Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients
Francesc Graus,Florence Keime-Guibert,Ramón Reñé,Baya Benyahia,Teresa Ribalta,Carlos Ascaso,Geòrgia Escaramís,Jean Yves Delattre +7 more
TLDR
The predictors of mortality and PEM evolution found in the study may be important in the design of future therapeutic protocols, and emphasize the importance of early diagnosis and treatment of the underlying tumour.Abstract:
We reviewed 200 patients with paraneoplastic encephalomyelitis (PEM) and anti-Hu antibodies to show possible clinical differences with respect to previous series, and to identify patient, tumour and treatment-related characteristics associated with neurological disability and survival. The median age of the 200 patients was 63 years (range 28–82 years) and 75% were men. The predominant neurological syndromes were sensory neuropathy (54%), cerebellar ataxia (10%), limbic encephalitis (9%) and multifocal involvement (11%). Sensorimotor neuropathies with predominant motor involvement were observed in only 4% of the patients. Pathological or X-ray evidence of a tumour was obtained in 167 patients (83%) and was a small-cell lung cancer (SCLC) in 74% of those with histological diagnosis. Coexistence of extrathoracic tumours with SCLC was rare (0.5%). Positive Hu immunoreactivity was observed in the extrathoracic tumours of six out of seven patients in whom autopsy or long-term follow-up ruled out a coexisting SCLC. PEM preceded the diagnosis of the tumour in 71% of patients (mean delay ± SD 6.5 ± 7.0 months; range 0.1–47 months). In the 24 patients in whom the tumour diagnosis was the initial event, PEM predicted the progression or relapse of the tumour in 87% of them. No tumour was found in 33 patients, including four who had a post-mortem study and four with >5 years of follow-up. In a logistic regression analysis, treatment of the tumour, associated or not with immunotherapy, was an independent predictor of improvement/stabilization of PEM [odds ratio 4.56; 95% confidence interval (CI) 1.62–12.86]. Cox multivariate analysis indicated that the variables independently associated with mortality were: age >60 years [relative risk (RR) 1.49; 95% CI 1.05–2.12], Rankin score at diagnosis >3 (RR 1.60; 95% CI 1.12–2.28), more than one area of the nervous system affected (RR 1.61; 95% CI 1.08–2.40), and absence of treatment (RR 2.56; 95% CI 1.76–3.71). We conclude that, unlike previous series, the majority of our patients were male, and there was a low occurrence of predominantly motor neuropathies and extrathoracic tumours coexisting with SCLC. When the diagnosed extrathoracic tumour expresses Hu antigens, further tests to rule out a coexisting SCLC are probably unnecessary. Finally, the predictors of mortality and PEM evolution found in the study may be important in the design of future therapeutic protocols, and emphasize the importance of early diagnosis and treatment of the underlying tumour.read more
Citations
More filters
Journal ArticleDOI
Paraneoplastic anti–N‐methyl‐D‐aspartate receptor encephalitis associated with ovarian teratoma
Josep Dalmau,Erdem Tüzün,Hai-Yan Wu,Jaime Masjuan,Jeffrey E. Rossi,Alfredo Voloschin,Joachim M. Baehring,Haruo Shimazaki,Reiji Koide,Dale King,Warren P. Mason,Lauren H Sansing,Marc A. Dichter,Myrna R. Rosenfeld,David A. Lynch +14 more
TL;DR: The autoantigens of a new category of treatment‐responsive paraneoplastic encephalitis are reported, and it is proposed that this category should be combined with existing treatment-responsive encephalopathy categories.
Journal ArticleDOI
Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis
Josep Dalmau,Eric Lancaster,Eugenia Martinez-Hernandez,Myrna R. Rosenfeld,Rita J. Balice-Gordon +4 more
TL;DR: Patients' antibodies cause a titre-dependent, reversible decrease of synaptic NMDAR by a mechanism of crosslinking and internalisation, which reveals a probable pathogenic relation between the depletion of receptors and the clinical features of anti-NMDAR encephalitis.
Journal ArticleDOI
Recommended diagnostic criteria for paraneoplastic neurological syndromes
Francesc Graus,Jean Yves Delattre,Jean-Christophe Antoine,Josep Dalmau,Bruno Giometto,Wolfgang Grisold,J. Honnorat,P. A. E. Sillevis Smitt,Ch Vedeler,Jan J.G.M. Verschuuren,Angela Vincent,Raymond Voltz +11 more
TL;DR: An international panel of neurologists interested in PNS recommended new criteria for those in whom no clinical consensus was reached in the past and defined “classical” syndrome and onconeural antibody as “well characterised”.
Journal ArticleDOI
Antibodies to Kv1 potassium channel-complex proteins leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvan's syndrome and acquired neuromyotonia.
Sarosh R. Irani,Sian K Alexander,Patrick Waters,Kleopas A. Kleopa,Philippa Pettingill,Luigi Zuliani,Elior Peles,Camilla Buckley,B Lang,Angela Vincent +9 more
TL;DR: The identification of leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 as the major targets of potassium channel antibodies, and their associations with different clinical features, begins to explain the diversity of these syndromes.
Preoperative staging of non-small-cell lung cancer with positron-emission tomography.
RM Pieterman,Jwg van Putten,JJ Meuzelaar,E. L. Mooyaart,W Vaalburg,Gerard H. Koëter,Fidler,Jan Pruim,Hendricus Groen +8 more
TL;DR: The use of PET to identify the stage of the disease resulted in a different stage from the one determined by standard methods in 62 patients: the stage was lowered in 20 and raised in 42.
References
More filters
Book
Applied Logistic Regression
David W. Hosmer,Stanley Lemeshow +1 more
TL;DR: Hosmer and Lemeshow as discussed by the authors provide an accessible introduction to the logistic regression model while incorporating advances of the last decade, including a variety of software packages for the analysis of data sets.
Book ChapterDOI
Regression Models and Life-Tables
TL;DR: The analysis of censored failure times is considered in this paper, where the hazard function is taken to be a function of the explanatory variables and unknown regression coefficients multiplied by an arbitrary and unknown function of time.
Journal ArticleDOI
Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide
Andrew T. Turrisi,KyungMann Kim,Ronald Blum,William T. Sause,Robert B. Livingston,Ritsuko Komaki,Henry N. Wagner,Seena C. Aisner,David H. Johnson +8 more
TL;DR: Four cycles of cisplatin plus etoposide and a course of radiotherapy beginning with cycle 1 of the chemotherapy resulted in overall two- and five-year survival rates of 44 percent and 23 percent, a considerable improvement in survival rates over previous results.
Preoperative staging of non-small-cell lung cancer with positron-emission tomography.
RM Pieterman,Jwg van Putten,JJ Meuzelaar,E. L. Mooyaart,W Vaalburg,Gerard H. Koëter,Fidler,Jan Pruim,Hendricus Groen +8 more
TL;DR: The use of PET to identify the stage of the disease resulted in a different stage from the one determined by standard methods in 62 patients: the stage was lowered in 20 and raised in 42.