Complex Regional Pain Syndromes

               Complex Regional Pain Syndromes

                                      DR KS Dhillon

Introduction

There are two types of complex regional pain syndromes (CRPS). The type 1 CRPS was formerly known as reflex sympathetic dystrophy (RSD) and the type II CRPS was formerly known as causalgia. The International Association for the Study of Pain (IASP) has agreed on the diagnostic criteria for these two syndromes. 

The natural course and pathophysiology of these debilitating pain syndromes remain elusive and their treatment remains controversial [1].

Epidemiology

The incidence of CRPS in the US is 5.5 per 100,000 person-years. It affects females more often then males (4:1). The incidence increases with age up until 70 years old. Sixty percent occurs in the upper limbs and 40% occurs in the lower limbs. Risk factors include, trauma with an exaggerated response to injury, prolonged immobilization, surgery, depression or anxiety, ACE inhibitors use at the time of trauma, smoking, history of migraines or asthma and fibromyalgia.

Pathophysiology

Despite the fact that these syndromes have been around for a century and despite the existence of a wealth of literature and discussions, the pathophysiology of CRPS remains elusive.

There are multiple pathophysiologic mechanisms involved in the pathogenesis of CRPS. These include:

1. Altered intradermal innervation after injury

More experimental and clinical evidence is accumulating which supports the hypothesis that even in CRPS 1 there is some form of nerve trauma that triggers events that leads to CRPS even though there are no clinical signs of nerve injury. There is a small nerve fiber neuropathy [2,3,4,5].

There is C-fiber and A-delta fiber abnormal excitation and firing and this is associated with the co-release of peptidergic neuropeptides [6,7,8,9]. Skin biopsies show significantly lower densities of epidermal neurites (up to 29% lower) in CRPS-affected limbs as compared to contralateral unaffected limbs [4]. Primarily the nociceptive fibers are affected. 

Albrecht et al [10]  found several neuropathologic alterations in CRPS affected skin including:

Presence of numerous abnormal thin caliber axons innervating hair follicles.

Decrease in epidermal, sweat gland, and vascular innervation.

Loss of Calcitonin gene-related peptide (CGRP) expression on    remaining innervation to vasculature and sweat glands. 

Inappropriate expression of Neuropeptide Y (NPY) on innervation to superficial arterioles and sweat glands. 

Loss of vascular endothelial integrity and vascular hypertrophy. 

There is evidence of widespread cutaneous neuropathologic changes in the skin of individuals with CRPS.

2.Central Sensitization.

When tissue injury or nerve injury produces persistent or intense noxious input, increased excitability of nociceptive neurons in the spinal cord can occur leading to central sensitization. This enhancement in the function of neurons and circuits in nociceptive pathways is caused by increases in membrane excitability and synaptic efficacy along with a reduction of inhibition. This is a manifestation of the plasticity of the somatosensory nervous system in response to inflammation and neural injury [11]. 

With central sensitization previously subthreshold synaptic inputs to nociceptive neurons can get recruited. Normal inputs can elicit sensory responses which produce pain hypersensitivity. 

With central sensitization there is an exaggerated response to nociceptive stimuli (hyperalgesia) and normally non painful stimuli such as light touch or cold can activate nociceptive pathways (allodynia) [12].

Mediation in central sensitization is by the nociception-induced release of neuropeptides, such as bradykinin and substance P. Amino acid glutamate acts at spinal N-methyl-d-aspartic acid receptors to produce the excitatory stimulus [12,13].

 3.Local peripheral sensitization

Tissue trauma can elicit local peripheral sensitization. Following peripheral tissue trauma, the primary afferent fibers in the injured area release several pronociceptive neuropeptides such as substance P and bradykinins. These neuropeptides increase background firing of nociceptors in response to nociceptive stimuli. They also decrease the firing threshold for thermal and mechanical stimuli [14,15]. These two effects lead respectively, to the hyperalgesia and allodynia that is seen in CRPS [16].

Peripheral and central sensitization leads to significantly reduced acute pain thresholds in the affected extremity in patients with chronic CRPS. 

4.Circulating Catecholamines

There is a change in the signs and symptoms of CPRS as the condition moves from the acute to the chronic phase. This is partly due to alteration  in catecholaminergic mechanisms. 

In the acute phase there is unilateral inhibition of sympathetic vasoconstrictor neurons and this leads to a warmer affected limb in the acute stage.

In the chronic stage secondary changes in neurovascular transmission occur and this leads to vasoconstriction and cold skin. The levels of norepinephrine drop on the affected side. With these lower norepinephrine levels there is diminished local sympathetic nervous system (SNS) outflow. Despite this reduced SNS outflow there are exaggerated vasoconstrictive responses in chronic CRPS patients. This paradoxical pattern is believed to be a result of receptor up-regulation of peripheral adrenergic receptors [2].

Hypersensitivity to circulating catecholamines leads to exaggerated sweating and vasoconstriction. This leads to a cool, blue, sweaty extremity which typically is seen in patients with chronic CRPS. The vasoconstriction  leads to local tissue hypoxia which contributes to development of trophic changes seen in patients with CRPS via  local tissue hypoxia [17].

5.Altered Sympathetic Nervous System Function

Excessive sympathetic nervous system (SNS) outflow leading to vasoconstriction is responsible for the  autonomic features of CRPS, such as a cool and bluish limb. The pain in CRPS is also sympathetically maintained [18]. After trauma adrenergic receptors become expressed on nociceptive fibers. This expression of adrenergic receptors on nociceptive fibers leads to sympatho-afferent coupling. SNS outflow can trigger these receptors leading to pain in patients with CRPS [2].

High SNS activity increases pain in patients with sympathetically mediated CRPS pain. Excessive SNS outflow is, however, not the only cause of CRPS pain and other symptoms [2]. 

6.Inflammatory Factors

After tissue trauma immune cells such as lymphocytes and mast cells secrete proinflammatory cytokines such as interleukin-1β, -2, -6, and tumor necrosis factor (TNF)-α which induces inflammation in patients with CRPS [19]. These substances can also increase plasma extravasation in tissue, leading to localized edema which is seen in patients with CRPS.

Various triggers such as nerve injury lead to release of proinflammatory cytokines and neuropeptides from nociceptive fibers. These cytokines and neuropeptides produce neurogenic inflammation in patients with CRPS [20]. Some of the neuropeptides which produce neurogenic inflammation include substance P, calcitonin gene-related peptide (CGRP), and bradykinin. 

These neuropeptides can produce vasodilation which leads to redness and warmth of the extremity. The neuropeptides also increase plasma extravasation which can produce an edematous extremity seen in patients  acute CRPS [7]. 

Substance P and TNF-α can activate osteoclasts which produce osteoporosis which can frequently be seen in CRPS patients. CGRP can increase hair growth and increase sweating which is sometimes seen in patients with CRPS [7,21]. 

7.Brain Plasticity

In patients with CRPS there is a reorganization of somatotopic maps in the brain. Neuroimaging studies show that in patients with CRPS there is reduction in size of representation of the affected limb in the cerebral cortex as compared to the non-affected limb [22,23,24,25,26]. Studies show that these alterations return to normal after the CRPS has been successfully treated [24,25]. This evidence suggests that brain plasticity occurs in the development of CRPS.

A study by Maihöfner et al [23] showed that the degree of somatotopic reorganization significantly correlated with CRPS pain intensity and the degree of hyperalgesia. 

CRPS patients with cerebral reorganization also demostrate impaired two-point tactile discrimination [25] and an impaired ability to localize tactile stimuli as well as perceive sensations outside of the stimulated nerve distribution [27]. 

Somatotopic reorganization can account for the fact that sensory deficit to pinprick and touch in CRPS patients is present throughout the affected body quadrant or the whole on side of the body [28].

8.Psychologic Factors

In the past many assumed that CRPS is a psychogenic disorder because the pathophysiology of the syndrome was poorly understood. There is however no evidence to show that CRPS is a psychogenic disorder. 

Psychological factors such as anxiety, depression and anger can be associated with increased catecholamine release which can exacerbate the vasomotor signs of CRPS and also increase pain intensity [29,30,31].

9.Genetic Factors

Several studies have shown that genetic factors may be involved in CRPS [32]. Genetic factors play an important role in causing familial aggregation of diseases. Several studies have reported familial aggregation in CRPS [32]. 

Genetic associations have been reported between CRPS and polymorphisms in human leukocyte antigens [33] and tumor necrosis factor [34]. Kimura et al [35] found that there is an association between CRPS and polymorphism in the ACE gene, which is located on the long arm of the chromosome.

Another indicator of increased genetic susceptibility for CRPS is the fact that patients with a more severe phenotype are of a younger age at onset as compared to patients in whom the disease has remitted or stabilized [36,37].

Classification of CRPS

CRPS is classified according to a classification by Lankford and Evans. Stages of RSD include:

• Acute stage: Onset is 0-3 months. There is burning pain, warmth, redness, hyperhidrosis, swelling, hyperesthesia, cold intolerance, joint stiffness. The x-rays are normal but the three-phase bone scan is positive
• Subacute (dystrophic): The onset is 3-12 months. There is worsening pain, stiffness, dry skin, cyanosis and skin atrophy. X rays show subchondral osteopenia.
• Chronic (atrophic): The onset is more then 12 months. There is diminished pain, fibrosis, glossy skin, joint contractures with loss of hair and nails. The x rays show extreme osteopenia.

Diagnosis of CRPS

The diagnosis of CRPS is made by using certain clinical criteria.  The most commonly used diagnostic criteria is one endorsed by the International Association for the Study of Pain (IASP). 

The 1996 IASP criteria for CRPS include:

(1) CRPS is a syndrome which develops after an initiating noxious event

(2) Spontaneous pain, hyperalgesia or allodynia occurs which is not limited to the territory of a single peripheral nerve, and is out of proportion to the inciting event;

(3) Presence of edema, changes in color and temperature, or abnormal sweating in the region of the pain since the inciting event and

(4) The diagnosis of CRPS is excluded by the presence of conditions that would account for the degree of pain and dysfunction.

To make a diagnosis of CRPS, criteria 2,3 and 4 must be fulfilled [38].

The original 1996 IASP criteria was later revised by the Budapest consensus group (accepted and codified by the Committee for

Classification of Chronic Pain of the International Association for the Study of Pain)

The general features of the syndrome include:

CRPS is characterized by a continuing (spontaneous and/or evoked) regional pain that is disproportionate in time or degree to the usual course of any known trauma or other lesion. 

The pain is regional (not in a specific nerve territory or dermatome) and usually has a distal predominance of abnormal motor, sensory, vasomotor, sudomotor, and/or trophic findings. The syndrome exhibits variable progression over time.

There are now two versions of the proposed diagnostic criteria: a clinical version and a research version. The clinical version is meant to maximize diagnostic sensitivity with adequate specificity and the research version is meant to equally balance optimal sensitivity and specificity [39].

Clinical diagnostic criteria for CRPS include [39]:

1) Continuing pain, which is disproportionate to the inciting event

2) Must have at least one symptom in three of the four following categories

• Sensory: Presences of hyperalgesia and/or allodynia
• Vasomotor: Presences of temperature asymmetry and/or skin color changes and/or skin color asymmetry
• Sudomotor/Edema: Presences of edema and/or sweating changes and/or sweating asymmetry
• Motor/Trophic: presences of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)

3) Must display at least one sign at time of evaluation in two or more of the following categories

• Sensory: Evidence of hyperalgesia (to pinprick) and/or allodynia (to light touch and/or deep somatic pressure and/or joint movement)
• Vasomotor: Evidence of temperature asymmetry and/or skin color changes and/or asymmetry Sudomotor/Edema: Evidence of edema and/or sweating changes and/or sweating asymmetry
• Motor/Trophic: Evidence of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)

4) There is no other diagnosis which better explains the signs and symptoms

A sign is counted only if it is observed at time of diagnosis.

Research diagnostic criteria for CRPS include [39]:

1) Continuing pain, which is disproportionate to the inciting event

2) Must have at least one symptom in each of the four following categories

• Sensory: Presences of hyperalgesia and/or allodynia
• Vasomotor: Presences of temperature asymmetry and/or skin color changes and/or skin color asymmetry
• Sudomotor/Edema: Presences of edema and/or sweating changes and/or sweating asymmetry
• Motor/Trophic: presences of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)

3) Must display at least one sign at time of evaluation in two or more of the following categories

• Sensory: Evidence of hyperalgesia (to pinprick) and/or allodynia (to light touch and/or deep somatic pressure and/or joint movement)
• Vasomotor: Evidence of temperature asymmetry and/or skin color changes and/or asymmetry Sudomotor/Edema: Evidence of edema and/or sweating changes and/or sweating asymmetry
• Motor/Trophic: Evidence of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)

4) There is no other diagnosis which better explains the signs and symptoms

A sign is counted only if it is observed at time of diagnosis.

Vascular and neurologic examinations should be carried out to help detect the presence of conditions which may mimic CRPS. Diabetic neuropathy, small-fiber peripheral neuropathies, entrapment neuropathies, discogenic disease, and thoracic outlet syndrome, should be ruled out. Other differential diagnoses include cellulitis, deep vein thrombosis, lymphedema, vascular insufficiency, and erythromelalgia [1].

Laboratory tests are not very useful in the diagnosis of CRPS. Certain tests can help to confirm clinical impressions.

Quantitative sensory tests, electromyogram, nerve conduction studies, quantitative sudomotor axon-reflex test, sympathetic block, thermography,

Doppler flowmetry, radiography and bone scintigraphy has been used to reinforce the diagnosis. Sympathetic blocks have been used to determine the involvement of the sympathetic nervous system in patients with CRPS.

Differential diagnosis

The differential diagnosis of CRPS include the following:

• Psychiatric disease
• Neuropathic pain
• Soft tissue infection
• Malingering
• Raynaud disease
• Chronic pain
• Thoracic outlet syndrome
• Erythromelalgia
• Arterial insufficiency

Treatment approach

Pain is usually the leading symptom of CRPS. Besides the pain, limb dysfunction is often seen in CRPS patients. Elements of psychological distress are common in most patients. Insomnia, anxiety and depression often develops in patients when pain persists. Hence the need for an integrated interdisciplinary treatment approach tailored to the individual patient [40]. 

The United Kingdom guidelines on CRPS list four pillars of CRPS care: 

1. Education 

2. Pain relief with medications and procedures 

3. Physical rehabilitation

4. Psychological intervention. 

All the four pillars are equally important and a range of specialties such as rheumatology, physiotherapy, neurology, pain medicine and surgery are required to address these pillars of care [40]. The main aim here is to reduce pain, restore function and enable the patients to manage their condition so that their quality of life can be improved. Full recovery is difficult to achieve in some patients, even when appropriate treatment is started early.

Functional restoration

Functional restoration is carried out by gradual and steady progression from activation of pre sensorimotor cortices to very gentle active movements [39]. This is followed by putting partial weight on the lower limb and walking and for the upper limb, start carrying light bags and objects. 

Progressive desensitization carried out by stimulating the skin silk, towels and other textiles.

Aggressive passive range of movement exercises should be avoided. There should be a gentle gradual increase in range of movements. The main aim is to achieve postural normalization, stabilization and a balanced use of the limb [41]. 

Vocational rehabilitation should be started. Attempts are made to help the patient return to work, school or homemaking or to any other endeavor necessary. All attempts are made to overcome psychological difficulties. Anxiety, depression, anger and personality disorders should be appropriately dealt with [41]. 

Pharmacological Management

There is a lack of good treatment trials for CRPS. Current practice is a bit chaotic and continues to use trial and error methods [41]. Some of the drugs used for treatment of CRPS include: 

1. Non-steroidal anti-inflammatory drugs (NSAIDs)

In the initial stages NSAIDs can be used to treat the pain and inflammation associated with CRPS. Long term use of NSAIDs can be harmful because of potential for gastric ulceration and renal failure. Pain relief is usually not very satisfactory with the use of NSAIDs.

2.Opoids

The use of opioids remains controversial and their efficacy varies. No controlled studies of opioid use in CRPS exists [41]. When NSAIDs are not effective opioids can be used. Opioids can initially be tried intravenously as patient controlled analgesia. In patients with a history of chemical dependence the use of opioids requires extreme caution. Opioid cannot be abruptly stopped. 

3.Tricyclic and heterocyclic antidepressants

Serotonin/norepinephrine reuptake blockers such as amitriptyline, desipramine and maprotiline have been found to be useful in the treatment of neuropathic pain syndromes. Shooting pain, spontaneous pain and allodynia can be treated with these agents. The dose needed for pain relief is usually lower then that used for depression.  

These antidepressants can overcome anxiety and also improve mood and sleep [41].

4.Corticosteroids

 Steroids are often used in CRPS patients who have redness, warmth and oedema of the limb due to inflammation. Steroids are useful for pain associated with joint movements and that associated with trophic changes [41].

5.Calcitonin Biphosphonates

Subcutaneous injections of calcitonin have been found to have some effect on reducing spontaneous pain in patients with CRPS [41].

6.Adrenergic Drugs

Systemic α blockers (phenoxybenzamine, prazosin, doxazosin, and terazosin) have been found to improve peripheral blood flow and tissue perfusion as well as reducing pain in patients with CRPS. A recent meta-analysis of medical therapies aimed at inhibiting sympathetic function however failed to establish the utility of sympathetic blockade [42]. Topical alpha-2 agonists such as clonidine have been found to be useful in treating discrete areas of hyperalgesia [43]. Epidural injections of clonidine have also been found to be effective for pain relief in patients with CRPS [44].

7.Capsaicin

High dose topical capsaicin has been found to be useful in treating localized areas of hyperalgesia in patients with CRPS [45].

8.Antiepileptic Drugs

Gabapentin, an anticonvulsant, is commonly prescribed for neuropathic pain in patients with CRPS. Gabapentin works by inhibitions of the K(+)-induced [Ca(2+) (i) [46].

A randomized, blinded trial in 58 patients with CRPS by van de Vusse et al [47] showed that gabapentin had a mild effect on pain. Another large placebo-controlled trial of gabapentin by Serpell [48] showed significant reduction in pain as compared to placebo in patients with CRPS.

Carbamazepine as well as phenytoin are widely used for treatment of CRPS pain [49,50].

9.Sodium Channel Blockers

Intravenous lidocaine through its sodium channel–blocking properties has demonstrated efficacy in treatment of neuropathic pain [51] and CRPS.

A study by Wallace et al [52] found that intravenous lidocaine caused a significant elevation of the hot pain thresholds in the painful areas. It also caused a significantly decreased response to stroking and cool stimuli in the allodynic areas. A decrease in pain scores to cool stimuli at all plasma levels was seen and also a decrease in spontaneous pain at the highest plasma level.

10.N-methyl-D-aspartate Antagonists

An increased expression of N-methyl-D-aspartate (NMDA) receptors play a role in neuropathic pain in CRPS. Hence, NMDA receptor antagonists can be used for the treatment of pain in CRPS patients. Drugs with relevant NMDA-blocking properties include ketamine, amantadine, memantine, dextromethorphan, and methadone [53].

Dextromethorphan, amantadine, and memantine, are weaker NMDA receptor blockers, and are expected to have fewer central nervous system side effects. 

A study by Kleinböhl et al [54] showed that Amantadine was beneficial for chronic musculoskeletal pain with reductions in experimental sensitization.  Memantine has been anecdotally useful for neuropathic pain but there are no published studies on the use of these drugs in CRPS patients. 

11.Thalidomide

Tumor necrosis factor alpha (TNF-α) is believed to be the cause of inflammation and pain in CRPS. Thalidomide inhibits TNF-α and hence can  reduce inflammation and pain in CRPS patients. Recently, there has been significant interest in the use of thalidomide as a treatment for CRPS. Although there are no published clinical trials on thalidomide use in CRPS, there are case reports demonstrating their efficacy [55, 56]. 

Neuromodulation for treatment in CRPS

A. Spinal Cord Stimulation (SCS)

SCS is used for pain relief in patients with neuropathic pain. It is applied with sophisticated techniques which include multi-output implanted pulse generators and a choice of electrodes. The pulse generators can be placed percutaneously or placed directly by way of a laminotomy. In SCS, low voltage electrical stimulation is delivered to the spinal cord or intraspinal nerve roots to block or decrease the sensation of pain.

There are several theories of mechanisms for the pain-relief with SCS. One of them is the gate control theory of pain, which was developed by Melzack and Wall. It proposes that when large sensory nerve fibers are stimulated there is activation of inhibitory interneurons which competitively inhibits the transmission of impulses from small nociceptive nerve fibers [57].

Studies in rats with neuropathic pain have shown that stimulation of the dorsal columns of the spine causes an increase in the release of g-amino butyric acid and a decrease in the release of the excitatory amino acid glutamate at the dorsal horn [58,59]. 

SCS can produce direct current blockade in neural tissue [60], activate supraspinal antinociceptive nuclei in the brain [61], and inhibit supraspinal and segmental sympathetic outflow [62] to achieve its antinociceptive effects. The aim of SCS is to achieve stimulation-induced paresthesias which is comfortable and can completely overlap the patient’s pain topography [63].

B.Peripheral Nerve Stimulation (PNS)

PNS can be used in patients with CRPS whose symptoms are mainly or entirely in the distribution of one major peripheral nerve.

Plate-type electrodes are placed surgically on affected nerves and tested for a few days. If 50% or more pain reduction and objective improvement in physical changes are achieved, then programmable generators are implanted.  

Hassenbusch et al [64] reported good long‐term results of peripheral nerve stimulation for reflex sympathetic dystrophy. Thirty (94%) of their 32 patients underwent permanent PNS placement. Sixty three percent of their patients had good or fair long term pain relief. In those patients in whom the treatment was successful the allodynic and spontaneous pain was reduced on a scale of 10 from 8.3 preimplantation to 3.5 at 2 to 4 years follow up. 

Though changes in vasomotor tone and patient activity levels were markedly improved, the motor weakness and trophic changes showed less improvement [64].

Behavioral Modification and Psychiatric Consultation

In the first 2 months of the disease no psychological intervention is needed because physcological issues would not have appeared because the patients expect to get well. 

From 2 to 6 months after the onset of the disease anxiety sets in because patients start wondering why they are not getting better. The International Association for the Study of Pain recommends that CRPS patients with pain after 2 months should receive psychological evaluation which includes psychometric testing, to identify and treat anxiety, depression, and or personality disorder [41]. 

Treatment includes behavioral modification, counselling, biofeedback, self-hypnosis, relaxation therapy and group therapy. Patient motivation and coping skills have to be improved. Low dose antidepressants can be given to reduce anxiety and pain.

Patients with pain longer than 6 months in duration invariably have some depression, anxiety and insomnia because the pain is not improving. At this stage, antidepressants such as amitriptyline are necessary. Continued support and education is essential. Biofeedback is needed for relaxation, temperature control and reduction of muscle tension. Family counselling and group therapy  with other patients, with spouse and other family members is useful at this stage. Sometimes use of strong opioids such as slow release morphine may be indicated [41].

Surgical Therapy

Surgical/ablative therapies  for CRPS include chemical sympathectomy, surgical sympathectomy and bilateral anterior cingulotomy.

1.Sympathectomy

The pain in CRPS is believed to sympathetically mediated and hence  

 attempts to interrupt the sympathetic nervous system have been used in the treatment of CRPS. 

Temporary and non-destructive interruption of the sympathetic nervous system can be carried out through injections of local anaesthetics or botulinum toxin. Longer-lasting destructive interruption can be carried out chemically or surgically. While carrying out chemical sympathectomies,  alcohol or phenol injections are used to destroy ganglia of the sympathetic chain. With chemical sympathectomy the effect is temporary until regeneration of the sympathetic chain occurs after three to six months [ 65]  Surgical ablation is performed by open removal or electrocoagulation of the sympathetic chain. It can be carried out through a minimally invasive procedure using stereotactic thermal or laser ablation. The effects of radiofrequency ablation can last up to one year [65]. 

When minimally invasive ablation is not possible, open sympathectomy  can be carried out.

Sympathectomy should be reserved for patients with severe CRPS who are refractory to other modalities of treatment. 

A Cochrane Database Systematic  Review by Strabue et al [66] found that the practice of surgical and chemical sympathectomy for CRPS is based on very little high quality evidence. They recommended that sympathectomy should be cautiously used in clinical practice, in carefully selected patients in whom other treatment options have failed.

Complications after sympathectomy are not uncommon. Most patients complain of soreness at the site of injections lasting 5 to 7 days.  Post sympathectomy neuralgia has been reported in patients undergoing ablation with phenol [66]. 

Furlan et al [67] carried out a systematic review of the late complications of surgical sympathectomies. They found that neuropathic complications occurred in about 11.9% of the patients undergoing cervico-dorsal and lumbar surgical sympathectomy. The incidence of compensatory hyperhidrosis was 52.3%, gustatory sweating 32.3%, phantom sweating 38.6%, and Horner’s syndrome 2.4%, in patients undergoing surgical cervico-dorsal sympathectomy. 

The authors concluded by saying that surgical sympathectomy can be  accompanied with several potentially disabling complications and that detailed informed consent should be taken when surgical sympathectomy is contemplated.

2.Bilateral anterior cingulotomy

Bilateral anterior cingulotomy has been used for treatment of patients with refractory chronic pain. 

Wilkinson et al [68] carried out a study to assess the outcome of bilateral anterior cingulotomy in patients with refractory chronic pain. Their study included 23 patients who underwent 28 cingulotomies. Eighteen patients were available for follow up study. Seventy-two percent of the patients reported improvement in their pain, 55% no longer needed narcotics, 67% had improvement in their family life, and 72% had improvement in their social interactions. Fifty-six percent of patients said that the cingulotomy was beneficial, and 28% of the patients had returned to their usual activities/work [68].

Post operative seizures were reported in some of the patients but the seizures were well controlled with medication.

The authors concluded that bilateral anterior cingulotomy is safe for patients with refractory chronic pain.

Prognosis

Some of the patients with CRPS make good early recovery but there are  others who develop lasting pain and disability. Unfortunately, there is little that is known about the prognostic factors which may be able to help differentiate between these two groups.

A Systematic Review by Jean et al [69] found that many CRPS patients recover within 6 to 13 months. There are a significant number of patients who experience some lasting symptoms, and some of these patients  experience chronic pain and disability. 

A 5.5 years follow up study of patients with upper limb CRPS by Geertzen et al in the Netherlands found that nearly 30% of the patients had to stop work for more then 1 year and 26% of the patients had to change jobs.

Severe cases of CRPS can lead to marked limitation of function. Most experts agree that the prognosis is poor when symptoms become chronic. 

Treatment is most effective when it is started early in the course of the disease. Hence early diagnosis and treatment may improve the prognosis. The prognosis in vast majority of children with CRPS is generally good.

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