Case Report Shows Ocular MG, Autoimmune Encephalitis Can Coexist

Myasthenia gravis (MG) and autoimmune synaptic encephalitis (AE) are both autoimmune conditions, but it is rare for them to coexist in the same patient. In a new case report, however, investigators outlined their experiences treating one such case.

Their report was published in BMC Neurology.

The case centers on a 24-year-old man who was diagnosed with anti-α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor AE. The AMPA and NMDA receptors mediate excitatory neurotransmission in the brain, explained the study authors.

The case began with an MG diagnosis. The patient had no history of previous autoimmune disease when he first sought medical care for diplopia and eyelid ptosis. He underwent a neurological examination, an MRI of the brain, and cerebrospinal fluid (CSF) analysis, all of which were normal. He also underwent a test for MG-associated antibodies, and all were negative. However, single-fiber electromyography revealed jitter and decrement in the m. orbicularis oculi. His diagnosis was seronegative ocular MG, and he was given pyridostigmine (Mestinon) and oral prednisolone, which the investigators said led to improvement in his symptoms.

After 3 months, however, the patient returned. This time, his symptoms were more severe. The patient said he had short-term memory loss, behavior changes, fatigue, a depressed mood, and an unsteady gait. Another series of examinations followed.

“MRI of the brain showed leptomeningeal contrast enhancement, compatible with inflammation or vasculitis,” the investigators reported. “CSF examination showed pleocytosis with 63 mononuclear cells, normal protein, signs of intrathecal IgG [immunoglobulin G] synthesis (IgG index, 0.92; range, 0.80-0.91), and the detection of oligoclonal bands.”

The patient was started on acyclovir (Avaclyr), ceftriaxone (Rocephin), and methylprednisolone.

On his fourth day in the hospital, a CSF examination identified a strong reaction for AMPAR in serum and CSF, although tests for other autoimmune encephalitis antibodies were negative. Neuroinfection screenings also produced negative results, they said, and so acyclovir and ceftriaxone therapy was stopped.

An MRI on day 7 suggested limbic encephalitis, and so the patient was continued on methylprednisolone, but also treated with intravenous immunoglobulin and rituximab (Rituxan). The patient had a poor response and continued to deteriorate. He was moved to the intensive care unit, where on his 43rd day in the hospital he tested positive for NMDA receptor antibodies in his CSF and serum.

“Electroencephalography at that time showed diffusely reduced amplitudes but no sign of status epilepticus and no focal abnormalities,” the authors said.

After being sedated and ventilated, the patient became stable and had an initial favorable response to treatment. However, his psychiatric symptoms then increased, prompting a transfer to the hospital’s Psychiatric Department. He was then put on third-line immunosuppressive treatment and continued with cyclophosphamide pulses once a month for 6 months. The patient gradually improved and was transferred to a neurorehabilitation unit after several months. At his 1-year follow-up, the patient had almost completely recovered, but there were some lingering issues, including moderate reduced verbal and nonverbal episodic memory, slightly impaired executive abilities, and the need for a highly structured daily routine. The patient, an engineering student, was eventually able to return to his studies.

The study authors said the case shows that AE can coexist with other autoimmune disorders.

“Patients with seronegative MG, including ocular MG, may develop autoimmune encephalitis with more than 1 cell-surface antibody,” they concluded.

Reference

Schäfer J, Christensen PB, Jensen K. AMPA and NMDA receptor antibody autoimmune encephalitis preceded by ocular myasthenia gravis: a case report. BMC Neurol. Published online March 10, 2023. doi:10.1186/s12883-023-03129-2