Pathogenesis, diagnosis and treatment of paraneoplastic neurologic syndromes

ABSTRACT

Introduction: Paraneoplastic neurological syndromes (PNS) are a rare heterogeneous group of neurological diseases associated with tumors. These syndromes are the result of a cross-reactive immune response against antigens shared by the tumor and the nervous system. The discovery of an increasing number of autoantigens and the identification of tumoral factors leading to a substantial antitumoral immune response makes this topic highly innovative.

Areas covered: This review covers the clinical, oncological, pathophysiological aspects of both immunological PNS groups. One is associated with autoantibodies against intracellular onconeural antibodies, which are highly specific for an underlying tumor, although the disease is mainly T-cell mediated. In contrast, PNS associated with pathogenic surface-binding/receptor autoantibodies, which are often responsive to immunosuppressive treatment, may manifest as paraneoplastic and non-paraneoplastic diseases. The most frequent tumors associated with PNS are (small cell) lung cancer, gynecological tumors, thymoma, lymphoma, and, in children, neuroblastoma. A special interest is given to PNS, induced by immune checkpoint-inhibitors (ICIs).

Expert opinion: Research in PNS, including the group of ICI-induced PNS provide new insights in both the pathophysiology of PNS and tumor immune interactions and offers new treatment options for this group of severe neurological diseases.

KEYWORDS:

• Autoantibody
• encephalitis
• onconeural antibody
• paraneoplastic neurological syndrome
• tumor

Article highlights

• The detection of (an expanding number of) onconeural antibodies should prompt an extensive tumor search, if necessary, including fluorodeoxyglucose positron emission tomography, since these antibodies are highly specific for a paraneoplastic disease.

• PNS with classical onconeural antibodies do not respond to immunosuppressive treatment. In most cases, the only factor, which may stabilize the neurological syndrome, is tumor treatment.

• Encephalitis with surface/receptor autoantibodies can occur in paraneoplastic and non-paraneoplastic syndromes; therefore, a tumor search in these cases is necessary.

• In patients with surface/receptor antibody-associated encephalitis and paraneoplastic neuromuscular syndromes, prompt immunosuppression should be considered in parallel with tumor treatment.

• PNS induced by immune checkpoint inhibitors provide new insights in the pathophysiology of these syndromes.

Declaration of interest

The author has 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.