There is a great deal of research being done regarding the mechanisms of Parkinson's disease (PD) and possible targets for therapeutic cures. Yet, it is one of many conditions that remains incredibly hard to diagnose. PD patients are not typically diagnosed until the disease has progressed to 70-90% dopamine cell depletion when symptoms become observable in movement behaviors (Jankovic 2008).
By the time cell loss has progressed this far, it is very difficult to achieve a successful long-term treatment plan. Pharmaceuticals such as L-Dopa (Jubalt et al 2009) and rasagiline (Olanow et al 2009) are generally effective, but can lose their effect or cause dangerous side effects over time. Deep brain stimulation has been shown to be very effective behaviorally, but there it is an intense procedure which has occasionally been correlated with subsequent cognitive impairments (York et al 2008). Exercise therapies have also shown promise in recovery therapy, but have seemed more lasting in the peripheral nervous system than the dopamine system of the CNS (Goodwin et al 2009; Petzinger et al 2007; Muhlack et al 2007).
When it is so important to try to identify markers of PD before it progresses beyond our current ability to treat it in a lasting way, Dr. Ronald Postuma and colleagues out of Montreal, Quebec, Canada have identified REM sleep behavior disorder (RBD) as a possible indication of developing PD. RBD is the loss of muscle atonia that normally occurs during REM sleep, causing a person to thrash unconsciously.
Their study is a beautiful longitudinal representation of several patients diagnosed with RBD in the 1980s who developed either PD or dementia by 2004. Of their 17 final RBD patients, 6 (5m/1f) had developed PD and 11 (10m/1f) developed dementia.
The Postuma group suggests that there might be a discrete pathological condition specific to "RBD-then-neurodegeneration"which has different early manifestations than PD alone. A very interesting concept as RBD, dementia and PD are all distinctive in their Lewy body and ß-amyloid
deposition. If further study of the evolution of RBD into PD shows a strong correlation, this could be a giant leap forward in terms of PD diagnosis and early treatment. There may indeed be a distinct pathology to this progression or there may not be. In any case, this is a very important study in the field of neurodegenerative disorders, and I believe it is expecially important to get longitudinal studies like this one funded.
The staging model of PD developmnt proposed by Braak et al in 2003 proposes that the effects of PD begin in the olfactory area of the brain, spreading to autonomic and sleep-involved regions, and finally to dopamine loss in the nigrostriatal pathway and several downstream cortical pathways (Braak et al 2003). The Braak model, in conjunction with this new proposal from Postuma et al, leaves me wondering about Restless Leg Syndrome (RLS) as another possible indicator of PD.
The connection between RLS and PD is in dopaminergic transmission, as suggested by Dr. David Rye in 2004. A study by Tan et al in 2002 found that prevalence of RLS in PD patients was not significantly different from incidence in their healthy population, roughly 15%. The Tan study was not looking at progression of RLS into PD, however, so it is possible, as suggested in the Postuma study, that RLS-PD may have its own unique pathology.
To date, I have not found any longitudinal studies of RLS progressing into RBD or PD.
