Paraneoplastic cerebellar degeneration is an uncommon autoimmune disorder characterized clinically by progressive, ultimately incapacitating
ataxia and pathologically by destruction of cerebellar Purkinje cells, with variable loss of other cell populations. The disorder is most commonly associated with gynecological and
breast carcinomas,
small cell carcinoma of the lung, and
Hodgkin's disease and in most cases comes on prior to identification of the underlying
neoplasm. The hallmark of
paraneoplastic cerebellar degeneration is the presence of an immune response reactive with intracellular
proteins of Purkinje or other neurons or, less commonly, against neuronal
surface antigens. Evidence-based treatment strategies for
paraneoplastic cerebellar degeneration do not exist; and approaches to
therapy are thus speculative. Diagnosis and treatment of the underlying
neoplasm is critical, and characterization of the antibody response involved may assist in
tumor diagnosis. Most investigators have initiated treatment with
corticosteroids,
plasma exchange, or
intravenous immunoglobulin G.
Cyclophosphamide,
tacrolimus,
rituximab, or possibly
mycophenolate mofetil may warrant consideration in patients who fail to stabilize or improve on less aggressive
therapies.
Plasma exchange has been of questionable benefit when used alone but should be considered at initiation of treatment to achieve rapid lowering of circulating paraneoplastic
autoantibodies. Because the course of illness is one of relentless neuronal destruction, time is of the essence in initiating treatment. Likelihood of clinical improvement in patients with longstanding symptoms and extensive neuronal loss is poor.