The name is a mouthful and the disease’s effects can be devastating—but the treatment is relatively simple, once the cause is known.
Autoimmune meningoencephalomyelitis, or swelling of the brain and spinal cord due to an immune system reaction, can cause headache, progressive weakness, confusion, and blurred vision. Steroid therapy is effective but must start early for optimal results. Yet the condition is often misdiagnosed, delaying treatment.
Mayo Clinic Laboratories is the only laboratory in the world to offer testing for a novel form of autoimmune meningoencephalomyelitis. Known as autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy, the condition was identified by Mayo Clinic in 2016. The GFAP antibody test is offered as part of Mayo Clinic Laboratories’ encephalitis and myelopathy evaluations.
“Autoimmune GFAP astrocytopathy is a rapidly progressive disorder and can be potentially devastating neurologically. However, it is exquisitely steroid responsive,” says Andrew McKeon, M.B., B.Ch., M.D., an autoimmune neurologist at Mayo Clinic. “It’s important to start treatment right away, before receiving test results, if the condition is suspected.”
Patients generally present with some combination of the signs and symptoms of meningitis, encephalitis, and myelitis. The onset is gradual, with signs and symptoms progressing over a period of days or weeks. Mayo Clinic identifies three or four GFAP antibody-positive cases a week; about 10% are children. The condition might be mistaken for a chronic fungal infection, tuberculosis, central nervous system vasculitis, or sarcoidosis.
In people with autoimmune GFAP astrocytopathy, swollen optic discs might be apparent on examination with an ophthalmoscope. MRI may—or may not—show a characteristic pattern of enhancement. “It looks like linear radial abnormalities coming out from the lateral ventricles,” Dr. McKeon says.
Most significantly, patients often have high levels of white blood cells in their spinal fluid. “That is the clue that generally unites these patients, in our experience,” Dr. McKeon says.
For that reason, Mayo Clinic Laboratories recommends testing of spinal fluid. “We sometimes see people who are positive for the GFAP antibody in both serum and cerebrospinal fluid. But many patients are positive only in spinal fluid. A serum evaluation alone would miss the diagnosis,” Dr. McKeon says. “Sometimes people are reluctant to do lumbar punctures, especially in children. But we really need to test the cerebrospinal fluid.”
Other antibodies associated with inflammatory demyelinating diseases, such as myelin oligodendrocyte glycoprotein (MOG) antibody, are better detected in serum. “If there’s uncertainty as to whether the patient has GFAP or MOG antibodies, it’s best to order both serum and cerebrospinal fluid testing,” Dr. McKeon says.
Test results are generally available in seven days.
Encephalitis was long thought to be caused primarily by infections. But in a 2018 study, Mayo Clinic researchers found that autoimmune encephalitis is as common as the infectious disease. That discovery underlined the need for precise diagnostic testing for people with encephalitis, as the autoimmune and infectious diseases require different treatment.
Patients who test positive for the GFAP antibody are generally treated initially with methylprednisolone and then oral prednisone, at high doses. “In our experience patients respond very quickly,” Dr. McKeon says. “If the condition is recognized within a few months of onset, the symptoms can be reversible.”
However, Dr. McKeon has also seen patients who first presented a year after symptoms began. Those patients had progressed to dementia and wheelchair dependence. “That is a possible outcome if autoimmune GFAP astrocytopathy isn’t recognized quickly,” he says.
Most patients require long-term treatment to avoid relapse. In some people the condition apparently resolves spontaneously. “But we don’t have any way to distinguish those patients, so we recommend treating everybody,” Dr. McKeon says.
Mayo Clinic’s autoimmune neurology clinic has deep experience with the diagnosis and treatment of autoimmune GFAP astrocytopathy and other autoimmune neurologic disorders. Appointments with specialists in the autoimmune neurology clinic can be scheduled through the Neurology Appointment Center.
“What differentiates us is our very specific focus on patients who are diagnosed with an autoimmune encephalitis or meningitis in our lab, as opposed to other inflammatory diseases such as multiple sclerosis,” Dr. McKeon says. “We have a lot of experience initiating steroid and autoimmune suppressant therapies, slowly tapering doses, and closely monitoring patients to ensure good outcomes.”
Even after steroid treatment, some people with autoimmune GFAP astrocytopathy continue to experience symptoms. Mayo Clinic’s autoimmune neurologists work with headache neurologists and specialists in physical medicine and rehabilitation, and psychology and psychiatry, to manage those symptoms.
About 25% of adults who are GFAP antibody-positive also have a tumor. Women with the GFAP antibody might have coexisting NMDA receptor antibodies and benign ovarian tumors. Malignancies have been detected in some older GFAP-positive patients. Children who are GFAP-positive generally don’t have tumors.
“The next phase is to try to better understand this disease and further improve treatment,” Dr. McKeon says. “Our neurologists are pursuing those efforts.”