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Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract.  Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage.  Medical technology is constantly changing, and we reserve the right to review and update our policies periodically.

Description

Policy

Policy Guidelines

Benefit Application

Rationale

Quantitative sensory testing (QST) can either be used as the initial diagnostic test or as a monitoring test in patients to assess ongoing sensory deficits. The type of data required to validate QST in these 2 different settings are 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 2 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. (1) The AAN indicated QST poses technical challenges in the methodology of testing, reproducibility, and psychophysical factors that 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. (2) 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 at this time.

Literature Review

Current Perception Threshold Testing

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.

In 1999, the American Association of Electrodiagnostic Medicine (AAEM) published a technology review of the Neurometer® device. (3) This evaluation suggested the following criteria for the evaluation of the device:

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 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, which was consistent with the hypothesis that abnormalities of small nerve fibers precede those of 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.

In promotional material (4), the Medi-Dx 7000™ device is presented as an alternative to the Neurometer® with the capability of identifying abnormalities in branches of individual nerves. A literature review failed to identify any articles in the published peer-reviewed literature specifically focusing on the Medi-Dx 7000™ device.

In an updated review of the literature, 2 studies reported on attempts to establish the diagnostic utility of current perception threshold testing. (5, 6) In Yamashita, 48 patients with lumbar radiculopathy were compared with 11 healthy controls to evaluate current perception thresholds using the Neurometer®. (5) 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 the unaffected legs. Current perception threshold values in the affected legs were also significantly higher in control subjects at 2000 and 250 Hz frequencies 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 19 healthy volunteers. (6) 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. However, none of these studies sufficiently address the AAEM recommendations for research to validate the clinical utility of current perception threshold testing.

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. (7, 8) In addition, no clinical practice guidelines were found that addressed the use of PSSD. As noted here, 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 interoperator variability and increase reproducibility; and to establish sensitivity and specificity comparisons to appropriate standards.

Vibration Testing

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. (9) 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.

Thermal Testing

A literature update in August 2009 indicates increasing use of QST with thermal stimuli for the detection of small fiber neuropathy in a variety of clinical conditions. For example, Attal and colleagues conducted a study to identify early clinical markers and predictors of neurotoxity with the chemotherapy drug oxaliplatin. (10) Out of 67 consecutive patients with mainly colorectal cancer, 48 (72%) were able to be evaluated prospectively before, during and after 9 cycles of oxaliplatin (n = 28) or cisplatin (n =20) treatment. Eighteen of the oxaliplatin patients were re-assessed at 12 months. Evaluation with QST included detection/pain thresholds for mechanical, vibration, cold and heat stimuli. Thermal testing (cold or heat) 2 weeks after the 3rd cycle identified sustained neurotoxicity during oxaliplatin treatment, while cold-evoked symptoms lasting 4 days or more after the 3rd cycle predicted chronic neuropathy (odds ratio of 22; 95% CI 1.5 - 314.7) and severe neuropathy (odds ratio of 39; 95% CI 1.8 - 817.8). These results are limited by the small number of patients and large confidence intervals. Additional study is needed to evaluate the predictive value of abnormal thermal QST and their clinical implications.

In 2008, Devigli et al. published a retrospective review of 486 patients referred for suspected sensory neuropathy. (11) A total of 150 patients met the entry criteria for the study, which included symptoms suggesting sensory neuropathy and availability of 1) clinical examination, including spontaneous and stimulus-evoked pain, 2) a sensory and motor nerve conduction study, 3) warm and cooling thresholds assessed by quantitative sensory testing (QST) and 4) skin biopsy with distal intraepidermal nerve fiber (IENF) density. Based on the combined assessments, neuropathy was ruled out in 26 patients; 124 patients were diagnosed with sensory neuropathy, and of these 67 patients were diagnosed with small nerve fiber neuropathy. Using a cutoff of 7.63 IENF/mm at the distal leg (based on the 5th percentile of controls), 59 patients (88%) were considered to have abnormal IENF (small nerve fiber) density. Only 7.5% of patients had abnormal results for all 3 examinations (clinical, QST, skin biopsy), 43% of patients had both abnormal skin biopsy and clinical findings, and 37% of patients had both abnormal skin biopsy and QST results. The combination of abnormal clinical and QST results was observed in only 12% of patients. These results indicate that most of the patients evaluated showed IENF density of less than 7.63 together with either abnormal spontaneous or evoked pain (clinical examination) or abnormal thermal thresholds (QST). The authors of this study recommended a new diagnostic “gold standard” based on the presence of at least 2 of 3 abnormal results (clinical, QST, and IENF density). Additional prospective studies are needed to evaluate whether the addition of thermal QST results in improved outcomes over clinical diagnosis alone.
Other study results raise questions about the reliability of QST. For example, one study noted “significant” variability in thermal perception thresholds during a 1-hour time in 24 female volunteers. (12) In another small study, mean QST thresholds for vibration, cold, warmth, and heat pain were no different in 10 patients with type 2 diabetes and painful neuropathy than in 15 healthy control subjects. (13) In the same study, QST thresholds were also evaluated in 12 patients with type 2 diabetes and advanced painless neuropathy; these were found to be significantly higher than the control thresholds for all of the stimuli, suggesting that QST was not able to detect early stages of neuropathy. The study found that a new functional test of dermal vasodilation, called the LDI (laser Doppler imager) flare, showed significant changes in both the painful (mild) and painless (severe) neuropathy patients.

Clinical Input Received through Physician Specialty Societies and Academic Medical Centers

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.

Summary

Use of QST for the detection of large fiber neuropathy has not been shown to be as effective as standard nerve conduction studies. One potentially promising application of QST is the use of thermal stimuli for early detection of small fiber neuropathy. However, questions remain about the reliability and clinical utility of quantitative sensory nerve conduction testing. Evidence at this time is insufficient to demonstrate an improvement in net health outcome with this technology. Therefore, the policy statement remains unchanged; this is considered investigational.

Technology Assessments, Guidelines and Position Statements

A 2003 report from the American Academy of Neurology (AAN) 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. (1) 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).

The American Association of Electrodiagnostic Medicine (AAEM) published a technology literature review on quantitative sensory testing (light touch, vibration, thermal, and pain) in 2004. (14) 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 2 QSTs that can be attributed to experimental error.

In 2005, the AAEM, in conjunction with the AAN and American Academy of Physical Medicine and Rehabilitation (AAPM&R) developed a formal case definition of distal symmetrical polyneuropathy based on a systematic analysis of peer-reviewed literature supplemented by consensus from an expert panel. (15) QST was not included as part of the final case definition, given that the reproducibility of QST ranged from poor to excellent, and the sensitivities and specificities of QST were found to vary widely among studies.

In 2004 the European Federation of Neurological Societies published guidelines on neuropathic pain assessment. (16) 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.

Medicare National Coverage

In February 2002, Medicare announced a national non-coverage policy on sensory nerve conduction threshold testing. Requests for reconsideration were submitted by both the makers of the Neurotron® and the Medi-Dx 7000™ devices. On reconsideration, in July 2003, Medicare affirmed its non-coverage policy, concluding that any use of sensory nerve conduction threshold testing to diagnose sensory neuropathies or radiculopathies is not reasonable and necessary. (17) This decision was reaffirmed effective April 2004. Medicare has not addressed coverage for PSSD testing. No additional information about Medicare coverage was found during the 2006 review.

References:

1. Shy ME, Frohman EM, So YT et al. Quantitative sensory testing: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2003; 60(6):898-904.
2. Siao P, Cros DP. Quantitative sensory testing. Phys Med Rehabil Clin N Am 2003; 14(2):261-86.
3. Technology review: the Neurometer Current Perception Threshold (CPT). AAEM Equipment and Computer Committee. American Association of Electrodiagnostic Medicine. Muscle Nerve 1999; 22(4):523-31.
4. www.ndanerve.com
5. 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.
6. 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.
7. 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; 45(3):252-7.
8. 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.
9. 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.
10. Attal N, Bouhassira D, Gautron M et al. Thermal hyperalgesia as a marker of oxaliplatin neurotoxicity: a prospective quantified sensory assessment study. Pain 2009; 144(3):245-52.
11. Devigili G, Tugnoli V, Penza P et al. The diagnostic criteria for small fibre neuropathy: from symptoms to neuropathology. Brain 2008; 131(Pt 7):1912-25.
12. Palmer ST, Martin DJ. Thermal perception thresholds recorded using method of limits change over brief time intervals. Somatosens Mot Res 2005; 22(4):327-34.
13. Krishnan ST, Quattrini C, Jeziorska M et al. Abnormal LDIflare but normal quantitative sensory testing and dermal nerve fiber density in patients with painful diabetic neuropathy. Diabetes Care 2009; 32(3):451-5.
14. Chong PS, Cros DP. Technology literature review: quantitative sensory testing. Muscle Nerve 2004; 29(5):734-47.
15. England JD, Gronseth GS, Franklin G et al. Distal symmetrical polyneuropathy: definition for clinical research. Muscle Nerve 2005; 31(1):113-23.
16. Cruccu G, Anand P, Attal N et al. EFNS guidelines on neuropathic pain assessment. Eur J Neurol. 2004; 11(3):153-62.
17. Medicare Decision Memorandum for Reconsideration of National Coverage Determination: Sensory Nerve Conduction Threshold Testing; http://www.cms.hhs.gov/coverage/download/id26.pdf.

Index

Policy History