Small-cell lung cancer, paraneoplastic cerebellar degeneration and the Lambert-Eaton myasthenic syndrome Journal Article
| Authors: | Mason, W. P.; Graus, F.; Lang, B.; Honnorat, J.; Delattre, J. Y.; Valldeoriola, F.; Antoine, J. C.; Rosenblum, M. K.; Rosenfeld, M. R.; Newsom-Davis, J.; Posner, J. B.; Dalmau, J. |
| Article Title: | Small-cell lung cancer, paraneoplastic cerebellar degeneration and the Lambert-Eaton myasthenic syndrome |
| Abstract: | Several cancers, especially lung, ovarian and breast, can cause paraneoplastic cerebellar degeneration. The presence of different antineuronal antibodies associated with different cancers and paraneoplastic cerebellar degeneration suggests that several immunological mechanisms may result in the same neurological disorder. In patients with small-cell lung cancer paraneoplastic cerebellar degeneration may occur with or without Hu antineuronal antibodies (HuAb), indicating that patients with the same tumour can develop paraneoplastic cerebellar degeneration by different immunological mechanisms. Furthermore, paraneoplastic cerebellar degeneration sometimes occurs in association with the Lambert-Eaton myasthenic syndrome. In order to try to understand the clinical implication of antineuronal antibodies in patients with small-cell lung cancer we examined the serum of 57 patients with presenting symptoms of paraneoplastic cerebellar degeneration for the presence of HuAb and P/Q- and N-type voltage-gated calcium channel antibodies. Patients with paraneoplastic cerebellar degeneration who were HuAb positive were compared with HuAb negative patients with respect to neurological symptoms, course of the neurological disorder response to treatment, tumour prognosis, pathological findings, and cause of death. The tumour outcome and serological findings of these patients were also compared with those of 109 small-cell lung cancer patients without paraneoplastic syndromes of the CNS. Titres of HuAb were classified as 'high' (immunoblot titre > 1 : 10,000) or 'low' ( < 1 : 10,000), the latter similar to the antibody titres detected in some small-cell lung cancer patients without paraneoplastic symptoms. Twenty-five patients with paraneoplastic cerebellar degeneration (44%) had high titres of HuAb, four (7%) had low titres of HuAb, and 28 (49%) were HuAb negative; for clinical comparisons with the patients with high titres of HuAb, the four patients with low antibody titres were included in the HuAb negative cohort. None of the 109 small-cell lung cancer patients without paraneoplastic symptoms had high titres of HuAb. The presence of high titres of HuAb defined a subset of patients who differed from the HuAb negative paraneoplastic cerebellar degeneration cohort, HuAb positive patients were more likely to be female (P < 0.01), to have multifocal neurological disease (brainstem encephalopathy and sensory neuropathy being common extracerebellar manifestations) (P < 0.002), and be severely disabled (P < 0.005). A total of nine patients (16%) from both paraneoplastic cerebellar degeneration groups developed electrophysiologically confirmed Lambert-Eaton myasthenic syndrome. Seven of these nine patients had serum available for P/Q-type voltage-gated calcium channel antibody testing and all seven were positive. In addition, 20% of HuAb negative paraneoplastic cerebellar degeneration patients without clinically identified Lambert-Eaton myasthenic syndrome had P/Q-type voltage-gated calcium channel antibodies, while only 2% of small-cell lung cancer patients without paraneoplastic symptoms had these antibodies. Treatment of the tumour and/or immunomodulation did not alter the course of paraneoplastic cerebellar degeneration, but improved Lambert-Eaton myasthenic syndrome symptoms. At the time of death, in 60% of HuAb positive and 20% of HuAb negative paraneoplastic cerebellar degeneration patients, the tumour was either not evident or localized to the chest (P < 0.007); neurological disease was the cause of death of 65% HuAb positive paraneoplastic cerebellar degeneration and 10% HuAb negative paraneoplastic cerebellar degeneration patients (P < 0.001). Irrespective of the serological findings and cause of death, paraneoplastic cerebellar degeneration patients who received standard treatment for the small-cell lung cancer, had shorter survival (1- and 2-year survival after cancer diagnosis of 46% and 28%, respectively) than all age-, tumour-stage- and treatment-matched group of 59 small-cell lung cancer patients without paraneoplastic dis ase (1- and 2-year survival, estimates, 76% and 31%, respectively). The pathological findings of five HuAb positive paraneoplastic cerebellar degeneration patients examined at autopsy included diffuse encephalomyelitis with severe loss of Purkinje cells in four patients, but no apparent Purkinje cell loss in one; three patients also had involvement of posterior nerve roots or dorsal root ganglia. |
| Keywords: | adult; cancer survival; clinical article; controlled study; aged; aged, 80 and over; middle aged; survival analysis; disease course; antineoplastic agents; cerebellum; purkinje cell; ovary cancer; sensory neuropathy; breast cancer; lung neoplasms; incidence; neurons; cause of death; lung small cell cancer; symptom; immunotherapy; spinal cord; immunoblotting; immunomodulation; sex difference; age distribution; inflammatory infiltrate; autopsy; autoantibody; antibody detection; eaton lambert syndrome; paraneoplastic syndrome; nerve cell; brain stem; autoantibodies; serology; antibody titer; sex distribution; disability; immunopathogenesis; carcinoma, small cell; nerve degeneration; dentate gyrus; paraneoplastic cerebellar degeneration; dorsal root; paraneoplastic syndromes; ion channel gating; cell loss; calcium channel; calcium channels; cerebellum degeneration; cancer; humans; prognosis; human; male; female; priority journal; article; lambert-eaton myasthenic syndrome |
| Journal Title: | Brain |
| Volume: | 120 |
| Issue: | 8 |
| ISSN: | 0006-8950 |
| Publisher: | Oxford University Press |
| Date Published: | 1997-08-01 |
| Start Page: | 1279 |
| End Page: | 1300 |
| Language: | English |
| DOI: | 10.1093/brain/120.8.1279 |
| PUBMED: | 9278623 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work