Paraneoplastic cerebellar degeneration
Clinical features
Paraneoplastic cerebellar degeneration (PCD) is characterized by the
rapid development of a severe pancerebellar dysfunction. The postmortem
study shows extensive loss of Purkinje neurons with relative preservation
of other cerebellar neurons. Inflammatory infiltrates in the deep cerebellar
nuclei and brainstem are also identified in some patients. PCD has mostly
been reported in association with gynecologic tumors, breast cancer,
lung cancer, particularly small cell lung carcinoma (SCLC), and Hodgkin's
lymphoma. The clinical picture is similar in all patients with PCD independent
of the associated tumor. The patient subacutely develops truncal and
appendicular ataxia, and dysarthria. Ataxia is initially asymmetric
in 40% of the patients. After a few months symptoms stabilize, leaving
the patient severely disabled. Most of the patients have diplopia, horizontal
nystagmus, and half of them have rotatory or downbeating nystagmus.
Signs and symptoms of involvement of other areas of the neuraxis are
common but usually mild. CT and MRI studies are normal or demonstrate
cerebellar atrophy particularly in the latter stages of the disease.
Associated antibodies
Anti-Yo antibodies are present in the great majority of patients with
PCD and cancer of the ovary, breast, or other gynecological malignancies.
In two thirds of anti-Yo PCD patients the neurological symptoms develop
before the diagnosis of the tumor.
Anti-Tr antibodies are markers of patients
with PCD and Hodgkin disease. Unlike anti-Yo antibodies, anti-Tr antibodies
usually disappear after treatment of the tumor or, in a few patients,
are only found in the CSF. Anti-Tr antibodies are found in a few patients
with a subacute cerebelar syndrome, identical to PCD who never develop
Hodhkin’s disease or solid tumors.
Anti-voltage-gated calcium channel (VGCC) antibodies are present in
near 40% of patients with PCD and lung cancer, usually SCLC. About half
of these patients present a coincident Lambert Eaton myasthenic syndrome
(LEMS).
Anti-Hu antibodies are reported in 23%
of patients with PCD and lung cancer. These patients rarely harbour
VGCC antibodies. The frequency of anti-Hu antibodies is much higher
in those patients who present a cerebellar syndrome, lung cancer, and
symptoms of involvement of other areas of the nervous system (paraneoplastic
encephalomyelitis).
A few patients with PCD and lung cancer present anti-CV2(CRMP5),
anti-Zic4 or anti-Ma
antibodies.
Treatment
As in many paraneoplastic neurological syndromes of the central nervous
system, PCD rarely improves with treatment. The best chance to at least
stabilize the syndrome is to induce a complete response of the tumor.
Immunotherapy rarely is effective but a trial with intravenous immunoglobulins,
steroids or plasmapheresis is indicated because there are a few patient
who improved. Patients with anti-Tr antibodies are more likely to improve
than those with anti-Hu or anti-Yo antibodies.
Selected references
1. Peterson K, Rosenblum MK, Posner JB. Paraneoplastic
cerebellar degeneration: a clinical analysis of 55 anti-Yo antibody-positive
patients. Neurology 1992;42:1931-37.
2. Graus F, Lang B, Pozo-Rosich P, et al. P/Q type calcium-channel antibodies
in paraneoplastic cerebellar degeneration with lung cancer. Neurology
2002;59:764-6.
3. MasonWP, Graus F, Lang B, et al. Small-cell lung
cancer, paraneoplastic cerebellar degeneration and the Lambert-Eaton
mysthenic syndrome. Brain 1997;120:1279-300.
4. Shams’ili S, Grefkens J, de Leeuw B, et al.
Paraneoplastic cerebellar degeneration associated with antineuronal
antibodies:analysis of 50 patients. Brain 2003;126:1409-18.
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