Clinical Policy Title: Autonomic Nervous System Monitoring for Neuropathy

Clinical Policy Title: Autonomic Nervous System Monitoring for Neuropathy Clinical Policy Number: 09.01.01 Effective Date: September 1, 2013 Initial Review Date: February 18, 2013 Most Recent Review Date: April 15, 2015 Next Review Date: April 2016 Policy contains: Autonomic nervous system monitoring for neuropathy. Related Policies: None ABOUT THIS POLICY: Keystone First has developed clinical policies to assist with making coverage determinations. Keystone First s clinical policies are based on guidelines from established industry sources, such as the Centers for Medicare & Medicaid Services (CMS), state regulatory agencies, the American Medical Association (AMA), medical specialty professional societies, and peer-reviewed professional literature. These clinical policies along with other sources, such as plan benefits and state and federal laws and regulatory requirements, including any state- or plan-specific definition of medically necessary, and the specific facts of the particular situation are considered by Keystone First when making coverage determinations. In the event of conflict between this clinical policy and plan benefits and/or state or federal laws and/or regulatory requirements, the plan benefits and/or state and federal laws and/or regulatory requirements shall control. Keystone First s clinical policies are for informational purposes only and not intended as medical advice or to direct treatment. Physicians and other health care providers are solely responsible for the treatment decisions for their patients. Keystone First s clinical policies are reflective of evidence-based medicine at the time of review. As medical science evolves, Keystone First will update its clinical policies as necessary. Keystone First s clinical policies are not guarantees of payment. Coverage policy Keystone First considers the use of autonomic nervous system monitoring for neuropathy to be clinically proven and, therefore, medically necessary when overseen and interpreted by a physician of the appropriate specialty (neurologist or cardiologist) and when the following criteria are met: Autonomic Nervous System Tested Cardiovascular System Medically Appropriate Test Heart rate response to standing (HRSTAND). Heart rate response to the Valsalva maneuver (HRVM). Heart rate response to deep breathing (HRDB). Resting heart rate variability (resting HRV). Blood pressure response to standing (tilt table). 1

Autonomic Nervous System Tested Medically Appropriate Test Direct Nerve Measurement Needle insertion nerve conduction studies. Sudomotor Function Tests Peripheral Sensory Perception Threshold Tests Sympathetic Skin Response Test (SSR). Quantitative Sudomotor Axon reflex test (QSART). Vibration perception threshold test. Thermal perception threshold test. Limitations: All other uses of autonomic nervous system monitoring for neuropathy are not medically necessary. Such uses include, but are not limited to, the following: Autonomic Nervous System Tested* Cardiovascular System Tests Considered Not Medically Necessary For the 24-hour heart rate variability (24-hour HRV). Resting heart rate (resting HR). Blood pressure response to hand grip (BPHG). 24-hour ambulatory blood pressure monitoring (ABPM). Baroreflex sensitivity (BRS). Prolonged head-up tilt-table tests alone. The full Ewing battery (combination of HRSTAND, HRVM, HRDB, BPSTAND, and BPHG tests). Direct Nerve Measurement Sudomotor Function Tests Peripheral Sensory Perception Threshold Tests Pupillary Function Tests Surface nerve conduction studies. Surface or needle insertion Electromyogram (EMG). Sweat test. Thermoregulatory sweat test. Silastic sweat imprint. Electrical current perception threshold test. Resting pupil diameter. Light reflex pupillography (LRP). Pharmacological reflex pupillography (PRP). Gastric Emptying Tests (GETs) Direct imaging or ultrasonic gastric emptying tests. Symptom Scoring Methods Diabetic neuropathy examination (DNE) scoring system. Serum Autonomic Neurotransmitters Serum assay for vasoactive intestinal peptide (VIP). Neuropeptide Y. Any other autonomic neurotransmitter. 2

Autonomic Nervous System Tested* Autonomic Neurotransmitter Imaging Tests Considered Not Medically Necessary Planar scintigraphy. Single-photon emission computed tomography (SPECT). Positron emission tomography (PET). *NOTE: Several of the tests listed above have appropriate indications for specific determinations of function; however, the evidence is insufficient to demonstrate their ability to measure autonomic nerve functionality. Additionally, the use of autonomic nervous system monitoring tests as part of a lie detector test, used for non-medical reasons, is not medically necessary. Alternative covered services: Physician office visits. Appropriate therapy sessions. Background Dysfunction of the autonomic nervous system (ANS) may involve conditions that affect either the sympathetic or parasympathetic nerves. The resulting deregulation may be clinically insignificant or may result in a number of symptoms based upon the body organs affected. ANS dysfunction that affects the cardiovascular system may result in either rapid resting heart rate or slowing. Blood pressure may drop on standing, a term called orthostatic hypotension. Any of these cardiovascular effects may result in syncope, or loss of consciousness. ANS dysfunction affecting other organs may result in genitourinary symptoms (e.g. urinary incontinence, erectile dysfunction, incomplete voiding/neurogenic bladder), gastrointestinal symptoms (gastroparesis, diarrhea or constipation), sweating problems with excessive or inadequate sweat production that can affect body temperature control, or vision difficulties from inappropriate pupillary constriction. Control of the symptoms is dependent upon determination of the cause. A number of disease entities may be responsible for ANS dysfunction. Diabetes is the most prevalent cause. However, other medical conditions may affect ANS function. They include, but are not limited to, Parkinson s disease, alcoholism, medication side-effects, multiple system atrophy (Shy-Drager syndrome), amyloid neuropathy, distal small fiber neuropathy, reflex sympathetic dystrophy, spinal cord conditions, multiple sclerosis and a number of other diseases. Tests for ANS abnormalities become part of the diagnostic strategy and must be selected based upon the specific set of symptoms. A given test may be appropriate in one setting but not another. Not all of the tests available are well studied. The level of evidence for any given test is based upon the reliability and reproducibility of that modality. Tests for autonomic dysfunction may be used for diagnosis, prognosis or monitoring of the condition. Appropriate application and interpretation of ANS testing requires a detailed knowledge of the testing criterion and a match between the tests of suspected clinical/functional impairment with the autonomic activity being tested. Autonomic testing may be indicated to exclude or confirm rarer autonomic disorders. 3

Methods Searches: Keystone First searched PubMed and the databases of: UK National Health Services Centre for Reviews and Dissemination. Agency for Healthcare Research and Quality s National Guideline Clearinghouse and other evidencebased practice centers. The Centers for Medicare & Medicaid Services. Searches of PubMed were conducted on March 19, 2015, to update initial searches that were conducted in February 2013 using the terms ( autonomic, or sympathetic, or parasympathetic, or visceral )and neuropathy, and ( detecting, or screening, or testing, or monitoring ). Included were: Systematic reviews, which pool results from multiple studies to achieve larger sample sizes and greater precision of effect estimation than in smaller primary studies. Systematic reviews use predetermined transparent methods to minimize bias, effectively treating the review as a scientific endeavor, and are thus rated highest in evidence-grading hierarchies. Guidelines based on systematic reviews. Economic analyses, such as cost-effectiveness, and benefit or utility studies (but not simple cost studies), reporting both costs and outcomes sometimes referred to as efficiency studies which also rank near the top of evidence hierarchies. Findings: POLICY UPDATE March 2015 Keystone First identified one systematic review update (Hayes 2014) of their previous 2010 report, and one new systematic review of iodine-123 (123I)-labeled metaiodobenzylguanidine (MIBG) myocardial scintigraphy for diagnosing pre-motor Parkinson s Disease (Sakakibara 2014). The new findings of both reviews would not alter the results of the original policy. Autonomic neurotransmitter imaging was added under policy limitations, as the evidence is insufficient to support its use for ANS monitoring of neuropathy, and, therefore, is not medically necessary. This addition does not change the results of those tests found to be clinically proven and medically necessary. Glossary Autonomic nervous system These are the parts of the nervous system that control involuntary activities such as heart rate, sweat production, pupillary responses and gastrointestinal motility. The autonomic nervous system has two divisions: the sympathetic and the parasympathetic nerves. Gastroparesis The incomplete emptying of the stomach resulting from autonomic nervous system dysfunction. Medically Necessary- A service or benefit is Medically Necessary if it is compensable under the MA Program and if it meets any one of the following standards: The service or benefit will, or is reasonably expected to, prevent the onset of an illness, condition or disability. 4

The service or benefit will, or is reasonably expected to, reduce or ameliorate the physical, mental or developmental effects of an illness, condition, injury or disability. The service or benefit will assist the Member to achieve or maintain maximum functional capacity in performing daily activities, taking into account both the functional capacity of the Member and those functional capacities that are appropriate for Members of the same age. Nervous system The system in the body that regulates cognitive, voluntary and involuntary activities. This includes the brain, the spinal cord, the peripheral nervous system and the autonomic nervous system. Parasympathetic nervous system The portion of the autonomic nervous system that tends to oppose the activity of the sympathetic nervous system. The parasympathetic nervous system acts to slow the heartbeat and dilate the blood vessels. It regulates several glands including the production of tears and saliva and stimulates motility and secretions of the gastrointestinal system. Sympathetic nervous system That portion of the autonomic nervous system that tends to oppose the activity of the parasympathetic nervous system. The sympathetic nervous system acts to raise the heart rate and cause constriction of the blood vessels. It regulates the function of the sweat glands as part of control of body temperature. The sympathetic nervous system may be activated by conditions of stress. Related policies: Keystone First Utilization Management program description. References Professional society guidelines/other: American Autonomic Society and the American Academy of Neurology. Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. The Consensus Committee of the American Autonomic Society and the American Academy of Neurology. Neurology. 1996 May;46(5):1470. England JD, Gronseth GS, Franklin G, et al. American Academy of Neurology; American Association of Neuromuscular and Electrodiagnostic Medicine; American Academy of Physical Medicine and Rehabilitation. Evaluation of distal symmetric polyneuropathy: the role of autonomic testing, nerve biopsy, and skin biopsy (an evidence-based review). Muscle Nerve. 2009;39(1):106 115. Peer-reviewed references: Figueroa JJ, Dyck PJ, Laughlin RS, et al. Autonomic dysfunction in chronic inflammatory demyelinating polyradiculoneuropathy. Neurology. 2012 Mar 6;78(10):702 8. Hayes Inc,. Hayes Medical Technology Report. Autonomic nervous system monitoring for neuropathy. Lansdale, PA: Hayes Inc.; January, 2010. [UPDATED February 2014] Hilz MJ, Dütsch M. Quantitative studies of autonomic function. Muscle Nerve. 2006 Jan;33(1):6 20. 5

Illigens BM, Gibbons CH. Sweat testing to evaluate autonomic function. Clin Auton Res. 2009 Apr;19(2):79 87. Low PA; Vernino S; Suarez G. Autonomic dysfunction in peripheral nerve disease. Muscle Nerve. 2003; 27(6):646 61. Low P, Tomalia V, Park KJ. Autonomic functions tests: Some clinical applications. J Clin Neurol. 2013 Jan;9(1): 1 8. Low VA, Sandroni P, Fealey RD, Low PA. Detection of small-fiber neuropathy by sudomotor testing. Muscle Nerve. 2006 Jul;34(1):57 61. Sakakibara R, Tateno F, Kishi M, Tsuyusaki Y, Terada H, Inaoka T. MIBG myocardial scintigraphy in premotor Parkinson's disease: a review. Parkinsonism Relat D. 2014;20(3):267 273. Clinical trials Searched clinicaltrials.gov on March 19, 2015 using terms autonomic OR sympathetic OR parasympathetic Open Studies Exclude Unknown Interventional Studies test NOT drug. 26 studies found. 4 relevant. Physiopathological Study of Autonomic Failure in Parkinson's Disease. Available at: http://clinicaltrials.gov/show/nct01748409. Cardiac Autonomic Function in Women with Microvascular Coronary Dysfunction. Available at: http://clinicaltrials.gov/show/nct01568177. The Diagnostic Performance of Tilt Test in Athletes. Available at: http://clinicaltrials.gov/show/nct02316860. Qualitative Sweat Distribution during Tilt Table Procedure. Available at: http://clinicaltrials.gov/show/nct02329548. Centers for Medicare & Medicaid Services (CMS) national coverage determinations (NCDs): 70.2.1 Services provided for the Diagnosis and Treatment of Diabetic Sensory Neuropathy with Loss of Protective Sensation (aka Diabetic Peripheral Neuropathy). http://www.cms.gov/medicare-coveragedatabase/details/ncd-details.aspx?ncdid=171&ver=1. Local coverage determinations (LCDs): L35174 Autonomic Function Testing Louisiana, South Carolina. http://www.cms.gov/medicare-coveragedatabase/details/lcd-details.aspx?lcdid=35174&ver=4&contrid=268&contrver=1. L34788 Autonomic Function Tests Pennsylvania. http://www.cms.gov/medicare-coveragedatabase/details/lcd-details.aspx?lcdid=34788&ver=6&contrid=318&contrver=1. 6

L34788 Autonomic Function Tests Pennsylvania. http://www.cms.gov/medicare-coveragedatabase/details/lcd-details.aspx?lcdid=34788&ver=6&contrid=323&contrver=1. L34788 Autonomic Function Tests Pennsylvania. http://www.cms.gov/medicare-coveragedatabase/details/lcd-details.aspx?lcdid=34788&ver=6&contrid=324&contrver=1. L34788 Autonomic Function Tests Louisiana. http://www.cms.gov/medicare-coveragedatabase/details/lcd-details.aspx?lcdid=34788&ver=6&contrid=326&contrver=1. L34788 Autonomic Function Tests Louisiana. http://www.cms.gov/medicare-coveragedatabase/details/lcd-details.aspx?lcdid=34788&ver=6&contrid=328&contrver=1. Commonly submitted codes Below are the most commonly submitted codes for the service(s)/item(s) subject to this policy. This is not an exhaustive list of codes. Providers are expected to consult the appropriate coding manuals and bill accordingly. CPT Code Description Comment 95921 Testing of autonomic nervous system function, cardiovagal innervation (parasympathetic function), including 2 or more of the following: heart rate response to deep breathing with recorded R-R interval, valsalva ratio, and 30:15 ratio 95922 Testing of autonomic nervous system function, vasomotor adrenergic innervation (sympathetic adrenergic function), including beat-to-beat blood pressure and R-R interval changes during valsalva maneuver and at least 5 minutes of passive tilt 95923 Testing of autonomic nervous system function, sudomotor, including 1 or more of the following: quantitative sudomotor axon reflex test (QSART), silastic sweat imprint, thermoregulatory sweat test, and changes in sympathetic skin potential 95924 Combined parasympathetic and sympathetic adrenergic function testing with at least 5 minutes of passive tilt 95943 Simultaneous, 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-9 Code Description Comment 249.60 Secondary diabetes with neurological manifestations, not stated as uncontrolled 249.61 Secondary diabetes with neurological manifestations, uncontrolled 7

250.60 Diabetes with neurological manifestations, type II or unspecified type, not stated as uncontrolled 250.61 Diabetes with neurological manifestations, type I, not stated as uncontrolled 250.62 Diabetes with neurological manifestations, type II or unspecified, uncontrolled 250.63 Diabetes with neurological manifestations, type I, uncontrolled 332.0 Parkinson s disease 333.0 Shy-Drager syndrome 337.1 Peripheral autonomic neuropathy in disorders classified elsewhere 337.20 Reflex sympathetic dystrophy unspecified 337.21 Reflex sympathetic dystrophy, upper limb 337.22 Reflex sympathetic dystrophy, lower limb 337.29 Reflex sympathetic dystrophy, other specified site 337.9 Unspecified disorder of autonomic nervous system [POTS syndrome] 340 Multiple sclerosis 356.4 Idiopathic progressive polyneuropathy 356.8 Other specified idiopathic peripheral neuropathy 356.9 Unspecified idiopathic peripheral neuropathy 357.2 Polyneuropathy in diabetes 357.4 Polyneuropathy in diseases classified elsewhere 357.5 Alcoholic neuropathy ICD-10 Code Description Comment E08.40 Diabetes mellitus due to underlying condition with diabetic neuropathy, unspecified E08.41 Diabetes mellitus due to underlying condition with diabetic mononeuropathy E08.42 Diabetes mellitus due to underlying condition with diabetic polyneuropathy E08.43 E08.49 E09.40 E09.41 E09.42 E09.43 E09.49 Diabetes mellitus due to underlying condition with diabetic autonomic (poly)neuropathy Diabetes mellitus due to underlying condition with other diabetic neurological complication Drug or chemical induced diabetes mellitus with neurological complications with diabetic neuropathy, unspecified Drug or chemical induced diabetes mellitus with neurological complications with diabetic mononeuropathy Drug or chemical induced diabetes mellitus with neurological complications with diabetic polyneuropathy Drug or chemical induced diabetes mellitus with neurological complications with diabetic autonomic (poly)neuropathy Drug or chemical induced diabetes mellitus with neurological complications with other diabetic neurological complication E10.40 Type 1 diabetes mellitus with diabetic neuropathy, unspecified E10.41 Type 1 diabetes mellitus with diabetic mononeuropathy E10.42 Type 1 diabetes mellitus with diabetic polyneuropathy E10.43 Type 1 diabetes mellitus with diabetic autonomic. (poly)neuropathy E10.49 Type 1 diabetes mellitus with other diabetic neurological complication E11.40 Type 2 diabetes mellitus with diabetic neuropathy, unspecified 8

E11.41 Type 2 diabetes mellitus with diabetic mononeuropathy E11.43 Type 2 diabetes mellitus with diabetic autonomic (poly)neuropathy E11.49 Type 2 diabetes mellitus with other diabetic neurological complication E13.40 Other specified diabetes mellitus with diabetic neuropathy, unspecified E13.41 Other specified diabetes mellitus with diabetic mononeuropathy E13.42 Other specified diabetes mellitus with diabetic polyneuropathy E13.43 Other specified diabetes mellitus with diabetic autonomic (poly)neuropathy E13.49 Other specified diabetes mellitus with other diabetic neurological complication G13.0 Paraneoplastic neuromyopathy and neuropathy G13.1 Other systemic atrophy primarily affecting central nervous system in neoplastic disease G60.0 Hereditary motor and sensory neuropathy G60.2 Neuropathy in association with hereditary ataxia G60.3 Idiopathic progressive neuropathy G60.8 Other hereditary and idiopathic neuropathies G60.9 Hereditary and idiopathic neuropathy, unspecified G61.9 Inflammatory polyneuropathy, unspecified G62.9 Polyneuropathy, unspecified G63 Polyneuropathy in diseases classified elsewhere G65.0 Sequelae of Guillain-Barre syndrome G65.1 Sequelae of other inflammatory polyneuropathy G65.2 Sequelae of toxic polyneuropathy G90.2 Horner's syndrome G90.4 Autonomic dysreflexia G90.50 Complex regional pain syndrome I, unspecified G90.511 Complex regional pain syndrome I of right upper limb G90.512 Complex regional pain syndrome I of left upper limb G90.513 Complex regional pain syndrome I of upper limb, bilateral G90.519 Complex regional pain syndrome I of unspecified upper limb G90.521 Complex regional pain syndrome I of right lower limb 9

G90.522 Complex regional pain syndrome I of left lower limb G90.523 Complex regional pain syndrome I of lower limb, bilateral G90.529 Complex regional pain syndrome I of unspecified lower limb G90.59 Complex regional pain syndrome I of other specified site G90.8 Other disorders of autonomic nervous system G90.9 Disorder of the autonomic nervous system, unspecified HCPCS Level II Description Comment 10