Brain, Vol 120, Issue 8 1279-1300, Copyright © 1997 by Oxford University Press
WP Mason, F Graus, B Lang, J Honnorat, JY Delattre, F Valldeoriola, JC Antoine, MK Rosenblum, MR Rosenfeld, J Newsom-Davis, JB Posner and J Dalmau
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). (ABSTRACT TRUNCATED)
ARTICLES
Small-cell lung cancer, paraneoplastic cerebellar degeneration and the Lambert-Eaton myasthenic syndrome
Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S.-Y. Lim, W. P. Mason, N. P. Young, R. Chen, J. H. Bower, A. McKeon, S. J. Pittock, and A. E. Lang Polymyoclonus, Laryngospasm, and Cerebellar Ataxia Associated With Adenocarcinoma and Multiple Neural Cation Channel Autoantibodies Arch Neurol, October 1, 2009; 66(10): 1285 - 1287. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Titulaer, R. Klooster, M. Potman, L. Sabater, F. Graus, I. M. Hegeman, P. E. Thijssen, P. W. Wirtz, A. Twijnstra, P. A.E. S. Smitt, et al. SOX Antibodies in Small-Cell Lung Cancer and Lambert-Eaton Myasthenic Syndrome: Frequency and Relation With Survival J. Clin. Oncol., September 10, 2009; 27(26): 4260 - 4267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. J. Liao, P. Safa, Y.-R. Chen, R. A. Sobel, E. S. Boyden, and R. W. Tsien Anti-Ca2+ channel antibody attenuates Ca2+ currents and mimics cerebellar ataxia in vivo PNAS, February 19, 2008; 105(7): 2705 - 2710. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L Bataller, K A Kleopa, G F Wu, J E Rossi, M R Rosenfeld, and J Dalmau Autoimmune limbic encephalitis in 39 patients: immunophenotypes and outcomes J. Neurol. Neurosurg. Psychiatry, April 1, 2007; 78(4): 381 - 385. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Dalmau, R. G. Gonzalez, and M. F. Lerwill Case 4-2007 -- A 56-Year-Old Woman with Rapidly Progressive Vertigo and Ataxia N. Engl. J. Med., February 8, 2007; 356(6): 612 - 620. [Full Text] [PDF]
|
|
|
|
|
|
J Honnorat Understanding the physiopathology of paraneoplastic and genetic cerebellar ataxia. J. Neurol. Neurosurg. Psychiatry, December 1, 2006; 77(12): 1299 - 1300. [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Kleopa, L. B. Elman, B. Lang, A. Vincent, and S. S. Scherer Neuromyotonia and limbic encephalitis sera target mature Shaker-type K+ channels: subunit specificity correlates with clinical manifestations Brain, June 1, 2006; 129(6): 1570 - 1584. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. de Beukelaar and P. A. S. Smitt Managing paraneoplastic neurological disorders. Oncologist, March 1, 2006; 11(3): 292 - 305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. G. Mitchell, V. L. Brumm, C. G. Azen, K. E. Patterson, S. K. Aller, and J. Rodriguez Longitudinal Neurodevelopmental Evaluation of Children With Opsoclonus-Ataxia Pediatrics, October 1, 2005; 116(4): 901 - 907. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Younes-Mhenni, M. F. Janier, L. Cinotti, J. C. Antoine, F. Tronc, V. Cottin, P. J. Ternamian, P. Trouillas, and J. Honnorat FDG-PET improves tumour detection in patients with paraneoplastic neurological syndromes Brain, October 1, 2004; 127(10): 2331 - 2338. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F Graus, J Y Delattre, J C Antoine, J Dalmau, B Giometto, W Grisold, J Honnorat, P S. Smitt, C. Vedeler, J J G M Verschuuren, et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes J. Neurol. Neurosurg. Psychiatry, August 1, 2004; 75(8): 1135 - 1140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Shams'ili, J. Grefkens, B. de Leeuw, M. van den Bent, H. Hooijkaas, B. van der Holt, C. Vecht, and P. Sillevis Smitt Paraneoplastic cerebellar degeneration associated with antineuronal antibodies: analysis of 50 patients Brain, June 1, 2003; 126(6): 1409 - 1418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Bernal, S. Shams'ili, I. Rojas, R. Sanchez-Valle, A. Saiz, J. Dalmau, J. Honnorat, P. Sillevis Smitt, and F. Graus Anti-Tr antibodies as markers of paraneoplastic cerebellar degeneration and Hodgkin's disease Neurology, January 28, 2003; 60(2): 230 - 234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Graus, B. Lang, P. Pozo-Rosich, A. Saiz, R. Casamitjana, and A. Vincent P/Q type calcium-channel antibodies in paraneoplastic cerebellar degeneration with lung cancer Neurology, September 10, 2002; 59(5): 764 - 766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M Selim and D A Drachman Ataxia associated with Hashimoto's disease: progressive non-familial adult onset cerebellar degeneration with autoimmune thyroiditis J. Neurol. Neurosurg. Psychiatry, July 1, 2001; 71(1): 81 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Graus, F. Keime-Guibert, R. Rene, B. Benyahia, T. Ribalta, C. Ascaso, G. Escaramis, and J. Y. Delattre Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients Brain, June 1, 2001; 124(6): 1138 - 1148. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Bataller, F. Graus, A. Saiz, and J. J. Vilchez Clinical outcome in adult onset idiopathic or paraneoplastic opsoclonus-myoclonus Brain, February 1, 2001; 124(2): 437 - 443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Shuper, J. Stein, J. Goshen, L. Kornreich, I. Yaniv, I. J. Cohen, and P. Tiqva Subacute Central Nervous System Degeneration in a Child: An Unusual Manifestation of Ifosfamide Intoxication J Child Neurol, July 1, 2000; 15(7): 481 - 483. [Abstract] [PDF]
|
|
|
|
|
|
A. Mygland, A. Vincent, J. Newsom-Davis, H. Kaminski, F. Zorzato, M. Agius, N. E. Gilhus, and J. A. Aarli Autoantibodies in Thymoma-Associated Myasthenia Gravis With Myositis or Neuromyotonia Arch Neurol, April 1, 2000; 57(4): 527 - 531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. O. Dalmau and J. B. Posner Paraneoplastic Syndromes Arch Neurol, April 1, 1999; 56(4): 405 - 408. [Full Text] [PDF]
|
|
|
|
|
|
A Saiz, J Dalmau, M H. Butler, Q Chen, J Y Delattre, P De Camilli, and F Graus Anti-amphiphysin I antibodies in patients with paraneoplastic neurological disorders associated with small cell lung carcinoma J. Neurol. Neurosurg. Psychiatry, February 1, 1999; 66(2): 214 - 217. [Abstract] [Full Text]
|
|
|
|
|
|
J. C. Antoine, L. Absi, J. Honnorat, J.-M. Boulesteix, T. de Brouker, C. Vial, M. Butler, P. De Camilli, and D. Michel Antiamphiphysin Antibodies Are Associated With Various Paraneoplastic Neurological Syndromes and Tumors Arch Neurol, February 1, 1999; 56(2): 172 - 177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. O. Dalmau and J. B. Posner Neurological Paraneoplastic Syndromes Neuroscientist, November 1, 1998; 4(6): 443 - 453. [PDF]
|
|