Parkinsons Disease Case

Parkinson’s Disease

Presentation and epidemiology.

Parkinson’s disease (PD) is a common progressive neurodegenerative disorder characterised by the cardinal motor signs of resting tremor, bradykinesia, rigidity and in the later stages postural reflex impairment [J Jankovic]  . Numerous non-motor symptoms occur at all stages of disease, and in advanced stages cognitive and neuropsychiatric  symptoms often develop [J Jankovic]  It is the second most common neurodegenerative disease after Alzheimers [wildefeldt] and affects males more than females in a 3:2 ratio [wildefeldt]. Approximately 1% of the NZ population [CARADOC-DAVIES] are afflicted and over 7 million worldwide(Yao, Hart, & Terzella, 2013) with global projections estimate PD to surpass 9 million by the year 2030 [wildefeldt]. The disease becomes increasingly common as people age with average age of disease onset between 40-80 years of age [wildefeldt]. PD carries a two-fold increased relative risk for mortality [wildefeldt] and a 5 times increased risk to sustain fall-related injury [wildefeldt]].

 [CARADOC-DAVIES] – Is the prevalence of parkinsons disease in nz really changing

Etiological Risk Factors

The etiology of PD remains uncertain though there are considerable epidemiological relations suggesting a likely involvement of both genetic and environmental protective and risk factors [wildefeldt]..

There is strong evidence for an inverse relationship of PD with smoking habit (50% decreased risk) [wildefeldt]. , evidence for coffee consumption is moderate [wildefeldt]., and fairly moderate for ‘high serum uric acid concentration’[wildefeldt].]. Also light-moderate alcohol consumption may possibly confer a weak protective effect [wildefeldt].]

The greatest risk factor for PD is increased age [wildefeldt].]. Monogenetic causes are currently indicated in at least 5% of PD cases though this is likely to increase as research progresses. About 20 genes have been identified so far and new causal genes are being discovered at a rate of one every 3-6 months [RABIN]  . A familial component infers a 2-3% increased risk of developing PD in an individuals lifetime [wildefeldt].]. First degree relatives of PD patients have an ‘estimated two-fold to sevenfold increased relative risk for PD’[Shulman]. The vast majority of cases involve a genetic predisposition rather than monogenetic cause. This genetic predisposition when combined with environmental factors can lead to the development of PD, though there currently exists little information on gene-environment interactions [wildefeldt].]. Environmental factors seemingly associated with PD are herbicides and pesticides. There is conflicting evidence though generally pesticides showed a stronger and more consistent association, insecticides in particular [wildefeldt]. Dietary factors do not appear to contribute to PD though tentative evidence points to a detrimental effect in milk or dairy product consumption, particularly in men [wildefeldt].

[Shulman] – Parkinsons disease: Genetics and Pathogenesis 

[RABIN] - http://movementdisorderscenter.org/files/2013/06/2-Cause-and-Prevalence-of-PD.pdf

Pathophysiology

At a physiological level there is a neuropathological loss of dopamine producing cells in the substantia nigra pars compacta of the basal ganglia [BURKE]. This results in a loss of the neurotransmitter dopamine in the striatum and compromises upon its role in movement pathways; coordinating intention with body movement and controlling fine-motor function [BURKE].

Movement is modulated via the simultaneous actions of the direct and indirect pathways of the basal ganglia. The direct pathway helps to loosen an ‘inhibitory leash’ on thalamic activity, in doing so allows for a readily stimulated motor cortex and thus amplification of movement signals with intention [Galvez-Jimenez ]. When there is a dearth of the dopamine in the striatum as in PD, there is inadequate amount of dopamine to amplify the motivation for movement. Rendering the striatum incapable of adequately loosening the inhibitory leash on the thalamus hence muscle movements remain tuned down too much producing the typical bradykinesia and  rigidity of [Maria C Rodriquez].-.

In the same manner the indirect pathway is impacted upon in its capacity to attenuate excessive reductions in movement and modulate optimal activity for an intended task at hand [Galvez-Jimenez ], this is particularly announced during fine tuning movements [Maria C Rodriquez].-. Additionally the ability to prevent spontaneous unwanted muscle contractions is compromised leading to the production of involuntary muscle activity such as resting tremor and other dyskinesias [Maria C Rodriquez].

The onset of the hallmark cardinal signs of PD occurs once 50-60% of nigral neurons are lost and “about 80-85% of dopamine content of the striatum is depleted” [MAAROUF]. Advanced disease progression is characterised by postural and gait impairment, autonomic failure and cognitive

[MAAROUF] - Cerebrospinal fluid biomarkers of neuropathologically diagnosed Parkinson's disease subjects http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681206/ 

[Visanji] - The prion hypothesis in Parkinson's disease: Braak to the future. http://www.actaneurocomms.org/content/1/1/2 

Braak staging model for progression.

With the loss of neurons that project on the nigrostriatal pathway appear the formation of little clumps of proteins in the surviving neurons, called Lewy bodies[SHOBHA]. These are eosinophilic intracytoplasmic inclusions [SHOBHA] and the result of protein abnormalities or an aberrant protein degradation system[BURKE]. It is thought one of the mechanisms of cell death in PD is the accumulation of these toxic ‘waste’ proteins within the cell coming to impair cellular function and eventually resulting in cellular energy failure, and finally cell death [BURKE].