>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
