A Brief Primer of Parkinson's Disease
Parkinson's disease is a brain disease
Parkinson’s disease (PD) is a progressive neuromuscular disorder that has a mean onset of 55 years of age and affects about 0.15% percent of the population. The incidence of the disorder increases markedly with age. The disorder was first described on 1817 by James Parkinson in his “Essay on the Shaking Palsy.” In 95% of cases there is no genetic linkage and these cases are termed sporadic Parkinson’s disease, but in the remaining cases the disorder is inherited (Dauer & Przedborski, 2003). Secondary Parkinsonism can be induced by a number of drugs or disorders including dopamine antagonists, hypoxia, and brain tumors.
The Cause of PD
The etiology (cause) of PD is unknown but the neuropathological signs of the disorder are relatively well understood. The loops connecting the midbrain structures of the basal ganglia and the thalamus consist of both inhibitory and excitatory pathways that combine together to form two basic routes: a direct route that promotes actions (excitatory loops) and an indirect inhibitory route that decreases or inhibits actions. The two pathological characteristics of PD are: 1) the loss of the nirgrostriatal dopaminergic neurons and 2) the appearance of Lewy bodies. The loss of dopaminergic neurons means that a lack of the brain neurotransmitter dopamine is a hallmark feature of PD. The nirgrostriatal tract is one of the major brain projections involved in movement. However, the principal pathology of PD affects the dopamine-producing neurons in a brain area known as the substantia nigra pars compacta. Dopamine is produced by substantia nigra neurons from DOPA (which is also a precursor of melanin) and transported along the axons of these neurons to the striatum. With the onset of the symptoms of PD the dopamine levels in the putamen (another brain area that plays a role in movement) are depleted by nearly 80% with about a 60% loss of dopaminergic neurons in the substantia nigra (Fearnley, & Lees, 1991). As the disease progresses there is further loss of dopaminergic neurons in the basal ganglia. The loss of these neurons, which normally contain prominent amounts of darker neuro-melanin, produces the classic depigmentation of the substantia nigra in PD patients (the substantia nigra looks black due to high levels of melanin and low levels of dopaminergic neurons). The other hallmark feature of PD is the appearance of Lewy bodies which are intraneuronal inclusion bodies made up of protein. The accumulation of high levels of Lewy bodies leads to neuronal degeneration and to cell death in the brain. While the brain is capable of some repair it cannot repair a massive loss of tissue like say a deep cut in your arm is repaired. Once a substantial number of neurons die one cannot regain function.
The loss of dopaminergic neurons in the basal ganglia leads to the classic triad of symptoms found in PD: 1) tremor, 2) rigidity and 3) bradykinesia with affect both excitatory and inhibitory pathways in the basal ganglia (Forno, 1996). Tremors in PD include a fine motor tremor usually most pronounced at rest (resting tremor) but exacerbated with movement and the classic pill-rolling tremor. Rigidity consists of increased tone of muscles (passive movement of the arms or legs is difficult). Bradykinesia consists of reduced speed of most normal movements, especially fine motor control. Bradykinesia is also evident in the general lack of excessive movements, such as decreased expressive gestures, decreased facial movements, and a lack of facial expressions. This also results in a “shuffling gait” in PD patients where patients walk as if their feet are magnetized and stuck to a metal floor. Other symptoms include sudden cessation of movement (freezing), akinesia (difficulty initiating movement), and bradyphrenia (slowed thought). In later stages cognitive abilities also become affected and there is a high rate of dementia as the disease progresses (Forno, 1996). The movement disorder in PD can be sporadic at times as there is another subcortical route that is involved in gross motor movements that bypasses the basal ganglia via the cerebellum, so PD patients are sometimes able to walk or run normally in emergency situations. Treatment for PD often consists of dopamine agonists (medicines that enhance dopamine actions in the brain) and Levadopa which replaces it (Dauer & Przedborski, 2003).
Dauer, W. & Przedborski, S. (2003). Parkinson’s disease: Mechanisms and models. Neuron, 39, 889–909.
Fearnley, J.M. & Lees, A.J. (1991). Aging and Parkinson’s disease: substantia nigra regional selectivity. Brain 114, 2283–2301.
Forno, L.S. (1996). Neuropathology of Parkinson’s disease. Journal of Neuro-pathology and Experimental Neurology, 55, 259–272.
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