girija and others-
The little noticed study from St. Judes a month ago provides a partial explanation for at leas two and possibly three subtypes based on age at onset and the role of environment. Bear with me while I explain my reasoning.
The St. Jude team Found that spraying influenza H5N1 into a mouse's nose led to a ten-day progression along the route's described by Braak- nose to olfactory bulb and gastric wall to vagal nerve to brainstem to SN. This resulted in the activation of microglia and neuronal damage plus alpha-synuclein clumping, all leading to PD.
In short they showed that viral (and probably bacterial) impacts can trigger the immune system cascade that leads to PD. This cascade, once begun, requires, we are told, at least 20 years to prodce symptoms. If that 20 years was a firm figure, which it is not, then it would be possible to trace a 70 years old man's tremor back to a long-forgotten cold at the age of 50. This viral induction could explain the standard senior onset subtype of PD, the closest thing there is to "normal" PD.
However, there is another and far more elaborate cascade that would account for young onset. P.M. Carvey at Rush and J.S. Hong and Bin Liu have shown that there is another path leading to the same cascade described by the St. Jude team. Pre-natal exposure to bacterial endotoxins triggers the same cascade once puberty is passed. This would indicate first symptoms at about the age of 35 to 40 - young onset. The endotoxin also shows synergetic actions with various toxins, metals, etc. The fetal exposure also affects the endocrine stress response in a manner that might explain our unique relationship to same.
Finally, the third variety could result from a viral exposure at any age with a "plain vanilla" course of progression.
Note that this also accounts for the complexity of PD.
Quote:
Originally Posted by girija
Mainly, research seemed to confirm existence of subtypes. While other could not corraborate. Some even suggested there are no subtypes but just a representation of the various stages of disease progression and response to meds. This may be a viable explanation for some PWP, but I think that anyone who knows a few PWP would beg to differ on this.
Laura
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Laura,
Good point. To me, the basic classification of subtypes based on physical features of PD are tremor-dominant and rigidity dominant types. That is the first thing I noticed about PD (tremor vs rigidity) and is not a response to meds atleast during the early stages of PD. I just started reading about PD sub-types a few days ago and like you surprised by what I found out there.
Have you seen any studies that classify Tremor vs rigidity as the first order of classification??
Some time ago, there was a poll going on this subject, does anyone remember what the conclusions were?
Thanks
girija[/QUOTE]