Hi,

This topic was broached under the Stalevo thread, but I think there has been sufficient interest to merit its own headline.

We discussed that Jankovic et al. at Baylor U had noted the clinical observation of two distinct subtypes of PD: Tremor-Dominant and Postural-Instability-Gait-Dominant.

Debi Brooks added that MJFF had funded research on subtypes and the potential impact they might have on clinical trials and treatments.

Based on additional questions and comments by Girija and Rick, I began to wonder whether there were any proof beyond clinical and PWP observation to the existence of PD subtypes, and I stumbled upon this research gem originally posted by Ann in Lyon:


At last, other works have largely confirm Braak's staging of LB-pathology in PD and added other considerations to the initial pattern with different morphological lesion patterns for the clinical subtypes of PD (Jellinger K.A).

a) The akinetic-rigid type shows more severe cell loss in the ventrolateral part of substantia nigra zona compacta (SNZC) that projects to the dorsal putamen than the medial part projecting to caudate nucleus and anterior putamen, with negative correlation between SNZC cell counts, severity of akinesia-rigidity, and dopamine loss in the posterior putamen. Reduced dopaminergic input causes overactivity of the GABA ergic inhibitory striatal neurons projecting via the "indirect loop" to SN zona reticulata (SNZR) and medial pallidum (GPI) leading to inhibition of the glutamatergic thalamo-cortical motor loop and reduced cortical activation.

b) The tremor-dominant type shows more severe neuron loss in medial than in lateral SNZC and damage to the retrorubral field A8 containing only few tyrosine hydroxylase and dopamine transporter immunoreactive (IR) neurons but mainly calretinin-IR cells. A8 that is rather preserved in rigid-akinetic PD (protective role of calcium-binding protein?) projects to the matrix of dorsolateral striatum and ventromedial thalamus. Together with area A10 it influences the strial efflux via SNZR to thalamus and from there to prefrontal cortex ".

This difference is noted in post-mortem analysis. Fascinating too is the research conducted by Mito, Yoshida, et al. (2005) Journal of the Neurological Sciences. Researchers scanned both PWP subtypes by SPECT and found that the PIGD dominant participants registered reduced blood flow in the anterior cortex, with no significant blood flow reduction in those who were Tremor dominant compared to the norm group. This, in turn, indicates there are different pathologies and neurochemical processes at work in each type.

This in part may explain why and how we experience PD so differently and hopefully leads to progress for much more effective treatments than what we now have. Girija had asked if these subtypes are now a first order of classification? I don't know if neurologists routinely classify newly diagnosed patients; I received a verbal reassurance from my MDS that because I presented with a tremor and that remained my main symptom that I had a "milder" form of PD. lol. as if this somehow lessens the blow. I do think that this research has exciting implications for refining diagnoses and helping us better understand what we're experiencing and to better chart a course of long term treatment. My neuros have done neither but here's' hoping that things will change; I'm left wondering where does the neurologist fit into all of this? Do any of them advocate on the need for change? PAN pressures lawmakers, we press for change with pharma and the research community, but who challenges the neurologist? I think I now need to respectfully start asking my doctors some of these questions.

Laura