Medicine Section - Quantitative Sensory Testing

IMPORTANT REMINDER

Regence Medical Policies are developed to provide guidance for members and providers regarding coverage in accordance with contract terms. Benefit determinations are based in all cases on the applicable contract language. To the extent there may be any conflict between the Medical Policy and contract language, the contract language takes precedence.

PLEASE NOTE: Contracts exclude from coverage, among other things, services or procedures that are considered investigational or cosmetic. Providers may bill members for services or procedures that are considered investigational or cosmetic. Providers are encouraged to inform members before rendering such services that the members are likely to be financially responsible for the cost of these services.

Description

Quantitative sensory testing (QST) systems are used for the noninvasive assessment and quantification of sensory nerve function in patients with symptoms of or the potential for neurologic damage or disease. QST systems measure and quantify the amount of physical stimuli required for sensory perception to occur in the patient. Stimuli use in QST includes touch, pressure, pain, thermal (warm and cold), or vibratory stimuli. Depending on the type of stimuli used, QST can assess small or large fiber function. QST with touch and vibration can evaluate large myelinated A alpha and A beta sensory fibers. Thermal stimuli can assess small myelinated fibers and unmyelinated sensory nerve function.

QST is used to assist in the diagnosis and management of a variety of conditions such as diabetic neuropathy and other uremic and toxemic neuropathies, as well as, carpal tunnel syndrome and other nerve entrapment/compression disorders or damage. QST has not been established for use as a sole tool for diagnosis and management but has been used in conjunction with standard evaluation and management procedures (e.g., physical and neurological examination, monofilament testing, pin prick, grip and pinch strength, Tinel, Phalen and Roos sign, etc.) to enhance the diagnosis and treatment planning process and confirm physical findings with quantifiable data. As sensory deficits increase, the perception threshold of QST will increase which may be informative in documenting progression of neurologic damage or disease.

Because QST combines the objective physical sensory stimuli with the subject patient response, it is psychological in nature and requires that its use be in patients who are alert, able to follow directions and cooperative. Due to the subjective component of testing, psychological factors must be taken into consideration during testing and in evaluating test results; thus reducing the degree of objectivity QST can provide.

Three QST methods are highlighted in this policy: current perception threshold testing, voltage-actuated sensory nerve conduction threshold testing, and pressure-specified sensory device testing.

Current Perception Threshold Testing

Electromyographic nerve conduction (EMG-NCV) tests are diagnostic studies designed to evaluate the function of large myelinated nerve fibers, i.e., the motor nerves, and thus do not evaluate the function of smaller myelinated and unmyelinated sensory nerves, which may show pathologic changes before the involvement of the motor nerves. Current perception threshold testing, also referred to as sensory nerve conduction threshold (sNCT) testing, involves the quantification of the sensory threshold to transcutaneous electrical stimulation and thus has been explored as a technique to evaluate the sensory nerves.  In current perception threshold testing, typically three different frequencies are tested: 5 Hz, designed to access C fibers; 250 Hz, designed to assess A-delta fibers; and 2,000 Hz, designed to assess the A-beta fibers. Results are compared with those of a reference population. Current perception threshold testing has been investigated for a broad range of clinical applications, including evaluation of peripheral neuropathies, detection of carpal tunnel syndrome, spinal radiculopathy, evaluation of the effectiveness of peripheral nerve blocks, quantification of hypoesthetic and hyperesthetic conditions and differentiation of psychogenic from neurologic disorders.

The Neurometer® Current Perception Threshold (Neurotron, Inc.) approved by the U.S. Food and Drug Administration (FDA) for the use of measuring the threshold for sensory nerve conduction.

Voltage-actuated Sensory Nerve Conduction Threshold (VsNCT)

The Medi-Dx 7000™ (Neuro Diagnostic Associates) is a voltage-actuated sensory nerve conduction test (VsNCT) device approved by the FDA as “a diagnostic device that allows the quantitative detection of various sensory neurological impairments caused by various pathological conditions or toxic exposures. The Medi-Dx 7000 diagnostic examination may be conducted as part of the neurological examination or for screening to detect peripheral neuropathies.”(5) VsNCT measures the nerve impulse itself rather than the nerves response to a stimulus. VsNCT determines whether the nerve’s function is normal, hyper-functioning or hypo-functioning. VsNCT is proposed as a method of testing to detect pre-ganglionic dorsal nerve-root pathology earlier than other nerve conduction studies to allow a better and earlier positive outcome for the patient.

Pressure-Specified Sensory Testing

Pressure-specified sensory testing is a method to assess nerve function by quantifying the thresholds of pressure detected with light, static and moving touch. The Nk Pressure-Specified Sensory Device™ (Nk Biotechnical Engineering) consists of one or two blunt probes and sensitive transducers to measure and record the perception thresholds of pressure on the surface of the body in grams per square millimeter. The device has been used to aid in the diagnosis and assessment of nerve function, including diabetic peripheral neuropathy, carpal tunnel syndrome, and other nerve entrapment or compression syndromes, and post-operative assessment of sensory outcomes after liposuction, breast reduction mammoplasty, etc. The Nk Pressure-Specified Sensory Device™ received FDA 510k marketing clearance n August of 1994 (k934368).

Vibration Perception Threshold Testing

Vibration perception threshold devices measure the patient’s threshold of detection of a vibratory stimulus. Vibratory QST is used to assess the function of large myelinated sensory nerve fibers. The Vibration Perception Threshold (VPT) meter (Xilas Medical) received FDA 510(k) marketing clearance in 2003 (K030829). The CASE IV Computer Aided Sensory Evaluator (WR Medical Electronics, Stillwater, MN) received FDA 510(k) marketing clearance in 1992 (K910624); CASE IV measures vibration or thermal thresholds.

Reports noted during the 2006 literature review continue to describe various potential uses of this testing.  Some potential uses being described include use in identifying diabetics at risk for foot ulceration, in identifying superimposed entrapment neuropathy in patients with diabetes, and in detecting abnormalities in patients with reflex sympathetic dystrophy.

Policy/Criteria

Quantitative sensory testing is considered investigational, including but not limited to the following:

1. Current perception threshold testing
2. Voltage-actuated sensory threshold testing
3. Pressure-specified sensory device testing
4. Vibration perception threshold device testing

Scientific Background

QST can either be used as the initial diagnostic test or can be used as a monitoring test in patients to assess ongoing sensory deficits. The type of data required to validate QST in these two different settings is different. For example, as an initial diagnostic test, one would like to see standard measures of diagnostic performance, such as sensitivity, specificity, positive and negative predictive values as compared to conventional tests, such as monofilament testing, pinprick, etc. In some cases, QST has been proposed as an alternative to nerve conduction studies, and in this setting, one would like to compare the diagnostic performances of these two tests. When used as a monitoring technique, test/retest reliability is an important outcome, as well as defining a clinically significant change in sensory perception. As with any diagnostic test, it is important to evaluate how the results of the test will be used to enhance patient management, either in terms of instituting more prompt or more effective therapy, or in the avoidance of more invasive tests, such as nerve conduction studies.

In a 2003 report, the American Academy of Neurology (AAN) noted QST should not be used as a sole method for diagnosis of pathology. (2) The AAN indicated QST poses technical challenges in the methodology of testing, reproducibility, and psychophysical factors which limit the objectivity of testing results. Siao and Cros noted in a review that QST is influenced by many extraneous factors and may be subject to misinterpretation and misuse. (3) In addition, normal reference levels do not exist and the reproducibility of QST has not been firmly established. Also, there are no generally recognized standards for QST techniques, performance and interpretation.

Current Perception Threshold Testing

In 1999 the American Association of Electrodiagnostic Medicine (AAEM) published a technology review of the Neurometer® device. (2) This evaluation suggested the following criteria for the evaluation of the device:

• A prospective study
• Independent ascertainment of the clinical condition evaluated
• A detailed description of the methodology
• Attention to testing conditions that could potentially affect the results
• A suitable reference population from the same laboratory
• Criteria for abnormality obtained from the reference population and defined in statistical terms

The AAEM assessment concluded that there is inadequate scientific literature meeting the above criteria to validate the clinical role of current perception threshold testing. Much of the literature compares the results of the Neurometer® testing to nerve conduction studies in patients with known disease. In many instances the results of the Neurometer® testing demonstrated more numerous or pronounced abnormalities compared to nerve conduction studies, consistent with the hypotheses that abnormalities of small nerve fibers precede those of the large nerve fibers tested in nerve conduction studies. However, this observation could also be related to the fact that use of the Neurometer® involves testing at multiple sites with 3 different frequencies and that any identified abnormality is considered significant. Testing the perception threshold at different frequencies is designed to evaluate the function of different subclasses of nerve fibers. However, this hypothesis has not been adequately evaluated, in part due to a lack of a diagnostic gold standard for comparison purposes. In this situation, validation of a diagnostic technology requires study of how the technique is used in the management of the patient and whether subsequent changes in the management of the patient are associated with improved health outcomes. Finally, results of the Neurometer® testing are compared to a normal reference population. The review by the AAEM found that the source of the normal values was not apparent from the published literature. The AAEM assessment concluded with the following recommendations regarding research to validate the clinical utility of the Neurometer®:

• Reference values need to be established for well-characterized and representative populations.
• Reproducibility and interoperator variability of the Neurometer® CPT normal values need to be established and expressed statistically in control subjects and patients with specific diseases.
• The sensitivity and specificity need to be established and compared to an appropriate standard.

Voltage-actuated Sensory Nerve Conduction Threshold (VsNCT)

In promotional material (5), the Medi-DX 7000™ device is presented as a way to assess the pre-ganglionic dorsal nerve-root fibers to rule in or out radiculopathy as the etiology of spinal, or radiating pain. A literature review failed to identify any articles in the published peer-reviewed literature specifically focusing on the Medi-Dx 7000™ device. However, a 2002 issue of The Internet Journal of Anesthesiology (6) reported results of a study comparing voltage-actuated sensory nerve conduction (V-sNCT) to physical examination in forty-nine patients with L5-S1 radicular pain scheduled for lysis of epidural adhesions. All patients underwent pre-procedure V-sNCT. The results were compared to abnormal nerve roots documented by epidurography and to neurological exam consisting of motor, reflex and sensory tests. The epidurography confirmed that V-sNCT positively identified abnormal nerve roots with a sensitivity of 94.6% while neurological exam positively identified nerve root abnormality with a sensitivity of 61.7% (p=less than 0.05). Specificity was not significantly different between V-sNCT and neurologic exam. The study has several limitations: it is not a randomized comparison; neither patient nor investigator were blinded to the intervention potentially lending bias to the outcomes; the study sample was small, and health outcomes resulting from management decisions made based on the V-sNCT results are not reported. Based on the available evidence, conclusions concerning the effect of voltage-actuated sensory nerve conduction testing on patients with peripheral neuropathies and other neurological impairments cannot be made. As noted above, in the evaluation of current perception threshold testing, further research is needed to validate the clinical utility of V-sNCT; to establish reference values for well-characterized and representative populations; to establish normal values in control subjects and patients with specific diseases to reduce interoperator variability and increase reproducibility; and to establish sensitivity and specificity comparisons to appropriate standards.

In an updated review of the literature, two studies reported on attempts to establish the diagnostic utility of current perception threshold testing. (7,8) In the study by Yamashita and colleagues, forty-eight patients with lumbar radiculopathy were compared with eleven healthy controls to evaluate current perception thresholds using the Neurometer®. (7) The authors reported finding significantly higher current perception threshold values in the affected legs of patients with lumbar radiculopathy at 2000, 250, and 5 Hz frequencies than in their unaffected legs. Current perception threshold values in the affected legs of the patient group were also significantly higher than in control subjects at 2000 and 250 Hz frequency but not significantly different at 5 Hz. The authors concluded that current perception threshold testing may be useful in quantifying sensory nerve dysfunction in radiculopathy patients. However, there was no discussion of how this quantification could be used in the management of the patient.

Park and colleagues attempted to validate current perception threshold testing against the gold standard references for thermal sensory testing and von Frey tactile hair stimulation in a randomized, double-blind, placebo-controlled trial on nineteen healthy volunteers. (8) The authors reported finding that all current perception threshold measurements showed a higher degree of variability than thermal sensory testing and von Frey measurements but concluded that there is some evidence that similar fiber tracts may be measured, especially C-fiber tract activity at 5 Hz, with current perception threshold, thermal sensory, and von Frey testing methods.

Results of published studies appear promising. However, none of the studies published through September 2005 sufficiently address the AAEM recommendations for research to validate the clinical utility of current perception threshold testing. Therefore, the policy statement is unchanged.

Pressure-Specified Sensory Testing

A review of the literature on pressure-specified sensory device (PSSD) testing found there is not sufficient evidence to demonstrate that PSSD testing will provide any further information than what can ordinarily be determined during standard evaluation and management of patients with potential nerve compression, disease or damage. Standard evaluation and management consists of physical examination techniques and may include Semmes-Weinstein monofilament testing, and in some more complex cases, NCV testing. While PSSD may be a useful adjunct in neurosensory testing, no clinical trials were identified that demonstrated that use of the PSSD resulted in earlier and/or more accurate diagnoses of nerve damage and improved patient outcomes. Nor were any studies found that examined this technology for patient selection criteria for carpal or tarsal tunnel release, plexus neurolysis, etc. (9,10) Additionally, no clinical practice guidelines were found that addressed the use of PSSD. As noted above, in the evaluation of current perception threshold testing, further research is needed to validate the clinical utility of PSSD; to establish reference values for well-characterized and representative populations; to establish normal values in control subjects and patients with specific diseases to reduce inter operator variability and increase reproducibility; and to establish sensitivity and specificity comparisons to appropriate standards.

An updated literature search through September 2005 did not return any new published clinical trial data validating the clinical utility of pressure-specified sensory testing; therefore, the policy is unchanged.

An updated review of the literature through September 2006 did not return any new clinical trial evidence that would alter the policy criteria as written.  While studies using these technologies continue to be conducted, the impact of these tests on improving clinical outcomes has not been shown.  There also continues to be questions about the performance of the tests; one recent study noted the “significant” variability in thermal perception thresholds in a one-hour period in 24 female volunteers. (11)

An updated literature search based on Medline through September 2007 returned a number of clinical studies which continue to address the validity of QST, stimulation parameters and protocols for selected groups of patients. (12-16) However, none of the studies published thus far have studied the impact of QST testing on patient management decisions and the health outcomes of patients.  Studies continue to report conflicting results concerning the potential usefulness of QST. (14)

In 2005 the American Academy of Neurology (AAN) reaffirmed the 2003 assessment of QST in assessing various pain syndromes.  Based on current knowledge the AAN rated the evidence a “Level U” recommendation, meaning that the data available are inadequate or conflicting and the value of the test is unproven. (2)

2008 Update

In 2004 the European Federation of Neurological Societies published guidelines on neuropathic pain assessment. (19) The task force concluded that QST is helpful to quantify the effects of treatments on allodynia and hyperalgesia (grade A recommendation), but recommends the use of simple tools such as a brush and high-threshold von Frey filaments. Because QST abnormalities are also found in non-neuropathic pains, QST abnormalities cannot be taken as a conclusive demonstration of neuropathic pain. The recommendations also indicated that QST is expensive and time consuming, and thus difficult to use in clinical practice.

A search of the MEDLINE database was performed through February 2008. A multicenter study funded by a pharmaceutical company compared vibration threshold testing (CASE IV, biothesiometer, C64 graduated tuning fork) with standard nerve conduction studies (NCS) in 195 (86% follow-up) subjects with diabetes mellitus. (17) The tests were performed independently by trained technicians; all NCS evaluations were sent to a central reading center. Intra-class correlation coefficients for the tests ranged from 0.81 to 0.95, indicating excellent to highly reproducible results. Correlation coefficients for the various vibration QST instruments were moderate at -0.55 (CASE IV vs. tuning fork) to 0.61 (CASE IV vs. biothesiometer). In contrast, the correlation coefficient between CASE IV and a composite score for nerve conduction was low (r = 0.24). These results indicate that vibration threshold testing could not replace NCS testing, but might provide a complementary outcome measure. Overall, questions remain about the clinical utility of sensory nerve conduction threshold testing. Evidence is insufficient to demonstrate an improvement in health outcomes.

Physician Specialty Society and Academic Medical Center Input

In response to the request for input from Physician Specialty Societies and Academic Medical Centers, input was received through the American Academy of Neurology and one academic medical center regarding use of quantitative sensory testing while the policy was under review. Input from both sources agreed with the policy statement that QST is considered investigational, as adopted in the policy in April 2008.

A 2003 report from the American Academy of Neurology concluded that QST is probably (level B recommendation) an effective tool in the documentation of sensory abnormalities and in documenting changes in sensory thresholds in longitudinal evaluation of patients with diabetic neuropathy. (2) Evidence was weak or insufficient to support the use of QST in patients with other conditions (small fiber sensory neuropathy, pain syndromes, toxic neuropathies, uremic neuropathy, acquired and inherited demyelinating neuropathies, or malingering). General recommendations indicated that QST results should not be the sole criterion used to diagnose structural pathology, or either a peripheral or central nervous system (CNS) origin. Abnormalities on QST must be interpreted in the context of a thorough neurologic examination and other appropriate testing, such as electromyography (EMG), nerve biopsy, skin biopsy, or appropriate imaging studies.

The American Association of Electrodiagnostic Medicine published a technology literature review on quantitative sensory testing (light touch, vibration, thermal, and pain) in 2004. (18) The review concluded that QST is a reliable psychophysical test of large- and small-fiber sensory modalities, but is highly dependent on the full cooperation of the patient. Abnormalities do not localize dysfunction to the central or peripheral nervous system, and no algorithm can reliably distinguish between psychogenic and organic abnormalities. The AAEM technology review also indicated that QST has been shown to be reasonably reproducible over a period of days or weeks in normal subjects, but for individual patients, more studies are needed to determine the maximum allowable difference between two QSTs that can be attributed to experimental error.

In 2004 the European Federation of Neurological Societies published guidelines on neuropathic pain assessment. (19) The task force concluded that QST is helpful to quantify the effects of treatments on allodynia and hyperalgesia (grade A recommendation), but recommends the use of simple tools such as a brush and high-threshold von Frey filaments. Because QST abnormalities are also found in non-neuropathic pains, QST abnormalities cannot be taken as a conclusive demonstration of neuropathic pain. The recommendations also indicated that QST is expensive and time consuming, and thus difficult to use in clinical practice.

References

1. BlueCross and BlueShield Association Medical Policy reference Manual, Policy No.2.01.39
2. Shy M, Frohman M, So Y, et al. Quantitative sensory testing: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2003;60:898-904
3. Siao P, Cros D. Quantitative sensory testing. Phys Med Rehabil Clin N Am 2003;14(2):261-286
4. Technology Review: the Neurometer Current Perception Threshold (CPT). Muscle Nerve 1999;22:523-31
5. www.ndanerve.com (Verified 10/24/08)
6. Cork RC, Saleemi S, Hernandez L, et al  Predicting nerve root pathology with voltage-actuated sensory nerve conduction threshold. The Internet Journal of Anesthesiology 2002;6(1):1-8 at www.ispub.com (Verified 10/24/08)
7. Yamashita T, Kanaya K, Sekine M et al. A quantitative analysis of sensory function in lumbar radiculopathy using current perception threshold testing. Spine 2002;27(14):1567-70
8. Park R, Wallace MS, Schulteis G. Relative sensitivity to alfentanil and reliability of current perception threshold vs. von Frey tactile stimulation and thermal sensory testing. J Peripher Nerv Syst 2001;6(4):232-40
9. Weber R, Schuchmann J, Albers J et al. A prospective blinded evaluation of nerve conduction velocity versus Pressure-Specified Sensory Testing in carpal tunnel syndrome. Ann Plast Surg 2000 Sep+Ads-45(3):252-7
10. Howard M, Lee C, Dellon AL. Documentation of brachial plexus compression (in the thoracic inlet) utilizing provocative neurosensory and muscular testing. J Reconstr Microsurg 2003;19(5):303-12
11. Palmer ST, Martin DF. Thermal perception thresholds recorded using method of limits change over brief time intervals.  Somatosens Mot Res 2005;22:327-34
12. Svic G, Berstrom EMK, Frankel HL et al. Perceptual threshold to cutaneous electrical stimulation in patients with spinal cord injury. Spinal Cord 2006;44:560-6
13. Eisenberg E, Backonja MM, Fillingim RB et al. Quantitative sensory testing for spinal cord stimulation in patients with chronic neuropathic pain. Pain Practice 2006;6(3):161-5
14. Sorensen L, Molyneaux L, Yue DK. The level of small nerve fiber dysfunction does not predict pain in diabetic neuropathy. A study using quantitative sensory testing. Clin J Pain 2006;22(3):261-5
15. Rolke R, Baron R, Maier C et al. Quantitative sensory testing in the German Research Network on neuropathic pain (DFNS): Standardized protocol and reference values. Pain 2006;123:231-43
16. Bird SJ, Brown MJ, Spino C et al. Value of repeated measures of nerve conduction and quantitative sensory testing in a diabetic neuropathy trial. Muscle Nerve 2006;34:214-24
17. Kincaid JC, Price KL, Jimenez MC et al. Correlation of vibratory quantitative sensory testing and nerve conduction studies in patients with diabetes. Muscle Nerve 2007;36(6):821-7
18. Chong PS, Cros DP. Technology literature review: quantitative sensory testing. Muscle Nerve 2004;29(5):734-47
19. Cruccu G, Anand P, Attal N et al. EFNS guidelines on neuropathic pain assessment. Eur J Neurol. 2004;11(3):153-62

Cross References

None

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