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Parkinson Disease – Pathophysiology And Causes

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Parkinson Disease

Parkinson disease is a progressive degenerative disease that was first described in 1817 by the English neurologist James Parkinson, who named it agitated paralysis. Parkinson disease is a idiopathic neurological disorder.

Disease onset usually occurs between 50 and 65 and affects 1% of the population older than 60 years and over 6% of the population aged between 74 and 80 years. Parkinson disease is more common in men, sex ration being 1.5/1 for males . Onset before age of 40 years is very rare. Parkinson disease incidence is 200 cases per 100,000 inhabitants and has a lower frequency in Asia and Africa.

Parkinson Disease Pathophysiology

Major anatamopathologic aspect of Parkinson disease consists in the disappearance of pigmented dopaminergic neurons in substantia nigra (pars compact), especially in the ventro-lateral part which projects into the putamen. On section, this structure appears pale and depigmented. The normal concentration of dopamine in the putamen and caudate nucleus, the so-called neo-striatum dopaminergic pathway, is decreased by approximately 80% in Parkinson disease, which underlies dopamine precursors therapy. Approximately 60% -80% of dopaminergic neurons are lost before the clinical onset of symptoms.

Parkinson Disease

Parkinson Disease

In the remaining pigmented neurons are highlighted eosinophilic cytoplasmatic inclusions called Lewy bodies, which are considered by some authors the histological markers of Parkinson disease. However, Lewy bodies are not pathognomonic for Parkinson disease, because, beside the fact that Lewy bodies are found in all cases of Parkinson disease, they also occur in elderly individuals who do not have Parkinson disease and can be considered as a presymptomatic phase of the disease. Lewy bodies may also occur in postencephalitic parkinsonism, in some cases of Parkinson-plus syndrome or other rare diseases such as Hallervorden-Spatz disease. In cases of Parkinson disease associated with dementia, Lewy bodies were highlighted in the cortex (dementia with Lewy bodies). Lewy bodies contain alpha-synuclein, a protein found in the synaptic gap, and phosphorylated neurofilaments, phospholipids and cytoskeleton elements, different from Pick bodies and neurofilaments found in Alzheimer’s disease. The cause of substantia nigra cellular degeneration is not known.

Parkinson disease is not a disease that affects only the dopaminergic pathways, many other structures being depopulated. Thus, locus ceruleus, the main source of nonadrenergic innervation of the central nervous system and dorsal motor nucleus of the vagus nerve are usually depopulated. Lesions are found in nonpigmented cell groups of Meynert nucleus, which is the main source of cholinergic innervation of the neocortex, as well as in the unnamed substance, hypothalamus, mammillary bodies, the midbrain reticular formation and raphe dorsal nucleus (serotonergic innervation source). Injuries were also found in intermediolateral tract of the spinal cord (the origin of sympathetic fibers) and sympathetic ganglia. These disseminated lesions show that Parkinson disease is a multisystemic neurological disorder.

Parkinson Disease Causes

The exact cause of Parkinson disease is still unknown, but is hypothesized that most cases are the result of a combination between genetic and environmental factors.

Parkinson Disease

Parkinson Disease

Among the environmental factors that may be involved in development of Parkinson disease are mentioned:

  • Pesticides, rural life, exposure to herbicides and proximity to industrial plants;
  • In some cases was observed the development of parkinsonism similar to Parkinson disease, after self-injection of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridina), similar to chemical pesticides and herbicides. After exposure to this substance patients developed bradykinesia, rigidity and tremor, which improved after administration of dopamine precursors. It was assumed that some environmental toxin, similar to MPTP, could cause Parkinson disease, but until now no specific agent was identified;
  • The oxidative hypothesis states that free radicals resulting from oxidative metabolism of dopamine have a role in the development of Parkinson disease.

Heredity is not a major factor in the development of Parkinson disease, but researches suggest that genetic factors are very important when disease begins after age 50 years. In a small group of patients with Parkinson disease were noted mutation of alpha-synuclein gene, called PD1. These individuals were characterized by early age of disease onset (mean age 47.5 years), rapid progression (mean age at death  56.1 years), lack of tremor, and good response to dopamine precursors therapy.