I quite agree that this thread has generated thoughtful discussion with a variety of viewpoints and we’re all still struggling, as are the researchers, with understanding the phenomenon that is “MS”. Thanks for starting it Finn.
In light of the discussion about inflammation and neurodegneration and possible theories, I can’t help but bring up again the theory about HPA hyperactivity and MS. My non-scientific, non-medical background leads me to believe, rightly or wrongly, that this theory could explain some of the inflammation and neurodegeneration that’s evident in MS.
First, the theory,
The Role of the Stress Response Systems for the Pathogenesis and Progression of MS
Insensitivity to glucocorticoid and beta-adrenergic modulation might be involved in overshooting inflammation in MS, whereas hyperactivity of the HPA axis has been linked to neurodegeneration and increased disability.
HPA hyperactivity is roughly the equivalent of high levels of the stress hormone cortisol (as nearly as I can tell) and as the abstract indicates, high and increasing levels of cortisol have been linked to cognitive and physical disease progression in people with MS.
Now, that theory postulates insensitivity to “glucocorticoids”, as an explanation for overshooting inflammation in MS. But recent information suggests that the high cortisol levels in people with MS
(aka HPA hyperactivity) might itself invite inflammation
. The title of the following abstract is a good one, and the message is basically we all thought steroids were “anti-inflammatory” and it turns out that may not always be the case.An Inflammatory Review of Glucocorticoid Actions in the CNS
In recent years, the classic view that glucocorticoids, the adrenal steroids secreted during stress, are universally anti-inflammatory has been challenged at a variety of levels….
More recently, chronic exposure to GCs has been found to have pro-inflammatory effects on the specialized immune response to injury in the central nervous system. Here we review the evidence that in some cases, glucocorticoids can increase pro-inflammatory cell migration, cytokine production, and even transcription factor activity in the brain.
So, it seems high cortisol levels could theoretically account for the inflammation in people with MS, in addition to the “glucocorticoid insensitivity” mentioned in the abstract.
Now, on to the HPA hyperactivity (aka high cortisol levels) and neurodegeneration. It’s thought that in about about 50% of the individuals who experience depression (not MS research), it is the high levels of cortisol that precede and contribute to the depression, cognitive impairment and hippocampal atrophy (death of neurons)
. That idea is best illustrated on page 4 of this article:Depression, Antidepressants and the Shrinking Hippocampus
The following abstract presents some of the same info about cortisol. Association of Depression with Medical Illness: Does Cortisol Play A Role?
Data are strongest for a relationship between elevated cortisol and depression, hippocampal atrophy, cognitive impairment, abdominal obesity, and loss of bone density.
And, here’s another. Hippocampal Volume, Spectroscopy, Cognition, and Mood in Patients Receiving Corticosteroid Therapy
CONCLUSIONS: Patients receiving chronic corticosteroid therapy have smaller hippocampal volumes, lower N-acetyl aspartate ratios, and declarative memory deficits compared with controls. These findings support the idea that corticosteroid exposure appears to be associated with changes in hippocampal volume and functioning in humans.
Anyway, I find the whole “HPA hyperactivity” theory intriguing and thought it belonged in this “thread” since it appears that high levels of the stress hormone cortisol might be a factor in both the inflammation and neurodegeneration in MS.
Enough of that.
Raven and Bromley
—I’m thrilled to learn of your tremendous improvements with Campath. That’s wonderful news, I hope it continues well into the future and I wish you both the best.
—I was delighted to learn you’d have your hormone levels tested. You know I think everyone should consider physiologically balanced levels of all hormones. Here I highlighted some potential pitfalls of high cortisol levels, but there’s plenty of pre-clinical evidence suggesting several hormones (DHEA, estrogen, progesterone and testosterone) have significant neuroprotective properties that might be relevant to better managing the MS disease process.
Minocycline appears to offer great neuroprotection as well. I’m sorry and surprised it’s not readily available in Finland.
Take care all. I’ve enjoyed the perspectives and ensuing discussion. "De-stress"