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Neuroimmunology Testing Services Neuroimmunology Neuroimmunology testing services Neuroimmunology Quest Diagnostics is your source for neuroimmunological testing with expanded offerings for several autoimmune neurological disorders Neuroimmunology is the field of autoimmune disorders Table 1 Autoimmune neurological disorders that affect the central nervous system (CNS) and range Autoimmune ataxia, Movement disorders in diversity from neuromuscular and movement disorders epilepsy, chorea to neuro-oncology. Clinical neuroimmunology testing is a rapidly growing field driven by the increasing amount of Myasthenia gravis, Neuromuscular disorders newly discovered neural autoantibodies. Lambert Eaton It is important to test for these antibodies as many Paraneoplastic neurological are associated with treatable neurological diseases. Neuro-oncology Autoantibody-mediated neuroimmunological disorders can syndrome (PNS) arise from tumors, genetic predisposition, or even infections Autoimmune dementia, such as polyneuropathy disorder and Guillain-Barré Brain function disorders syndrome (GBS) (which can result from the Zika virus). encephalopathy Testing can be useful to exclude an immunological disorder Multiple sclerosis (MS), Demyelinating that may be responsible for the neurological symptoms neuromyelitis optica (NMO) present in a patient. When a patient presents with symptoms suggesting a CNS autoimmune disorder, early identification Guillain-Barré syndrome Peripheral nervous of antibodies can help direct therapy in patients likely to (GBS), peripheral and system (PNS) disorders improve with treatments such as immunotherapy. sensory neuropathies Table 2 ICD-10 Codes1 ICD Code Symptom Description ICD Code Symptom Description ICD Code Symptom Description Neuro-oncology Tests (Paraneoplastics) Neuromyelitis Optica Myasthenia Gravis G62.9 Polyneuropathy, unspecified G36.0 Neuromyelitis optica [Devic] H53.2 Diplopia Hereditary and idiopathic Myasthenia gravis without G60.9 G35 Multiple sclerosis G70.00 neuropathy, unspecified (acute) exacerbation R42 Dizziness and giddiness Myasthenia gravis with R20.2 Paresthesia of skin G70.01 (acute) exacerbation G95.9 Disease of spinal cord, unspecified M62.81 Muscle weakness (generalized) M62.81 Muscle weakness (generalized) Other long term (current) Unspecified disturbances Z79.899 Unspecified ptosis of R20.9 drug therapy H02.409 of skin sensation unspecified eyelid R41.3 Other amnesia E78.5 Hyperlipidemia, unspecified Unspecified ptosis of H02.403 bilateral eyelids Demyelinating disease of central R27.0 Ataxia, unspecified G37.9 nervous system, unspecified H02.402 Unspecified ptosis of left eyelid G60.3 Idiopathic progressive neuropathy M12.9 Arthropathy, unspecified H02.401 Unspecified ptosis of right eyelid R20.0 Anesthesia of skin Acute transverse myelitis in G37.3 demyelinating disease of central R53.1 Weakness nervous system R53.83 Other fatigue E03.9 Hypothyroidism, unspecified H46.9 Unspecified optic neuritis Unspecified abnormalities R26.9 of gait and mobility Deficiency of other specified E53.8 Paraneoplastic neuromyopathy B group vitamins G13.0 and neuropathy Neoplasm of unspecified behavior D49.9 of unspecified site 2 Quest Diagnostics | Neuroimmunology Paraneoplastic and other CNS disorders Paraneoplastic neurological syndromes (PNS) are a set of Paraneoplastic antibodies degenerative autoimmune disorders due to the remote In a majority of PNS, the neurological symptoms appear effects of cancer. Identification of a specific paraneoplastic before the cancer has been identified. Identification antibody can guide the search for an underlying malignancy. of paraneoplastic antibodies can direct the search for an underlying cancer, increasing the likelihood of making Early detection and quick treatment can make a an early diagnosis of the tumor and treating the difference in patient outcomes neurological symptoms. “Patients with disorders of the CNS associated with autoantibodies can now be diagnosed and treated.”2 Other CNS autoantibodies The positive identification of specific antibodies can help Immunotherapy and other treatments have been successful direct therapy to improve patient outcomes, avoid treatment in patients with antibodies against LGI1, CASPR2, VGKC, that may harm the patient, and/or aid in early detection and NMDA (NR1) and GAD65. Early detection may enable treatment of cancer. better outcomes.2 Figure 1 Interpretation of “Paraneoplastic Antibody Evaluation with Reflex to Titer and Western Blot, Basic (Test Code 93876) Panel” Patient with suspected paraneoplastic neurological syndrome Paraneoplastic Antibody Evaluation with Reflex to Titer and Western Blot, Basic Reflex tests AChR modulating Positive Myasthenia gravis antibody AChR binding antibody positive or equivocal Cerebellar degeneration, CRMP5 / CV2 encephalomyelitis/limbic Positive Western blot encephalitis, sensory neuropathy, chorea, or optic neuritis AMPAR1, AMPAR2, or Encephalomyelitis or AMPAR, GABABR, GABABR positive limbic encephalitis AMPAR1, AMPAR2, or NMDAR suggested GABABR, NMDAR (CBA) by tissue IFA Encephalitis with psychiatric manifestations, seizures, dyskinesias, NMDAR Positive dystonia, and autonomic instability Encephalomyelitis or ANNA3 positive by tissue IFA ANNA3 titer >1:40 sensory neuropathy NMO antibody suggested by Aquaporin 4 (NMO) Positive Neuromyelitis optica tissue IFA pattern Encephalomyelitis, PCA2 positive by tissue IFA PCA2 titer >1:40 cerebellar degeneration Striated muscle Striated muscle >1:40 Myasthenia gravis or thymoma antibody positive antibody titer AGNA/SOX1, amphiphysin, This figure was developed by Quest Diagnostics based on ANNA1, ANNA2, references 3 – 13. It is provided for informational purposes CRMP5/CV2, GAD65, PCA1, Western blot, only and is not intended as medical advice. A physician’s test Positive PCA2, or PCA-Tr (DNER) quantitative selection and interpretation, diagnosis, and patient positive, indeterminate, or management decisions should be based on his/her education, suggested by IFA clinical expertise, and assessment of the patient. gAChR, VGCC (N-type), VGCC (P/Q-type), or VGKC positive Quest Diagnostics | Neuroimmunology 3 Neuroimmunology Figure 2 Interpretation of “Paraneoplastic Antibody Evaluation, CSF, Basic (Test Code 94536) Panel” Patient with suspected paraneoplastic neurological syndrome Paraneoplastic Antibody Evaluation, CSF, Basic Reflex tests AMPAR1, AMPAR2, GABABR, AMPAR1, AMPAR2, NMDAR1, CASPR2, LGI1 GABABR, NMDAR1, AMPAR1, AMPAR2, or Encephalomyelitis or limbic encephalitis suggested by tissue IFA CASPR2, LGI1 (CBA) GABABR titer >1:10 Encephalitis with psychiatric Titer for positive Positive (any test) NMDAR1 titer >1:10 manifestations, seizures, dyskinesias, antibody dystonia, and autonomic instability CASPR2 or LGI1 titer Limbic encephalitis, neuromyotonia, >1:10 or Morvan syndrome ANNA3 positive by ANNA3 titer >1:10 Encephalomyelitis or sensory neuropathy tissue IFA NMO antibody suggested by Aquaporin 4 (NMO), Aquaporin 4 (NMO), Positive >1:10 Neuromyelitis tissue IFA pattern CBA titer optica PCA2 positive by tissue IFA PCA2 titer >1:10 Encephalomyelitis, cerebellar degeneration AGNA/SOX1, amphiphysin, ANNA1, ANNA2, CRMP5/CV2, GAD65, PCA1, Western line blot, Positive (signal Refer to table for interpretation or PCA-Tr (DNER) positive, quantitative intensity >11) indeterminate, or suggested by IFA VGKC, LGI1, CASPR2 antibody Neuronal (V-G) K+ suggested by tissue IFA >20 pmol/L Refer to table for interpretation pattern Channel Ab, CSF This figure was developed by Quest Diagnostics based on references 8, 12, 23, and 24. It is provided for informational purposes only and is not intended as medical advice. A physician’s test selection and interpretation, diagnosis, and patient management decisions should be based on his/her education, clinical expertise, and assessment of the patient. 4 Quest Diagnostics | Neuroimmunology Table 3 Para antibodies and associated cancers and clinical significance Associated neurologic syndrome Associated tumor or cancer type Autoantibody target neuropathy Autonomic encephalitis/Brainstem opsoclonus-myoclonus Cerebellar degeneration Encephalomyelitis / LE LEMS gravisMyasthenia optica Neuromyelitis Neuromyotonia Sensory neuropathy Stiff person Other cancer Breast lymphoma Hodgkin's Lung cancer Ovarian cancer Prostate cancer cancer cell Renal SCLC tumor Testicular Thymoma Other AChR • ° AGNA/SOX1 • • • • • ° AMPAR • • • • • • Amphiphysin • • • ° • ° ANNA1 (Hu) • • • • • ° gynecological ANNA2 (Ri) • • ° • ° tumors ANNA3ª • • • Aquaporin 4 (NMO) • • • CRMP5/CV2 • • • • •b ° ° GABABR • •c ° gastrointestinal, lymphoid, gAChR d • • • • • • • ° • melanoma, bladder pancreatic, GAD65 • • • • • • • thymic cancer NMDAR •e °f •f PCA1 (Yo) • • ° PCA2ª • • • PCA-Tr (DNER) • ° Striated muscle • ° VGCC, N-type • ° VGCC, P/Q-type • • ° VGKC • • •g • • ° indicates tumor type(s) most frequently associated with the antibody; LE, limbic encephalitis; LEMS, Lambert-Eaton myasthenia gravis, SCLC, small-cell lung cancer. a Case report d Cortical and neuropsychiatric presentation f Teratoma b Chorea, optic neuritis e Encephalitis with psychiatric manifestations, seizures, g Morvan syndrome c Tumor dyskinesias, dystonia, and autonomic instability Quest Diagnostics | Neuroimmunology 5 Neuroimmunology AQP4 autoantibody for neuromyelitis optica (NMO) When the syndrome is severe, and multiple sclerosis Finding NMO early can make a difference. Consider NMO (MS) is ruled out, could it be neuromyelitis optica? in the following patients with ON or TM (or both) and an NMO is a rare and severe disease
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