The Correlation of Thermal FLIR Imaging and Severity Score in Patients With Newly Diagnosed CRPS
Conditions: CRPS (Complex Regional Pain Syndromes)
Sponsor: Hospital for Special Surgery, New York

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The Correlation of Thermal FLIR Imaging and 
Severity Score in Patients with Newly Diagnosed 
CRPS 
FUNDER: 
Department of Anesthesiology 
PROTOCOL NO.: 
2022-2175 
VERSION & DATE: 
2/16/2023 
 
 
 
 
 
 
 
 
 
 
 
 
This document contains the confidential information of the Hospital for Special Surgery.  It is provided to you and your company’s personnel for 
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the prior written consent of the Hospital for Special Surgery.  No other use or reproduction is authorized by Hospital for Special Surgery, nor does 
the Hospital for Special Surgery assume any responsibility for unauthorized use of this protocol. 
 

 
Protocol Number: 2022-2175 
Version Date: 2/17/2023 
 
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TABLE OF CONTENTS 
TABLE OF CONTENTS ............................................ 2 
PROTOCOL SYNOPSIS ........................................... 3 
1.0 
INTRODUCTION ............................................. 5 
2.0 
OBJECTIVE OF CLINICAL STUDY ............... 5 
3.0 
STUDY HYPOTHESES .................................. 6 
4.0 
STUDY DESIGN ............................................. 6 
4.1 
Study Duration ................................................................................................................ 6 
4.2 
Endpoints ....................................................................................................................... 6 
4.2.1 
Primary Endpoint ...................................................................................................... 6 
4.2.2 
Secondary Endpoints ................................................................................................ 6 
4.3 
Study Sites ..................................................................................................................... 6 
5.0 
STUDY POPULATION ................................... 6 
5.1 
Number of Subjects ........................................................................................................ 6 
5.2 
Inclusion Criteria............................................................................................................. 7 
5.3 
Exclusion Criteria ........................................................................................................... 7 
5.4 
Randomization ............................................................................................................... 7 
6.0 
PROCEDURES ............................................... 7 
6.1 
Surgical Procedure ......................................................................................................... 7 
6.2 
Medical Record Requirements ....................................................................................... 7 
6.3 
Data Collection ............................................................................................................... 7 
7.0 
STATISTICAL ANALYSIS .............................. 8 
8.0 
ADVERSE EVENT ASSESSMENT ................ 8 
9.0 
REFERENCES................................................ 8 
 
 
 

 
Protocol Number: 2022-2175 
Version Date: 2/17/2023 
 
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PROTOCOL SYNOPSIS 
Protocol Title: 
The Correlation of Thermal FLIR Imaging and Severity Score in 
Patients with Newly Diagnosed CRPS 
Protocol Number: 
2022-2175 
Protocol Date: 
2/17/2023 
Sponsor: 
Department of Anesthesiology 
Principal 
Investigator: 
Semih Gungor, MD 
Products: 
Forward Looking Infrared (FLIR) camera 
Objective: 
This study aims to determine the severity of CRPS in newly diagnosed 
patients by using thermal camera imaging (FLIR). 
Study Design: 
Cross-sectional Study 
Enrollment: 
30 
Subject Criteria: 
Inclusion: 
• 
The patient is between 18 and 85 years old 
• 
Providing CRPS diagnostic criteria by using Budapest Clinical 
criteria 
• 
The patient is affected with CRPS in a unilateral limb 
• 
The patient has had pain and other symptoms for more than 3 
months. 
 
Exclusion: 
• 
Patients with suspected disc herniation, spinal stenosis, 
myelopathy, and suspected radiculopathy in detailed examinations 
and examinations (MRI, CT) 
• 
Systemic or local infection 
• 
Malignancy 
• 
Pregnancy 
• 
Uncontrollable medical and psychiatric condition 
• 
Patients diagnosed with dysautonomia, sympathetic dysfunction 
(such as Raynaud disease or Buerger disease), sweating 
disorders (such as acquired idiopathic generalized anhidrosis), and 
patients on vasoactive drugs, the mechanism of action is directly 
on the vascular tone 
Study Duration: 
1 year 
Data Collection: 
Sources: EPIC, Medical Records, and Patient Reported. 
 
Variables: Name, MRN, DOB, Race, Ethnicity, Gender, Height, 
Weight, BMI, ASA class, email address, phone number, co-morbidities 
(diabetes, high blood pressure, cholesterol, rheumatological 
conditions, allergies), medications to manage pre-existing conditions 
(opioids and non-opioids), surgery details (surgeon, anesthesiologist, 
surgery type, tourniquet use, duration), anesthesia details, NRS pain 
scores, nerve block success, duration of block. 

 
Protocol Number: 2022-2175 
Version Date: 2/17/2023 
 
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Statistical Analysis: 
1. Proposed analysis (e.g., student’s t-test, ANOVA, chi-
square, regression, etc.): We will rely on students t-test when 
comparing pairs of groups and ANOVA when comparing 
multiple groups; regression will be used to assess strength of 
relationship between NRS and objective diffusion metrics.  
2. Interim analysis planned?: No 
3. Alpha level:  0.05 
4. Beta or power level:  0.2 
5. Primary outcome variable estimate (mean +/- s.d. for 
continuous outcome, frequency/percentage for 
categorical variable):  
6. Number of groups being compared (use 1 for paired 
analysis within the same subjects):  1 
7. Effect size or change expected between groups:   
8. Resulting number per group: 30 
9. Total sample size required: 30   
 
 
 
 

 
Protocol Number: 2022-2175 
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1.0 INTRODUCTION 
CRPS can present with sympathetically maintained pain in an extremity after an injury. In 
sympathetically maintained pain, physiologic activation of cutaneous vasoconstrictor neurons 
projecting to the painful limb enhances spontaneous pain and hyperalgesia [2]. It has been postulated 
that there is pathological interaction between sympathetic and afferent neurons within the skin. For 
the diagnosis of CRPS, international criteria, “Budapest Criteria,” has been used. However, this 
diagnostic Budapest Criteria does not give information about the severity of CRPS. Therefore, a 
severity score named ‘CRPS Severity Score (CSS)’ was derived and validated). CSS depends on the 
presence/absence of 17 clinically characteristic signs and symptoms for dichotomous (yes/no) [6]. 
Based on the presence/absence of these 17 clinically assessed signs and symptoms of CRPS, a 
CRPS Severity Score (CSS) can be assigned. Higher CSS was associated with significantly higher 
clinical pain intensity, distress, and functional impairments, as well as more significant bilateral 
temperature asymmetry and thermal perception abnormalities [5].  
In CRPS, the abnormalities are thought to be either caused by hyperactivity or hypoactivity in 
sympathetic vasoconstrictor and sudomotor neurons on the affected side. Existing studies showed 
that skin temperature asymmetry between the affected and contralateral extremities around 0.6-2 °C 
is useful for diagnosing CRPS [2,3,7]. Bruehl et al. suggested that thermography can be a valuable 
component for a diagnosis, and a 0.8-1.0°C temperature difference may be considered for the 
diagnosis of CRPS [2]. Wasner et al. [8] showed that a maximal skin temperature side difference of 
more than 2.2 °C during changes in the environmental temperature using a thermal suit is highly 
sensitive and specific for distinguishing CRPS from other extremity pain syndromes. The diminished 
blood flow may be caused by either sympathetic dysfunction, hypersensitivity to circulating 
catecholamines, or endothelial dysfunction [3]. The diminished blood will lead to significant 
temperature asymmetry and thermal perception abnormalities, demonstrating a positive correlation 
with higher CSS.  
One publication studied the correlations between the ΔT, pain score, and CSS [4]. In this study, 
investigators used direct skin temperature measurements and did not use FLIRR images for 
comparison. According to this study, the ΔT did not correlate with pain score or with CSS in CRPS 
patients. There has been no similar study utilizing FLIRR images. As we discussed before, 
determining the severity of the disease in the early period is important for planning proper treatment 
to prevent disease progression. This study aims to evaluate whether there is any correlation between 
the skin temperature asymmetry measured by FLIRR images and pain score (NRS) and CSS in the 
early period of the disease.  
2.0 OBJECTIVE OF CLINICAL STUDY 
 
CRPS patients have an increased chance of remission with treatment in the early 
period of the disease. Similarly, determining the severity of the disease in the early 
period is important for planning appropriate treatment to prevent progression. The 
lack of an objective method for understanding the severity and possible 
progression of CRPS is a critical reason for delayed CRPS treatment. If infrared 
(FLIR) imaging can be used for determining the severity of CRPS in newly 
diagnosed patients and if any correlation is shown between the quantification of 
‘the Δ heat index value’ measured by FLIR imaging and the severity score for 
CRPS in newly diagnosed patients, this result of this research can be helpful in 
daily clinical practice. 

 
Protocol Number: 2022-2175 
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3.0 STUDY HYPOTHESES 
 
Evaluation of the temperature difference between the normal limb and affected limb with Infrared 
(FLIR) images obtained by a thermal camera can be used as objective criteria to evaluate the severity 
of CRPS in newly diagnosed CRPS patients. 
In more detail, the hypotheses of the project can be listed as follows: 
• Hypothesis 1: When comparing the FLIR images difference between the 
normal limb and CRPS affected limb, there will be significant differences in the  
temperature of two extremities due to CRPS-related dysfunction in circulation and 
perfusion. 
• Hypothesis 2: Infrared FLIR camera is a more reliable and rapid method for 
determining the severity of CRPS in newly diagnosed patients. 
• Hypothesis 3: When a significant difference in temperature between two 
extremities caused by perfusion problems is observed, this change (the Δ heat 
index value) will be correlated with the pain level (delta pain NRS value) and CRPS 
severity; this will enable quantification of the correlation between the temperature difference 
and the NRS/severity score in CRPS patients. 
4.0 STUDY DESIGN 
 
4.1 
Study Duration 
February 2023 – February 2024 
4.2 
Endpoints 
4.2.1 
Primary Endpoint 
• 
In newly diagnosed patients, the severity score of CRPS will be higher in the presence of 
a higher Δ heat index value. 
4.2.2 
Secondary Endpoints 
• 
In newly diagnosed patients, the NRS will be higher in the presence of a higher Δ heat 
index value. 
4.3 
Study Sites 
 
This study will take place at the 75th St campus of the Hospital for Special Surgery (HSS). 
5.0 STUDY POPULATION 
5.1 
Number of Subjects 
30 

 
Protocol Number: 2022-2175 
Version Date: 2/17/2023 
 
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5.2 
Inclusion Criteria 
Subjects of either gender will be included if they: 
o 
The patient is between 18 and 85 years old 
o 
Providing CRPS diagnostic criteria by using Budapest Clinical criteria 
o 
The patient is affected with CRPS in a unilateral limb 
o 
The patient has had pain and other symptoms for more than 3 months 
 
5.3 
Exclusion Criteria 
Subjects will be excluded from the study if they: 
o 
Patients with suspected disc herniation, spinal stenosis, myelopathy, and suspected 
radiculopathy in detailed examinations and examinations (MRI, CT) 
o 
Systemic or local infection 
o 
Malignancy 
o 
Pregnancy 
o 
Uncontrollable medical and psychiatric condition 
o 
Patients diagnosed with dysautonomia, sympathetic dysfunction (such as Raynaud 
disease or Buerger disease), sweating disorders (such as acquired idiopathic generalized 
anhidrosis), and patients on vasoactive drugs, the mechanism of action is directly on the 
vascular tone 
5.4 
Randomization 
Participants will not be randomized to multiple groups. All patients will receive the FLIR 
camera. 
6.0 PROCEDURES 
6.1 
Surgical Procedure 
Sympathetic nerve block  
6.2 
 Medical Record Requirements 
 
Using EPIC, research staff will review the patient's medical history to determine eligibility to 
participate in the study. 
 
PHI that will be reviewed: 
 
Name, DOB, preferred language, medical history, allergies, current outpatient medication, 
weight & body mass index 
 
6.3 
Data Collection 
 
The following data will be collected: 
 
Pre-operative/Baseline 
Name, MRN, DOB, Race, Ethnicity, Gender, Height, Weight, BMI, ASA class, email address, 
phone number, medications, co-morbidities, NRS value 

 
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Surgical procedure 
• 
Surgery details (date of surgery, surgeon, laterality, duration, tourniquet use) 
• 
Anesthesia details (neuraxial, PNB, medications given) 
• 
FLIR camera imaging 
 
Follow-up visits (PACU, Discharge, Post-operative day of surgery (POD) 10, 30, 
90) 
• 
NRS value 
• 
FLIR camera imaging 
7.0 STATISTICAL ANALYSIS 
Proposed analysis (e.g., student’s t-test, ANOVA, chi-square, regression, etc.): We will rely 
on students t-test when comparing pairs of groups and ANOVA when comparing multiple groups; 
regression will be used to assess strength of relationship between NRS and objective diffusion 
metrics. 
Interim analysis planned?: No 
Alpha level:  0.05 
Beta or power level:  0.2 
Primary outcome variable estimate (mean +/- s.d. for continuous outcome, 
frequency/percentage for categorical variable):  
Number of groups being compared (use 1 for paired analysis within the same subjects):  1 
Effect size or change expected between groups:  
Resulting number per group: 30 
Total sample size required: 30 
 
8.0 ADVERSE EVENT ASSESSMENT 
All Adverse Events (AEs) will be reported in the final study report. 
 
9.0 REFERENCES 
1. Baron R, Schattschneider J, Binder A, Siebrecht D, Wasner G. Relation between sympathetic 
vasoconstrictor activity and pain and hyperalgesia in complex regional pain syndromes: a 
case-control study. Lancet 2002;359:1655–1660. 
2. Bruehl S, Lubenow TR, Nath H, Ivankovich O. Validation of thermography in the diagnosis of 
reflex sympathetic dystrophy. Clin J Pain 1996;12:316–25. 
3. Groeneweg, G., Huygen, F.J., Coderre, T.J. et al. Regulation of peripheral blood flow in 
Complex Regional Pain Syndrome: clinical implication for symptomatic relief and pain 
management. BMC Musculoskelet Disord 10, 116 (2009). https://doi.org/10.1186/1471-2474-
10-116 
4. Jeon SG, Choi EJ, Lee PB, Lee YJ, Kim MS, Seo JH, Nahm FS. Do severity score and skin 
temperature asymmetry correlate with the subjective pain score in the patients with complex 
regional pain syndrome? Korean J Pain. 2014 Oct;27(4):339-44. doi: 
10.3344/kjp.2014.27.4.339. Epub 2014 Oct 1. PMID: 25317283; PMCID: PMC4196499. 
5. Harden NR, Bruehl S, Perez RSGM, Birklein F, Marinus J, Maihofner C, Lubenow T, 
Buvanendran A, Mackey S, Graciosa J, Mogilevski M, Ramsden C, Schlereth T, Chont M, 
Vatine JJ. Development of a severity score for CRPS. Pain. 2010 Dec;151(3):870-876. doi: 
10.1016/j.pain.2010.09.031. Epub 2010 Oct 20. PMID: 20965657. 

 
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6. Harden RN, Bruehl S, Perez RS, Birklein F, Marinus J, Maihofner C, Lubenow T, 
Buvanendran A, Mackey S, Graciosa J, Mogilevski M, Ramsden C, Chont M, Vatine JJ. 
Validation of proposed diagnostic criteria (the ‘‘Budapest Criteria”) for Complex Regional Pain 
Syndrome. Pain 2010;150:268–74. 
7. Krumova EK, Frettlöh J, Klauenberg S, Richter H, Wasner G, Maier C. Long-term skin 
temperature measurements - a practical diagnostic tool in complex regional pain syndrome. 
Pain. 2008 Nov 15;140(1):8-22. doi: 10.1016/j.pain.2008.07.003. Epub 2008 Aug 23. PMID: 
18723287. 
8. Wasner G, Schattschneider J, Baron R. Skin temperature side differences - a diagnostic tool 
for CRPS? Pain 2002;98:19-26.