In the news: exciting research findings about AE, PANS and PANDAS!

On a subject that you know is extremely important to me and to so many physicians, it is with great excitement that I share some important news and a brilliant video that discusses the mechanisms involved in Autoimmune Encephalitis (AE).

First, the news: Dr. Dritan Agalliu and the esteemed team at the Agalliu Lab, Department of Neurology at Columbia University Irving Medical Center have found that the olfactory route can be used as gateway to the central nervous system (CNS) by immune cells in an animal model.

And as you’ll see, the video very clearly explains and depicts these mechanisms and expands in visual detail upon the important research findings:

This latest study is especially significant in that we know infectious triggers are now recognized in post-COVID 19 with “diverse types of neuropsychiatric symptoms, such as encephalopathy, mood changes, psychosis, neuromuscular dysfunction, or demyelinating processes (that) may accompany acute viral infection, or may follow infection by weeks, months, or longer.” We invite to read more about this very subject in one of our recent blog articles as well that speaks to the links and impact on brain health.

The field of neuropsychiatry literally has been turned on its head with the current science of psychoneuroimmunology. And as more and more research has identified additional paths of disease initiation, evidenced further by the Columbia University findings, it also reinforces the critical need for early diagnosis and appropriate treatment in all neuro-specific and other autoimmune disorders.

Patients and their families simply cannot afford delays in receiving effective care – this not only prolongs their suffering, it certainly leads to disease progression that may be far more severe or irreversible. We see in our own practice the consequences of treatment delay in both pediatric and adult AE cases. It’s quite clear that without taking the right steps to tamp down the “fire” that attacks the brain, these misdirected immune responses just continue to wreak havoc on our neurological functions.

All of this points more than ever to just how imperative it is to obtain early diagnosis and proceed with treatment in AE and any autoimmune disease. Not only do these immune response mechanisms manifest in AE, but they also apply to every neurodegenerative disease from autism to Alzheimer’s. We MUST look for whatever sparked the misdirection in the first place in order to best treat our patients.   

The right treatment begins with understanding the disease mechanisms.

As exemplified in the Columbia University video, AE and similar disorders evolve as a result of several things that can compromise our immune defenses:

1.   AE refers to a group of autoimmune disease whereby the body’s immune system attacks the brain and triggers neurological and/or psychiatric symptoms.

2.   Post-infectious basal ganglia encephalitis (BGE) is a subset of AE that is initiated by infections (bacterial, fungal or viral). The basal ganglia are the brain’s structures responsible for motor movement, cognitive function, and behavior.

3.   How do recurrent infections lead to BGE?  
a.   Repeated exposures to infectious triggers such as Group A Streptococcus (GAS) causes the body to launch an immune response. The body then produces antibodies to fight the infection. But certain patients also produce AUTOANTIBODIES that subsequently attack healthy brain cells (and can also apply to whatever repeated exposure is triggering the immune response).

4.   How do these autoantibodies lead to brain problems? 
a.   Repeated GAS infections in the mucous membranes in the nose, throat, tonsils, etc. lead to the production of TH 17 cells and TH1 lymphocytes in the surrounding tissue; these are pro-inflammatory cells common in many autoimmune diseases. These cells then direct an immune response against host tissue.
b.   These inflammatory T-cells in the mucous membranes of the nose travel along the olfactory nerve and the cribriform plate to directly access the brain. This action stimulates the release of inflammatory cytokines that direct the microglia, our brain’s primary immune cells, to direct further immune activation in the brain. Cytokines are essentially signaling molecules that are released by cells and have a specific effect on the interactions and communications between cells. When something goes awry, this results in a cytokine storm.   
c.   This cytokine storm first triggers the breakdown of the blood-brain-barrier (BBB) by damaging the tight junctions in the BBB and also through a direct increase of endothelial cell transcytosis that travels through and across cells that line the BBB. It’s important to remember that the purpose of the BBB is to protect against circulating toxins or pathogens while at the same time allowing vital nutrients to reach our brain.
d.    Th17 lymphocytes also play a critical role in the breakdown of the BBB.
e.    These mechanisms can create a “leaky” BBB so that the autoantibodies and inflammatory immune cells enter the brain.

5.    Once the autoantibodies cross into the brain is when the onset of neuropsychiatric and/or neurological symptoms may begin.

The key takeaways.

It is patently clear that we must continue to investigate these processes to better understand the relationship of unrecognized communication between the CNS and the adaptive cellular immune response to infections.  

Through additional research of this CNS-immune response relationship, can we also identify how other neuro-autoimmune diseases, such as multiple sclerosis (MS), neuromyelitis optica (NMO), acute disseminated encephalomyelitis (ADEM) and other inflammatory diseases subsequently develop?

Identifying the root cause of any disease is always critical and the findings from this study support the importance not only of early diagnosis, but also the role immunomodulating therapy such as IVIg may play in treating these disorders.

We have to understand why the brain comes under siege by infection or other impacts - and what is it in our environment that may trigger inflammatory responses to the degree our brains are literally under siege? While PANS and PANDAS is seen most often in children, we know too that many adults are afflicted and often for years prior to diagnosis. But our patients, their loved ones and the communities we share are counting on all of us to find the answers and pursue the best protocols and treatment available. And as always, we are grateful to be part of this journey and your lives.

In health and with great hope,
Dr. Suzanne Gazda

Additional reading:
https://finance.yahoo.com/news/video-pandas-network-shows-infections-193000132.html

For more information about Agalliu Lab see:
http://columbiaagalliulab.org/

Visit our Helpful Links section for patient resources and support groups. https://www.suzannegazdamd.com/helpful-links.html

---