Paraneoplastic immune-mediated neurological effects of systemic cancers

Abstract

Cancer patients may develop paraneoplastic neurological conditions associated with autoantibodies directed against neural or neuromuscular tissues. These syndromes are frequently manifested in advance of the cancer presentation by several months or years necessitating a detailed and expensive investigation to search for the presence of a malignancy. In such cases additional assistance may be obtained by the early employment of whole body 18F flurodeoxyglucose positron emission tomography as a cancer screening imaging procedure for early cancer diagnosis and potential therapy. Effective therapy of the primary cancer consists the best current therapy for a given paraneoplastic syndrome. However, other forms of immune modulation, such as plasma exchange, intravenous gamma globulin, other immune therapies and symptomatic treatment for certain PNS may have additional benefit.

Keywords::

• cancer
• FDG PET
• immunotherapy
• paraneoplastic neurological syndrome

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Paraneoplastic neurological syndromes (PNS) are immune-mediated cancer manifestations involving the nervous system or muscles frequently occurring months or years prior to cancer diagnosis.

• The most common PNS include neuropathy, cerebellar degeneration, encephalitis, opsoclonus–myoclonus syndrome, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin abnormalities syndrome, myasthenic syndrome, myasthenia, stiff-person syndrome, and peripheral nerve hyperexcitability syndrome.

• PNS may be associated with antibodies directed against intracellular antigens, or against cell membrane antigens.

• PNS exhibited antibodies against intracellular antigens are mediated via T-cell immune responses and are usually resistant to therapeutic interventions.

• PNS with antibodies against cell membrane antigens depend on B-cell-mediated immunity and have a more favorable response to treatment.

• FDG PET especially as a first-line investigational imaging procedure may reveal the primary cancer and contribute to its prompt treatment.

• The laboratory investigation should include assessment of the various known paraneoplastic antibodies in the sera of the patients.

• Therapeutic strategies include specific therapy of the primary tumor, and nonspecific immunotherapies such as plasma exchange, intravenous immune γ globulin, corticosteroids, other immune therapies and symptomatic therapies depending on each PNS.