The initial interferon trials showed a dose dependent impact on efficacy, but when interferon is given earlier in the process the size of the dosage doesn't seem to matter as much? Any idea why this might be?
I was diagnosed with RRMS this past summer. Fifteen years ago, I had a severe case of arthritis throughout my body and was tested for many things but never had an MRI. As the weather warmed, my arthritis dissipated. Could this have been the onset of MS that went undiagnosed?
MS'ers with disability will note that when they get an infection their physical functioning deteriorates markedly and they often have a recrudescence of old symptoms due to the effect of a fever on the conduction of nerve fibres in previously damaged pathways. Because of this there is a theoretical risk that this may make MS progression worse.
We do know that common colds and infections can trigger relapses; this typically occurs in the 4 to 6 week period after the onset of the infection. As attacks are associated weakly with disease progression it is plausible that infections may make progression worse.
Re: "The initial interferon trials showed a dose dependent impact on efficacy, but when interferon is given earlier in the process the size of the dosage doesn't seem to matter as much? Any idea why this might be?"
The answer is statistical; the studies are not large enough or have sufficient power to show the dose effect in CIS. If the trials had 1,000s of subjects the dose response would be evident.
Re; "I was diagnosed with RRMS this past summer. Fifteen years ago, I had a severe case of arthritis throughout my body and was tested for many things but never had an MRI. As the weather warmed, my arthritis dissipated. Could this have been the onset of MS that went undiagnosed?"
Unlikely. It is very difficult for me to give personal neurological opinions on this blog for the simple reason that I don't have all the information at hand. We are however considering starting a web-based virtual clinic to do this. That is if you are interested.
When I am sick, for a few days to a week after the symptoms subside, I have a temporary increase in old symptoms. However this occurs even without a fever. Excluding the fever, do you know of any mechanism that could cause explain this?
Why is the CNS so poor at repairing the damage done by MS? I know in the early stages it's able to stimulate some repair, but it soon goes to seed. Why is that?
Re: "Why is the CNS so poor at repairing the damage done by MS? I know in the early stages it's able to stimulate some repair, but it soon goes to seed. Why is that?"
The million dollar question. I suspect that whatever causes MS is not eliminated and continues to do its damage. Eventually all the compensatory mechanisms get exhausted and progressive disease ensues. What is the cause? I wish I knew, but EBV must be up there with a good chance of being the culprit or at least a partner in crime.
I thought it was well understood that extensive astrogliosis, mostly in the spine where there is less room, inhibits remyelination and renders CNS cells more vulnerable to the destructive forces. Isn't it so?
In nerves in the rest of the body, the default pathway is regrow and repair.
In the nerves in the central nervous system the default pathway is not to regrow. Why is that so? as this outcome has evolved for a reason..well one can only speculate, maybe its all about connectivity and not wanting to changing wiring, maybe it could trigger pain.
However some of these stop-rewiring pathways are known and inhibitors of these inhibitory molecules are to be tried in MS. Others are less well advanced.
For making myelin the default pathway is repair and this occurs in MS. However this occurs less efficiently with age (see the blog for more details) and as damage continues then the supply of the repairing cells is exhausted.
Furthermore there are factors that prevent the immature myelin forming cells from maturing into myelinating cells. These need to be inhibited. A number of these factors are now known.
Once an astrocytic scar is formed as a repair solution, then this is a further barrier to replacing the myelin.
One of the biggest problems is that the disease process that drives the damage is not completely irradicated by many of the current drugs.
Could we have some comments on www.guardian.co.uk/society/2012/feb/18/fasting-protect-brain-diseases-scientists
It says that starvation causes more neurons to grow. Could it apply to MS too?
Makes me think all of us, MSers and others, should fast once or twice a week for better health. That happens to be a inherited belief here in India, which I never believed.
Re: "It says that starvation causes more neurons to grow. Could it apply to MS too?"
There is a whole science that has emerged on the effect of calorie-restriction and fasting and its effects on longevity or survival and neuroprotection. Some of the pathways that are activated by fasting are neuroprotective. May we can talk Mouse Doctor 1 & 2 into designing some animal studies to test this hypothesis? But then who is going to pay for the experiments? I estimate that they will come in at around £80,000. We will need a grant.
"Could we have some comments on www.guardian.co.uk/society/2012/feb/18/fasting-protect-brain-diseases-scientists"
It is sort of difficult to comment on this because the source is a media article based on a recent meeting report rather than a published paper. Without getting to the source it could be about anything, you know how the press get it wrong.
I seem to remember reporting on this type of work in the past but cannot find it on the blog. If you remember please let us know
However based on work in rodents where there was a suggesting that a binge and fast regime helped mice to surive longer the guys from the US also suggest that it can influence how nerves grow.
However lets us remember this is mice and if you put lab mice near a building site, it stresses MS-like disease away. Does living near a building site affect MS? Withdrawing food surely can be stressful to animals.
It is said in the news paper article that they waiting for human results. I would suggest that we wait and see if there is something in it before starving ourselves.
Prof G may want to give real advice on this I cannot.
Do colds make MS progression worse?
ReplyDeleteThe initial interferon trials showed a dose dependent impact on efficacy, but when interferon is given earlier in the process the size of the dosage doesn't seem to matter as much? Any idea why this might be?
ReplyDeleteI was diagnosed with RRMS this past summer. Fifteen years ago, I had a severe case of arthritis throughout my body and was tested for many things but never had an MRI. As the weather warmed, my arthritis dissipated. Could this have been the onset of MS that went undiagnosed?
ReplyDeleteRe: "Do colds make MS progression worse?"
ReplyDeleteUnfortunately, there is no data on this.
MS'ers with disability will note that when they get an infection their physical functioning deteriorates markedly and they often have a recrudescence of old symptoms due to the effect of a fever on the conduction of nerve fibres in previously damaged pathways. Because of this there is a theoretical risk that this may make MS progression worse.
We do know that common colds and infections can trigger relapses; this typically occurs in the 4 to 6 week period after the onset of the infection. As attacks are associated weakly with disease progression it is plausible that infections may make progression worse.
Why do you ask?
Re: "The initial interferon trials showed a dose dependent impact on efficacy, but when interferon is given earlier in the process the size of the dosage doesn't seem to matter as much? Any idea why this might be?"
ReplyDeleteThe answer is statistical; the studies are not large enough or have sufficient power to show the dose effect in CIS. If the trials had 1,000s of subjects the dose response would be evident.
Re; "I was diagnosed with RRMS this past summer. Fifteen years ago, I had a severe case of arthritis throughout my body and was tested for many things but never had an MRI. As the weather warmed, my arthritis dissipated. Could this have been the onset of MS that went undiagnosed?"
ReplyDeleteUnlikely. It is very difficult for me to give personal neurological opinions on this blog for the simple reason that I don't have all the information at hand. We are however considering starting a web-based virtual clinic to do this. That is if you are interested.
When I am sick, for a few days to a week after the symptoms subside, I have a temporary increase in old symptoms. However this occurs even without a fever. Excluding the fever, do you know of any mechanism that could cause explain this?
ReplyDeleteRe - "Why do [I] ask?"
ReplyDeleteI think colds make my MS progression worse. I honestly do.
Hey MouseDoc,
ReplyDeleteHave you considered expanding your collection:
http://www.giantmicrobes.com/us/products/kissingdisease.html
(not meant as an advert, but delete if you want)
Sounds like the idea present for G
ReplyDeleteI meant to say Ideal
ReplyDeleteI had to look up this meaning http://www.urbandictionary.com/define.php?term=man+flu
ReplyDeleteProf Mouse should be more sympathetic
Why is the CNS so poor at repairing the damage done by MS? I know in the early stages it's able to stimulate some repair, but it soon goes to seed. Why is that?
ReplyDeleteRe: "Why is the CNS so poor at repairing the damage done by MS? I know in the early stages it's able to stimulate some repair, but it soon goes to seed. Why is that?"
ReplyDeleteThe million dollar question. I suspect that whatever causes MS is not eliminated and continues to do its damage. Eventually all the compensatory mechanisms get exhausted and progressive disease ensues. What is the cause? I wish I knew, but EBV must be up there with a good chance of being the culprit or at least a partner in crime.
Re "The million dollar question."
ReplyDeleteI thought it was well understood that extensive astrogliosis, mostly in the spine where there is less room, inhibits remyelination and renders CNS cells more vulnerable to the destructive forces. Isn't it so?
In nerves in the rest of the body, the default pathway is regrow and repair.
ReplyDeleteIn the nerves in the central nervous system the default pathway is not to regrow. Why is that so? as this outcome has evolved for a reason..well one can only speculate, maybe its all about connectivity and not wanting to changing wiring, maybe it could trigger pain.
However some of these stop-rewiring pathways are known and inhibitors of these inhibitory molecules are to be tried in MS. Others are less well advanced.
For making myelin the default pathway is repair and this occurs in MS. However this occurs less efficiently with age (see the blog for more details) and as damage continues then the supply of the repairing cells is exhausted.
Furthermore there are factors that prevent the immature myelin forming cells from maturing into myelinating cells. These need to be inhibited. A number of these factors are now known.
Once an astrocytic scar is formed as a repair solution, then this is a further barrier to replacing the myelin.
One of the biggest problems is that the disease process that drives the damage is not completely irradicated by many of the current drugs.
Could we have some comments on www.guardian.co.uk/society/2012/feb/18/fasting-protect-brain-diseases-scientists
ReplyDeleteIt says that starvation causes more neurons to grow. Could it apply to MS too?
Makes me think all of us, MSers and others, should fast once or twice a week for better health. That happens to be a inherited belief here in India, which I never believed.
Re: "It says that starvation causes more neurons to grow. Could it apply to MS too?"
ReplyDeleteThere is a whole science that has emerged on the effect of calorie-restriction and fasting and its effects on longevity or survival and neuroprotection. Some of the pathways that are activated by fasting are neuroprotective. May we can talk Mouse Doctor 1 & 2 into designing some animal studies to test this hypothesis? But then who is going to pay for the experiments? I estimate that they will come in at around £80,000. We will need a grant.
"Could we have some comments on www.guardian.co.uk/society/2012/feb/18/fasting-protect-brain-diseases-scientists"
ReplyDeleteIt is sort of difficult to comment on this because the source is a media article based on a recent meeting report rather than a published paper. Without getting to the source it could be about anything, you know how the press get it wrong.
I seem to remember reporting on this type of work in the past but cannot find it on the blog. If you remember please let us know
However based on work in rodents where there was a suggesting that a binge and fast regime helped mice to surive longer the guys from the US also suggest that it can influence how nerves grow.
However lets us remember this is mice and if you put lab mice near a building site, it stresses MS-like disease away. Does living near a building site affect MS?
Withdrawing food surely can be stressful to animals.
It is said in the news paper article that they waiting for human results. I would suggest that we wait and see if there is something in it before starving ourselves.
Prof G may want to give real advice on this I cannot.
The full text of the article is available free (in case you are interested). It doesn't talk about MS
ReplyDeletehttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2622429/
Thanks.
ReplyDeleteThe important issue is the human studies have yet to be done in a controlled way