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Paraneoplastic Autonomic Neuropathy Workup

  • Author: Daniel Mordechai Goldenholz, MD, PhD; Chief Editor: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS  more...
 
Updated: Dec 23, 2014
 

Laboratory Studies

Serum analysis for the presence of antineuronal autoantibody using immunohistochemistry and immunoblotting is the key to diagnosis. Since there is an overlap between the clinical picture of individual paraneoplastic autoantibodies, screening for them using a panel of autoantibodies is appropriate. Lumbar puncture is often indicated, with ample volume of cerebrospinal fluid (CSF) sent for cytologic analysis in addition to the other usual tests. The spinal fluid often reveals a mononuclear pleocytosis, elevated protein, oligoclonal bands, and paraneoplastic antineuronal antibodies.

Evidence of another process (eg, diabetes, scleroderma, amyloidosis) should be considered and excluded by appropriate serologic tests and/or biopsies.

Serological markers of malignancies (eg, CEA, PSA, NSE, CA19-9, AFP, β-HCG, and ProGRP, if available) can help to identify a cancer that is not readily apparent by imaging.

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Imaging Studies

If the patient is not known to harbor a malignancy, then chest scanning (eg, high resolution CT scan) is indicated, since small-cell lung cancer is most often the associated tumor. If any abnormalities are seen, then bronchoscopic or transthoracic needle biopsy is usually required. If no tumor is found, fluorodeoxyglucose-positron emission tomography (FDG-PET) should be considered as it markedly increases the detection rate of malignancy.[40] Imaging of the abdomen, pelvis, and brain is normally indicated to look for a primary tumor or metastasis. Mammography and gynecological ultrasonographic examinations can be of value in women, and testicular ultrasonography in men. If no malignancy is found at presentation, repeating the work-up every 3-6 months is advisable[39] for the first 4 years (or the first 2 years in the case of LEMS).[40]

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Other Tests

Electromyography (EMG)/nerve conduction velocity (NCV) studies can identify a neuropathy or defect of neuromuscular transmission if present. Heart rate variability and autonomic skin responses can be performed in most laboratories. More extensive autonomic testing may be helpful to prove autonomic dysfunction in milder cases, although it is usually not necessary.

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Histologic Findings

The images below show typical histologic findings from a patient with small-cell lung cancer and autoimmune paraneoplastic autonomic failure. Loss of neurons is evident in autonomic ganglia and dorsal root ganglia, as well as within the CNS. Inflammatory infiltrates are also typical in the vicinity of neuron loss. Similar findings have been reported for autoimmune-mediated paraneoplastic autonomic dysfunction caused by other cancers.

Paraneoplastic autonomic neuropathy. HistopathologParaneoplastic autonomic neuropathy. Histopathology of peripheral nerve and sympathetic ganglion from a patient with autonomic failure, oat-cell carcinoma of the lung, and positive anti-HU antibody titer. (a) Peripheral nerve in longitudinal section stained with Luxol fast blue-periodic acid-Schiff (PAS) showing scattered wallerian degeneration (arrowheads). (b) Low-power view of a paravertebral sympathetic ganglion stained with hematoxylin and eosin (H&E). Arrowhead indicates perivascular mononuclear infiltrates. (c) High-power view of the same sympathetic ganglion showing degenerating neurons (single arrowheads) and mononuclear infiltrates (double arrowhead). Magnification bars in a and b indicate 100 mm; c is 50 mm.
Paraneoplastic autonomic neuropathy. Hematoxylin aParaneoplastic autonomic neuropathy. Hematoxylin and eosin (H&E)–stained sections from dorsal root ganglion showing the hallmark histopathology of anti-HU disease; a and c are from a healthy patient; b and d are from a patient with autonomic failure, oat-cell carcinoma of the lung, and positive titer of anti-HU antibodies. The arrowheads in b and d indicate degenerating sensory neurons. Also note the interstitial hypercellularity and decreased numbers of neurons in b and d. Magnification bar in b indicates 100 mm and applies also to a. Similarly, the magnification bar in d indicates 50 mm, which also applies to c.
Paraneoplastic autonomic neuropathy. Central nervoParaneoplastic autonomic neuropathy. Central nervous system sections from a patient with autonomic failure, oat-cell carcinoma of the lung, and positive titer of anti-HU antibodies stained with hematoxylin and eosin (H&E). (a) Inferior olive showing a cluster of mononuclear cells (arrowhead); (b) hippocampus showing perivascular mononuclear infiltrate (arrowhead); (c) midbrain section showing a vessel encased in a mononuclear infiltrate; (d) ventral horn of the thoracic spinal cord showing clusters of mononuclear cells around degenerating motor neurons (arrowheads). Magnification bars indicate 100 mm. The bar in b applies also to a and the bar in d also applies to c.

The underlying tumor is often heavily infiltrated by inflammatory cells.

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Contributor Information and Disclosures
Author

Daniel Mordechai Goldenholz, MD, PhD Resident Physician, Department of Neurology, University of California Davis Medical Center

Daniel Mordechai Goldenholz, MD, PhD is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Coauthor(s)

Dianna Quan, MD Professor of Neurology, Director of Electromyography Laboratory, University of Colorado School of Medicine

Dianna Quan, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Neurological Association

Disclosure: Nothing to disclose.

Ronald G Wiley, MD, PhD Professor of Neurology and Pharmacology, Vanderbilt University, Chief of the Neurology Service, Veterans Affairs Tennessee Valley Healthcare System

Ronald G Wiley, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, American Association for the Advancement of Science, New York Academy of Sciences, Society for Neuroscience

Disclosure: Nothing to disclose.

Bjorn E Oskarsson, MD Assistant Professor, Department of Neurology, University of California Davis

Bjorn E Oskarsson, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Jorge C Kattah, MD Head, Associate Program Director, Professor, Department of Neurology, University of Illinois College of Medicine at Peoria

Jorge C Kattah, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, New York Academy of Sciences

Disclosure: Nothing to disclose.

Chief Editor

Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS Professor Emeritus of Neurology and Psychiatry, Clinical Professor of Medicine, Clinical Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University; Neuroscience Director, Department of Neurology, Crouse Irving Memorial Hospital

Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS is a member of the following medical societies: American College of International Physicians, American Heart Association, American Stroke Association, American Academy of Neurology, American Academy of Pain Medicine, American College of Forensic Examiners Institute, National Association of Managed Care Physicians, American College of Physicians, Royal College of Physicians, Royal College of Physicians and Surgeons of Canada, Royal College of Surgeons of England, Royal Society of Medicine

Disclosure: Nothing to disclose.

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Paraneoplastic autonomic neuropathy. Histopathology of peripheral nerve and sympathetic ganglion from a patient with autonomic failure, oat-cell carcinoma of the lung, and positive anti-HU antibody titer. (a) Peripheral nerve in longitudinal section stained with Luxol fast blue-periodic acid-Schiff (PAS) showing scattered wallerian degeneration (arrowheads). (b) Low-power view of a paravertebral sympathetic ganglion stained with hematoxylin and eosin (H&E). Arrowhead indicates perivascular mononuclear infiltrates. (c) High-power view of the same sympathetic ganglion showing degenerating neurons (single arrowheads) and mononuclear infiltrates (double arrowhead). Magnification bars in a and b indicate 100 mm; c is 50 mm.
Paraneoplastic autonomic neuropathy. Hematoxylin and eosin (H&E)–stained sections from dorsal root ganglion showing the hallmark histopathology of anti-HU disease; a and c are from a healthy patient; b and d are from a patient with autonomic failure, oat-cell carcinoma of the lung, and positive titer of anti-HU antibodies. The arrowheads in b and d indicate degenerating sensory neurons. Also note the interstitial hypercellularity and decreased numbers of neurons in b and d. Magnification bar in b indicates 100 mm and applies also to a. Similarly, the magnification bar in d indicates 50 mm, which also applies to c.
Paraneoplastic autonomic neuropathy. Central nervous system sections from a patient with autonomic failure, oat-cell carcinoma of the lung, and positive titer of anti-HU antibodies stained with hematoxylin and eosin (H&E). (a) Inferior olive showing a cluster of mononuclear cells (arrowhead); (b) hippocampus showing perivascular mononuclear infiltrate (arrowhead); (c) midbrain section showing a vessel encased in a mononuclear infiltrate; (d) ventral horn of the thoracic spinal cord showing clusters of mononuclear cells around degenerating motor neurons (arrowheads). Magnification bars indicate 100 mm. The bar in b applies also to a and the bar in d also applies to c.
 
 
 
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