Autoimmune Encephalitis
By Jean McCaslin, RN IgCN Clinical Nurse Educator - May 23, 2024
Autoimmune Encephalitis (AE), also referred to as antibody-mediated encephalitis is a disorder that is easily confused with other neurological disorders. The initial presentation can range from acute to sub-acute, in patients of any age, with recent history of infective processes or cancers, or without, and further confounding diagnosticians.
In recent years, significant progress has been made in the research surrounding AE, improving detection and treatment. Rapid detection, differentiation, and early treatment have significantly improved outcomes. This nursing blog will ultimately highlight the types of AE that are shown most responsive to immune-based therapies.
Symptoms are variable for encephalitis of any type. They can include agitation, psychosis, ataxia, tremors, seizures, unusual limb movement, insomnia, or fever, to name a few. Many different physicians may be involved in the diagnostic and treatment team. Differential diagnosis can include infection, toxins, metabolic encephalopathy, mitochondrial disorders, vascular disorders, nutritional deficiencies, demyelinating disorders, malignancy, or movement disorders. Over time, autoantibodies have been identified that are linked to specific symptoms, positive testing and progression. Algorithms have been developed to assist physicians to rule-in or rule-out other disorders, as well as to hone-in on the types of AE most likely to respond to immunotherapies.
In recent years, scientists have learned through studying these autoantibodies that some launch intra-cellular attacks while others attack brain surface cells. This is an important discovery as early treatment is key in these disorders. Cell surface synaptic antibodies seem to be directly and specifically symptom causing and appear to respond well to immunotherapies. In contrast, intracellular AE seems to be linked with poorer prognosis.
The onset of AE is typically subacute, with symptoms developing over weeks to months. Neurological/neurocognitive symptoms progress over time and can include encephalopathy, cognitive difficulty, psychosis, and seizures. Some patients may present with brain-stem syndromes, dysautonomia, and movement disorders. The prevalence of AE is similar to infective encephalitis of 13.7 per 100,000.
Delayed treatment is one of the factors most consistently associated with poor outcomes with AE. A comprehensive work-up for AE typically includes bloodwork, lumbar puncture, EEG, and cultures (when infection suspected). As AE has been associated with certain cancers such as lung, breast, ovary, and testicular cancer, pelvic CT and/or sonogram, mammogram, PET or MRIs may be done. When the MRI or CSF are abnormal in the presence of newly diagnosed seizures, neurocognitive symptoms, or movement disorders, this is considered a diagnostic "red-flag".
Most importantly, autoantibody testing should be done to confirm if the AE is an intracellular or surface cell attack. This information is considered key in order to determine treatment.
As nurses, we may be involved in the infusions of IV antibiotics, steroids, or IVIG therapy as patients await a differential diagnosis. Others may perform plasmapheresis. It is important to understand the fear and uncertainly our patients are experiencing during this critical time. Even after a diagnosis has been made, response to any of these treatments is not guaranteed. For parents and children afflicted by AE, the anxiety is perhaps most devastating.
AE treatment depends on the underlying cause and symptoms and may include anti-infective medications to fight viral or bacterial infections, medications to control seizures, and immunotherapy such as plasmapheresis or IVIg.
One to two weeks after first-line therapy has been completed, patients may be treated with second-line treatment, such as rituximab, cyclophosphamide or a combination.
Maintenance therapy includes one or a combination of rituximab, IVIG, mycophenolate (CellCept®), Zidovudine (AZT), or cyclophosphamide.
In closing, early identification and differentiation of AE is critical. Supporting patients through the peril of frightening symptoms, exhaustive testing, a new and serious diagnosis, and ultimately the administration of immunotherapies is imperative. I encourage readers to further your knowledge on this fascinating topic; specifically, the multitude of autoantibodies associated with AE, as well as ongoing clinical trials on this topic. I have cited references.
Cleveland Clinic Journal of Medicine https://www.ccjm.org/content/88/8/459
The International Autoimmune Encephalitis Society has physician speaker videos on YouTube that are very informative as well. “Autoimmune Encephalitis Misdiagnosis” Eoin P Flanagan Mayo Clinic College of Medicine Rochester MN. It covers diagnosis as well as misdiagnosis and advances in MRI and new antibody discoveries.
