Insights | Case Studies | Talking To Your Doctor | Aetna Policy Perspective | Treatments
The following articles are taken from the PARC PEARL published by the PARC organization.
Our publication addresses the latest issues surrounding CRPS e.g. research, drugs, treatments, conferences and current developments. Most of all, we feature personal stories of those suffering with CRPS and positive ways to cope. The PARC PEARL is suitable for patients and professionals or anyone with a keen interest in CRPS.
CRPS Patient Story
When I was young, everything was at my fingertips. I was a sister, a daughter, a friend. An accomplished athlete, I was seconds away from qualifying for the Canadian National Track and Field Team. I was at the top of class; I was an accomplished pianist for 12 years.
Then, RSD came into my life. After surgeries on my feet for athletic injuries, I awoke to a wheelchair, two casts on my legs, and pain that was only getting worse. The casts came off, no relief. I couldn't walk; my legs were purple and cold as ice. My arms were beginning to change as well. The right side of my face was numb. Then, it started with my eyebrows, the hair fell out. My eyelashes were next, followed by all the hair on my head. It will never grow back. I was 15.
I'm terrified, I thought. I'm alone. I'm alone and no one can understand what this feels like; my body is disintegrating from the inside out and no one can see that anything is wrong. But I was wrong.
I was not alone; there were others like me, and doctors who understood that it wasn't a matter of me seeking attention, the need to have more friends, or something that could be cured with psychological counselling. It is something everyone must be diligent with and accept in your own time, because there is life after RSD, a beautiful life with a future. My name is Sarah, and here is how I broke through that dark place to become happy and live a successful, productive, and optimistic life.
1) You are never alone.
For those with the disease, one cannot help but feel a sense of alienation from family, friends, peers. While it is impossible for them to understand your burden, they are there to help you. Confide in them; it will make you stronger. When you feel you're alone, reach out to someone who knows - PARC, a clinic, your community, anyone. In the world at this very moment, there are thousands who feel exactly what you do, who can understand and help you with tips and tricks to get you through the dark times. For me, this was my family, and this was my doctors. I was fortunate enough to be sent to Dr. Hooshmand's Neurological Clinic in Vero Beach, Florida, and the Seattle Children's Hospital RSD Unit. With their help, I got my confidence back. I became strong and able to fight back.
2) RSD does not define you.
You can have a fulfilling life with RSD. You must remember that it is something challenging you; it does not control you or your mind. Keep your mind clear of the negative, stay focused on the tasks you must do to break through that wall of pain, and be diligent. You have the power to control it. Pace yourself, take it minute by minute, task by task, one day at a time. You have the power to do anything you want; never say the words, "I can't". There is always another way to get the job done. RSD changes your life, it does not take your life. The power to live it successfully and peacefully starts with you.
3) You are a new person.
With this disease comes new routines, new challenges. Your life has undoubtedly changed. With RSD, you truly become a new person. Let this person be positive, and accepting of limitations as well as strengths. You have life, choose to live it with wholehearted enthusiasm. When I was able to get out of my wheelchair after two years, I walked slowly, assisted with canes. My therapist took my cane and nailed it to her office wall. Without it, I was forced to stand up straight. Sure, I fell down. Of course it hurt, it was indescribable. But the only thing in my mind was a visual of me walking, unassisted, down that hallway. It likely took me an hour, maybe all afternoon, but I did it. I was 18. Once you change your outlook from a negative place of limitation to that of possibilities, your body becomes a tool to get you there. You will only have success. What I've learned is to never compare yourself to the way you were before RSD. It changes you. I accept I will never compete again, but that will not stop me from living my new life to the fullest, enjoying a walk outside, or appreciating what I have.
I am now 24 years old. I have finished a Bachelor's degree, and am working full time. I am able to live on my own again, unassisted. Sure, I have bad days. We all do. But the most important thing I've learned is to not worry about the little things, and not worry about what could happen in the future. One step at a time, that's all I need.
While the clinics I attended helped me back on my feet, (literally), I still have RSD and it is still part of my daily routine. Don't get down on yourself because it won't go away. Enjoy what you can do, enjoy your family, your community. Sit outside and look at the beauty surrounding you. Your life is a beautiful gift, make the most of it. Focus on your abilities instead of weaknesses and you will find the key to living life with RSD: this thing does not own you, it does not control you, it does not define you. Only you have the power to choose what your life will be.
by Sarah Ruggins
by Louise O’Donnell-Jasmin, author, pain patient and editor.
“With this book I invite you to discover the formidable strength of the human spirit in the fight against chronic pain. The marvelous collaboration of all these people has served to make this book the most important work on chronic pain published to date, conceived by an individual suffering from chronic pain for an audience made up of people suffering from chronic pain and their loved ones, and written by health care professionals working in a variety of sectors as well as by the people living with pain on a daily basis.”
This 388 page book is divided into six sections:
Next is the psychological and social aspects of pain which includes perceptions of pain, pain and emotions, working with chronic pain sufferers, surviving a loved one’s chronic pain, mood disorders and chronic pain.
The very heart of the book is the section on treatment options and pain management. This section consists of the many therapies used to treat pain. Some of the topics include: pain prevention, the patient's role, sleep and chronic pain, breathing, relaxation and visualization, hypnosis, exercise, medications, role of the pharmacist, role of the nurse, invasive therapies, physical rehabilitation, occupational therapy, physiotherapy, acupuncture, and pain tools.
The next section is patient associations for pain and professionals. Lastly are the pain clinics and rehabilitation centers.
After each chapter patient testimonials are offered. These deeply personal stories highlight patients’ struggles with pain and their fight to overcome adversity. These stories are a wonderful tribute to the human spirit, to its tenacity, strength and courage.
Certainly the book is a practical guide to dealing with pain. Anyone with chronic pain or CRPS can pick up the book, find an explanation of their particular illness, explore various treatments and find hope in the countless inspiring stories of patients. These successful pain patients lead support groups, serve as directors on Boards, are certified to lead pain management courses for patients, and some have started their own associations. They know what it is like to suffer with pain and have made it their life’s calling to help others by paving the way for those who are still struggling.
PROFESSIONALS AND PATIENTS
The authors are pain experts in their field; doctors, psychologists, therapists and psychiatrists. These are some of the busiest professionals with already packed schedules, who took the time to write about their discipline and share their experience and considerable expertise on pain management. Moreover, the experts are all Canadian pain professionals.
These specialists provide the information and know how but the patients provide the reader with most important ingredient : hope.
"Meditation is one of the best ways to rise above pain and forge a positive attitude. It increases your metal energy, so your brain can launch an effective counterattack against pain. It allows you to slip into a state of absolute calm, called the sacred space, that triggers regeneration and healing of your mind, body and spirit.” - Dr. Dharma Singh Khalsa
Find a quiet comfortable spot where you will not be disturbed.
An Insurance Perspective
The following is provided as a view into how an insurance company specifies RSD/CRPS diagnostic and treatment coverage.
Aetna 2015 Policy
Sudomotor testing is used in the clinical setting to evaluate and document neuropathic disturbances that may be associated with pain. The quantitative sudomotor axon reflex test (QSART), thermoregulatory sweat test (TST), sympathetic skin responses, and silastic sweat imprints are tests of sympathetic cholinergic sudomotor function. All of these tests measure only post-ganglionic sudomotor function.
The QSART device was first reported in detail in 1983 and its clinical use has spread since that time for the evaluation of autonomic dysfunction (Low, et al., 1983; Kennedy, et al., 1984; Low, et al., 1985; Cohen, et al., 1987; Fealey, et al., 1989; Maselli, et al., 1989; Low, et al., 1990; Kahara, et al., 1991; Levy, et al., 1992; Kihara, et al., 1983; Crandall, et al., 1995; Lang, et al., 1995; Sandroni, et al., 1998; O'Suilleabhain, et al., 1998; Birklein, et al., 1998; Hoeldtke et al., 2001; Vinik, et al., 2003; Low, 2003; Bickel, et al., 2004; Singer, et al., 2004; Low, 2004; Low, et al., 2004; Hilz, et al., 2006; Smith, et al., 2006; Low, et al., 2006; Nolano, et al., 2006). The QSART measures axon reflex-mediated sudomotor responses quantitatively and evaluates post-ganglionic sudomotor function. Recording is usually carried out from the forearm and 3 lower extremity skin sites to assess the distribution of post-ganglionic deficits. Normative values for QSART have been established.
The sympathetic skin response is another test of sudomotor function (Maselli, et al., 1989; Levy, et al., 1992; Fagias & Wallin, 1980a; Fagias & Wallin, 1980b; Lidberg & Wallin, 1981; Shahani, et al., 1984; Soliven, et al., 1987; Uncini, et al., 1988; Niakan & Harati, 1988; Dellantonio, et al., 1989; Elie & Guihaneus, 1990; Baser, et al., 1991; Caccia, et al., 1991; Berne, et al., 1992; Drory & Korczyn, 1993; Paresi, et al., 1995; Linden & Berlit, 1995; Abbott, et al., 1996; Baron & Maier, 1996; Magerl, et al., 1996; Shivji, et al., 1999; Illigens & Gibbons, 2008). Widely used in the past, sympathetic skin response measures change in skin resistance following a random electric stimulation, and provides an index of sweat production. However, this is non-thermoregulatory sweat that occurs on the palms and soles, is of different pharmacological and physiologic properties, and involves somatic afferents. The medical literature proves that this test is of relatively low sensitivity and uncertain specificity, as compared to QSART.
The thermoregulatory sweat test (TST) is another widely used clinical test for evaluating sudomotor function (Hilz & Dutch, 2006; Nolano, et al., 2006; Illigens & Gibbons, 2009; Cheshire & Freeman, 2003; Lipp, et al., 2009; Stewart, et al., 1992; Jacobson & Hiner, 1998; Birklein, et al., 2001; Atkinson & Fealey, 2003; Schiffmann, et al., 2003; Nakazato, et al., 2004; Kimpinski, et al., 2009). The TST evaluates the distribution of sweating by a change in color of an indicator powder. The test is sensitive, and its specificity for delineating the site of lesion is greatly enhanced when used in conjunction with QSART.
Quantitative direct and indirect reflex testing (QDIRT) and silastic sweat imprint methods are also widely used, but do not have the same level of clinical data supporting their use (Kihara, et al., 1993; Illigens & Gibbons, 2009; Gibbons, et al., 2001; Perretti, et al., 2003; Berghoff, et al., 2006; Manganelli, et al., 2007). Sweat imprints are formed by the secretion of active sweat glands into a plastic (silastic) imprint. The test can determine sweat gland density, a histogram of sweat droplet size and sweat volume per area.
Presently, post-ganglionic sudomotor function is assessed by means of QSART or silicone impressions. Quantitative direct and indirect reflex testing is a technique for assessing post-ganglionic sudomotor function. This technique combines some of the advantages of silicone impressions and QSART by providing data on droplet number, droplet topographic distribution, and temporal resolution in direct and axon reflex-mediated regions.
Gibbons et al (2008) described their findings on the use of QDIRT for evaluating sudomotor function. In this study, sweating in 10 healthy subjects (3 women and 7 men) was stimulated on both forearms by iontophoresis of 10 % acetylcholine. Silicone impressions were made and topical indicator dyes were digitally photographed every 15 seconds for 7 minutes after iontophoresis. Sweat droplets were quantified by size, location, and percent surface area. Each test was repeated eight times in each subject on alternating arms over 2 months. Another 10 subjects (5 women and 5 men) had silicone impressions, QDIRT, and QSART performed on the dorsum of the right foot. The percent area of sweat photographically imaged correlated with silicone impressions at 5 minutes on the forearm (r = 0.92, p < 0.01) and dorsal foot (r = 0.85, p < 0.01). The number of sweat droplets assessed with QDIRT correlated with the silicone impression, although the droplet number was lower (162 +/- 28 versus 341 +/- 56, p < 0.01, r = 0.83, p < 0.01). The sweat response and sweat onset latency assessed by QDIRT correlated with QSART measured at the dorsum of the foot (r = 0.63, p < 0.05; r = 0.52, p < 0.05). The authors concluded that QDIRT measured both the direct and the indirect sudomotor response with spatial resolution similar to that of silicone impressions, and with temporal resolution similar to that of QSART. They noted that QDIRT provides a novel tool for the evaluation of post-ganglionic sudomotor function. Furthermore, they stated that more research is needed to ascertain the utility of QDIRT in disease states that alter sudomotor structure or function.
One limitation of QDIRT is that ambient room temperature and humidity need to be controlled to prevent cool dry air from causing evaporation of sweat production. Furthermore, normative values for QDIRT need to be established to avoid over-diagnosis of sudomotor dysfunction.
Sudomotor testing has data to suggest it may be the most sensitive means to detect a peripheral small fiber neuropathy (Low, et al., 2006). Hoitsma et al (2003) reported that sympathetic skin responses testing appeared to be of little value in diagnosing small-fiber neuropathy in patients with sarcoidosis. On the other hand, Hoitsma et al (2004) noted that QSART is useful for diagnosing small fiber neuropathy.
Sudomotor testing is also the only way to detect isolated damage to sudomotor nerves in a number of different disease states such as Ross Syndrome, Harlequin Syndrome, diabetes, multiple system atrophy, Parkinson’s disease, autoimmune autonomic ganglionopathy, and pure autonomic failure (Low, et al., 1983; Kennedy, et al, 1984; Low, et al., 1990; Kihara, et al., 1991; Kihara, et al., 1993; Sandroni, et al., 1998; O'Suilleabhan, et al., 1998; Low, 2003; Bickel, et al., 2004; Low, 2004; Low, et al., 2006; Niahan & Harati, 1998; Baser, et al., 1991; Illigen & Gibbons, 2009; Cheshire & Freeman, 2003; Stewart, et al., 1992; Ross, 1958; Petagan, et al., 1965; Schondorf & Low, 1993; Kihara, et al., 1993; Wolfe, et al., 1995; Rex, et al., 1998). The clinical implications of testing and outcomes are reviewed in detail in a number of different studies across different diseases (Cheshire & Freeman, 2003).
Autonomic testing (including sudomotor testing) is recommended for all patients with type 2 diabetes at the time of diagnosis and 5 years after diagnosis in individuals with type 1 diabetes (Boulton, et al., 2005; Tesfaye, et al., 2010; Spallone, et al., 2011a; Bernardi, et al., 2011; Spallone, et al., 2011b; Spallone, et al., 2011c). Individuals with diabetes that have autonomic neuropathy have a significantly higher mortality, and guidelines for anesthesia, surgery and medical therapies to affect outcomes have been established (Boulton, et al., 2005; Spallone, et al., 2011a; Vinik & Ziegler, 2007).
Argiana et al (2011) noted that diabetic foot ulcers affect almost 5 % of the patients with diabetes and carry a huge physical, emotional, and financial burden. Almost 80 % of amputations in patients with diabetes are preceded by a foot ulcer. Simple tests (e.g., monofilament, tuning fork, vibration perception threshold determination, ankle reflexes, and pinprick sensation), alone or in combination, have been studied prospectively and can be used for identification of patients at risk. Newer tests examining sudomotor dysfunction and skin dryness have been introduced in recent years. In cross-sectional studies, sudomotor dysfunction assessed by either sympathetic skin response or Neuropad (Miro Verbandstoffe GmbH, Wiehl-Drabenderhöhe, Germany) testing has been consistently associated with foot ulceration. The authors concluded that prospective studies are needed to establish if sudomotor dysfunction can predict foot ulcers and if simple methods assessing sudomotor dysfunction (e.g., Neuropad testing) can be included in the screening tests for the prevention of this complication.
Peltier and colleagues (2010) stated that postural tachycardia syndrome (POTS) is a heterogeneous disorder characterized by excessive orthostatic tachycardia in the absence of orthostatic hypotension and by sympathetic nervous system activation. Post-ganglionic sudomotor deficits have been used to define a neurogenic POTS subtype. Norepinephrine levels above 600 pg/ml have also been used to delineate patients with a hyperadrenergic state. These reseachers determined the relationship of sudomotor abnormalities to other aspects of dysautonomia in POTS. Autonomic function was quantified in 30 women through tests of cardio-vagal, adrenergic, and sudomotor function including QSART and spectral indices. Differences between patients with and without sudomotor dysfunction as defined by QSART and between patients with and without hyperadrenergic POTS were assessed with Mann-Whitney U test and Mantel-Haenszel Chi-Square test using a p value of 0.01 for significance. Spearman correlation coefficients were used to test raw sweat volume correlations with other variables. Of 30 women (aged 20 to 58), 17 patients (56 %) had an abnormal QSART that was typically patchy and involved the lower extremity, while 13 patients had normal QSART results. Other autonomic tests, catecholamines or spectral indices did not correlate with QSART results. No differences in autonomic tests or spectral indices were observed between hyperadrenergic and non-hyperadrenergic POTS. The authors concluded that these findings confirmed that a large subset of POTS patients have sudomotor abnormalities that are typically patchy in distribution but do not correlate with other tests of autonomic function. They stated that further studies are needed to determine the best method of endophenotyping patients with POTS.
Manek and associates (2011) stated that the pathophysiological factors of primary Raynaud phenomenon (RP) are unknown. Preliminary evidence from skin biopsy suggests small-fiber neuropathy (SFN) in primary RP. In a pilot study, these investigators aimed to quantitatively assess SFN in patients with primary RP. Consecutive subjects with an a priori diagnosis of primary RP presenting to the authors' outpatient rheumatology clinic over a 6-month period were invited to participate. Cases of secondary RP were excluded. All participants were required to have normal results on nail-fold capillary microscopy. Assessment for SFN was performed with autonomic reflex screening, which includes QSART, and cardiovagal and adrenergic function testing, TST, and quantitative sensory test (QST) for vibratory, cooling, and heat-pain sensory thresholds. A total of 9 female subjects with a median age of 38 years (range of 21 to 46 years) and a median symptom duration of 9 years (range of 5 months to 31 years) were assessed. Three participants had abnormal results on QSART, indicating peripheral sudomotor autonomic dysfunction; 2 participants had evidence of large-fiber involvement with heat-pain thresholds on QST. Heart rate and blood pressure responses to deep breathing, Valsalva maneuver, and 70-degree tilt were normal for all participants. Furthermore, all participants had normal TST results. In total, 3 of the 9 participants had evidence of SFN. The presence of SFN raises the possibility that a subset of patients with primary RP have an underlying, subclinical small-fiber dysfunction. The authors concluded that these data open new avenues of research and therapeutics for this common condition. The findings of this small, pilot study need to be validated by well-designed studies.
Guidelines from the American College of Occupational and Environmental Medicine (2008) make no recommendation for use of Quantitative Sudomotor Axon Reflex Test (QSART) to assist in the diagnostic confirmation of CRPS because of insufficient evidence.
An International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis’s practice guideline on “Chronic fatigue syndrome/myalgic encephalomyelitis” (2012) stated that “No specific diagnostic laboratory test is currently available for ME/CFS, although potential biomarkers are under investigation”.
Siepmann et al (2012) noted that although piloerector muscles are innervated by the sympathetic nervous system, there are at present no methods to quantify pilomotor function. In a pilot study, these researchers quantified piloerection using phenylephrine hydrochloride in humans. A total of 22 healthy volunteers (18 males, 4 females) aged 24 to 48 years participated in 6 studies. Piloerection was stimulated by iontophoresis of 1 % phenylephrine. Silicone impressions of piloerection were quantified by number and area. The direct and indirect responses to phenylephrine iontophoresis were compared on both forearms after pre-treatment to topical and subcutaneous lidocaine and iontophoresis of normal saline. Iontophoresis of phenylephrine induced piloerection in both the direct and axon reflex-mediated regions, with similar responses in both arms. Topical lidocaine blocked axon reflex-mediated piloerection post-iontophoresis (mean [SD], 66.6 [19.2] for control impressions versus 7.2 [4.3] for lidocaine impressions; p < 0.001). Subcutaneous lidocaine completely blocked piloerection. The area of axon reflex-mediated piloerection was also attenuated in the lidocaine-treated region post=iontophoresis (mean [SD], 46.2 [16.1]cm2 versus 7.2 [3.9]cm2; p < 0.001). Piloerection was delayed in the axon reflex region compared with the direct region. Normal saline did not cause piloerection. The authors concluded that phenylephrine provoked piloerection directly and indirectly through an axon reflex-mediated response that is attenuated by lidocaine. Piloerection is not stimulated by iontophoresis of normal saline alone. They stated that the quantitative pilomotor axon reflex test (QPART) may complement other measures of cutaneous autonomic nerve fiber function.
Quattrini et al (2007) measured foot skin vasodilator responses to acetylcholine (Ach) and sodium nitroprusside (SNP) and vasoconstrictor responses to sympathetic stimulation in 5 healthy control subjects, 10 non-neuropathic diabetic (NND) patients, 10 diabetic patients with painless neuropathy (PLDN), and 8 diabetic patients with painful diabetic neuropathy (PDN). In PDN, there were significantly reduced responses to Ach (ANOVA, p = 0.003) and vasoconstrictor inspiratory gasp (ANOVA, p < 0.001) but not to SNP (not significant). Post-hoc analysis showed significant differences in Ach-induced vasodilation between PDN and non-diabetic control subjects (p < 0.05) as well as between PDN and NND (p < 0.05) but not PDN and PLDN (not significant). There were no significant differences for SNP-induced vasodilation. However, there were significant differences in the vasoconstrictor response between PDN and control, NND, and PLDN (p < 0.01). This study found an impairment of cutaneous endothelium-related vasodilation and C-fiber-mediated vasoconstriction in PDN. Inappropriate local blood flow regulation may have a role in the pathogenesis of pain in diabetic neuropathy. The authors stated that prospective studies are needed to determine the temporal relationship of these changes in relation to the emergence of neuropathic pain.
The use of autonomic nervous system function testing for cardiovagal innervation has clinical data supporting its use. It is the only way to measure the function of the parasympathetic, or cardiovagal, nervous system (O'Suilleabhain, et al., 1998; Low, 2003; Singer, et al., 2004; Low, et al., 2004; Low & Opfer-Gehrking, 1993; Salo, et al., 1996; Novak, et al., 1996; Low, et al., 1997; Wright, et al., 1999; Benarroch, 2002; Goldstein, et al., 2003; Thaisetthawatkul, et al., 2004; Sanya, et al., 2005; Benarrach, et al., 2006; Wang, et al., 2008; Goldstein, et al., 2010).
Autonomic testing (including cardiovagal testing) is recommended for all patients with type 2 diabetes at the time of diagnosis and 5 years after diagnosis in individuals with type 1 diabetes (Boulton, et al., 2005; Tesfaye, et al., 2010; Spallone, et al., 2011a; Bernardi, et al., 2011; Spallone, et al., 2011b; Spallone, et al., 2011c). Individuals with diabetes that have cardiac autonomic neuropathy have a significantly higher mortality, and guidelines for anesthesia, surgery and medical therapies to affect outcomes have been established (Boulton, et al., 2005; Spallone, et al., 2011a; Vinik & Ziegler, 2007). Cardiovagal testing has been demonstrated in a number of disease states as an early marker of autonomic parasympathetic dysfunction (O'Suilleabhain, et al., 1998; Low, et al., 2004; Novak, et al., 1996; Thaisetthawatkur, et al., 2004; Beske, et al., 2002; Gibbons & Freeman, 2006; Goldstein, et al., 2009). Some disorders preferentially affect autonomic nerve fibers, such as amyloidosis and autoimmune autonomic ganglionopathy, and do not exhibit abnormalities of somatic nerve fiber tests (Low, et al., 2003). Heart rate variability is a simple and reliable test of cardiovagal function. It has a sensitivity of 97.5% for detection of parasympathetic dysfunction in diabetes when age related normative values are used (Low, et al., 1997; Dyck, et al., 1992). The heart rate response to deep breathing, tilt table test and the heart rate response to the Valsalva maneuver are considered standard clinical tests of autonomic function and are sensitive, specific and reproducible methods for grading the degree of autonomic dysfunction (Low, 1993).
Freeman and Chapleau (2013) stated that autonomic testing is used to define the role of the autonomic nervous system in diverse clinical and research settings. Because most of the autonomic nervous system is inaccessible to direct physiological testing, in the clinical setting the most widely used techniques entail the assessment of an end-organ response to a physiological provocation. The non-invasive measures of cardiovascular parasympathetic function involve the assessment of heart rate variability while the measures of cardiovascular sympathetic function assess the blood pressure response to physiological stimuli. Tilt-table testing, with or without pharmacological provocation, has become an important tool in the assessment of a predisposition to neurally mediated (vasovagal) syncope, the postural tachycardia syndrome, and orthostatic hypotension. Distal, post-ganglionic, sympathetic cholinergic (sudomotor) function may be evaluated by provoking axon reflex mediated sweating, e.g., the quantitative sudomotor axon reflex test (QSART) or the quantitative direct and indirect axon reflex test (QDIRT). The thermoregulatory sweat test provides a non-localizing measure of global pre- and post-ganglionic sudomotor function. Frequency domain analyses of heart rate and blood pressure variability, microneurography, and baroreflex assessment are currently research tools but may find a place in the clinical assessment of autonomic function in the future.
Siepmann et al (2013) noted that among the few well-established techniques to diagnose autonomic dysfunction are head-up-tilt table testing, heart rate variability measurement and axon-reflex based sudomotor testing. Recent research focused on the development of novel techniques to assess autonomic function based on axon-reflex testing in both vasomotor and pilomotor nerve fibers. However, these techniques are clinically not widely used due to technical limitations and the lack of data on their utility to detect autonomic dysfunction in patients with neuropathy.
In a community-based cross-sectional study, Saint Martin et al (2013) evaluated the role of the cardiac autonomic nervous system (ANS), as measured according to spontaneous cardiac baroreflex sensitivity (BRS), in the type and degree of cognitive performance in healthy young-elderly individuals, taking into account the presence of other vascular risk factors. A subset of participants, aged 66.9 ± 0.9, from a prospective study that aimed to assess the influence of ANS activity on cardiovascular and cerebrovascular morbidity and mortality (n = 916) were included in this study. All subjects underwent a clinical interview, neuropsychological testing, and autonomic and vascular measurements. Three cognitive domains were defined: (i) attentional (Trail-Making Test Part A, (ii) Stroop code and parts I & II), and (iii) executive (Trail-Making Test Part B, Stroop part III, verbal fluency and similarity tests), and memory (Benton visual retention test, Grober and Buschke procedure). Subjects were stratified according to their scores into normal, low, and impaired performers. After adjustments to demographic and vascular data, participants with moderate autonomic dysregulation (3 < BRS ≤ 6) were determined to be 1.82 times as likely to have memory impairment (odds ratio (OR) = 1.82, 95 % confidence interval (CI): 1.13 to 3.17, p = 0.02) and those with severe autonomic dysregulation (BRS ≤ 3) to be 2.65 as likely (OR = 2.65, 95 % CI: 1.40 to 5.59, p = 0.006) as participants with normal BRS (> 6). The authors concluded that in older individuals without dementia, autonomic dysregulation seems to have a direct, gradual, and independent effect on memory. Moreover, they stated that future studies are needed to evaluate the long-term effects of BRS and other markers of the ANS on cognitive decline.
Testing sympathetic adrenergic function is the primary method for evaluating patients with syncope, orthostatic hypotension, postural tachycardia syndrome and postural dizziness (Gibbons & Freeman, 2006; Faraji, et al., 2011; Sundkvist, 1981; Sundkvist, et al., 1981; Abraham, et al., 1986; Kenny, et al., 1986; Turkka, et al., 1987; Bergstrom, et al., 1987; Abi Samra, 1988; Ruviele, et al., 1990; Thilenius, et al., 1991; Grubb, et al., 1991; Sra, et al., 1991; Benditt, et al., 1991; Navarro, et al., 1991; Kupoor, 1992; Fouad, et al., 1993; Calkins, et al., 1993; Mathias, et al., 2001; Lahrmann, et al., 2006). Testing is sensitive, specific, and is useful across diseases to diagnose patients with autonomic dysfunction. Sympathetic adrenergic testing (in conjunction with cardiovagal and sudomotor function testing) has been shown to aid in diagnosis, management and outcomes in patients with autonomic dysfunction or syncope of unexplained cause(Gibbons & Freeman, 2006; Faraji, et al., 2011; Sundkvist, 1981; Sundkvist, et al., 1981; Abraham, et al., 1986; Kenny, et al., 1986; Turkka, et al., 1987; Bergstrom, et al., 1987; Abi Samra, 1988; Ruviele, et al., 1990; Thilenius, et al., 1991; Grubb, et al., 1991; Sra, et al., 1991; Benditt, et al., 1991; Navarro, et al., 1991; Kupoor, 1992; Fouad, et al., 1993; Calkins, et al., 1993; Mathias, et al., 2001; Lahrmann, et al., 2006' Freeman, 2006; Oka, et al., 2007; Low, 2008; Gibbons, et al., 2011).
Autonomic testing (including adrenergic testing) is recommended for all patients with type 2 diabetes at the time of diagnosis and 5 years after diagnosis in individuals with type 1 diabetes (Boulton, et al., 2005; Tesfaye, et al., 2010; Spallone, et al., 2011a; Bernardi, et al., 2011; Spallone, et al., 2011b; Spallone, et al., 2011c). Individuals with diabetes that have cardiac autonomic neuropathy have a significantly higher mortality, and guidelines for anesthesia, surgery and medical therapies to affect outcomes have been established (Boulton, et al., 2005; Spallone, et al., 2011a; Vinik & Ziegler, 2007).
There are studies that support the role of autonomic testing in improving clinical outcomes (Low, et al., 2006; Nolano, et al., 2006; Illigens & Gibbons, 2009; Gibbons & Freeman, 2006; Low, 1993; Mathias, et al., 2001; Gibbons, et al., 2001; Gibbons, et al., 2008; Gibbons & Freeman, 2010; Gibbons & Freeman, 2005, Maguire, et al., 20008; Schurmann, et al., 2000; Donadio, et al., 2008). One of the longest running and most detailed examples includes the DCCT trial of diabetic autonomic neuropathy where cardiovagal function was better in individuals with tight glycemic control even 13 years after the end of the study (Pop-Busui, et al., 2009). This data strongly supports the utility of autonomic testing to impact clinical outcomes. Patients with cardiac autonomic neuropathy have an increased risk of silent myocardial ischemia (Vinik, et al., 2003), major cardiac events (Vinik & Ziegler, 2007) and is a predictor of cardiovascular mortality (Vinik & Ziegler, 2007; Maser, et al., 2003).
There are studies of the impact of autonomic testing on clinical treatment. A few examples of the many situations where autonomic testing is of clinical use include: There are several devices on the market (e.g., ANSAR, Critical Care Assessment) that state that they offer complete autonomic assessment in 10-15 minutes. In contrast to standard autonomic testing (as described above), the use of “autonomic testing” by these automated devices has not been validated, nor is there data to show they are clinically meaningful. This testing is typically performed without a 5 minute tilt table test and beat-to-beat blood pressure monitoring. These automated testing devices have been promoted for use by physicians with little or no training in autonomic testing, and little understanding of autonomic nervous system physiology.
Many of the references to ANSAR testing offered by the manufacturer are in abstract form or are published in journals that are not indexed by the National Library of Medicine's PubMed database of peer-reviewed medical publications. Of the full-length articles that were published in peer-reviewed journals indexed in PubMed, three are to animal studies, one is a case report, four are to review articles and not primary research studies, and two are to studies that observe autonomic activity following trauma. One of the references is to a study that reports on changes in management of subjects with ANSAR testing; however, there is no comparison group managed without ANSAR testing.
None of the articles in peer-reviewed publications index in PubMed are of clinical studies proving the value of ANSAR testing. Of the peer-reviewed published evidence, one of the references is to a case report (Turner & Colombo, 2004); case reports do not provide high quality evidence.
Three of the ANSAR references in peer-reviewed publications indexed in PubMed are to animal studies: Akselrod, et al., 1981; Akselrod, et al., 1985; Akselrod, et al., 1987.
A study by Arora, et al. (2008) documents changes in alpha-1 agonist (midodrine) with ANSAR testing in persons with diabetes; however, there is no comparison group of subjects managed without ANSAR testing. Thus, this study does not provide evidence that clinical outcomes were improved with ANSAR testing compared to management without ANSAR testing in persons with diabetes.
Two of the studies of ANSAR testing in peer-reviewed publications indexed by the National Library of Medicine (PubMed) are to observations of autonomic activity following trauma. A study by Fathizadeh, et al. (2004) reports on cardiovascular changes and autonomic activity (by ANSAR testing) in trauma subjects. However, ANSAR testing results were not used in managing patients in this study. A study by Colombo, et al. (2008) is also a descriptive study, reporting on changes in autonomic activity in trauma subjects.
Several of the ANSAR references are to review articles, and not primary clinical studies. A reference from Vinik & Ziegler, et al. (2007) is a review of diabetic cardiovascular autonomic neuropathy. The authors mention ANSAR testing as a method of autonomic nervous system functioning; however, the article was not a clinical study of ANSAR testing. An additional reference from Akselrod, et al. (1988) is a review article and is not primary research. An editorial from Vinik (2010) reviews the relationships between neuropathy and cardiovascular disease in diabetes; this is not a clinical study, and no specific reference is made to ANSAR testing. The reference to Vinik (2003) is also a review article and not a clinical study.
Several references to ANSAR testing are abstracts, rather than full-length peer-reviewed publications: Waheed, et al., 2006; Arora, et al., 2008; Aysin & Aysin, 2006; Aysin, et al., 2007; Vinik, et al., 2004; Boyd, et al., 2010; Boyd, et al., 2010; Nemechek, et al., 2009; Nemechek, et al., 2009; Pereira, et al., 2011, Baker, et al., 2011; Rothstein, et al., 2011. Abstracts do not undergo the level of peer-review as full-length publications, and provide insufficient information to adequately evaluate the clinical study.
Several of the references to ANSAR are to the Touchpoint Briefings in U.S. Cardiology, U.S. Neurology, and U.S. Endocrinology; these journals are not of sufficient quality to be indexed by the National Library of Medicine in the PubMed database of peer-reviewed published medical literature: Vinik & Murray, 2008; Vinik, et al., 2007; Tobias, et al., 2010; Nanavanti, et al., 2010. An article by Vinik & Murray (2008) is a review article that includes case reports. An article by Vinik, et al. (2007) is also a review article, and is not a clinical study. An article by Nanavanti, et al. (2010) described a study where therapies in atrial fibrillation were changed based upon ANSAR testing; however, there is no comparison group of subjects managed without ANSAR testing, so no conclusions about the benefits of ANSAR testing can be drawn from this study. A study by Tobias, et al. (2010) reports on observations regarding a large number of subjects who underwent ANSAR testing at six primary care ambulatory clinics, and those with parasympathetic excess were treated according to certain protocols; this study did not include a comparison group of subjects managed without ANSAR testing, so no conclusions can be drawn on the effectiveness of ANSAR testing in improving clinical outcomes.
Siepmann et al (2014) stated that axon-reflex-based tests of peripheral small nerve fiber function, including techniques to quantify vasomotor and sudomotor responses following acetylcholine iontophoresis, are used in the assessment of autonomic neuropathy. However, the established axon-reflex-based techniques, laser Doppler flowmetry (LDF) to assess vasomotor function and QSART to measure sudomotor function, are limited by technically demanding settings as well as inter-individual variability and are therefore restricted to specialized clinical centers. New axon-reflex tests are characterized by quantification of axon responses with both temporal and spatial resolution and include "laser Doppler imaging (LDI) axon-reflex flare area test" to assess vasomotor function, the QDIRT to quantify sudomotor function, as well as the quantitative pilomotor axon-reflex test (QPART), a technique to measure pilomotor nerve fiber function using adrenergic cutaneous stimulation through phenylephrine iontophoresis. The effectiveness of new axon-reflex tests in the assessment of neuropathy is currently being investigated in clinical studies.
CPT Codes / HCPCS Codes / ICD-10 Codes
Information in the [brackets] below has been added for clarification purposes. Codes requiring a 7th character are represented by "+":
ICD-10 codes will become effective as of October 1, 2015:
CPT codes covered if selection criteria are met:
95921Testing of autonomic nervous system function; cardiovagal innervation (parasympathetic function), including two or more of the following: heart rate response to deep breathing with recorded R-R interval, Valsalva ratio, and 30:15 ratio
95922 vasomotor adrenergic innervation (sympathetic adrenergic function), including beat-to beat blood pressure and R-R interval changes during Valsalva maneuver and at least five minutes of passive tilt
95923 sudomotor, including one or more of the following: quantitative sudomotor axon reflex test (QSART), silastic sweat imprint, thermoregulatory sweat test, and changes in sympathetic skin potential
95924Testing of autonomic nervous system function; combined parasympathetic and sympathetic adrenergic function testing with at least 5 minutes of passive tilt
CPT codes not covered for indications listed in the CPB:
95943Simultaneous, independent, quantitative measures of both parasympathetic function and sympathetic function, based on time-frequency analysis of heart rate variability concurrent with time-frequency analysis of continuous respiratory activity, with mean heart rate and blood pressure measures, during rest, paced (deep) breathing, Valsalva maneuvers, and head-up postural change
ICD-10 codes covered if selection criteria are met:
E09.42Polyneuropathy in diabetes
E10.40 - E10.49
E11.40 - E11.49
E13.40 - E13.49Diabetes with neurological manifestations
E85.0 - E85.9Amyloidosis
G60.3Idiopathic progressive neuropathy
G60.8Other hereditary and idiopathic neuropathies
G60.9Hereditary and idiopathic neuropathy, unspecified
G63Polyneuropathy in diseases classified elsewhere
G90.50 - G90.59Complex regional pain syndrome l (CRPS l)
G90.9Disorder of the autonomic nervous system, unspecified [postural tachycardia syndrome] [not covered for paradoxical parasympathetic syndrome]
M35.00 - M35.09Sicca syndrome [Sjegren]
R00.0Tachycardia, unspecified [postural tachycardia syndrome]
R55Syncope and collapse
ICD-10 codes not covered for indications listed in the CPB::
G04.90Encephalitis and encephalomyelitis, unspecified
I10Essential (primary) hypertension
I73.00 - I73.01Raynaud's syndrome
K21.9Gastro-esophageal reflux disease without esophagitis
K58.0 - K58.9Irritable bowel syndrome
R53.82Chronic fatigue, unspecified
The above policy is based on the following references:
Policy HistoryAdditional Information
Copyright Aetna Inc. All rights reserved. Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.
Great Paper on the Findings of a Study Involving 824 CRPS Patients
Focus is the Spread of CRPS
Talking to your Doctor
“Doctors aren’t mind readers. We have to be told when you are in pain, what your pain is like, and what affects it. And the only person who an accurately do that is you.” Paul Blake MD
BEFORE THE VISIT:
CHART A COURSE
Before you visit the doctor take the time to map out your strategy. What do you expect to get out of the appointment? For example, make a list of symptoms. Hand your list to the doctor when he walks into the room. This will help the doctor focus and quickly address your concerns.
TAKE YOUR BEST SHOT
A patient gets about 18 seconds to explain a medical problem before the doctor interrupts with questions. What would you like to say to the doctor in two or three sentences? Make sure you state your request as what you expect the doctor to do for you. For example, “ I would like some advice about coping better with flare-ups without using drugs.”
Anticipate the five questions that your doctor is most likely to ask about your pain.
DURING THE VISIT:
Stick to the facts when you are describing pain. If you stick to the script, the doctor can quickly begin to think about a diagnosis.
HEY DOC, FEEL IT TOO
Just saying it hurts isn’t going to help your doctor understand your pain. Be specific and let him know how the pain is disrupting your life. If your pain is preventing you from playing tennis, walking, gardening or doing household chores, let it be known. Communicating how it affects you will help the doctor understand and do something about it.
USE THE LINGO
The more accurately you can describe your pain, the better the chances that your doctor can help you find relief. For example, Use words like stinging, burning, shooting, stabbing, aching, cramping, throbbing or jabbing. Be specific about the type of pain and where the pain is and travels. For example, a sharp stabbing pain in your legs and back that goes all the way to your toes, will need different treatment than a burning pain that begins in your hip and travels down your thigh.
PICK A TARGET
If you have more than one pain, zero in on the most bothersome one first. Telling him that your hurt everywhere will not be helpful. For example, this pain is unique because it is a jabbing in my lower back. It does not respond to pain meds the way my other pain does.
If you do not understand an explanation, do not hesitate to say “ I still don’t quite get it. Can you explain it again?” Your doctor is there to educate you and treat you.
If your doctor does not seem to understand your problem, ask him to repeat what he thinks your problem is. If it does not match what you said, try restating the problem. “Can I explain it to you better or differently?” That way he won’t feel as if you are attacking him.
Ask your doctor to use pictures of visual aids that will make it easier to understand.
GET IT IN WRITING
Ask your doctor for flyers, step by step instructions or handouts that can help you understand your condition, and help you recall techniques for relieving pain.
BEFORE YOU LEAVE:
Take a few minutes to sit in the waiting room and go over the written materials or jot notes about the visit. If you don’t understand something, particularly the diagnosis, procedures, treatment or follow-up visit ask the nurse for clarification. If you are still confused, ask to speak briefly to the doctor.
CONNECT WITH THE DOCTOR
Ask the nurse when the best time would be to phone the doctor if you have a question or need advice between visits. If you leave a message, be sure to tell when you’re available. Some doctors will also have e-mail to respond to you.
If you are still uncomfortable about your diagnosis or treatment plan,
“there is nothing wrong with getting a second opinion for a complicated problem like pain. You are not necessarily going to hear the same thing from a second doctor. Most doctors do not get upset when you ask for another opinion.”
Source: Dollemore D and Eds. Prevention Health books for Seniors Seniors Guide to Pain Free Living
Treatment of CRPS
Complex regional pain syndrome (CRPS) is a chronic condition characterized by extreme pain. CRPS typically affects a limb, such as a leg or arm. In many cases, CRPS pain may prevent patients from using the limb as much as possible. Many patients find that CRPS pain worsens as time passes, as opposed to healing.
There is no known cure for the condition. However, patients may undergo treatment of CRPS through medical treatments, drugs, and physical therapy. Therapy typically consists of a treatment plan that is personalized for each individual’s symptoms. The various treatments are used to alleviate CRPS pain and maintain limb mobilization.
Medicinal Treatment of CRPS
Treatment of CRPS typically involves some sort of pain relief medication. Over-the-counter (OTC) pain relief treatment of CRPS may be used for pain and inflammation symptoms. These can include ibuprofen and aspirin, as found in OTC pain relief brands such as Motrin and Advil. Naproxen may also be used, such as Aleve. The patient’s doctor may prescribe stronger pain relief treatment of CRPS if OTC products do not improve the condition.
Other treatment of CRPS can include medicines such as:
Treatment of CRPS may involve physical therapy. Physical therapy can include guided exercises that work to encourage mobility, relieve pain, and build strength in the affected limb. Physical therapy is typically more effective during early stages of CRPS. Therefore, early diagnosis has a significant impact on the efficacy of physical therapy treatment of CRPS.
Topical treatment of CRPS includes application of heat and cold to the affected area. Applying cold can help to relieve sweating and swelling. If the limb temperature is cooler than the rest of the body, the application of heat may provide relief to the patient. Topical analgesics may also be used to reduce hypersensitivity.
Transcutaneous electrical nerve stimulation (TENS) is a treatment of CRPS that involves the application of electrical impulses to the patient’s affected nerve endings. Spinal cord stimulation may also be used. This treatment of CRPS involves the insertion of small electrodes along the patient’s spinal cord. Small electrical currents are then delivered to the spinal cord. As a result, the patient may experience pain relief.
Surgical Treatment of CRPS
Surgical treatment of CRPS is often used for patients who receive favorable yet temporary results from nerve-block treatments. Sympathectomy is a surgical procedure that involves the sympathetic nerve. The sympathetic nerve runs down the spinal column.
During a sympathectomy, a portion of the patient’s sympathetic nerve is cut and cauterized, or sealed. This treatment of CRPS is believed to suppress activity in the affected area, thereby reducing pain. However, sympathectomy treatment of CRPS is controversial. In some cases, it may worsen CRPS symptoms.
Alternative Treatment of CRPS
Alternative treatment of CRPS may include methods such as:
Ameer, Khalid, et al. “Diagnosis and Management of Complex Regional Pain Syndrome (CRPS).” Pakistan Armed Forces Medical Journal 4 (2010). Academic OneFile. Web. 2 Aug.
Bailey, Jacqueline, et al. “Imaging and Clinical Evidence of Sensorimotor Problems in CRPS: Utilizing Novel Treatment Approaches.” Journal of Neuroimmune Pharmacology. 8.3 (2013): 564-575. Print.
“Complex Regional Pain Syndrome Fact Sheet.” National Institute of Neurological Disorders and Stroke. National Institutes of Health, 12 Jul 2013. Web. 2 Aug 2013.
Langstaff, Michelle. “Alternative Therapy Brings Relief.” RSDSA. Reflex Sympathetic Dystrophy Syndrome Association. Web. 2 Aug 2013.
“New Complex Regional Pain Syndromes Study Findings Have Been Reported from Pain Center.” Biotech Week 8 Feb. 2012: 692. Academic OneFile. Web. 2 Aug. 2013.
Turk, Dennis C., Hilary D. Wilson, and Alex Cahana. “Pain 2: Treatment of Chronic Non-Cancer Pain.” The Lancet 377.9784 (2011): 2226-35. ProQuest. Web. 2 Aug. 2013.