Talk:Huntington's disease/GA5

GA Review
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Great to see an article nominated on such an important disease. I'll make more comments after a thorough reading, but here are my first reactions:
 * The lead does not do a good job of explaining the disease to the lay reader -- it doesn't create a mental picture of what happens to somebody with Huntington's, i.e., it can start at any age, and typically starts slowly, with small unexpected jerks of some body part or something like that. These get steadily worse over time until the nature of the disease is obvious.  In the early stages the symptoms are purely motor, but in later stages dementia sets in and the result becomes somewhat like Alzheimer's disease.  And so on.Looie496 (talk) 02:44, 5 April 2009 (UTC)
 * Better?--Garrondo (talk) 15:13, 5 April 2009 (UTC)
 * Satisfactory. Looie496 (talk) 15:41, 26 April 2009 (UTC)


 * Also the lead should say more clearly that the disease runs strongly in families -- if a parent has it, any child has a 50% chance of having it. The info is there, but it should be made easier to grasp.Looie496 (talk) 02:44, 5 April 2009 (UTC)
 * Done.--Garrondo (talk) 15:13, 5 April 2009 (UTC)
 * Okay. Looie496 (talk) 15:41, 26 April 2009 (UTC)


 * The section of cellular pathology doesn't quite match my understanding. As I understand it, in the early stages the main pathology is loss of neurons in the basal ganglia, and in the later stages there is also massive loss of neurons in the cerebral cortex.Looie496 (talk) 02:44, 5 April 2009 (UTC)
 * I have expanded the list of areas affected to cover all those from the reference, this includes the cerebal cortex, but may have to wait till daylight to see how the rest of the section now fits ( and whether to include in the diagram ). L&there4;V 23:23, 5 April 2009 (UTC)
 * The current wording is good enough, I think. Looie496 (talk) 15:41, 26 April 2009 (UTC)


 * I haven't read thoroughly enough to know whether this is touched on, but I think the article should explain that Huntington's raises really thorny issues relating to genetic testing. Basically, if one of your parents has it, you have a 50% chance of getting it.  Should you have yourself tested, so that you know for sure? Looie496 (talk) 02:44, 5 April 2009 (UTC)
 * This is touched from two different perspectives: First one on the section of genetic testing; and explains the psyhological consequences and difficulties of genetic testing. It is also touched in the society section in the ethics subsections and talks about the ethical concerns around genetic testing (minors and unborn). Bests.--Garrondo (talk) 15:13, 5 April 2009 (UTC)
 * Okay. Looie496 (talk) 15:41, 26 April 2009 (UTC)

Continued
Picking up again after a bit of a hiatus. In addition to a bit of copy-editing:

Signs and symptoms:


 * After the disease process begins but before diagnosis... Isn't it true that with genetic testing, diagnosis can occur before any symptoms at all have appeared?
 * 2nd paragraph, a bit too much blue. I would favor not wikilinking "weight loss" and "malnutrition", since very few readers are likely to follow those links from this article.
 * There is evidence of cognitive dysfunction before the manifestation of motor symptoms. Always or only sometimes?
 * Psychomotor function, controlling muscles, perception and spatial skills, is also affected. This is a very fuzzy sentence, which needs to be made clearer.

More to come, hopefully soon. Looie496 (talk) 21:26, 20 April 2009 (UTC)
 * Hopefully addressed these points, but: third point was covered in first paragraph, so removed it, is the first para clear enough in this regard? L&there4;V 22:18, 21 April 2009 (UTC)
 * All look okay now. Looie496 (talk) 15:46, 26 April 2009 (UTC)

Genetics
This section badly needs an introductory paragraph written at a lower level. Many readers, even ones with some biological background, won't be able to decipher it, and consequently will miss facts necessary to understand the following section, for example what the abbreviations HTT and mHTT mean. It should be possible to sum up the bottom line in a way that makes sense to a reader who has a general understanding of what a protein is and how genes are transcribed into proteins. Looie496 (talk) 21:27, 23 April 2009 (UTC)
 * Have written a paragraph as a summary of the section, might have caused some duplication, but allows reader to skim or delve. L&there4;V 11:56, 26 April 2009 (UTC)
 * Very helpful. I did a copy-edit and fixed one small error:  it isn't correct to say that a gene is dominant, only that a particular allele is dominant for a particular trait. Looie496 (talk) 15:55, 26 April 2009 (UTC)

Mechanism
This section too needs some sort of overview. The key point is that mHTT produces its harmful effects by damaging cells first in the striatum, then also in other parts of the brain. With the current organization the reader has to wade through several highly technical paragraphs before reaching this basic fact, and even then it doesn't come through clearly enough.
 * Have added a summary, plus a hint at protein interactions for good measure. L&there4;V 09:56, 27 April 2009 (UTC)
 * Needed a serious copy-edit, but I think it's okay now. Looie496 (talk) 17:35, 28 April 2009 (UTC)

HTT function I regret to say that this whole paragraph is a complete hash. It has no organization and many of the sentences are vaguely worded.
 * !st attempt, I think beginning and end are better now, but I'm unsure how the deviation into animal models in the middle reads, I think it's necessary as there's less concrete results for humans, but maybe a seperate section for HTT in animal models might be a possibility. L&there4;V 10:30, 27 April 2009 (UTC)
 * This is better now, but I still have problems with the sentence that starts "There are differences in..." Are there really humans who have no HTT gene at all, as the sentence seems to be saying?  If not (as I suspect), this sentence needs to be clarified. Looie496 (talk) 17:35, 28 April 2009 (UTC)
 * I have checked the refs and what and changed the sentence accordingly. Absence of the gene has not been observed in humans; only its disruption in a single case.--Garrondo (talk) 07:26, 29 April 2009 (UTC)

Cellullar changes due to mHTT Also poorly organized. It seems like the last few sentences, starting with "Chaperone proteins...", are tacked on to a paragraph that was already complete. They need to be integrated better or else moved to a new paragraph.
 * Another attempt, hopefully haven't broken the facts, but will double check with refs if the flow is correct. L&there4;V 12:30, 27 April 2009 (UTC)
 * I've done a copy-edit of the revised paragraph, but there were a few parts I wasn't sure I understood, so this still needs to be checked. Looie496 (talk) 17:46, 28 April 2009 (UTC)

Macroscopic changes due to mHTT This part needs to bring out clearly that the greatest early pathology is in the medium spiny cells of the striatum, and that other sorts of damage show up gradually as the disease progresses.


 * This section also needs some text to connect the cellular manifestations with the symptoms. The basic story, as I understand it, is that the basal ganglia control behavior by maintaining a constant inhibition on all the motor systems involved in voluntary and habitual behavior, and that actions are executed by releasing this inhibition.  In HD, the damage to the basal ganglia causes behaviors and behavior-components to be released unpredictably and erratically, leading to chorea symptoms. Looie496 (talk) 21:55, 23 April 2009 (UTC)
 * I took a shot at handling this myself. I won't be offending if you're unhappy with any of the added material. Looie496 (talk) 15:57, 26 April 2009 (UTC)

Diagnosis
The lead here should point out that because a person with a Huntingtonian parent has a 50% chance of having the condition, the motivation for such a person to be genetically tested is very strong.

Clinical Instead of "abnormal movements", how about making this more concrete, e.g., unexpected and uncontrollable movements of some part of the body. It would also be nice to give an example or two here if possible.

Genetic This section is better written than most of the article. My only suggestion here is that there is no need to cite the same article eight times in a row.

Other parts okay with a bit of copy-editing. Looie496 (talk) 22:16, 23 April 2009 (UTC)
 * Have hopefully addressed above points. L&there4;V 14:53, 27 April 2009 (UTC)


 * Now happy with everything here except one sentence in Differential diagnosis: "A minority of causes of HDL diseases are known..." -- I don't understand what this means. Looie496 (talk) 18:03, 28 April 2009 (UTC)
 * Clarified...? L&there4;V 00:37, 29 April 2009 (UTC)

Management
I'm pretty happy with everything here except this paragraph:

"Although there are relatively few studies of rehabilitation for HD, its general effectiveness has been demonstrated in other pathologies such as stroke[33] or head trauma.[34] A multidisciplinary approach is key to limiting disability.[35] There is some evidence for the usefulness of physical therapy and speech therapy but more rigorous studies are needed for health authorities to endorse them.[36]"

Using reviews of stroke and head trauma to justify statements about HD constitutes original synthesis. The middle sentence misrepresents its source ([35]), which is a pilot study of rehab therapy that comes to tentative conclusions. The last sentence is okay. Looie496 (talk) 22:24, 23 April 2009 (UTC)
 * I understand the critique: The explanation is that it was copied from the multiple sclerosis article. The OR is not mine; but of review articles on Multiple sclerosis that propose rehabilitation even if there are no studies that prove its efficacy for multiple sclerosis since it works in other diseases (stroke or head trauma). I can look for reviews on rehabilitation in HD and I will try to improve the paragraph. Bests.--Garrondo (talk) 14:43, 27 April 2009 (UTC)
 * Changed into Although there are relatively few studies of rehabilitation for HD there is some evidence for the usefulness of physical therapy and speech therapy but more rigorous studies are needed for health authorities to endorse them. A multidisciplinary approach may be important to limit disability. I have tried to give less importance to the pilot study; but if we consider that it is still too much I would neither mind to simply eliminate the last sentence and its reference and leave only the first one. Bests.--Garrondo (talk) 07:28, 28 April 2009 (UTC)
 * I'm happy with the whole section as currently revised. Looie496 (talk) 18:08, 28 April 2009 (UTC)

Prognosis
All looks good. Looie496 (talk) 18:16, 28 April 2009 (UTC)

Epidemiology
Looks okay with some minor copy-editing. Looie496 (talk) 18:16, 28 April 2009 (UTC)
 * Do you mean it needs more copy editing ( other than the copy ed you did (thanks))? L&there4;V 00:40, 29 April 2009 (UTC)
 * No more needed that I can see, sorry for lack of clarity. Looie496 (talk) 00:48, 29 April 2009 (UTC)

History

 * I have doubts about the Salem Witch Trials stuff. The first source is not high-quality, and I can't access the second one, but hunting around on Google Scholar I find essentially nothing to substantiate this idea.  I'm open to being convinced that this belongs but haven't yet been able to see why.  Everything else looks okay with a bit of copy-editing. Looie496 (talk) 18:43, 28 April 2009 (UTC)
 * It's you that has done the convincing -couldn't find anything concrete either so we'll leave speculation to the salem witch trials article, I don't think it added to article anyway. Removed L&there4;V 23:56, 28 April 2009 (UTC)

Society and Culture
Everything here looks okay to me. Looie496 (talk) 18:43, 28 April 2009 (UTC)

Research directions

 * I don't understand what "Neurochemically induced mice or monkeys were first available" means. What is a "neurochemically induced mouse"?

The rest looks okay. Looie496 (talk) 18:57, 28 April 2009 (UTC)
 * Have clarified, with a little copy ed in following sentences for good measure. L&there4;V 00:22, 29 April 2009 (UTC)

Images
I don't really feel that the images of tetrabenazine and aspiration pneumonia contribute anything to this article. All the others are okay. Looie496 (talk) 18:57, 28 April 2009 (UTC)
 * I would not say they do not add anything... They probably add much less than other images, but as this article is quite hard to illustrate my point of view is that they are better than nothing.Bests.--Garrondo (talk) 07:03, 29 April 2009 (UTC)

Summary
The article is thoroughly comprehensive, and the sourcing is excellent. Even after copy-editing the prose quality leaves something to be desired, but I don't think there is anything show-stopping. Once the issues I have identified are addressed, I will be ready to promote the article. Looie496 (talk) 18:57, 28 April 2009 (UTC)

Promoting
Okay, it looks like everything has come together, and I'm going to promote the article. Kudos to Lee and Garrondo for stepping up the plate and making all the changes I've called for. Looie496 (talk) 16:33, 29 April 2009 (UTC)
 * And thanks to yourself for the time and assistive edits, Looie496 ! :) L&there4;V 01:02, 30 April 2009 (UTC)