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]
