Journal of Medical Cases, ISSN 1923-4155 print, 1923-4163 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Med Cases and Elmer Press Inc
Journal website http://www.journalmc.org

Case Report

Volume 7, Number 1, January 2016, pages 33-42


Complex Regional Pain Syndrome: Diagnostic and Treatment Conundrum

Figures

Figure 1.
Figure 1. Edematous and hyperemic right lower extremity.
Figure 2.
Figure 2. Bone scintigraphy showing increased tracer uptake in the right L5-S1 distribution.

Tables

Table 1. Budapest Criteria 2010 [2]
 
1) Continuing pain, which is disproportionate to any inciting event
2) Must report one symptom in three of the following four categories;
  Sensory: hyperesthesia and/or allodynia
  Vasomotor: temperature asymmetry and/or changes in skin color
  Sudomotor/edema: edema and/or sweating asymmetry or changes
  Motor/trophic: decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes
3) Must display at least one sign out of the following two or more categories;
  Sensory: evidence of hyperalgesia (to pinprick) or allodynia (to light touch) and/or joint movement
  Vasomotor: evidence of temperature asymmetry and/or changes in skin color
  Sudomotor: evidence of edema and/or sweating asymmetry or changes
  Motor/trophic: evidence of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes
4) There is no other condition that explains the signs and symptoms

 

Table 2. Studies Evaluating Bisphosphonates in Complex Regional Pain Syndrome-I
 
StudyDesignDrug and regimenNumber (n) of patients and duration (D) of follow-upPain assessment following treatmentOutcomesComments
n: number; D: duration; NRS: numeric rating scale; VAS: visual analogue scale.
Varenna et al, 2013 [12]Randomized, double blind, placebo-controlled, multicenter trialIntravenous neridronate-100 mg (four times over 10 days)n = 82 patients
D = 1 year
Decrease in VAS by 46 mm in treatment group vs. 22 mm in placebo group1) Better quality of life in treatment group
2) At 1 year all patients were asymptomatic
1) In early stage CRPS-1 patients neridronate provides long-term pain relief and quality of life
2) First study showing conclusive evidence of the efficacy
Robinson et al, 2004 [22]Randomized, double blind, placebo-controlled studySingle dose intravenous pamidronate 60 mgs vs. salinen = 27
D = 3 months
VAS at 3 months was lower in treatment group (P = 0.043)1) Reduction in patient’s global assessment of disease severity in the treatment group
2) Higher SF-36 score in treatment group in function at 3 months (P = 0.047)
1) Small study and single dose administration makes generalizability of efficacy harder
2) Nevertheless, this study highlights the place for bisphosphonates in CRPS
Manicourt et al, 2004 [23]1) Randomized, double blind, placebo-controlled study
2) Posttraumatic CRPS-I patients
Oral alendronate 40 mg for 8 weeksn = 40 (20 + 20)
D = 24 weeks
1) VAS: significant reduction (P < 0.001) during initial 12-week period
2) Mean VAS was 33% of placebo group at 12 weeks
1) Improvement in joint mobility, edema of legs, tolerance to pressure and spontaneous pains
2) Biomarker urinary N-telopeptide was measured
1) One patient dropped out due to upper GI intolerance
2) Reduction in urinary N-telopeptide (NTX) was noted in treatment group
Adami et al, 1997 [24]Randomized, placebo-controlled study1) Intravenous alendronate (7.5 mg) or placebo daily for 3 days
2) Two weeks later all patients received 7.5 mg IV alendronate for 3 days
n = 20
D = 12 months
Reduction in spontaneous pain (P < 0.001)1) Improvement in motion and edema of extremity (P < 0.001) vs. control group (P < 0.01)
2) Control group who received alendronate showed improvement after first 2 weeks while receiving alendronate
1) Reduction in pain by 50-75% was seen in majority of patients in study group
2) At 1 year 9/20 patients were in remission
3) Optimal dose and duration of therapy remains to be established
Varenna et al, 2000 [25]1) Randomized, double blind, placebo-controlled study
2) Cross-over trial
1) Intravenous clodronate 300 mg daily for 10 days vs. placebo
2) Placebo group received clodronate after initial 10 days
n = 32
D = 6 months
VAS (0 - 100 mm) - treatment group had overall reduction in pain (93.6) at 6 months1) Clinical global assessment (0 - 3) -decreased (P = 0.001)
2) Efficacy verbal score (0 - 3) - 11/32 patients EVS = 1.6
3) Urinary telopeptide (marker of bone resorption)-significant decreases at 40 days (P = 0.0003)
1) At 6 month, VAS continued to improve
2) No correlation between VAS and telopeptide marker was seen
3) Clodronate infusion was well tolerated-mechanism of action seems to be different when compared to other bisphosphonates

 

Table 3. Studies Evaluating the Role of Spinal Cord Stimulation in Complex Regional Pain Syndrome
 
AuthorStudy designNumber of patients and duration of follow-upPain scoreComments
n: number; D: duration; NRS: numeric rating scale; VAS: visual analogue scale; PT: physical therapy; PTSD: post-traumatic stress disorder.
Geurts et al, 2013 [26]Prospective cohort study on CRPS-In = 84
D = 12 years
30% reduction in VAS in 40% of patientsOverall reduction in pain was less than 50%
At 12 years follow up 60% patients continue to use the implant
Kemler et al, 2008 [27]Randomized controlled trial-5 year follow-upn = 36 (SCS + PT)
18 patients PT only
D = 2 year
*24 patients received permanent implant
SCS + PT was similar to PT only in terms of pain relief1) In subgroup analysis global perceived effect and pain relief was superior in patients who had SCS
2) SCS efficacy decreases with time but patient satisfaction remains high
van Eijis et al, 2012 [28]Prospectiven = 6 (out of 74 patients) received early SCS
D = 12 months
35% reduction in mean pain reliefImprovement in mental component of SF-36
No functional improvement was noted in any patient
SCS beneficial in early stage CRPS
Moriyama et al, 2012 [29]Prospective, open label, multicenter studyn = 14 (CRPS)
D = 6 months
Reduction in mean VAS (79 to 22 mm) and QOL from 0.4 to 0.1 at 6 monthsAlthough shorter follow results are presented, significant reduction in pain and improvement in QOL was noted
Sears et al, 2011 [30]Prospective evaluation of patients who had SCS (1997 - 2008)n = 35
D = 4.4 years
More than 50% pain reduction in CRPS patientsGreater patient satisfaction at 4 years
Kemler et al, 2004 [31]Randomized controlled trial-2 year follow upn = 36 (SCS + PT)
18 patients PT only
D = 2 year
*24 patients received permanent implant
n = 18 (PT only)
Significant improvement in SCS group (P = 0.001)1) Global perceived effect was superior in SCS group (43% vs. 6%)
2) Improvement in health related QOL in SCS group
3) No improvement in functional status
4) High initial costs are offset by low overall healthcare costs compared to controls ($60,000 cheaper/patient)
Kumar et al, 2011 [32]Retrospective review of CRPS patientsn = 25
D = 88 months
Follow-ups at entry, 3, 12 and 88 months
VAS: baseline 8.4, at 3 months (4.8) and at 88 months (5.6)Regression in effect but beneficial (P < 0.01) at last follow-up
SCS is beneficial in early stage of CRPS (< 1 year)
Reduction in analgesic consumption by 25%
Improvements noted in disability, SF-36 and functional status
Reig et al, 2009 [33]Retrospective 20 year analysis of SCSn = 260
CRPS-I = 40 patients
VAS in CRPS was 77 ± 135% did not have pain relief;
48% had good pain relief;
7.5 % had excellent pain relief;
40% had poor pain relief;
Overall complication rate was 28%.
Bennett et al, 1999 [34]Retrospective, multicenter study on CRPS-1 patients.
Two different systems were implanted
n = 101
D = 3 years
Significant reduction in pain (P = 0.0001) in patients who received dual octrode systemHigh frequency stimulation and multi-electrode stimulation is superior
Kumar et al, 1997 [35]Retrospectiven = 12
D = 41 months
Upper limb injury = 5 patients
Lower limb injuries = 7 patients
VAS and McGill questionnaire showed 75% (n = 8) and 50% (n = 4) reduction in painEarly stage CRPS and younger patients respond better with SCS implantation
Verdolin et al, 2007 [36]Retrospective, observational study in veterans1) n = 10 (7 LE pain and 3 UE pain)
2) Symptom duration was less than 1 year
1) Mean NRS 1.6 (pre-SCS NRS 7.6)
2) Reduction in morphine equivalent consumption in CRPS (P = 0.006) patients
1) SCS improved PT efforts
2) Early stage SCS is useful in both CRPS-I and II
3) Co-existing PTSD does not affect SCS efficacy
4) Long-term follow results needs to be seen

 

Table 4. Studies Showing Effectiveness of Cognitive Behavior Therapy in Chronic Pain Conditions
 
AuthorsTechniquesConditionsResults
Lee et al, 2002 [48]CBT/ physical therapy
Children and adolescents
CRPS89% improvement in functional status
No need for assistive devices
No severe atrophy and contractures
Van Hoof et al, 2012 [50]Short intensive CBT
Pain management
Chronic low back pain> 65% significant difference
73% reduction of health care use
57% reduction in analgesic consumption
14% decrease in opioid use
Monticone et al, 2014 [51]Multidisciplinary CBT
Disability/kinesiophobia
Chronic low back pain61% improvement in disability
100% returned to activities/work
100% discontinued medications
Knox et al, 2014 [52]CBT - compliance and effectivenessLumbar painIncreased compliance predicted greater effect size and decrease in pain/disability
Heutink et al, 2014 [53]Multidisciplinary CBTSpinal cord injury/neuropathic pain9 - 12 months decrease in pain intensity and pain related disability and anxiety levels
Increase in activity