> From: David Langridge <[log in to unmask]>
> >Dear David and others,
> >
> >David, you wrote in a mail long ago that you wished to know the
> >physiological causes of diph.dysk. I have often tried to find them. And
> >now, I for the first time found something that does not clarify the whole
> >problem, but makes a start. I found the text in: Ray L. Watts and William
> >C.Koller: Movement Disorders, Neurologic Principles and Practice: chapter
> >14: Pharmacological treatment of Parkinson's disease page 204;
> >Quote:
> >The emergence of response oscilations is usually associated with the
> >appearance of L-dopa induced abnormal involuntary movements. According to
> >their relation to L-dopa response cycles, they are commonly divided into
> >three main types:
> >a. "Peakdose" or "interdose" dyskinesias occur when there is a full L-dopa
> >motor response and are characterized by phasic ( choreic or ballistic)
> >asymmetric limb movements, but may also involve facial grimacing as well as
> >trunk and neck rotations
> >b."Biphasic dyskinesias are clincally linked to transition periods (onset
> >or wearing-off of benefit from an individual dose)and frequenly contain
> >phasic and dystonic elements
> >causing bizarr twisting movement of the trunk and extremeties. Again, limb
> >involvement
> >may be asymmetric.
> >c."Off-period dystonia occurs after the motor response has worn off and may
> >initially linked to the early morning hours ("early morning dystonia"). It
> >characteristically of unilateral distal painfull dystonic limb cramps, most
> >often involving one foot.
> >The exact pathophysiology of dyskinesias is not fully understood, but they
> >are probably related to striatal dopamine receptor changes after
> >dopaminergic denervation and chronic exposure to l-dopa, These receptor
> >alterations include changes of sensitivity, relative balance between
> >different receptor subtypes and different translational and neuromodulatory
> >system responses, The denervation induced imbalance between D1 and D2
> >receptor controlled direct and indirect outflow pathways appears to be
> >sustained by L-dopa, perhaps through its predominant action on the D1
> >receptor.
> >
> >This is a start. If I find more I'll inform you.
> >
> >Ida Kamphuis, Holland
> >
> >--------------------------------------------------------------
> >Vriendelijke Groeten / Kind regards,
> >
> >Ida Kamphuis mailto: [log in to unmask]
> >
> >
> IDA
>
> Thankyou for your research.I found the bit about receptors hard to
> understand but it at least gives more credence to this diphasic thing
> which SOME still doubt.I bet there are no end of unreported cases about
> simply because this problems with dyskinesia mainly occur some time after
> sinemet has been taken and a lot of people even those who should know better
> think that the symptoms are caused by pd rather than the drug.Keep up the
> good work.
>
> David Langridge
Hi
The first thing I read on PD after I was diagnosed was Dr.Harvey
Sagar's book " Parkinson's Disease " in which he explains dyskinesia
as occuring at max dopamine or peak dose ie too much dopamine . but
very interestingly he says this occurs 1/2 hour after taking L-dopa .
He also says that there is an end of dose dyskinesia for which he has
no explanation .
What he is describing in his peak dose dyskinesia is the first phase
of biphasic dyskinesia because the maximum concentration of dopamine
in the brain occurs 1 to 1 1/2 hours after taking the L-dopa . I
dont believe in peak dose dyskinesia except where the first and
second phase have run together . I sometimes get this effect when I
do not tke enough L-dopa . Too much L-dopa does not produce
dyskinesia but slight dizzyness .
Dr . Sagar along with much of the medical profession are twisting
the data to fit their theories . I believe that concentrating too
much on the different receptors etc. is not seeing the wood for the
trees .
peace
Alastair ( [log in to unmask] )
