Paraneoplastic neurologic disorders in small cell lung carcinoma

Gozzard, Paul; Woodhall, Mark; Chapman, Caroline; Nibber, Anjan; Waters, Patrick; Vincent, Angela; Lang, Bethan; Maddison, Paul

doi:10.1212/wnl.0000000000001721

Cited by 110 publications

(104 citation statements)

References 23 publications

(24 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The results of our study confirm that neural autoantibodies are frequently found in patients with SCLC, even in neurologically asymptomatic patients, as we previously reported for patients with thymoma . Interestingly, IgGs targeting extracellular domains of plasma membrane antigens (e.g.…”

Section: Discussionsupporting

confidence: 91%

See 1 more Smart Citation

Paraneoplastic autoimmunity and small‐cell lung cancer: Neurological and serological accompaniments

et al. 2019

View full text Add to dashboard Cite

Paraneoplastic neurological autoimmunity is often associated with small‐cell lung cancer (SCLC), a highly malignant neuroendocrine tumor. Paraneoplastic autoimmunity often correlates with longer survival. We describe the paraneoplastic neurological manifestations of patients with SCLC with and without SCLC‐predictive autoantibodies and the correlation between autoimmunity and survival. We reviewed the records of 116 patients (51% male) from the Mayo Clinic with histopathologically confirmed SCLC for whom stored serum was available for neural autoantibody testing. Cancer was limited stage in 41%; the median age at diagnosis was 64 years. Paraneoplastic neurological manifestations were recorded in 61% (decreasing frequency: peripheral neuropathy, dysautonomia, cognitive decline, cerebellar ataxia, neuromuscular junction disorder, seizures, cranial neuropathy, movement disorder, brainstem disorder, or myelopathy). Neural autoantibodies, some with pathogenic potential, were detected in the sera of SCLC patients with and without neurological autoimmunity. The most frequent among patients with neurological manifestations were: anti‐neuronal nuclear antibody‐type 1, voltage‐gated calcium channel (VGCC)‐N‐type, VGCC‐P/Q‐type, glutamic acid decarboxylase 65 (GAD65), SOX1, and muscle acetylcholine receptor (AChR); while the most common in patients without neurological manifestations were: GAD65, muscle‐AChR, and VGCC‐P/Q‐type. Neither cancer stage at diagnosis nor survival correlated with neurological manifestations or autoantibody‐positivity, except for shorter survival in patients with myelopathy. The only predictor of longer survival was limited‐stage disease at diagnosis.

show abstract

Section: Discussionsupporting

confidence: 91%

“…The profile of neural autoantibodies in a patient's serum reflects the onconeural antigens expressed by the tumor . It is not unusual for multiple autoantibodies and paraneoplastic disorders to co‐exist in one patient …”

Section: Introductionmentioning

confidence: 99%

Paraneoplastic autoimmunity and small‐cell lung cancer: Neurological and serological accompaniments

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Interestingly, the presence of preexisting neural antigen‐specific cells in those with or without disease may be consistent with the frequent detection of neurological autoantibodies, particularly of the IgM subclass, in healthy control subjects 18. Similarly, screening of patients without neurological symptoms who have tumors and paraneoplastic autoantibodies, for example, GABA B ‐receptor antibodies and small cell lung carcinoma,19 may identify those with a potentially increased rate of irAEs. As an alternative to a T cell‐directed mechanism of action, as PD‐1 and CTLA‐4 are also expressed on B cells and some myeloid cells, and PD‐L1 on neurons and tumor cells, the checkpoint inhibitors may have additional direct actions via other cell types 2.…”

Section: Discussionsupporting

confidence: 52%

Seronegative antibody‐mediated neurology after immune checkpoint inhibitors

Wilson

Menassa

Davies

et al. 2018

Ann Clin Transl Neurol

Self Cite

View full text Add to dashboard Cite

Checkpoint inhibitor medications have revolutionized oncology practice, but frequently induce immune‐related adverse events. During autoimmune neurology practice over 20 months, we prospectively identified four patients with likely antibody‐mediated neurological diseases after checkpoint inhibitors: longitudinally extensive transverse myelitis, Guillain–Barré syndrome, and myasthenia gravis. All patients shared three characteristics: symptoms commenced 4 weeks after drug administration, responses to conventional immunotherapies were excellent, and autoantibodies traditionally associated with their syndrome were absent. However, serum immunoglobulins from the myelitis and Guillain–Barré syndrome patients showed novel patterns of tissue reactivity. Vigilance is required for antibody‐mediated neurology after checkpoint inhibitor administration. This phenomenon may inform the immunobiology of antibody‐mediated diseases.

show abstract

“…36 One or more SCLC-related autoantibodies are demonstrable in the serum of 90% of patients with SCLC who present with neurologic impairment unrelated to metastases and in 40% of SCLC patients without any evident neurologic disorder. 37 Multiple neural-specific IgGs and paraneoplastic disorders often coexist in a single patient. 37 The SCLC-related IgGs identified most commonly are specific for SOX transcription factor proteins (SOX1 and SOX2), Hu proteins (antineuronal nuclear autoantibody [ANNA] type 1), voltage-gated calcium channels (VGCCs; P/Q type and N type), collapsin response-mediator protein 5 (CRMP5), metabotropic g-aminobutyric acid (GABA) type B receptors, amphiphysin, and microtubule-associated protein 1B (antigen of Purkinje cell cytoplasmic autoantibody [PCA] type 2).…”

Section: Small Cell Lung Cancermentioning

confidence: 99%

Neurologic Autoimmunity in the Era of Checkpoint Inhibitor Cancer Immunotherapy

Ζεκερίδου

Lennon

2019

Mayo Clinic Proceedings

View full text Add to dashboard Cite

Neurologic autoimmune disorders in the context of systemic cancer reflect antitumor immune responses against onconeural proteins that are autoantigens in the nervous system. These responses observe basic principles of cancer immunity and are highly pertinent to oncological practice since the introduction of immune checkpoint inhibitor cancer therapy. The patient's autoantibody profile is consistent with the antigenic composition of the underlying malignancy. A major determinant of the pathogenic outcome is the anatomic and subcellular location of the autoantigen. IgGs targeting plasma membrane proteins (eg, muscle acetylcholine receptor -IgG in patients with paraneoplastic myasthenia gravis) have pathogenic potential. However, IgGs specific for intracellular antigens (eg, antineuronal nuclear antibody 1 [anti-Hu] associated with sensory neuronopathy and small cell lung cancer) are surrogate markers for CD8 þ T lymphocytes targeting peptides derived from nuclear or cytoplasmic proteins. In an inflammatory milieu, those peptides translocate to neural plasma membranes as major histocompatibility complex class I protein complexes. Paraneoplastic neurologic autoimmunity can affect any level of the neuraxis and may be mistaken for cancer progression. Importantly, these disorders generally respond favorably to early-initiated immunotherapy and cancer treatment. Small cell lung cancer and thymoma are commonly associated with neurologic autoimmunity, but in the context of checkpoint inhibitor therapy, other malignancy associations are increasingly recognized.

show abstract

Paraneoplastic neurologic disorders in small cell lung carcinoma

Cited by 110 publications

References 23 publications

Paraneoplastic autoimmunity and small‐cell lung cancer: Neurological and serological accompaniments

Paraneoplastic autoimmunity and small‐cell lung cancer: Neurological and serological accompaniments

Seronegative antibody‐mediated neurology after immune checkpoint inhibitors

Neurologic Autoimmunity in the Era of Checkpoint Inhibitor Cancer Immunotherapy

Contact Info

Product

Resources

About