Paraneoplastic Autonomic Neuropathy Clinical Presentation

  • Author: Daniel Mordechai Goldenholz, MD, PhD; Chief Editor: Tarakad S Ramachandran, MBBS, FRCP(C), FACP   more...
 
Updated: May 11, 2012
 

History

Patients may present with autonomic neuropathy prior to diagnosis of cancer, at the time of cancer diagnosis, or after the treatment of cancer. Autonomic neuropathy often presents as orthostatic hypotension. This may be profound, keeping patients bedridden in spite of aggressive therapy to maintain blood pressure. However, careful evaluation may reveal more widespread disturbances. Abnormal gastrointestinal motility may cause a spectrum of problems from mild constipation and nausea to intestinal pseudo-obstruction[38] due to autoimmune attack on myenteric neurons. Urinary incontinence, erectile dysfunction, dry eyes, dry mouth, and abnormalities of sweating are also common.

Concomitant somatic neuropathy is common and may cause pain and sensory loss, often in a length-dependent "stocking and glove" pattern but occasionally in a patchy distribution. Pain may be lightning like or burning. When motor nerves are affected, patients may report weakness.

If the paraneoplastic process involves the CNS, symptoms can include reduced level of consciousness, seizures, impaired memory or cognitive problems, personality change (ie, limbic encephalitis), ataxia, or even focal signs such as aphasia. CNS involvement may occur early or late; it often is responsible for profound morbidity and death.

One of the minor symptoms seen in LEMS is an unpleasant metallic taste. In the setting of weakness this symptom is suggestive of LEMS, but it may not be reported by the patient and often it needs to be solicited.

A patient may manifest a paraneoplastic syndrome with any combination of autonomic, peripheral, or CNS involvement.[15]

As with any paraneoplastic neurological degeneration, autonomic dysfunction has been described with many types of cancer. These include small-cell lung cancer and other lung tumors, thymoma, and ovarian and breast carcinoma. In some cases, paraneoplastic autonomic dysfunction occurs in the apparent absence of cancer. In patients without known cancer, any clinical history suggesting an underlying tumor (e.g., unexplained weight loss) or high risk for particular cancers (eg, heavy smoking, personal or family history of cancer) can help suggest a link between autonomic symptoms and an underlying malignancy. Finding the primary tumor can prove very difficult in some patients.

The clinical course is usually subacutely progressive over weeks to months, leading to a bedridden condition if untreated, and often in spite of treatment.

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Physical

Physical findings in patients with paraneoplastic autonomic failure resemble those of any patient with autonomic dysfunction and include the following:

  • Orthostatic hypotension, often profound, in the absence of volume depletion
  • Impaired pupillary light responses
  • Absence of heart rate changes with respiration
  • Abnormal Valsalva response
  • Abnormal cold pressor response
  • Dysrhythmias such as bradycardia, tachycardia, or asystole[23]

Peripheral sensory neuronopathy often is evident as patchy superficial sensory loss and asymmetrically abnormal stretch reflexes.

Patchy asymmetric weakness and dyscoordination, or abnormal mental status, may occur in patients with CNS involvement.

Proximal muscle weakness is seen in LEMS.

Prior chemotherapy with vincristine typically causes areflexia that is diffuse and symmetric. Cisplatin can cause a sensory neuropathy and hearing loss, both of which are typically symmetric.

Carcinomatous meningitis can closely mimic the presentation of paraneoplastic encephalomyeloneuropathy.

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Causes

Paraneoplastic autonomic dysfunction is a secondary effect of cancer. Small-cell lung cancer is particularly likely to cause paraneoplastic syndromes, but many types of malignancy can cause these types of syndromes, including teratoma, neuroblastoma, retinoblastoma, oligodendroglioma, melanoma, leiomyosarcoma, hematological tumors, and cancers of the thymus, gastrointestinal tract, rectum, prostate, breast, fallopian tubes, uterus, bladder, kidney, pancreas, testicles, malignancies and ovary.[9, 15, 39, 22, 16, 29]

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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)

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 and American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.

Dianna Quan, MD  Associate Professor of Neurology, Director, 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, and Phi Beta Kappa

Disclosure: e-medicine Honoraria Other; Pfizer Consulting fee Consulting

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 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, and Society for Neuroscience

Disclosure: Nothing to disclose.

Specialty Editor Board

Amy A Pruitt, MD  Associate Professor of Neurology, University of Pennsylvania School of Medicine; Attending Neurologist, Hospital of the University of Pennsylvania

Amy A Pruitt, MD is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

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

Disclosure: Medscape Salary Employment

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, and New York Academy of Sciences

Disclosure: Biogen Honoraria Consulting; Bayer Corporation Honoraria Consulting

Selim R Benbadis, MD  Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association

Disclosure: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Pfizer Honoraria Speaking, consulting; Sleepmed/DigiTrace Honoraria Speaking, consulting

Chief Editor

Tarakad S Ramachandran, MBBS, FRCP(C), FACP  Professor of Neurology, Clinical Professor of Medicine, Clinical Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University; Chair, Department of Neurology, Crouse Irving Memorial Hospital

Tarakad S Ramachandran, MBBS, FRCP(C), FACP is a member of the following medical societies: American Academy of Neurology, American Academy of Pain Medicine, American College of Forensic Examiners, American College of International Physicians, American College of Managed Care Medicine, American College of Physicians, American Heart Association, American Stroke Association, Royal College of Physicians, Royal College of Physicians and Surgeons of Canada, Royal College of Surgeons of England, and Royal Society of Medicine

Disclosure: Abbott Labs None None; Teva Marion None None; Boeringer-Ingelheim Honoraria Speaking and teaching

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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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