Once considered hopeless, autoimmune cerebellar ataxia can improve with immunotherapy

Nearly half of patients with autoimmune cerebellar ataxia who were treated with immunotherapy showed neurologic improvement, according to a cohort study published online September 28, 2015 in JAMA Neurology.

Autoimmune cerebellar ataxia in adults, which usually comes on rapidly and progresses quickly, can have disabling neurologic deficits, including dysarthria, disorders of gait and balance, and limb ataxia. But, little has been published about treatment responses and neurologic outcomes for patients with this disorder.

“Historically, we found cerebellar ataxia to be a hopeless disease,” said lead author of the study Andrew McKeon, MB, BCh, MD, neurologist at the Mayo Clinic, in Rochester, MN. “Although usually severe, treatment responses can be gratifying, particularly in patients with nonparaneoplastic disorders.”

Neurologists divide autoimmune cerebellar ataxia disorders into those that are paraneoplastic (triggered by cancer in the body) or nonparaneoplastic (autoimmune disorders of the central nervous system unrelated to cancer).

In this study, researchers reviewed the medical records of 118 adult patients with autoimmune cerebellar ataxia who were seropositive for at least 1 neural autoantibody, had received at least 1 immunotherapy or cancer therapy, and had outcomes reported by a neurologist. Nearly three-quarters of the patients were women, and the median duration from symptom onset to last follow-up was 25 months. Of the 118 patients, 63 had paraneoplastic ataxia and 55 had nonparaneoplastic ataxia.

Neurologic improvements occurred in 54 patients, and 22 of these had a robust change in ambulatory ability. Improvements were attributable to immunotherapy and were significantly more common among patients with nonparaneoplastic disorders, the researchers reported. Immunotherapy treatments included corticosteroids, intravenous immunoglobulin, plasma exchange, and immunosuppressants.

Additional factors that predicted better immunotherapy response and neurologic outcomes included the detection of at least one or more plasma membrane protein (PMP) antibodies or glutamic acid decarboxylase 65-kDa isoform (GAD65) antibodies.

On the other hand, progression to wheelchair dependence occurred significantly faster among patients who had neuronal nuclear and/or cytoplasmic (NNC) antibodies.

"The autoimmune component is important because it indicates that, potentially, the patient has a treatable disease, but it may also indicate an underlying cancer that needs to be looked for,” Dr. McKeon said.

“What I would suggest for doctors to do for a patient who has a rapidly progressing neurological problem out of the blue—it’s not obviously a stroke, it’s not obviously a brain tumor or something like that—that autoimmune should be very, very high on the list,” Dr. McKeon said.