Serologic status and autoimmune cerebellar ataxia type predict treatment response

By Lucy Piper, Senior medwireNews Reporter

Patients with autoimmune cerebellar ataxia have better treatment responses and outcomes if they have the nonparaneoplastic form of the condition and are seropositive for neural plasma membrane protein (PMP) or glutamic acid decarboxylase 65 (GAD65) antibodies, suggests research.

Although autoimmune ataxia normally results in severe disability, researchers from the Mayo Clinic in Rochester, Minnesota, USA, found that 45.8% of 118 adults with the disorder showed neurologic improvement following one or more courses of immunotherapy or cancer therapy. This improvement was robust for 18.6% of patients, all of whom remained ambulatory.

Researcher Andrew McKeon and colleagues note that response to treatment was significantly more common among the 55 patients with nonparaneoplastic, versus the 63 with paraneoplastic, ataxia, with 76.4% still ambulatory at the last follow-up a median 25 months from symptom onset versus 31.7%.

Indeed, having nonparaneoplastic ataxia was the “single strongest predictor of a response to immunotherapy”, they report in JAMA Neurology.

Patients with this form of the disorder more commonly had robust responses (clear change in ambulatory status) to short-term immunotherapy (corticosteroids, intravenous immunoglobulin or plasma exchange) than patients with paraneoplastic ataxia, at 34.6% versus 7.8%, and progressed to depending on a wheelchair significantly more slowly.

The team comments that maintenance treatment was necessary to sustain a response for 16 of the patients.

“Treatment for 3 to 6 months with a slow taper of immunotherapy is more effective in general than short courses for a duration ranging from days to a few weeks”, they suggest.

A common characteristic of patients with paraneoplastic ataxia was seropositivity for Purkinje cell cytoplasmic antibody type 1 (PCA-1), also known as anti-Yo antibody, which was present in 58.7% of patients.

In all, 81 (68.6%) patients had antibodies directed against this or other neuronal nuclear and cytoplasmic (NNC) antibody types, while 22 (18.6%) had an antibody targeting a neural PMP receptor or ion channel and 15 (12.7%) had antibodies from both categories.

Those with NNC autoantibodies were wheelchair dependent significantly sooner than patients with seropositivity for antibodies targeting a neural PMP receptor or an ion channel.

Despite being an NNC antibody, GAD65, detected in 41 cases, was associated with patients progressing to wheelchair dependence more slowly, at similar rates to those with only PMP antibodies.

“[A]lthough detection of a paraneoplastic disorder or NNC antibody may portend a worse prognosis, this finding should not deter physicians from trials of immunotherapy in these patients because some may improve”, says the team.

“Sequential trials of corticosteroids, plasma exchange, and intravenous immunoglobulin could be undertaken in any patient with autoimmune ataxia, including those with paraneoplastic disorders, although these patients are less likely to respond over all.”

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