Paraneoplastic
neurologic disorders are rare, autoimmune disorders, which can be broken down into two groups: those in which antibody response is directed against intracellular neuronal or neuroglial
proteins (Group 1) and those in which the immune response is directed against
antigens within or subjacent to the neuronal cell membrane (Group 2). In both groups, detection and treatment of the underlying
neoplasm is critical and carries the best chance of clinical stabilization or remission.Syndromes in Group 2 frequently respond to
therapy. This may involve
corticosteroids,
plasma exchange (PE), or
intravenous immunoglobulin G (
IgG), depending on the specific
paraneoplastic syndrome.
Cyclophosphamide or
rituximab may be helpful in patients who fail to stabilize or improve on less aggressive
therapies.Treatment of syndromes in Group 1 is far more difficult, and proven treatment strategies do not exist. Younger men (< 40 years of age) with limbic or brainstem syndromes, testicular or
germ cell tumors, and anti-Ma2
antibodies may respond to specific
tumor treatment together with
immunotherapy. Patients with
paraneoplastic syndromes and
anti-Ri antibodies may respond to
corticosteroids and/or
cyclophosphamide. Evidence-based treatment guidelines do not exist for patients with other central
paraneoplastic syndromes such as cerebellar degeneration or encephalomyeloneuritis. Approaches to
therapy, apart from treating the underlying
tumor, are thus speculative.In patients with rapidly progressive symptoms classically suggestive of a
paraneoplastic neurologic syndrome, time is of the essence in arresting neurologic deterioration. Clinical improvement in patients with longstanding symptoms is unlikely. At the outset, one should move rapidly to define the antibody response involved, as this may also assist
tumor diagnosis. Treatment may include
prednisone, intravenous
IgG, and
cyclophosphamide;
rituximab plus
prednisone may be an alternative, either initially or in the face of continued
disease progression despite treatment with intravenous
IgG or
cyclophosphamide. Although PE is of questionable benefit, a single cycle of PE may be considered before other treatment, to achieve rapid lowering of circulating paraneoplastic
autoantibodies.