Report: Rare case of seronegative MG precedes autoimmune encephalitis

24-year-old man developed MG and then AE associated with multiple antibody types

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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A rare case of myasthenia gravis (MG) that preceded the onset of autoimmune encephalitis (AE) — a type of autoimmune disease affecting the brain — was described in a recent case report.

The 24-year-old man, who didn’t test positive for MG-associated antibodies, but did have two distinct types of AE-causing antibodies, had severe neurological symptoms, but recovered with aggressive immunosuppressive therapy.

The case illustrates how autoimmune disorders like MG and AE can occur together, researchers said in “AMPA and NMDA receptor antibody autoimmune encephalitis preceded by ocular myasthenia gravis: a case report,” which was published in BMC Neurology.

In MG, self-reactive antibodies attack components of the neuromuscular junction, where nerve cells and muscles meet to communicate.

In rare cases, MG has been reported to coexist with AE, which refers to a group of conditions wherein the immune system attacks the brain, leading to inflammation and a range of neurological or psychiatric symptoms. Several brain proteins may be targeted in AE, but each patient usually only has one specific antibody type.

Here, researchers described the case of a 24-year-old man with MG who later developed AE associated with multiple antibody types.

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Seronegative MG — no MG-causing antibodies detected

The man, who was healthy and had no history of autoimmune diseases, came to the hospital with a drooping eyelid, double vision, and impaired eye movements, all signs of ocular MG — a form of the disease wherein weakness is restricted to the muscles controlling movements in the eyes and eyelids. Neurological exams and brain MRI scans were normal.

The man was diagnosed with ocular MG following a series of nerve and muscle health tests, but was found to be seronegative, meaning no MG-causing antibodies were detected in his bloodstream.

Treatment with pyridostigmine (sold under the brand name Mestinon, among others) and prednisolone eased his symptoms. He returned to the hospital three months later reporting short-term memory loss, behavioral changes, fatigue, depression, and an unsteady gait, however.

New MRI findings were consistent with inflammation or vasculitis — a type of inflammation specifically affecting blood vessels. He also showed signs of an elevated white blood cell count and increased antibody production.

He was given acyclovir, an antiviral medication, and the antibiotic ceftriaxone for any possible underlying infections, in addition to methylprednisolone, an immune-suppressing agent.

An encephalitis diagnosis

The man tested positive for antibodies targeting AMPA receptors, brain signaling proteins that are a known target in AE. He tested negative for other AE-associated antibodies and for vasculitis or infection.

MRI findings led clinicians to suspect encephalitis and he received another course of immune-suppressing treatment, including methylprednisolone, intravenous immunoglobulin, and rituximab.

The man continued to deteriorate, developing restless movements, disorientation, problems in the muscles needed for speaking, swallowing, and chewing, and involuntary movements of the mouth and face.

He then tested positive for antibodies against NMDA receptors, another brain protein sometimes targeted in AE.

Due to the severity of his symptoms, he was sedated in the intensive care unit and connected to a ventilator for three days. He was later admitted to the psychiatric department with psychosis and started on anti-epileptic medications for seizures as well as a third line of more aggressive immunosuppressive treatment, including cyclophosphamide.

No signs of underlying infection, vasculitis, or cancer were found. Because the thymus gland has been implicated in driving MG and self-reactive antibody production, clinicians performed a thymectomy to remove it. No abnormalities were found, however.

The man gradually recovered over several months in the hospital and was transferred to a neurorehabilitation unit.

By his one-year follow-up, he’d made an almost complete recovery, but still showed mild to moderate impairments in memory and executive function — the set of skills needed to go about everyday life — requiring daily structure and support. He was unable to remember being in the hospital, but his cognitive function was improving and he was able to return to his engineering studies at the university.

Researchers said AMPA and NMDA receptor antibodies were likely responsible for his relatively severe and atypical disease presentation. The man’s case underscores that “patients with seronegative MG, including ocular MG, may develop autoimmune encephalitis with more than one [type of] antibody,” the researchers wrote.