Why Does the Prednisone Work?
I keep hearing debates about what actually causes HE. Thinking about it from another angle, why does the Prednisone work to suppress HE?
**After reading this post over, I realized this post is truly a stream of consciousness. I’m not sure it will make sense to anyone but me. So, sorry if this makes no sense.
Prednisone works from 2 possible directions: it suppresses the production of antibodies, and it reduces inflammation.
There is a lot of debate about what the antibodies are doing to cause the neurological problems. Are the antibodies themselves causing the HE or is the body’s response to the existing antibodies causing the HE?
In my case, I showed no signs of inflammation even in the most acute stages of my illness (in blood and scans). I find this to be strange. Swelling is the body’s natural response to damage after all. However, most people diagnosed with HE do not show signs of inflammation. Maybe the body doesn’t realize it is being damaged in a way that it would normally respond with inflammation.
So if there is no sign of an inflammatory process in most people, then is it really that reasonable to conclude that the neurological symptoms are a result of the body’s inflammatory response to the existence of the antibodies?
Wouldn’t it seem more likely that the antibodies themselves are actually attacking the brain, causing the neurological problems?
In the study, Anti-thyroperoxidase antibodies from patients with Hashimoto’s encephalopathy bind to cerebellar astrocytes, states “In immunofluorescence assays on monkey brain cerebellum sections, both HE patients’ sera and anti-TPO monoclonal antibodies (mAb) were able to bind cerebellar cells expressing glial fibrillary acid protein. Normal human astrocytes from primary cultures also reacted with anti-TPO mAb. Specific astrocyte binding of anti-TPO aAb suggests a role of these aAb in the HE pathogenesis.”
The glial fibrillary acid protein (GFAP) has a role in the functioning of the blood brain barrier. Disease related to GFAP is thought to interfere in astrocyte interactions with other cells as well as a possible inability to maintain the blood brain barrier.
So if the anti-TPO antibodies are binding to the cerebellar cells expressing GFAP, those cells might be interacting unusually with other cells and compromising the BBB.
HT -> results in overproduction of anti-thyroid antibodies -> intrathecal synthesis of autoantibodies into CSF -> anti-TPO antibodies bind to cerebellar cells -> possibly causing neurological symptoms
It appears that the antibodies are possibly directly responsible for neurological symptoms of HE. If true, this would serve to confirm that HE is a specific disease.
The question is what is allowing the antibodies through the BBB into the CSF so they can wreak havoc on our brains? In recent research it seems that although there is high prevalence of anti-thyroid antibodies in the serum of the normal population, those antibodies do not normally appear in the CSF of the normal population.
It appears that the process could be cyclic, that once the anti-TPO antibodies bind to the cells expressing GFAP it compromises the BBB. So the more antibodies that are binding would further compromise the BBB, possibly allowing more antibodies through the BBB. This would indicate that there should be a link between the level of the antibodies in the CSF and the severity of the symptoms.
If the antibodies are causing the problems, the Prednisone (or other steroids) would be working to suppress the production of these antibodies. This would be the primary benefit of the treatment.
Ending thoughts on this post:
This post was really a stream of consciousness. I made a lot of assumptions in order to make my conclusions. To me, this possible pathogenesis makes sense (and is based on a small number of recent studies). For someone with HE, the body’s autoimmune response creates an abundance of anti-thyroid antibodies (HT). These antibodies migrate into the CSF where they get to the brain and bind to the cells that regulate the BBB. Once these cells are compromised, they interfere with other cells, likely causing unusual neurological symptoms.
At this point, none of that is proven to be true. However, considering the efficacy of steroids in reducing the antibodies and thereby reducing symptoms, we should continue to search for a link between antibody levels in the CSF and the severity of the symptoms. This would be helpful in monitoring the treatment (for example when it would be safe to taper down the steroids). We should continue to develop safer treatments for reducing antibody levels in the CSF.