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Introduction
Parkinson Disease (PD) is a very complicated neurodegenerative condition including the motor and non-motor manifestations that lead to neuronal loss. Currently, only symptomatic therapies are available but nothing is known yet to prevent this degenerative process. This is a multi-factorial condition with multiple risk factors that includes increasing age, genetic vulnerability, and environmental determinants. All these factors mutually play a role in the pathogenic process of PD. Medical sciences have achieved major advances in understanding the process working behind PD development that are Nigral Dopaminergic Apoptosis, Protein Mutation, Oxidative stress, mitochondrial dysfunctioning, and inflammation. Gene mutations observed in PD are rare familial forms and their functions overlap extensively in studying the sporadic cases of the degenerative process but this model has not been possible to study when translated to animal subjects (Rascol et al., 2002).
PD is known as the most prevalent neurologic condition that effects one percent of the population over the age of 60. The two major findings regarding PD are the destruction of pigmented dopaminergic neurons present in SNpc (Substantial Nigera parse compacta) and the existence of Lewi bodies. The main feature of PD starts silently and emerges gradually taking a span of weeks or months. Tremor is the most common and earlier clinical manifestation of PD. The three primary signs of PD are rigidity, resting trimmer and bradykinesia. Balancing impairments are also included in its cardinal feature which is mostly developed in advance stage (Benjamin et al., 2001).
The present essay aims to describe the Parkinson disease, its pathophysiology, epidemiology, etiology, prognosis, prevention, and management.
Epidemiology
According to the report of Parkinson’s disease Foundation around 60,000 Americans are suffering from this neurodegenerative condition and still there are many that remained undiagnosed (Benjamin et al., 2001). The worldwide estimate is about seven to ten million people living with PD. A gender-based data revealed that men are 1.5 percent more prone to PD as compared to women. A review on PD epidemiology by Benjamin (2001), stated that 50/100,000 populace ratio was estimated for china while it was 657 for Argentina, 100 for North America and 250 for Europe. The social-economic determinants impact highly the prevalence of PD and its survival rate. The ethnic distribution of PD varies for different communities and races. According to Benjamin Europeans and North Americans show a high susceptibility towards PD that is hundred to three fifty per one hundred thousand populations. Asians and black Africans show a lower rate of PD incidence that is around one fifth to one tenth part of the white population. While mortality statistics observed for PD patients show that only thirty-seven percent cases of PD can be diagnosed as the leading cause of death. The data from 1962 to 1964 showed that mortality rate for US was two out of five hundred thousand among white men which is just half of non-white men (Benjamin et al., 2001). Moreover, the mortality rate is higher for people above the age of 75 as compared to people younger than the age of 70 (Parkinson's Disease Foundation).
Etiology
The etiology of PD is still not clear and its hypothesized that the environmental and genetic factors mutually stimulate the conditions.
Environmental Factors
The primary factors responsible for PD development are residing in a rural surroundings, pesticides and herbicides exposure, use of well water and living in the vicinity of any industrial plants. A case-control study showed that 33-80% PD cases were related to pesticide, herbicide or insecticide exposure (Pezzoli & Cereda, 2013).
Oxidation Hypothesis
According to Oxidation Hypothesis, the free radical generated from the oxidative metabolism of dopamine play a considerable role in the progression of PD. The monoamine oxidase (MAO) induced dopamine metabolism to produce hydrogen peroxide which if cannot be cleared sufficiently forms highly active hydroxyl radicals. The hydroxyl radicals directly interact with the lipids of cell membranes and causes lipid per-oxidation and cell destruction.
Genetic Factors
The genetic determinants for PD are of high importance when the disease onset age is below fifty. It is observed that PD shows the fifty percent sharing patterns of genes. An interesting fact of PD was that in a family of 592 persons, 50 had PD (Polymeropoulos et al., 1997). The responsible mutation in this condition was located at 4Q2123 band with ATOG substitution at Alpha-Synuclein genes. Overall three missense mutations are identified in this gene (Proukakis et al., 2013). According to a report, approximately eighteen loci are identified as PD linked mutations (SNCA, PRKN, LRRK2, ATP13A2, and PINK1) that are found associated with familial parkinsonism (Bekris, Mata & Zabetian, 2010). Other causes related to PD development are the conformational alterations of Alpha-Synuclein of lewi bodies and MPTP (1Methyl-4Phenyl-1,2,3,6-TetraHydroPyridine) intrusion to mitochondrial functions impacting the components of respiratory change.
Anatomy and Pathophysiology
PD is associated with Basal Ganglia that represent the accumulation of nuclei near the four brain base. The stratum is the nuclear complex of Basal Ganglia that acquired excitatory stimulus from the cerebral cortex. It also receives inhibitory as well as excitatory stimulus from dopaminergic cells of SNc. A set of direct and indirect pathways monitors the neuronal response of spiny neuron globus pallidus (GPi). GPi transmits inhibitory inputs towards the thalamic nuclei that are connected to the primary and supplementary motor spaces. The two main neuropathology assumptions for PD are the destruction of pigmented dopaminergic-neurons of SNpc and the existence of lewi-neurites. It is observed that around sixty to eighty percent of dopaminergic neurons are completely destructed before the emergence of PD. Lewi bodies are believed to depict the presymptomatic stage of PD which increases with age. The recent researches have revealed that lewi bodies are not limited to PD only as they are noticed in Hallervorden-Spatz disorder and several other disorders as well (Parkinson Disease: Practice Essentials, Background, Anatomy, 2016).
The two pathways functioning in Basal Ganglia circuit represents the altered functioning in PD pathophysiology where the output from the motor circuit is transported to the internal GPi and SNr (Substantia Nigeraparsereticulata). The inhibitory stimulus is forwarded to thalamo-cortical and impacts the movement. The lower striatal dopamine induction results in decrease inhibition of GPi SNr in the direct pathway. On the other hand in an indirect pathway, the lowered dopamine inhibition enhances the GPe inhibition causing the disinhibition of STn (Subthalamic nucleus). This elevated STn signal enhances the GPi SNr inhibitory output to the thalamus (Parkinson Disease: Practice Essentials, Background, Anatomy, 2016).
Prognosis, Diagnosis, Prevention, and Management
The diagnosis of PD is done on the basis of four major motor symptoms such as tremors, bradykinesia or slow movement, rigidity of limbs, neck and trunk and postural instability. Postural ability enables a person to stand upright in PD the person looses some essential reflexes required for an upright posture. This condition may result in a disbalancing and fall. Additionally, there are other secondary and non-motor symptoms that impact the PD patient. The secondary motor symptoms include freezing, expressionless face, micrographia (shrinkage in hand writing) and excessive accelerations. Other manifested symptoms may include dystonia, abnormal gross-motor coordination, lowered arm swing, speech problems, and difficulty in swallowing, sexual dysfunctions and drooling. The non-motor symptoms of PD include constipation, sleep and mood related disorders, orthostatic hypotension, vision and dental problems, depression, fatigue and anxiety (Parkinsons Disease Foundation).
There are multiple prevention and medication strategies for treating PD patients, although none has been successful in reversing the condition. The main challenge for PD patients is adherence to the medication regime and other recommendations by physicians. Mostly they need a caretaker that may be a family person or a health care professional to take care of therapeutic schedule as well as its outcomes. Mostly physicians prescribe dopamine agonists to PD patients. Moreover, other therapeutic agents include anti-cholinergics, COMT inhibitors and carbidopa therapy. Carbidopa or levodopa are the most potent recommended therapies for parkinsons which has set a breakthrough in medicinal history from 1960s. The addition of carbidopa in this therapy protects the levodopa conversion into dopamine. Sometimes physicians also prescribe antioxidants, vitamin C, vitamin E and nutritious diet as a preventive care to control the excessive production of free radicals which is a major part of PD progression. There are also surgical treatments available for treating PD and the most developed form is deep brain stimulation (DBS) in which the surgeon inserts the electrodes into the impacted brain regions with the help of MRI as well as neorophysiological mapping to place it accurately. An impulse generator is implanted near the collar bone that induces the electrical signals for the brain to stimulate motor functions (Rascol et al., 2002).
Conclusion
Parkinson Disease is a neurodegenerative disorder that has impacted a number of people. It is a condition that can neither be predicted or prevented nor cured to the reverse phase. The world famous boxer Muhammad Ali and first U.S. attorney general Janet Reno have been the victim of PD who faced multiple challenges associated with PD. They both started feeling the difference while shaking hands which they ignored but finally diagnosed with PD. Antioxidants are suggested as it has a potential to reduce the free radical development that may reduce the risk, but any accurate and 100% efficient preventive measure could not be identified yet.
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