Multiple Sclerosis Review?

[Steffen]

Hey all,
I just found this forum in the internet and wanted to take the chance to ask for some help.
I have to do a presentation on two papers (in the very very near future, so to say):
J.A. Bobholz et al., fMRI study of episodic memory in relapsing-remitting MS, 2006
Jeroen J.G. Geurts et al., Extensive Hippocampal Demyelination in Multiple Sclerosis, 2007

The thing is that this is an absolutely new topic for me and I was searching for a simple definition of MS. I'm especially interested in info about relapsing-remitting MS, i.e., what is so special about it, and some general info about what MS actually is and how the "simple" decline of myelin sheats impairs cognitive functions (in particular episodic memory). I would have suggested that only the transduction velocity would decrease and therefore some specific tasks would need more time to be solved, but this seems to be a very birdbrained idea. I read the papers in the hope they could inform me, but unfortunately they didn't. Further search in the internet couldn't provide me with nice texts about this, either.
Has anyone some good info to help me out? I'd really appreciate that
Thanks a lot in advance!

[Anand]

Hi Steffen,

Okay so there at least a couple of medicine students on the forum that could answer the questions on the definition of MS and whats special about relapsing-remitting MS much better than I can so I will leave that bit to them but I can explain the bit about the transduction velocity bit.

Okay so there is always this statement that myelination causes increased transduction velocity. But honestly what myelination really does is cause a decrease of membrane capacitance. Okay so this is a very physics like term. This decrease in membrane capacitance then contributes towards this increase in transduction velocity.

In an ideal neuron, when the current comes into the axon at the nodes of ranvier, the current spreads and when it reaches the next node it causes an action potential there. In real neurons though some of this current coming in is used up towards this capacitance so if you had large capacitance, less current could spread towards the next node and you would be less likely to generate a action potential at the next node.

Myelination as I mentioned decreases the membrane capacitance and thus less current is lost towards this and more goes towards spreading the action potential. In MS of course this myelination is lost and thus more current is wasted towards this capacitance and not enough current gets to the next node to bring that region to the threshold of action potential. As such, no action potential is generated and transmission is stopped and not slowed down.

I hope this helps with this question. I am in a bit of the rush at the moment. I might put in some other resources later.

[torinna]

Hello,

I am a medical doctor so I might be able to offer some information on MS in purely clinical terms. I don't know whether this will help any but here goes:

MS is a disease characterized by multiple symptoms and signs of brain and spinal cord dysfunction that are disseminated both in time and space.
Unfortunately, to my knowledge, there is no better definition- cause it really is an illness that presents in a variety of different ways and it's the pathology (inflammatory demyelination) which is the only sure hallmark of this disease.
A relapse is the appearance of a new neurological disturbance, and a remission is nothing other than an improvement of neurological function.
The relapsing-remitting course affects about 65-85% of all patients, and it's main feature is that relapses are well defined and separated by periods of recovery (with or without residual neurlogical impairment).

O.K, I hope this helped, at least a little bit
All the best 

[euglena]

Check out this article (especially the figures) for a good overview on MS.

http://www.medscape.com/viewarticle/459967


also:
http://www.emedicine.com/rc/rc/pimages/i24/s11/multiplesclerosis.htm

[Steffen]

Wow, I didn't expect that much, and in particular helpful, feedback in this short time. Thank you all 

So MS is even worse than I thought. It does not only slow down signal transduction but completely stops it. Appearing in a severe fashion in the spinal cord it could therefore lead to the offset of autonomous functions or paralysis (?). I mean, suppose the APs don't reach the end of the spine due to the high capacitance which has to be "filled". This could mean that possibly no signals arrive in the legs. Or MS could fully stop brainfunctions...

In relapsing-remitting MS it seems like the glial cells stop producing myelin sometime and after a recovery period(?) they just start producing again. Is there an explanation for that? To me, this sounds very strange. Like making a coffee break or something. Because the anew start of production shows that the cells are still capable of their duty, right?

offtopic: this forum seems very new (only 45 members yesterday). But I already like it and I hope discussions of this kind will be hold a lot.

[torinna]

Yeah, autonomic dysfunction is a very frequent symptom of MS, especially in the later stages of the disease. Usually it presents as bladder dysfunction (in the sense of urinary incontinence or urinary urgency). Frequently it is accompanied by sexual dysfunction.
Paralysis is, of course, one of the most frequent symptoms. It is, however, rarely complete. Unlike spinal cord injury which is likely to cause total paralysis (inability to move legs- at all), MS will almost never do that. Legs are more often affected than arms. The paralysis is of upper-motor-neuron type and frequently asymmetrical.

I hope this helps too
All the best

[Tatiana]

In relapsing-remitting MS it seems like the glial cells stop producing myelin sometime and after a recovery period(?) they just start producing again. Is there an explanation for that? To me, this sounds very strange. Like making a coffee break or something. Because the anew start of production shows that the cells are still capable of their duty, right?

@Steffen:probably you are done by this time with your presentation, but the topic is really exciting, so i just wanted to continue about RRMS. Ive heard couple of interesting things today concerning what you wrote in a passage above.

So, the first point is: there is a discrepance between clinical and subclinical activity in MS. in other words, there are many more lesions sometimes found in patients that had only little clinical manifestations, so demyelination does not always correspond to a relapse period.

Second thing is, i believe remission periods happen due to remyelination processes. Basically if you imagine brain of MS patient, there will be at any time areas where demyelination is going on, some areas where remyelination is going on, and in progressive disease also areas of cortical lesions. So probably when remyelination dominates in particular region responsible for a disfunction, patient experiences remission.

i hope this answers in part your question, though i don't know how exactly remyelination is happening.

[Steffen]

Today was my presentation and my prof complimented me on a good job. I wanted to thank all of you guys for your support 

I have not found any texts on de-/remyelination and remission periods (basically because I didn't search yet  ), but I thought about the remission right after I finished my presentation. What came to my mind is the following (please correct me, if I'm wrong in whatsoever):
The human antibodies are activated and attack the myelin around the neurons. One of the papers I presented claimed that these antibodies (they stained for them) are not found within demyelinated areas. So my assumption is that the oligodentrocytes and Schwann cells are all still intact but they are not able to produce enough myelin to compensate for the antibody attacks. However, when the antibodies are deactivated the glial cells have a chance to remyelinate the neurons up to the time, when antibodies get activated again. This could produce the relapsing-remitting time course.
A question concerning this, which I can't answer myself, because I have too little knowledge, is how long the remyelination would take and in which time intervals the relapses take place. If these are very different from each other my theory would fail 

Please keep in mind that this is only a guess, which came to my mind...

[euglena]

Antibody contribution to most types of MS is minimal.
Though immunoglobulins have been found in higher number in the CNS in some MS cases, fullfilling Koch's postulate, MS research so far has been pointed towards a Th1 (cell mediated) type disease.

[Steffen]

Ok, now I totally don't know, what you are talking about 
Every text I read concerning the definition of MS is about autoimmunity. Perhaps it's just a bad coincidence that I only read that kind of texts... What do you mean by saying "cell mediated"? A dysfunction in glial cells instead of an autoimmune attack on the myelin itself?

[Julian Neumann]

Th1 cell mediated does not mean that it´s not about autoimmunity...It´s just not about antibodies... It´s about the Cells of the immune system...

[Steffen]

Hm, it may be that I used the wrong word. In the study they stained for microglia and macrophages to which I wanted to refer with "antibodies" in my previous post. Sorry for that

[Julian Neumann]

Microglia and macrophages are indeed cells and not antibodies...
Antibodies are gamma-globulines which are produced by plasma-cells
and build complexes with antigenes...Macrophages "eat" these complexes, as they can build interactions with the constant chain of the antibodies...

[Julian Neumann]

[Steffen]

Although I don't know some of the terms and abbreviations I think I get the idea. Thanks a lot