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Human chorionic gonadotropin treatment of anti-Hu-associated paraneoplastic neurologicalsyndromes
  1. F van Broekhoven1,2,
  2. M T de Graaf1,3,
  3. J E Bromberg1,
  4. H Hooijkaas4,
  5. M J van den Bent1,
  6. J W de Beukelaar1,3,
  7. N A Khan4,
  8. J W Gratama3,
  9. J N van der Geest2,
  10. M Frens2,
  11. R Benner4,
  12. P A Sillevis Smitt1
  1. 1Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
  2. 2Department of Medical Oncology, Laboratory for Clinical and Tumor Immunology, Rotterdam, The Netherlands
  3. 3Departments of Immunology, Erasmus MC, Rotterdam, The Netherlands
  4. 4Departments of Neuroscience, Erasmus MC, Rotterdam, The Netherlands
  1. Correspondence to Peter Sillevis Smitt, Department of Neurology, Erasmus MC, Room H639, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; p.sillevissmitt{at}


Objective Paraneoplastic neurological syndromes associated with anti-Hu antibodies (Hu-PNS) are mediated by a T-cell immune response that is directed against the Hu antigens. In pregnancy, many Th1-mediated autoimmune diseases such as rheumatoid arthritis and multiple sclerosis regress. We hypothesised that this decreased disease activity during pregnancy may be related to high human chorionic gonadotropin (hCG) levels.

Methods 15 Hu-PNS patients were treated in a prospective, uncontrolled and unblinded trial with 10 000 IU daily of hCG administered by intramuscular injection during 12 weeks. Primary outcome measures were functional improvement defined as a decrease of one or more points on the modified Rankin Scale (mRS) or stabilisation in patients with mRS score ≤3 and improvement of neurological impairment assessed with the Edinburgh Functional Impairment Tests (EFIT). Secondary end points included the change in activities of daily living as evaluated using the Barthel Index.

Results Seven of 15 patients (47%) improved on the mRS or stabilised at mRS score ≤3. Four patients (27%) showed significant improvement of neurological impairment as indicated by an overall Edinburgh Functional Impairment Tests score of ≥1 point. Five patients improved on the Barthel Index (33%).

Conclusion Comparison with previous studies suggests that hCG may have immunomodulatory activity and may modify the course of Hu-PNS, although well-established confounding factors may have contributed in this uncontrolled trial.

  • Paraneoplastic neurological syndromes
  • anti-Hu
  • human chorionic gonadotropin
  • small cell lung cancer
  • paraneoplastic syndrome

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  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Erasmus University Medical Center Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.