Paraneoplastic neurological syndrome: an evolving story

Abstract

Paraneoplastic neurological syndrome (PNS) comprises a group of neurological disorders that result from a misguided immune response to the nervous system triggered by a distant tumor. These disorders frequently manifest before the diagnosis of the underlying neoplasm. Since the first reported case in 1888 by Oppenheim, the knowledge in this area has evolved rapidly. Several classic PNS have been described, such as limbic encephalitis, paraneoplastic cerebellar degeneration, encephalomyelitis, opsoclonus-myoclonus, sensory neuronopathy, Lambert-Eaton Myasthenic syndrome, and chronic gastrointestinal dysmotility. It is now recognized that PNS can have varied nonclassical manifestations that extend beyond the traditional syndromic descriptions. Multiple onconeural antibodies with high specificity for certain tumor types and neurological phenotypes have been discovered over the past 3 decades. Increasing use of immune checkpoint inhibitors (ICIs) has led to increased recognition of neurologic ICI-related adverse events. Some of these resemble PNS. In this article, we review the clinical, oncologic, and immunopathogenic associations of PNS.

Spontaneous regression of small cell lung cancer associated with Lambert-Eaton Myasthenic Syndrome: Case report

“…[ 12 ] found that among 14 cases who had spontaneously regressed lung carcinoma were patients with PNS, some who were positive for onconeural antibodies. PNS is among a group of neurological disorders [13] triggered by a distant tumor and not directly caused by cancer metastasis, side effects of cancer treatment, nutritional deficiencies, metabolic derangements, or coagulopathies [14] . PNS arises in the context of an immune response generated against antigens expressed on tumor cells that are also expressed in the nervous system [15] .…”

High-grade B-cell lymphoma with gastroduodenal involvement showing paraneoplastic cerebellar degeneration: a case report

“…Multiple PNSs are induced by immune reactions, which frequently manifest as antineuronal antibodies measurable in serum and cerebrospinal fluid ( 6 ). The onconeural antibodies typically associated with PCD include Purkinje cytoplasmic antibody 1 (PCA-1, Yo), Purkinje cytoplasmic antibody Tr (PCA-Tr, Tr) and metabotropic glutamate receptor 1 (mGluR1) ( 7 ). The presence of antibodies against intracellular onconeural autoantibodies highly suggests an underlying tumor.…”

Diagnosis and Treatment of Paraneoplastic Neurologic Syndromes

“…Clinical features encompass brainstem encephalitis, cerebellar degeneration, myelitis and/or sensory and autonomic neuropathies. Multifocal syndromes without encephalitis, including myeloneuropathy and paraneoplastic-subacute-combined degeneration, would also fall under this broad category [ 34 ]. The most common underlying malignancy is SCLC.…”

“…The most commonly associated malignancy is SCLC (70–80% of cases) [ 44 ]. Common onconeural antibodies associated with this disorder include: anti-Hu, amphiphysin, CRMP5 and PCA2 antibodies [ 34 ]. Prompt treatment with corticosteroids may help to improve the sensory deficit [ 45 ].…”