Zusammenfassung
Neurologische paraneoplastische Syndrome sind seltene, meist immunvermittelte Begleiterscheinungen von bösartigen Tumoren. Unter den zahlreichen Tumoren sind das Ovarial- und das Mammakarzinom eine häufige Ursache und damit eine Herausforderung an den Gynäkologen. Das typische Erscheinungsbild besteht in der raschen Entwicklung einer schweren neurologischen Behinderung bei einem bisher nicht bekannten und lokal begrenzten Tumor. Neben der paraneoplastischen zerebellären Degeneration mit einer schweren Ataxie als häufigstem Erscheinungsbild sind die limbische Enzephalitis, die Hirnstammenzephalitis, die sensorische Neuronopathie, das Stiff-Person-Syndrom, die Dermatomyositis und die paraneoplastische Retinopathie beschrieben. Der Meilenstein für die Diagnose sind onkoneurale Antikörper im Serum und Liquor, die sowohl an Tumorzellen als auch an Nervenzellen binden. Neurologische paraneoplastische Syndrome bei Frauen mit Ovarial- und Mammakarzinomen haben immer eine ungünstige Prognose. Die meisten Patienten bleiben trotz einer effektiven Antitumortherapie, die Voraussetzung für eine wirksame Immuntherapie ist, schwer behindert und die Mortalität ist hoch.
Abstract
Paraneoplastic neurologic disorders are rare manifestations of a malignant neoplasm and mostly immune-mediated. Out of a broad spectrum of tumors ovarian and breast carcinomas are frequently the underlying cause presenting a challenge for the gynecologist. The combination of a rapidly progressive severe neurologic disability and a small, as yet unknown tumor is the typical clinical presentation. In addition to the most frequent paraneoplastic cerebellar degeneration resulting in severe ataxia, limbic encephalitis, brain stem encephalitis, sensory neuropathy, stiff-person syndrome, dermatomyositis and paraneoplastic retinopathy have been described. The cornerstone for the diagnosis are onconeural antibodies in serum and cerebrospinal fluid reacting with both the nervous system and the underlying cancer. Paraneoplastic neurologic syndromes in women with ovarian or breast cancer imply a grave prognosis. Although antitumor therapy may be effective in many cases and are essential for the success of additional immunotherapy, most patients remain severely disabled and mortality is remarkably high.
Schlüsselwörter
Paraneoplastische Syndrome - gynäkologische Tumoren - Neurologische Symptomatik - onkoneurale Antikörper
Key words
Paraneoplastic syndromes - gynecologic tumors - neurologic signs - onconeural antibodies
Literatur
-
1
Darnell R B, Posner J B.
Paraneoplastic syndromes involving the nervous system.
N Eng J Med.
2003;
349
1543-1554
-
2
Lang B, Vincent A, Newsom-Davis J.
Paraneoplastic myasthenia: Autoantibodies to calcium channels shared by cancer cells and motor nerve terminals.
Progress Neuro EndocrinImmunology.
1990;
3
83-89
-
3
Yong I K.
Passively transferred Lambert-Eaton syndrome in mice receiving purified IgG.
Muscle & Nerve.
1986;
9
523-530
-
4
Candler P M, Hart P E, Barnett M, Rees J H.
A follow up study of patients with paraneoplastic neurological disease in the United Kingdom.
J Neurol Neurosurg Psychiatry.
2004;
75
1411-1415
-
5
Younes-Mhenni S, Janier M F, Cinotti L. et al .
FDG‐PET improves tumor detection in patients with paraneoplastic neurological syndromes.
Brain.
2004;
127
2331-2338
-
6
Linke R, Schröder M, Helmberger T, Voltz R.
Antibody-positive paraneoplastic neurologic syndromes: Value of CT and PET for tumor diagnosis.
Neurology.
2004;
63
282-286
-
7
Frings M, Antoch G, Knorn P, Freudenberg L, Bier U, Timmann D, Maschke M.
Strategies in detection of the primary tumor in anti-Yo associated paraneoplastic cerebellar degeneration.
J Neurol.
2005;
252
197-201
-
8
Graus F, Keime-Guibert F, René R. et al .
Anti-Hu-associated paraneoplastic encephalomyelitis: Analysis of 200 patients.
Brain.
2001;
124
1138-1148
-
9
Anderson N E, Rosenblum M K, Posner J B.
Paraneoplastic cerebellar degeneration.
Ann Neurol.
1988;
24
558-567
-
10
Schams'ili S, Grefkens J, de Leeuw B, van den Bent M, Hooijkaas H, van der Holt B, Vecht P S.
Paraneoplastic cerebellar degeneration associated with antineuronal antibodies: analysis of 50 patients.
Brain.
2003;
126
1409-1418
-
11
Abrey L E, Dalmau J O.
Neurologic complications of ovarian carcinoma.
Cancer.
1999;
85
127-133
-
12
Peterson K, Rosenblum M K, Kotanides H, Posner J B.
Paraneoplastic cerebellar degeneration. I. A clinical analysis of 55 anti-Yo antibody-positive patients.
Neurology.
1992;
42
1931-1937
-
13
Rojas-Marcos I, Rousseau A, Keime-Guibert F, Rene R, Cartalat-Carel S, Delattre J Y, Graus F.
Spectrum of paraneoplastic neurologic disorders in women with breast and gynecologic cancer.
Medicine (Baltimore).
2003;
82
216-223
-
14
Digre K B.
Opsoclonus in adults. Report of three cases and review of the literature.
Arch Neurol.
1986;
43
1165-1175
-
15
Bataller L, Graus F, Saiz A, Vilchez J J.
Clinical outcome in adult onset idiopathic or paraneoplastic opsoclonus-myoclonus.
Brain.
2001;
124
437-443
-
16
Jongen J LM, Moll W JB, Sivellis Smitt P AE, Vecht C J, Tijssen C C.
Anti-Ri positive opsoclonus-myoclonus-ataxia in ovarian duct cancer.
J Neurol.
1998;
245
691-692
-
17
Porta-Etessam J, Ruiz-Morales J, Millan J M, Ramos A, Martinez-Salio A, Berbel-Garcia A.
Epilepsia partialis continua and frontal features as a debut of anti-Hu paraneoplastic encephalomyelitis with focal frontal encephalitis.
Europ J Neurol.
2001;
8
359-360
-
18
Gultekin S H, Rosenfeld M R, Voltz R, Eichen J, Posner J B, Dalmau J.
Paraneoplastic limbic encephalitis: neurologic symptoms, immunologic findings and tumor association in 50 patients.
Brain.
2000;
123
1481-1494
-
19
Bloch M H, Chan Hwang W, Baehring J M, Chambers S K.
Paraneoplastic limbic encephalitis: Ovarian cancer presenting as an amnestic syndrome.
Obstet Gynecol.
2004;
104
1174-1177
-
20
Sillevis Smitt P AE, Grefkens J, de Leeuw B. et al .
Survival and outcome in 73 anti-Hu positive patients with paraneoplastic encephalomyelitis/sonsory neuronopathy.
J Neurol.
2002;
249
745-753
-
21
Sigurgeirsson B, Lindelof B, Edhag O. et al .
Risk of cancer in patients with dermatomyositis.
N Engl J Med.
1992;
326
363-367
-
22
Brown P, Marsden C D.
The stiff man and stiff man plus syndromes.
J Neurol.
1999;
246
48-52
-
23
Silverman I E.
Paraneoplastic stiff limb syndrome.
J Neurol Neurosurg Psychiat.
1999;
67
126-127
-
24
Adamus G, Ren G, Weleber R G.
Autoantibodies against retinal proteins in paraneoplastic and autoimmune retinopathy.
BMC Ophthalmol.
2004;
4
5-13
-
25
Furneaux H F, Reich L, Posner J B.
Autoantibody synthesis in the central nervous system of patients with paraneoplastic syndromes.
Neurology.
1990;
40
1085-1091
-
26
Drlicek M, Bianchi G, Bogliun G. et al .
Autoantibodies of the anti-Yo and anti-Ri type in the absence of paraneoplastic neurologic syndromes: A long term survey of ovarian cancer patients.
J Neurol.
1997;
244
85-89
-
27
Moll J WB, Hooijkaas H, van Goorbergh B CM, Roos L GE, Henzen-Logmans S C, Vecht C J.
Systemic and anti-neuronal auto-antibodies in patients with paraneoplastic neurological disease.
J Neurol.
1996;
243
51-56
-
28
Dalmau J, Posner J B.
Neurologic paraneoplastic antibodies (anti-Yo; anti-Hu; anti-Ri): The case for a nomenclature based on antibody and antigen specifity.
Neurology.
1994;
44
2241-2246
-
29
Scheid R, Honnorat J, Delmont E, Urbach H, Biniek R.
A new anti-neuronal antibody in a case of paraneoplastic limbic encephalitis associated with breast cancer.
J Neurol Neurosurg Psychiatry.
2004;
75
338-340
-
30
Moll J WB, Antoine J C, Brashear H R. et al .
Guidelines on the detection of paraneoplastic anti-neuronal-specific antibodies. Report from the workshop to the fourth meeting of the International Society of Neuro-Immunology.
Neurology.
1995;
45
1937-1941
-
31
Voltz R, Gultekin S H, Rosenfeld M R, Gerstner E, Eichen J, Posner J B, Dalmau J.
A serological marker of paraneoplastic limbic and brain-stem encephalitis in patients with testicular cancer.
N Eng J Med.
1999;
340
1788-1795
-
32
Vega F, Graus F, Chen Q M, Poisson M, Schuller E, Delattre J Y.
Intrathecal synthesis of the anti-Hu antibody in patients with paraneoplastic encephalomyelitis or sensory neuronopathy.
Neurology.
1994;
44
2145-2147
-
33
Sahashi K, Sakai K, Mano K, Hirose G.
Anti-Ma2 antibody related paraneoplastic limbic/brainstem encephalitis associated with breast cancer expressing Ma1, Ma2 and Ma3 mRNAs.
J Neurol Neurosurg Psychiatry.
2003;
74
1332-1335
-
34
Yoon Y H, Cho E H, Sohn J, Thirkill C E.
An unusual type of cancer-associated retinopathy in a patient with ovarian cancer.
Korean J Ophthalmol.
1999;
13
43-48
-
35
Llado A, Mannucci P, Carpentier A F, Paris S, Blanco Y, Saiz A, Delattre J Y, Graus F.
Value of Hu antibody determinations in the follow-up of paraneoplastic neurologic syndromes.
Neurology.
2004;
63
1947-1949
-
36
Aguirre-Cruz L, Charuel J L, Carpentier A F, Benyahia B, Delattre J Y, Musset L.
Clinical relevance of non-neuronal auto-antibodies in patients with anti-Hu oder anti-Yo paraneoplastic diseases.
J Neurooncol.
2005;
71
39-41
-
37
Graus F, Vega F, Delattre J Y, Bonaventura I, René R, Arbaiza D, Tolosa E.
Plasmapheresis and antineoplastic treatment in CNS paraneoplastic syndromes with antineuronal autoantibodies.
Neurology.
1992;
42
536-540
-
38
Uchuya M, Graus F, Vega F, René R, Delattre J Y.
Intravenous immunglobuline treatment in paraneoplastic neurologic syndromes with antineuronal antibodies.
J Neurol Neurosurg Osychiat.
1996;
60
388-392
-
39
Rojas-Marcos I, Graus F, Keime-Guibert F, René R, Delattre J Y, Ramón J M, Dalmau J, Posner J B.
Long-term clinical outcome of paraneoplastic cerebellar degeneration and anti-Yo antibodies.
Neurology.
2000;
55
713-715
Prof. Dr. Roland Besser
Neurologische Klinik
Klinikum Krefeld
Lutherplatz 40
47805 Krefeld
eMail: neurologie.besser@klinikum-krefeld.de
