Brain wave signatures enable faster diagnosis of autoimmune encephalitis

L-R: Drs Mastura Monif, Nabil Seery and Robb Wesselingh

by Dr Loretta Piccenna

Researchers from the Neuroimmunology, Neurology, Neuroinflammation Laboratory led by Dr Mastura Monif in the Department of Neuroscience have identified electroclinical biomarkers that differentiate one particular type of autoimmune encephalitis (AE), known as N-methyl D-aspartate receptor (NMDAR) antibody-associated encephalitis (anti-NMDAR) from other subtypes of AE. 

AE is a brain inflammation disorder caused by antibodies. A person’s immune system mistakenly targets different proteins in their brain causing damage and inflammation. This can result in different neurological symptoms including seizures and memory problems. AE can be classified into different subtypes based on the brain protein targeted by the antibodies produced. 

The most common subtypes are anti-NMDAR autoimmune encephalitis, anti-LGI-1 autoimmune encephalitis and seronegative autoimmune encephalitis (in which there is no identified antibody). While treatment is effective and available, the diagnosis of AE is not straightforward. Also, knowing which patients need more intensive treatment is tricky. 

Dr Nabil Seery, a neurologist at The Alfred Hospital and 1st year PhD student in the Neuroimmunology, Neurology, Neuroinflammation Laboratory has recently published a review that summarises the latest research findings from the field, specifically for anti-NMDAR AE. Anti-NMDAR AE is one of the most commonly defined types of AE seen in young females around 21 years of age. However, it can occur in older adults (over 45 years) and in young children.

Dr Seery said, “Anti-NMDAR encephalitis can be treated using medications that selectively reduce components of the immune system, but as the illness is different from person to person, it is challenging to both diagnose and manage. Importantly accurate biomarkers that determine future patient outcomes or response to immune therapy are not fully understood.”

Patients thought to have AE usually have numerous clinical tests to confirm a diagnosis. The tests can include brain magnetic resonance imaging (MRI), an electroencephalogram (EEG), and taking blood or cerebrospinal fluid samples to analyse the presence of inflammation. EEG is a procedure that measures brain electrical activity (brain waves) by using electrodes placed on the scalp. It can show different patterns or irregularities depending on the person’s health state.

Dr Robb Wesselingh (a neurologist at The Alfred Hospital and 3rd year PhD student in Dr Monif's research group), who is the first author of a study published in Epilepsy & Behavior last month, together with his colleagues identified four specific brain wave signatures that were more common in anti-NMDAR AE compared to other AE subtypes. These EEG alterations were: a hemispheric EEG abnormality, a fluctuating EEG abnormality, superimposed fast activity and prevalence of an abnormality in more than 50% of the EEG.

In addition, the team also found that a disruption in the brain wave patterns in EEG (known as abnormal background) was associated with poor functional outcomes at the time of discharge of the patient from the hospital.

“The EEG is a non-invasive and commonly performed investigation. Using specific changes on the EEG to improve diagnosis and inform prognosis of autoimmune encephalitis can not only provide patients with more rapid and appropriate treatment, it can also aid our understanding of some of the underlying disease mechanisms,” said Dr Wesselingh.

Dr Mastura Monif, the senior author of the study, said that it was important for patients with suspected autoimmune encephalitis to have a diagnosis as soon as possible because earlier treatment leads to better long-term recovery. The research findings, she said, "will assist clinicians to perform a quicker diagnosis of the type of autoimmune encephalitis a person has and therefore could help provide a targeted treatment strategy. Also systematic usage of EEG could assist in predicting which patients are more likely to have functional disability in the future.”

On Monday 21 February, Dr Monif gave a free webinar to the International Autoimmune Encephalitis Society community about AE and treatments as part of Autoimmune Encephalitis Awareness Month. Tuesday 22 February is World Encephalitis Day, a day in which global awareness is created for people who have been directly or indirectly affected by encephalitis.

There is currently no Australian peak body, foundation or support network dedicated to autoimmune encephalitis. Dr Monif, lead investigator on the Australian Autoimmune Encephalitis Consortium, and Head of the Neuroimmunology Neuroinflammation and Neurological Diseases lab commented, “a lot of work is happening due to our hard working PhD students (Robb Wesselingh, James Broadley, Sarah Griffith, Tracie Tan, Nabil Seery, and Mohammad Amin), our dedicated research coordinator (Tiffany Rushen) and our 60 collaborators from around Australia. Autoimmune encephalitis is a global issue and hopefully some of the efforts from Australia will add to the global knowledge gain.”

The Australian Autoimmune Encephalitis Consortium is a nationally funded project through the Medical Research Future Fund that explores using both retrospective data, and a prospective trial of patients with autoimmune encephalitis with the goal to gain a better understanding of its mechanisms and clinical manifestations, to identify accurate biomarkers for improvements in diagnosis, to improve treatment options and ultimately to enhance patient outcomes/quality of life.

Shortly plain language summaries developed by the team will be made available for both publications on the Consortium website.

References

Nabil Seery, Helmut Butzkueven, Terence J. O’Brien, Mastura Monif. Contemporary advances in anti-NMDAR antibody (Ab)-mediated encephalitis, Autoimmunity Reviews, Volume 21, Issue 4, 2022, 103057, ISSN 1568-9972 Link: https://doi.org/10.1016/j.autrev.2022.103057

Wesselingh R, Broadley J, Buzzard K, Tarlinton D, Seneviratne U, Kyndt C, Stankovich J, Sanfilippo P, Nesbitt C, D'Souza W, Macdonell R, Butzkueven H, O'Brien TJ, Monif M. Electroclinical biomarkers of autoimmune encephalitis. Epilepsy Behav. 2022 Jan 28;128:108571. doi: 10.1016/j.yebeh.2022.108571. Epub ahead of print. PMID: 35101840.