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starlight
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CH article--breaks down some useful points
« on: Jan 30th, 2008, 9:21pm »
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Thought maybe some might be interested in reading this article--I don't understand all the terms, but sounds like someone is doing some hard thinking trying to come up with a theory of cluster headache.  
 
 
http://jnnp.bmj.com/cgi/eletters/jnnp.2005.081158v1
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Re: CH article--breaks down some useful points
« Reply #1 on: Jan 30th, 2008, 9:24pm »
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Actually, it's a letter to an editor, not really an article but still it's worth reading.
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Re: CH article--breaks down some useful points
« Reply #2 on: Jan 31st, 2008, 7:06am »
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There's much about this I don't understand.... but I get the feeling this is more about an on-going argument among researchers than it is about actually looking for a cause of clusters.  
 
I will bet you that Dr. Gupta doesn't get along well with Dr. Ferrari...
 
Quote:
Unfortunately, this study [1] offers no mechanistic insight regarding cluster headache or any clue towards experiments that further shape our understanding. Science is a process; accretion of data in the absence of a central concept thwarts or impedes the process.

 
Gupta seems to be saying that collecting data is worse than useless unless one has preconceptions about what the data should say. I could be misinterpreting this, but it sounds like bullshit to me. He also rejects placing much importance on the results of neuro-imaging because "nothing can supplant careful thinking about the research question(s)." which makes me cynically suspect the pictures don't back up his theories.  
 
And some of the statements Gupta makes seem a little odd to me (at one point he seems to be saying clusters hurt more because we don't vomit like migraineurs do), but that could be due to my own ignorance.  
 
Another thing that makes me wonder what this is really about is that most of the references Gupta makes are to his own papers, some of which haven't been published yet.
 
But maybe I'm just in a bad mood...
 
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Kevin_M
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Re: CH article--breaks down some useful points
« Reply #3 on: Jan 31st, 2008, 8:06am »
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He also takes a different approach to CH than Goalsby and makes competing discussion for peripheral involvement rather than a hypothamalus/neural origin.
 
 
He seems to want a paradigm shift to consider his peripheral inclusion of primary involvement more in any "central concept", which he repeats considerably.
 
 
from the posted article:
 
Quote:
5. Therapeutic effect of oxygen and ergotamine and aggravation / precipitation by alcohol or nitroglycerine (glyceryl trinitrate) strongly indicate primary involvement of peripheral non-neuronal mechanisms.  
 
6. Prophylaxis with verapamil practically confirms a peripheral non- neuronal origin of cluster headache.

 
 
other letters of his:
 
Quote:
A pharmacological overview, therefore, finds but little in direct support for a central or brain neuronal origin of CH.  
 
Additionally, the case for a peripheral origin of CH appears to be logically defensible.  
 
 
[concerning gamma knife treatment]
More importantly, it unambiguously indicates that the source of origin of CH does not lie in the central neural axis (brain stem -- hypothalamic nexus).
 
[his opinion statement]
To elucidate further the pathophysiology of CH, a paradigm shift that squarely meets the challenge of the basic sciences involved is essential.  
 
http://jnnp.bmj.com/cgi/eletters/76/2/218

 
 
 
Quote:
Also, the striking immediate to short-term results of surgical procedures on the trigeminal nerve in the face of an intact central central neural axis, including the caudal trigeminal spinal nucleus with intact connections to spinal nerves such as the greater occipital nerve indicate a peripheral origin for the headache.  The critical limitations of therapeutic hypothalamic stimulation and of the pathogenetic extrapolations arising from such experimental management have been recently discussed at length [6]. Whereas CH is a strictly unilateral headache, functional and structural hypothalamic alterations [7] have not been shown to be lateralizing. The pathognomonic periodicity of CH is the main clinical feature that suggests a hypothalamic origin but in the absence of any neural / extra-neural lateralizing mechanism such a theory remains, at best, remotely plausible. in the first instance, should occur at all.  
 
If the hypothalamus is indeed the site of origin of TACs, it is not possible to explain the absence of salivation in disorders characterized by lacrimation and nasal congestion / rhinorrhoea; diffuse antidromic trigeminal nerve excitation also cannot explain the lack of salivation [5,8]. For this reason, surgery on the sphenopalatine ganglion as a definitive therapeutic measure does not appear rational; the results of such surgery as reported previously are also inconsistent [5,8].  
 
http://jnnp.bmj.com/cgi/eletters/76/3/301

 
« Last Edit: Jan 31st, 2008, 8:10am by Kevin_M » IP Logged
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Re: CH article--breaks down some useful points
« Reply #4 on: Jan 31st, 2008, 8:44am »
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So--what are these unspecified "peripheral non-neuronal mechanisms" of which he speaks?
 
Just askin'.
 
Best,
 
George
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Re: CH article--breaks down some useful points
« Reply #5 on: Jan 31st, 2008, 9:03am »
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Well, at least Dr. Vinod K Gupta writes a better Englisch than Dr. Ali Sultaneh.  Roll Eyes
 
 
                  smokin
 
 
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Re: CH article--breaks down some useful points
« Reply #6 on: Jan 31st, 2008, 9:22am »
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on Jan 31st, 2008, 8:44am, George_J wrote:
So--what are these unspecified "peripheral non-neuronal mechanisms" of which he speaks?
 
Just askin'.
 
Best,
 
George

 
Things like nitric oxide, calcium channel activity (and other ions), CGRP, substance P, endothelin, circulating histamine, interleukins, etc.  
 
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Re: CH article--breaks down some useful points
« Reply #7 on: Jan 31st, 2008, 9:35am »
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on Jan 31st, 2008, 7:06am, tommyD wrote:

And some of the statements Gupta makes seem a little odd to me (at one point he seems to be saying clusters hurt more because we don't vomit like migraineurs do), but that could be due to my own ignorance.  

 
I think he is saying that vomitting during a migraine can sometimes bring relief of that pain, but doesn't in cluster headache.  He also suggests that vomitting in CH might make things worse - not sure about the basis for that.  
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Re: CH article--breaks down some useful points
« Reply #8 on: Jan 31st, 2008, 10:27am »
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I googled this guy's name after reading this and I found an article he wrote in which he does say what he proposes--it's interesting.  Yes, he does disagree with Goadsby--but I wouldn't go so far as to call what he says "BS"--it does seem well thought out--not saying I agree--but the guy definitely seems to care about CH.  Let me try to find the article--if I don't get it up here now I'll have it up later.
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Re: CH article--breaks down some useful points
« Reply #9 on: Jan 31st, 2008, 10:33am »
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Here it is--it's a little weird to read b/c it's based on research that was done about someone who lost an eye, but anyway, if you can get through it he says what he proposes about CH--unless I'm wrong, and Lord knows someone on here will tell me if I am--I think he believes that it has to do with the eye and with abberations in cranial something or other--it's hard to read what he's saying and not at least think he may have a point.
 
http://www.biomedcentral.com/1471-2377/5/6/comments#201461
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Re: CH article--breaks down some useful points
« Reply #10 on: Jan 31st, 2008, 10:39am »
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Also, here's a letter he wrote to Goadsby:
 
http://jnnp.bmj.com/cgi/eletters/76/3/301
 
I take no position either way, plus this stuff isn't exactly easy reading.  Reading this stuff for me just gives me more information about the condition, and if anyone else finds it useful or food for thought, that is a good thing.
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Re: CH article--breaks down some useful points
« Reply #11 on: Jan 31st, 2008, 10:42am »
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one point he does make that I like is that he at least tries to address the issue of why CH are usually one-sided or as he puts it "locked in" (to that one side)--I know some people do switch sides and he knows that too--but he's just looking at that general characteristic and trying to understand it.
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Re: CH article--breaks down some useful points
« Reply #12 on: Jan 31st, 2008, 11:32am »
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Good to see someone kicking the tires and challenging the conventional wisdom.  
 
Personally, I think that hypothalamus activation is necessary, but not not enough to explain clusters.  So I usually cringe when I see someone explain clusters as a broken hypothalamus.  
 
Dr. Gupta seems to be more of a general headache guy than a CH specialist.  But he has some interesting food for thought. For example, atenolol is known to be useful in migraines. But it doesn't really cross the blood-brain barrier. So maybe it is acting peripherally.  He makes the same argument for verapamil ... verapamil does cross the BBB, but Gupta argues that it is so little and so slow that verapamil can't be acting on the hypothalamus.  
 
(edited to add this link, which suggests that verapamil does not cross the blood-brain barrier. So how does it act on the hypothalamus?)
 
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6SYR-3R38T KR-P&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=063fe0438db7fec2c42161c8a4a22b93  
« Last Edit: Jan 31st, 2008, 11:43am by monty » IP Logged

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Re: CH article--breaks down some useful points
« Reply #13 on: Jan 31st, 2008, 11:46am »
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on Jan 31st, 2008, 11:32am, monty wrote:
verapamil acting on the hypothalamus.

 
I don't think that has been any secret or been understood  
to work on the hypothalamus anyway.  
 
Thanks to the discussions of the 2003 convention being recorded,  
this was mentioned:
 
Quote:
The tiers of CH are the hypothalamus deformity at the top, followed by impaired  
pain modulation, and trigeminovascular system. When we treat CH with Imitrex,  
we treat at the trigeminal level. When we treat CH with verapamil, it is still at the  
trigeminal level.  When we treat CH with O2 it is still at the trigeminal level.  
Essentially, when we use the current available medications to treat CH,  
we are only treating the symptoms, not the cause.
 The cause lies in the  
hypothalamus and the challenge is to focus on formulating medications  
and procedures to treat the cause of CH.

 
 
 
 
« Last Edit: Jan 31st, 2008, 11:50am by Kevin_M » IP Logged
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Re: CH article--breaks down some useful points
« Reply #14 on: Jan 31st, 2008, 12:05pm »
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Thanks, that sounds reasonable as well.  
 
I am not saying that the hypothalamus is not an essential factor in CH.  Just that there is a bigger circuit or system involved.  
 
I wonder how many people (if any) get only phantom clusters with no severe pain?  If their hypothalamus misfires the way ours does, but the trigeminal is not compromised or susceptible, would they have clusters??
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