Anti-Purkinje cell antibodies (termed anti-Yo) can be found in the sera of about half of patients with paraneoplastic cerebellar degeneration and in the large majority of those related to carcinoma of the breast or female genital tract, linking the clinical syndrome and this antibody closely. Antibodies against a nuclear antigen, termed anti-Hu, may also be present; they are more closely linked to the paraneoplastic encephalomyelitis discussed further on. (Hu and Yo are taken from the names of patients in whom the antibody was first found.) In the Mayo Clinic series of 32 patients with paraneoplastic cerebellar degeneration, 16 had such antibodies; all were women and most of them had breast or ovarian cancers. Anderson and colleagues report a similar proportion but point out that several other anti-Purkinje antibodies besides the highly characteristic one may be found (see Table 30-6). Death occurred in 4 to 18 months. In an equal number of cases without antibodies, half are men with lung cancer, some of whom display the anti-Hu antibody. This leaves a proportion who have no circulating antibody but who are nonetheless found to have a concealed tumor that must be sought by other ancillary tests including CT or positron emission tomography (PET) of the body. In another small group, it must be conceded that no underlying tumor can be found despite extensive examinations and even at autopsy. The survival in these cases has varied widely from 6 months to several years and depends on the behavior of the underlying tumor.
Whether the anti-Yo antibodies are merely markers of an underlying tumor or the agents of destruction of the Purkinje cells is not clear. They bind to a C-myc protein that initiates a degeneration of Purkinje cells. Regardless of the pathogenic significance of the antibodies, their presence in a patient with the typical neurologic disorder has considerable diagnostic significance. As mentioned above, they usually indicate that there is an underlying breast or ovarian cancer, which may be asymptomatic and small enough to be completely resected. Other antibodies besides anti-Yo and anti-Hu are found on occasion, such as those against a glutamate receptor in patients with Hodgkin disease (Smitt et al). The differential diagnosis of subacute cerebellar ataxia is broad, as indicated in
Table 5-1. The main considerations are postinfectious cerebellitis, non-paraneoplastic autoimmune cerebellitis (in which the conventional antibodies are present without tumor), a rare variant of Creutzfeldt-Jakob disease, and various intoxications.
Treatment Reports of plasma exchange or intravenous immunoglobulin treatment early in the course of neurological symptoms suggest some benefit, but it should not be assumed that this approach will succeed in most patients, and our own experience has been discouraging in this regard. Early identification and removal of a tumor yields the best outcomes; however, most patients are left with substantial deficits.