociceptive foci
abnormal receptor distribution
alterations in receptor sensitivity (up-or-down regulation)

Following trauma a transient period of dystrophic extremity function is normal
It is abnormal for hyperpathia, allodynia, vasomotor disturbances and functional deficiencies to persist
Theories

1. Exaggerated and sustained normal inflammatory response

2. Backflow of nociceptive stimuli into the injured area releasing vasoactive neuropeptide substances ie substance P, calcitonin gene-related peptide, bradykinin, serotonin, somatostatin, neurokinin A, and others

Substance P especially has been shown to cause vasodilatation, increased vascular permeability, pavementing of leukocytes in venules, stimulation of phagocytosis, degranulation of mast cells, and stimulation of fibroblasts.

3. Altered response by sympathetic nervous system

this concept being increasing challenged
Experimental findings do not show hyperactivity of the sympathetic nervous system
placebo-controlled studies showed sympathetic block to be no more effective than the placebo
autonomic dysfunction now thought to either be sensitisation of sympathetic nervous system by local neuropeptides or mediated by neuropeptides themselves

4. Psychological

CPRS patients are more likely to be anxious, depressed, more dissatisfied with their bodies
most investigators believe these psychologic differences are a result rather than a cause of RSD

Demographics

most reports average about a 5% incidence after an inciting cause
The more common injuries and surgery, such as Colles fracture and carpal tunnel syndrome, have the highest frequency of cause
10% to 30% of patients have spontaneous occurrence with no evident precipitating cause or condition
F>M 3:1
mean age 45 (35-50); has been reported in children
increased incidence of cigarette smoking
Psychological factors such as stressful life event, and inadequate coping mechanisms influence the development and severity
No specific personality or psychological factor has been predisposed individual to CRPS

Prognosis

Most patients with Type 2 will improve with time
in other forms of RSD-CRPS, complete remission is rare
incidence of recurrent or migratory RSD is reported to be as high as 15% to 75%, often occurring at a different site
Overall, review of the literature gives the impression that most treatment methods result in approximately one third of patients with excellent to good relief, one third with some improvement, and one third with no improvement or worsening of symptoms.

Aetiology

Most common are

Colles fracture –11-37%
Carpal tunnel surgery 2-5%
Surgical trauma to superficial radial nerve and palmer branch of radial nerve
No cause in 30%

Clinical

Symptoms

most characteristic clinical feature of RSD is the peculiar disproportionate unremitting pain.
hyperpathia and allodynia
pain is constant and not completely relieved by rest, and it is aggravated by motion; activity; or temperature change (especially cold).
Mirror image (advancement to the contralateral extremity) up to 25%

Signs

first noticeable physical findings in RSD is the patient's avoidance of touch or functional use caused by pain
Trophic changes

Stiffness(70%) - passive better than active range of motion until late changes occur
Oedema– gives a glossy smooth appearance to skin
Atrophy of hair and nails(or hyperkeratosis)
Atrophy of intrinsics may be seen
Osteopenia involving cortical and cancellous bone
Autonomic changes
vasomotor changes include skin discolouration (mottled color change (redness or cyanosis))
difference in skin temperature - warmness more common early and coolness later in the course of the disorder
hyperhydrosis or dryness
Motor disturbances
Tremor (58%)
weakness
incoordination dystonia (35%)
decreased ROM

need to examine the cervical spine and neurological system to exclude other causes eg diabetes, small fibre peripheral neuropathies, entrapment neuropathies, thoracic outlet syndrome, DVT and cellulitis may all mimic CRPS, and assess shoulder as frozen shoulder can occur secondarily
look for myofascial trigger points – 50-70% incidence in CPRS patients
3 distinct clinical forms

1. CRPS Type 2

caused by partial injury to a proximal major mixed nerve
onset is immediate and its course usually includes some degree of spontaneous improvement
superior response to sympathetic block and sympathectomy
Nerve injuries are usually above the elbow and knee, and are most often caused by high-velocity missile wounds
Sympathetic block usually provides temporary relief of causalgia and repeated blocks may produce sustained relief in some cases
When only temporary relief consistently results, surgery is indicated, with sympathectomy remaining the treatment of choice

2. Shoulder-hand syndrome

pain of RSD originating in the shoulder, progressing distally
need to exclude Pancoast's tumor and visceral tumors

3. Sudeck's osteoporosis/atrophy

resembles the osteoporosis of disuse but onset of osteoporosis is much more rapid than can be explained by simple disuse, with findings as early as 4 to 6 weeks after onset of symptoms
consider calcitonin or bisphosphonate therapy, which may reverse the osteoblastic activity and the pain in Sudeck's osteoporosis

Stages of CRPS

Patients have enormous variation in their presenting symptoms, duration, and mixture of characteristics in each stage.
Many never progress beyond stage I, whereas others may rapidly progress to the dystrophic stage III within 3 to 6 months.
These stages have no great clinical value, other than as a convenient description of the clinical change and its prognostic implications

Stage I: acute

Lasts approximately 3 months (variable)
Constant burning or throbbing pain (intensity varies), atrophy, and hyperpathia
Trigger points may develop
Variable vasomotor changes, such as edema (aiding or nonprinting); color change (usually redness, sometimes cyanosis); temperature change (usually warming, sometimes coolness); increased sweating; sometimes dryness
Decreased joint range of motion caused by pain
Sometimes swollen fingernail ridging (occasional)
Increased hair growth or pigmentation (occasional)

Stage II: subacute

Lasts approximately 9 to 12 months (variable)
Constant aggravating pain (intensity varies)
Atrophy of skin and subcutaneous tissue
Loss of fingertip pads (pencil pointing)
Glossy, thin skin
Decreased hair growth
Cyanosis
Brawny edema
Joint ankylosis
Palmar fasciitis and Dupuytren's nodules (occasional)
Myofascial trigger points (usual)
Subchondral patchy osteoporosis (usual)

Stage III: chronic

Chronic intractable pain
Pale, cool, dry extremity
Thin, stretched skin
Muscle atrophy
Fixed flexion or extension contractures
Diminished hair growth (usual)
Patchy to generalized osteoporosis
Patient is chronically depressed and may contemplate suicide

Diagnostic testing

No one laboratory study is specific for RSD-CRPS, and it remains a clinical diagnosis
objective measurements are useful to support the diagnosis
typical patients with RSD have normal sedimentation rate, C-reactive protein level, leukocyte count, and concentrations of other acute-phase reactants, despite the appearance of inflammation

Electromyographic and nerve conduction studies

show no specific abnormality associated with RSD

Pain threshold evaluation

Quantitiative sensory tests are available to test and compare the respond to painful stimuli
Using monofilaments to assess hyperpathia and allodynia
Useful to monitor progress
use of a visual analog scale and a pain diagram drawn by the patient will add to functional assessment

Thermography

Temperature measurement by infrared thermography
most useful to help the clinician communicate with the patient about the illness and to monitor progress.

Radiology

1. Xray

considerable demineralization must occur for osteopenia to become visible on standard radiographic view which places patients at a late stage and a worse prognosis
also see diffuse juxtacortical demineralization and subchondral erosion and cysts

2. three phase technetium bone scan

in the phase III scan - diffuse tracer uptake in the delayed image is diagnostic according to Mackinnon
abnormalities seen in 50-80%
A normal bone scan does not rule out the diagnosis
useful test when positive, because it is seen well before standard radiographic change
positive scan has high specificity but low sensitivity
bone scans is not a prerequisite for diagnosis, does not correlate with response to treatment or predict recovery

Evaluation of autonomic control

Autonomic function controls sweating and microvascular perfusion
Evaluation of sympathetic control or dysfunction aids in diagnosis
May be evaluated by testing microvascular flow or sweating
Microvascular examination

Under normal circulation total digital flow is composed of 80 – 95 % thermoregulatory flow and 5-20 % nutritional flow
In CRPS impaired autonomic control leads to ischaemia secondary to reduced nutritional flow secondary to altered AV shunting
Analysed using microscopic epi-illumination of digital skin, combined with laser Doppler flux

Sudomotor evaluation

Galvanic skin conduction
Quantitative sweat response

Diagnostic sympathetic blocks

Traditionally used as a diagnostic test
IV infusion of phentolamine (alphaadrenergic blockade) or regional blocks stellate brachial plexus block
More recent evidence refutes this and shows it no more effective than placebo

Treatment

Multiteam approach with surgeon , therapist, pain specialist and psychologist
Early diagnosis is paramount- there is general belief that the earlier treatment is instituted, the better the prognosis
all techniques are directed at interruption of the reflex pain cycle

Surgical treatment

Sympathectomy
useful in well-selected patients, especially in cases with proximal nerve injury (causalgia)
The patient most likely to benefit from sympathectomy is one who obtains repeated, dramatic, temporary relief from sympathetic blocks but for whom the relief never lasts longer than the duration of the anaesthetic and in whom there is no placebo effect with use of saline for the block.
Surgery for neural dystrophic focus
Principles
need for urgent surgery to avoid a severe chronic pain syndrome
Use long-acting or continuous axillary block anaesthetic to avoid redevelopment of a pain reflex cycle – shown to be effective
Extensile exposure
Avoid tension on nerve repair site – use grafts if required
Prevent adhesion between skin and nerve – Z plasty, local flaps
If wound bed scarred, modify the bed
Minimise internal neurolysis
Prevent hematoma
Avoid constrictive postoperative dressing
Postoperative pain control
Post carpal tunnel
Preserve palmar cutaneous branch
Identify all branches
Treat neuroma by relocation or repairing if in continuity
If bed scarred, then modify local environment
autologous vein wraps – neuroma of palmar cutaneous nerve or branches of median nerve in palm
local flaps – PB, ADQ, PQ, lumbricals, hypothenar fat pad
regional flaps – fasciocutaneous, fascial
Superficial branch radial nerve
Identify nerve proximal and distal to scar
Options
nerve repair with graf
relocate into muscle/radius
cephalic vein wrap
Secondary joint deformities
Contemplate after maximal nonoperative improvement has been obtained
Minimum 3-6 months
Indications are joint pain without diffuse dystrophic symptoms and arthrofibrosis interfering with function
Implanted electrical stimulation
improvement by peripheral nerve block is a prerequisite, along with temporary success by transcutaneous nerve stimulation
best results when used in patients whose pain is “somatically” derived and not from “sympathetic overstimulation/RSD.”

Nonsurgical treatment

Hand therapy
foundation of treatment for most patients with RSD-CRPS
other modalities should serve as adjunct
imperative to establish baseline measurement criteria to monitor progress
these patients typically do not believe they are slowly improving until shown proof through objective measurements, such as reduced edema, increased grip strength, improved range of motion, temperature control, and so forth.
Techniques
“Rest and motion” are management principles that emphasize the need for partial rest in a splinted functional position and frequent physical activity and motion to the fullest pain-free extent
Heat to relax muscle spasm and improve joint motion
Treat myofascial trigger points with warm massage, stretch exercises, and injection of persistent trigger points
ultrasound over the stellate ganglion or the involved peripheral nerve
biofeedback - temperature biofeedback – most useful when clinical manifestations include pronounced temperature change
desensitization
stress loading
Stellate ganglion and other nerve blocks
remains the most widely accepted form of RSD-CRPS treatment
blocks are not uniformly successful and are no longer required for diagnosis, although widely used to classify sympathetically maintained pain (CRPS type I or II)
best suited for patients whose manifestations seem predominantly sympathetic, such as abnormal skin color, temperature, and sweat
usually injected with local anaesthetic
results verified by
Horner’s syndrome
Increase in skin temperature, venous engorgement, dry skin, mottled color, laser Doppler flux changes
Reflex pain firmly established at the central level is more likely to respond to other methods that activate the endogenous opioid internal pain control system, which is known to interfere with pain neurotransmitter production and secretion (eg, substance P). This endogenous mechanism might explain why “placebo blocks” are frequently successful in as many as 30% of patients
Brachial plexus blocks are useful to determine whether a patient's stiffness is caused by pain or fibrosis by assessing the passive range of motion while they are anesthetized and paralyzed.
Repeated local long-acting nerve blocks are sometimes successful in breaking the pain cycle in selected patients whose symptoms are confined to a specific neurologic region, (ie superficial radial nerve, or an isolated digit, such as an amputation stump with painful digital neuroma.)
Intravenous regional infusions
infusion of intravenous guanethidine sympathetic block into an extremity isolated by Bier block
Other common agents are reserpine,phentolamine, steroids and bretylium but no conclusive evidence
Recent randomized, double-blind controlled comparison of intravenous guanethidine, reserpine, and saline showed no difference at 24 hours. Similar studies using phentolamine showed no advantage over placebo. As yet, there has been no controlled study of bretylium tosylate
Systemic intravenous infusion
Lignocaine
Shown to relieve neuropathic pain and/or pain refractory to opioid therapy
antihyperalgesic effects on the peripheral as well as the central nervous system
membrane stabilising effect
Medical treatment

sympatholytics
clonidine (α2-adrenergic agonist), phenoxybenzamine (combined α1- and α2-antagonist)
Calcium channel blockers
Nifedipine, diltiazem (verapamil has predominantly cardiac effect and is not useful for RSD-CRPS)
function to decrease sympathetic smooth muscle tone and improve blood flow, warming digits by preventing calcium release and reducing vasoconstriction.
NSAIDS
of questionable value
Steroids
Proven beneficial in some patient- either with a short-term, high-dose method or with long-term use
Central acting agents
anticonvulsants – postulated to stabilise excitable nerve membrane and reduce hyperexcitability (Clonazepam, gabapentin)
baclofen (GABA agonist) – useful for ongoing muscle spasms and cramps
recently intravenous infusion of Alendronate has been shown to reduce pain and swelling and increasing ROM iin pts with CRPS
Antidepressants, anxiety, narcotic, and sleep medications
antidepressants(TCA) – provide analgesia and modulate sympathetic over activity
narcotics - One should exhaust other treatment techniques before resorting to chronic narcotic use.
Calcitonin
regulates bone metabolism
better results are reported when patients are treated soon after onset
best suited for patients with positive three-phase bone scan
Biphosphonates
by reducing local acceleration of bone remodelling - potent osteoclast blocking agents and their believed action to inhibit neuropeptide release from afferent nerve endings
most suitable in patients with abnormalities on bone scan

TENS
mechanism is hypothesized to be by activation of the endogenous opioid analgesic system to release endorphins that may inhibit pain at the level of the spinothalamic tract
particularly useful when there are minimal inflammatory or autonomic changes and pain is the predominant manifestation.
generally used as adjunctive therapy to assist with pain control.
most effective when initiated early.
Acupuncture
Using electrodes or transdermal needles
Better results in Asian patients (?due to higher expectations)

Principles in the treatment of RSD