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Paraneoplastic Neurological Syndromes, Initial Assessment FORMTEXT <Date>ATTN: FORMTEXT <Medical Director/ Physician Name>, M.D. FORMTEXT <Institution/Insurance Company> FORMTEXT <Street Address> FORMTEXT <City>, FORMTEXT <State>, FORMTEXT <Zip>RE: FORMTEXT <Patient Name>DOB: FORMTEXT <MM/DD/YYYY>Member ID: FORMTEXT <Insurance ID Number>Group #: FORMTEXT <Enter Group #>Dear Medical Director:I am requesting coverage for the Paraneoplastic Neurological Syndromes, Initial Assessment test on behalf of my patient FORMTEXT <patient name>. This assay tests for antibodies against the following antigens: amphiphysin, CV2 (crossveinless-2 protein), Hu (neuronal nuclear antibody type 1), Ma2 (positives tested on Ma1), Ri (neuronal nuclear antibody type 2), and Yo (Purkinje cell antibody type 1). I have determined that this test is medically necessary because of the following aspects of my patient’s history: FORMTEXT <Patient Name> is a FORMTEXT <age> -year-old FORMTEXT <gender > with a suspected diagnosis of <specific paraneoplastic syndrome suspected> due to the following symptoms and clinical findings:1. FORMTEXT <Symptom/clinical finding #1 with ICD-9 code>2. FORMTEXT <Symptom/clinical finding #2 with ICD-9 code>3. FORMTEXT <Symptom/clinical finding #3 with ICD-9 code><Add additional relevant clinical details.>Rationale for TestingParaneoplastic neurological syndromes (PNS) are rare immune-mediated disorders that result from damage to the nervous system due to remote effects of a primary tumor or its metastases. ADDIN REFMGR.CITE <Refman><Cite><Author>Titulaer</Author><Year>2011</Year><RecNum>156</RecNum><IDText>Screening for tumours in paraneoplastic syndromes: report of an EFNS task force</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>156</Ref_ID><Title_Primary>Screening for tumours in paraneoplastic syndromes: report of an EFNS task force</Title_Primary><Authors_Primary>Titulaer,M.J.</Authors_Primary><Authors_Primary>Soffietti,R.</Authors_Primary><Authors_Primary>Dalmau,J.</Authors_Primary><Authors_Primary>Gilhus,N.E.</Authors_Primary><Authors_Primary>Giometto,B.</Authors_Primary><Authors_Primary>Graus,F.</Authors_Primary><Authors_Primary>Grisold,W.</Authors_Primary><Authors_Primary>Honnorat,J.</Authors_Primary><Authors_Primary>Sillevis Smitt,P.A.</Authors_Primary><Authors_Primary>Tanasescu,R.</Authors_Primary><Authors_Primary>Vedeler,C.A.</Authors_Primary><Authors_Primary>Voltz,R.</Authors_Primary><Authors_Primary>Verschuuren,J.J.</Authors_Primary><Date_Primary>2011/1</Date_Primary><Keywords>Antibodies</Keywords><Keywords>diagnosis</Keywords><Keywords>Early Detection of Cancer</Keywords><Keywords>Encephalitis</Keywords><Keywords>Female</Keywords><Keywords>Humans</Keywords><Keywords>immunology</Keywords><Keywords>Limbic Encephalitis</Keywords><Keywords>Male</Keywords><Keywords>methods</Keywords><Keywords>Neoplasms</Keywords><Keywords>Neurology</Keywords><Keywords>Paraneoplastic Syndromes</Keywords><Keywords>Prognosis</Keywords><Keywords>Syndrome</Keywords><Reprint>Not in File</Reprint><Start_Page>19</Start_Page><End_Page>e3</End_Page><Periodical>Eur.J.Neurol.</Periodical><Volume>18</Volume><Issue>1</Issue><User_Def_5>PMC3086523</User_Def_5><Misc_3>10.1111/j.1468-1331.2010.03220.x [doi]</Misc_3><Address>Department of Neurology, Leiden University Medical Center, Leiden, Netherlands. m.j.titulaer@lumc.nl</Address><Web_URL>PM:20880069</Web_URL><ZZ_JournalStdAbbrev><f name="System">Eur.J.Neurol.</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>1 The tumor most commonly associated with PNS is small-cell lung cancer; others include ovarian carcinoma and teratoma, testicular cancer, thymoma, and Hodgkin lymphoma.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlRpdHVsYWVyPC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48

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ADDIN EN.CITE.DATA 1,2 PNS often exhibit a rapid clinical course resulting in severe disability, ADDIN REFMGR.CITE <Refman><Cite><Author>Rosenfeld</Author><Year>2012</Year><RecNum>152</RecNum><IDText>Paraneoplastic disorders of the CNS and autoimmune synaptic encephalitis</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>152</Ref_ID><Title_Primary>Paraneoplastic disorders of the CNS and autoimmune synaptic encephalitis</Title_Primary><Authors_Primary>Rosenfeld,M.R.</Authors_Primary><Authors_Primary>Dalmau,J.O.</Authors_Primary><Date_Primary>2012/4</Date_Primary><Keywords>Adolescent</Keywords><Keywords>Anti-N-Methyl-D-Aspartate Receptor Encephalitis</Keywords><Keywords>Antigens</Keywords><Keywords>Autoantibodies</Keywords><Keywords>Autoantigens</Keywords><Keywords>Autoimmune Diseases</Keywords><Keywords>complications</Keywords><Keywords>diagnosis</Keywords><Keywords>Encephalitis</Keywords><Keywords>etiology</Keywords><Keywords>Female</Keywords><Keywords>Humans</Keywords><Keywords>immunology</Keywords><Keywords>Immunotherapy</Keywords><Keywords>Male</Keywords><Keywords>Middle Aged</Keywords><Keywords>Paraneoplastic Syndromes,Nervous System</Keywords><Keywords>Proteins</Keywords><Keywords>Synapses</Keywords><Keywords>Syndrome</Keywords><Reprint>Not in File</Reprint><Start_Page>366</Start_Page><End_Page>383</End_Page><Periodical>Continuum (Minneap.Minn.)</Periodical><Volume>18</Volume><Issue>2</Issue><Misc_3>10.1212/01.CON.0000413664.42798.aa [doi];00132979-201204000-00012 [pii]</Misc_3><Address>Hospital Clinic/Institute of Biomedical Investigations, University of Barcelona, Spain</Address><Web_URL>PM:22810133</Web_URL><ZZ_JournalStdAbbrev><f name="System">Continuum (Minneap.Minn.)</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>2 although symptoms can fluctuate and be atypical or psychiatric in nature. ADDIN REFMGR.CITE <Refman><Cite><Author>de Beukelaar</Author><Year>2006</Year><RecNum>171</RecNum><IDText>Managing paraneoplastic neurological disorders</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>171</Ref_ID><Title_Primary>Managing paraneoplastic neurological disorders</Title_Primary><Authors_Primary>de Beukelaar,J.W.</Authors_Primary><Authors_Primary>Sillevis Smitt,P.A.</Authors_Primary><Date_Primary>2006/3</Date_Primary><Keywords>analysis</Keywords><Keywords>Antibodies</Keywords><Keywords>Antigens</Keywords><Keywords>Autoantibodies</Keywords><Keywords>Dermatomyositis</Keywords><Keywords>diagnosis</Keywords><Keywords>Encephalomyelitis</Keywords><Keywords>etiology</Keywords><Keywords>Humans</Keywords><Keywords>Immunologic Factors</Keywords><Keywords>immunology</Keywords><Keywords>Immunotherapy</Keywords><Keywords>Incidence</Keywords><Keywords>Paraneoplastic Syndromes,Nervous System</Keywords><Keywords>physiopathology</Keywords><Keywords>Prognosis</Keywords><Keywords>Sensation Disorders</Keywords><Keywords>Syndrome</Keywords><Keywords>therapy</Keywords><Reprint>Not in File</Reprint><Start_Page>292</Start_Page><End_Page>305</End_Page><Periodical>Oncologist.</Periodical><Volume>11</Volume><Issue>3</Issue><Misc_3>11/3/292 [pii];10.1634/theoncologist.11-3-292 [doi]</Misc_3><Address>Erasmus University Medical Center, Rotterdam, The Netherlands</Address><Web_URL>PM:16549814</Web_URL><ZZ_JournalStdAbbrev><f name="System">Oncologist.</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>3 The neurological symptoms of PNS usually precede identification of cancerPFJlZm1hbj48Q2l0ZT48QXV0aG9yPmRlIEJldWtlbGFhcjwvQXV0aG9yPjxZZWFyPjIwMDY8L1ll

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ADDIN EN.CITE.DATA 1,4 PNS are classified as classical or non-classical, depending on their association with cancer.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkdyYXVzPC9BdXRob3I+PFllYXI+MjAwNDwvWWVhcj48UmVj

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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkdyYXVzPC9BdXRob3I+PFllYXI+MjAwNDwvWWVhcj48UmVj

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ADDIN EN.CITE.DATA 5 In the classical PNS, neurological symptoms are often associated with the underlying cancer.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlJvc2VuZmVsZDwvQXV0aG9yPjxZZWFyPjIwMTI8L1llYXI+

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L1JlZm1hbj4A

ADDIN EN.CITE.DATA 2,5 These syndromes include encephalomyelitis, limbic encephalitis, subacute cerebellar degeneration, opsoclonus-myoclonus, subacute sensory neuropathy, and Lambert-Eaton myasthenic syndrome (LEMS).PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkdyYXVzPC9BdXRob3I+PFllYXI+MjAwNDwvWWVhcj48UmVj

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ADDIN EN.CITE.DATA 5 Diagnostic criteria for PNS require detection of a “well-characterized” onconeural antibody in certain situations.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkdyYXVzPC9BdXRob3I+PFllYXI+MjAwNDwvWWVhcj48UmVj

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ADDIN EN.CITE.DATA 5 Thus, the Paraneoplastic Neurological Syndromes, Initial Assessment tests for the 6 onconeural antibodies that are generally considered to be well characterized: anti-Hu, anti-Yo, anti-CV2, anti-Ri, anti-Ma2 (MaTa), and anti-amphiphysin. Classification of an onconeural antibody as well characterized is based on several considerations: 1) recognizable patterns on routine immunohistochemistry; 2) documented association with tumors (based on the number of published cases); 3) well-described association with neurological syndromes; 4) unambiguous identification of the antibodies among different studies; and 5) the frequency of the antibodies in patients with no detectable tumor.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkdyYXVzPC9BdXRob3I+PFllYXI+MjAwNDwvWWVhcj48UmVj

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ADDIN EN.CITE.DATA 5 In patients without confirmed cancer who present with either a classical or non-classical syndrome, detection of a well-characterized onconeural antibody is required to diagnose definite PNS.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkdyYXVzPC9BdXRob3I+PFllYXI+MjAwNDwvWWVhcj48UmVj

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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkdyYXVzPC9BdXRob3I+PFllYXI+MjAwNDwvWWVhcj48UmVj

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ADDIN EN.CITE.DATA 5 For patients with a classical syndrome and a known tumor, detection of an onconeural antibody is not required for diagnosis.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkdyYXVzPC9BdXRob3I+PFllYXI+MjAwNDwvWWVhcj48UmVj

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ADDIN EN.CITE.DATA 5 Field experts recommend close tumor surveillance in patients with classical PNS, with or without paraneoplastic antibodies, and in patients with non-classical PNS who have paraneoplastic antibodies. ADDIN REFMGR.CITE <Refman><Cite><Author>Rosenfeld</Author><Year>2012</Year><RecNum>152</RecNum><IDText>Paraneoplastic disorders of the CNS and autoimmune synaptic encephalitis</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>152</Ref_ID><Title_Primary>Paraneoplastic disorders of the CNS and autoimmune synaptic encephalitis</Title_Primary><Authors_Primary>Rosenfeld,M.R.</Authors_Primary><Authors_Primary>Dalmau,J.O.</Authors_Primary><Date_Primary>2012/4</Date_Primary><Keywords>Adolescent</Keywords><Keywords>Anti-N-Methyl-D-Aspartate Receptor Encephalitis</Keywords><Keywords>Antigens</Keywords><Keywords>Autoantibodies</Keywords><Keywords>Autoantigens</Keywords><Keywords>Autoimmune Diseases</Keywords><Keywords>complications</Keywords><Keywords>diagnosis</Keywords><Keywords>Encephalitis</Keywords><Keywords>etiology</Keywords><Keywords>Female</Keywords><Keywords>Humans</Keywords><Keywords>immunology</Keywords><Keywords>Immunotherapy</Keywords><Keywords>Male</Keywords><Keywords>Middle Aged</Keywords><Keywords>Paraneoplastic Syndromes,Nervous System</Keywords><Keywords>Proteins</Keywords><Keywords>Synapses</Keywords><Keywords>Syndrome</Keywords><Reprint>Not in File</Reprint><Start_Page>366</Start_Page><End_Page>383</End_Page><Periodical>Continuum (Minneap.Minn.)</Periodical><Volume>18</Volume><Issue>2</Issue><Misc_3>10.1212/01.CON.0000413664.42798.aa [doi];00132979-201204000-00012 [pii]</Misc_3><Address>Hospital Clinic/Institute of Biomedical Investigations, University of Barcelona, Spain</Address><Web_URL>PM:22810133</Web_URL><ZZ_JournalStdAbbrev><f name="System">Continuum (Minneap.Minn.)</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>2 A common clinical practice includes periodic cancer screening for at least 5 years. ADDIN REFMGR.CITE <Refman><Cite><Author>Rosenfeld</Author><Year>2012</Year><RecNum>152</RecNum><IDText>Paraneoplastic disorders of the CNS and autoimmune synaptic encephalitis</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>152</Ref_ID><Title_Primary>Paraneoplastic disorders of the CNS and autoimmune synaptic encephalitis</Title_Primary><Authors_Primary>Rosenfeld,M.R.</Authors_Primary><Authors_Primary>Dalmau,J.O.</Authors_Primary><Date_Primary>2012/4</Date_Primary><Keywords>Adolescent</Keywords><Keywords>Anti-N-Methyl-D-Aspartate Receptor Encephalitis</Keywords><Keywords>Antigens</Keywords><Keywords>Autoantibodies</Keywords><Keywords>Autoantigens</Keywords><Keywords>Autoimmune Diseases</Keywords><Keywords>complications</Keywords><Keywords>diagnosis</Keywords><Keywords>Encephalitis</Keywords><Keywords>etiology</Keywords><Keywords>Female</Keywords><Keywords>Humans</Keywords><Keywords>immunology</Keywords><Keywords>Immunotherapy</Keywords><Keywords>Male</Keywords><Keywords>Middle Aged</Keywords><Keywords>Paraneoplastic Syndromes,Nervous System</Keywords><Keywords>Proteins</Keywords><Keywords>Synapses</Keywords><Keywords>Syndrome</Keywords><Reprint>Not in File</Reprint><Start_Page>366</Start_Page><End_Page>383</End_Page><Periodical>Continuum (Minneap.Minn.)</Periodical><Volume>18</Volume><Issue>2</Issue><Misc_3>10.1212/01.CON.0000413664.42798.aa [doi];00132979-201204000-00012 [pii]</Misc_3><Address>Hospital Clinic/Institute of Biomedical Investigations, University of Barcelona, Spain</Address><Web_URL>PM:22810133</Web_URL><ZZ_JournalStdAbbrev><f name="System">Continuum (Minneap.Minn.)</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>2 Confirming the autoimmune etiology of neurological symptoms may also assist in effective therapeutic planning.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkdyb21hZHprYTwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+

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ADDIN EN.CITE.DATA 3,4 In summary, I am requesting that FORMTEXT <patient name> be approved for the Paraneoplastic Neurological Syndromes, Initial Assessment (test code 4500 offered by Athena Diagnostics; CPT codes 84181 [x1], 84182 [x5]). Testing for the 6 well-characterized onconeural antibodies with this assay may provide the following important benefits for my patient: Confirm the diagnosis of definite PNSDirect investigation of the underlying malignancyInform treatment selection, which may lead to improvement or stabilization of neurological symptomsPlease support my decision to pursue autoimmune testing for my patient. Feel free to contact me at FORMTEXT <physician phone> if you have additional questions.Sincerely, FORMTEXT <Physician Name>, MDNPI #: FORMTEXT <Physician NPI#>Contact information: FORMTEXT < Address> FORMTEXT <City>, FORMTEXT <State>, FORMTEXT <Zip>Contact Phone No.: FORMTEXT <phone number>References ADDIN REFMGR.REFLIST 1. Titulaer MJ, Soffietti R, Dalmau J, et al. Screening for tumours in paraneoplastic syndromes: report of an EFNS task force. Eur J Neurol. 2011;18:19-e3.2. Rosenfeld MR, Dalmau JO. Paraneoplastic disorders of the CNS and autoimmune synaptic encephalitis. Continuum (Minneap Minn ). 2012;18:366-383.3. de Beukelaar JW, Sillevis Smitt PA. Managing paraneoplastic neurological disorders. Oncologist. 2006;11:292-305.4. Vedeler CA, Antoine JC, Giometto B, et al. Management of paraneoplastic neurological syndromes: report of an EFNS Task Force. Eur J Neurol. 2006;13:682-690.5. Graus F, Delattre JY, Antoine JC, et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry. 2004;75:1135-1140.6. Gromadzka G, Karlinska AG, Lysiak Z, et al. Positivity of serum "classical" onconeural antibodies in a series of 2063 consecutive patients with suspicion of paraneoplastic neurological syndrome. J Neuroimmunol. 2013;259:75-80. ................
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