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Background <p>Type&#xa0;1&#xa0;antineuronal nuclear&#xa0;or “Hu” antibody&#xa0;(ANNA1/Hu-IgG) is associated with paraneoplastic neurological syndromes (PNS), and most often, small cell lung carcinoma (SCLC).</p> Objectives <p>To evaluate factors associated with disability and survival in ANNA1/Hu-IgG PNS and to compare the survival of patients with SCLC (with and without ANNA1/Hu-IgG PNS).</p> Methods <p>This was a single-center cohort study of 45 patients with ANNA1/Hu-IgG PNS.</p> <p>Kaplan–Meier methods were used to estimate time to mortality, wheelchair dependence, and modified Rankin Scale (mRS) score &gt; 2. Cox proportional hazards models and logistic regression were used to estimate hazard ratios (HRs) and odds ratios (ORs), respectively. Secondary analyses compared patients with ANNA1/Hu-IgG PNS to a cohort with SCLC. Survival was evaluated using Cox proportional hazards models, adjusting for age, sex, cancer stage, and treatment.</p> Results <p>Disability and survival were associated with clinical phenotype at onset, with limbic encephalitis having a greater hazard of mRS &gt; 2 (HR = 6.84, 95% CI = 2.12–22.04, <i>P</i> = 0.001) and greater odds of death (HR = 2.44, 95% CI = 1.05–5.66, <i>P</i> = 0.039). Among patients with SCLC, the patients with ANNA1/Hu-IgG PNS + SCLC (<i>n</i> = 26) compared to SCLC-only (<i>n</i> = 1513) had a 41% lower hazard of death, adjusting for age, sex, stage, and cancer treatment (HR = 0.59, 95% CI = 0.37–0.96, <i>P</i> = 0.033).</p> Conclusion <p>In ANNA1/Hu-IgG PNS, faster progression of disability and greater risk of mortality is associated with limbic encephalitis at onset, suggesting a potentially modifiable factor for early intervention. Patients with SCLC and ANNA1/Hu-IgG PNS survived longer than patients with SCLC without PNS, suggesting a survival advantage of paraneoplastic autoimmunity.</p>

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Progressive disability but survival advantage in anti-Hu/ANNA1 paraneoplastic neurological syndromes

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月3日

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  • Kimberly A. DiMauro,
  • Nicolas R. Thompson,
  • Brittany Lapin,
  • Nathan A. Pennell,
  • Glen Stevens,
  • Steven Shook,
  • Jeffrey A. Cohen,
  • Amy Kunchok

摘要

Background

Type 1 antineuronal nuclear or “Hu” antibody (ANNA1/Hu-IgG) is associated with paraneoplastic neurological syndromes (PNS), and most often, small cell lung carcinoma (SCLC).

Objectives

To evaluate factors associated with disability and survival in ANNA1/Hu-IgG PNS and to compare the survival of patients with SCLC (with and without ANNA1/Hu-IgG PNS).

Methods

This was a single-center cohort study of 45 patients with ANNA1/Hu-IgG PNS.

Kaplan–Meier methods were used to estimate time to mortality, wheelchair dependence, and modified Rankin Scale (mRS) score > 2. Cox proportional hazards models and logistic regression were used to estimate hazard ratios (HRs) and odds ratios (ORs), respectively. Secondary analyses compared patients with ANNA1/Hu-IgG PNS to a cohort with SCLC. Survival was evaluated using Cox proportional hazards models, adjusting for age, sex, cancer stage, and treatment.

Results

Disability and survival were associated with clinical phenotype at onset, with limbic encephalitis having a greater hazard of mRS > 2 (HR = 6.84, 95% CI = 2.12–22.04, P = 0.001) and greater odds of death (HR = 2.44, 95% CI = 1.05–5.66, P = 0.039). Among patients with SCLC, the patients with ANNA1/Hu-IgG PNS + SCLC (n = 26) compared to SCLC-only (n = 1513) had a 41% lower hazard of death, adjusting for age, sex, stage, and cancer treatment (HR = 0.59, 95% CI = 0.37–0.96, P = 0.033).

Conclusion

In ANNA1/Hu-IgG PNS, faster progression of disability and greater risk of mortality is associated with limbic encephalitis at onset, suggesting a potentially modifiable factor for early intervention. Patients with SCLC and ANNA1/Hu-IgG PNS survived longer than patients with SCLC without PNS, suggesting a survival advantage of paraneoplastic autoimmunity.