Therapy of paraneoplastic disorders of the CNS

Abstract

Paraneoplastic neurological syndromes affecting the CNS are rare, presenting in less than 1% of all those with cancer. However, they account for significant disability and may respond to treatment. The pathogenesis of paraneoplastic neurological syndromes is presumed to relate to loss of self-tolerance spilling over from the immune attack on the underlying neoplasm. Testing for anti-neuronal antibodies is now available in most tertiary laboratories, enabling targeted therapies. While the evidence base for treatment is limited, the response to treatment can be largely determined based on the location of the target antigen; antibodies against cell surface antigens responding well to treatments targeting the humoral response. Intracellular antigen-target syndromes respond less well, but may theoretically respond best to T-cell based therapies. In both cases, aggressive tumor therapy is indicated.

Keywords:

• anti-neuronal antibody
• CNS
• immunotherapy
• limbic encephalitis
• paraneoplastic

Acknowledgements

NLM Paul: draft and revision of the manuscript. T Kleinig: article concept and design, draft and revision of the manuscript.

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.

Key issues

• Classical paraneoplastic CNS syndromes include limbic encephalitis, opsoclonus–myoclonus and cerebellar degeneration. N-methyl-D-aspartate-receptor encephalitis is a newly identified clinically distinct syndrome.

• Paraneoplastic neurological syndromes (PNS) syndromes are immune-mediated, with two types of antigenic target identified: intracellular or cell surface.

• Certain PNS are associated with particular antibodies, such as cerebellar degeneration and anti-Yo.

• Certain antibodies are strongly associated with certain cancers, such as anti N-methyl-D-aspartate-receptor with ovarian teratoma, anti-Hu with small cell lung cancer. Identification of these antibodies should prompt search for the associated tumor.

• Early tumor detection offers greater chance for PNS stabilization and possible improvement.

• Treatment consists of prompt tumor treatment, immunotherapy and symptomatic treatment.

• Syndromes with neuronal cell surface antibodies usually respond to immunotherapy, targeting the humoral response and have a better prognosis.

• Immunotherapy with IVIG, plasma exchange and/or rituximab has minimal effect on PNS targeted at intracellular antigens

• Symptomatic treatment should be offered to all patients with PNS.

Notes