Parkinson’s disease is a common neurological disorder. It affects approximately 1% of individuals over the age of 60 years. It cases a form of disability which is progressive. However, the disability can be slowed down but not halted by treatment (Hauser, 2013). Neuropathology findings in the disease include the loss of pigmented dopaminergic neurons in the region of the substantia nigra pas compacts. There is also the presence of Lewy bodies and Lewy neurites (Lee et al, 2009). In most cases of Parkinson’s disease, a combination of genetic predisposition and environmental factors has been implicated in the evolution of the disease in different individuals. In about 10% of cases of Parkinson’s disease, a genetic cause can be identified. This subset of patients includes those who develop symptoms of the disease at a younger age group. The motor features of Parkinson’s disease begin insidiously (Lee et al, 2009). These symptoms evolve slowly over a period of weeks or months. Tremor is the initial symptom. Some cardinal signs of Parkinson’s disease are recognized. They include resting tremor, bradykinesia and rigidity. However, a fourth cardinal sign is sometimes mentioned which is Postural instability. This postural instability is a late manifestation in Parkinson’s disease (Hauser, 2013), (Lee et al, 2009).
Tremor is the initial symptom that the patient presents with. When a patient presents with tremor, the clinician evaluates the patient according to the history they present with, coupled with physical examination (Heyn & Stoppler 2013). This is done to rule out other causes of tremor (Lee et al, 2009). It is important to rule out drugs, toxins or even trauma as etiologies of the disease. Imaging studies are done in order to rule out the differential diagnoses. Magnetic Resonance Imaging of the brain may be done to rule out an evolving cerebrovascular disease, space occupying lesions or even a normal pressure hydrocephalous (Hauser, 2013).
Anatomy of the Basal Ganglia
The Basal ganglia of the brain is the region where Parkinsonism affects. A good understanding of the disease will require some few words about the normal anatomy of the region of the brain which is affected by Parkinsonism (Hauser, 2013).
The Basal ganglia are a group of nuclei which are found at the base of the brainstem region of the brain. The striatum of the Basal ganglia comprises of the Caudate nucleus and the Putamen. Together, these two nuclei constitute the largest nuclear complex that the basal ganglia possess. The striatum gets input that is excitatory from the substantia nigra pars compacts. These inputs are received by the projection neurons of which some project directly to the internal part of the Globus pallidus. The Globus Pallidus is the major site of output stimulus to the basal ganglia. The other projections are to the external part of the Globus pallidus (Lee et al, 2009). This forms a pathway that is indirect and which leads to the subthalamic nucleus. Both the direct and the indirect pathways function in regulating the output of the neurons from the Globus Pallidus. This leads to provision of input that is tonically inhibitory to the nuclei of the thalamus that are projected to the primary motor areas and the supplementary motor areas (Heyn & Stoppler 2013) , (Hauser, 2013).
Pathophysiology of the disease
Two major neuropathology findings are commonly found in the disease condition of Parkinson’s disease. They include the loss the dopaminergic neurons that are pigmented in the region of the substantia nigra pars compacta. The other is the presence of Lewy bodies and Lewy neurites.
Loss of the dopaminergic neurons of the substantia nigra pars compacta is most prominently found in the region of the ventral part of the lateral surface of the substantia nigra. The clinical signs of Parkinson’s disease become evident when up to 60-80% of the dopaminergic neurons are lost (Lee et al, 2009).
Etiology
The etiology of Parkinson’s disease is still largely unclear (PDF, 2013). However, in most cases, there is a hypothesis that Parkinson’s disease manifests as a result of synergistic effect of a combination of genetic and environmental factors. About 10% of Parkinson’s disease cases have been accounted for by genetic causes (PDF, 2013).
Environmental Causes
Some environmental risk factors have been attributed to the development of Parkinson’s disease. They include extensive use of pesticides, consumption of well water, living in a rural environment and proximity to industrial plants or quarries (Hauser, 2013).
Genetic Factors
The importance of genetic factors in the development of Parkinson’s disease is not straight forward (PDF, 2013). It was theorized that if genetic factors were to be very important in the development of the disease, then the concordance in monozygotic twins who are ideally genetically identical will be greater than the concordance in dizygotic twins who share only 50% of their genetic makeup. However, Parkinson’s disease studies found a concordance rate that was similar among both monozygotic and dizygotic twins.
Point genetic mutations have been implicated in the development of Parkinson’s disease (PDF, 2013).
Epidemiology
Parkinson’s disease has been recognized as one of the most common neurological disorders. It affects approximately 1% of the population of people aged 60 years and above. Parkinson’s disease has been estimated to have an incidence of 4 - 21 cases per 100000 populations yearly. The incidence and prevalence rates are said to increase with advancing age with the average age of onset being 60 years. Parkinson’s disease is also said to be commoner in women than men with a ratio of 3:2.
The treatment options available for Parkinson’s disease include symptomatic treatment and neuroprotective (disease modifying) therapy. At present, however, there is no therapy that has been proven to provide neuroprotection.
The gold standard for the symptomatic treatment of Parkinsonism is Levodopa, coupled with Carbidopa. Carbidopa is a peripheral inhibitor of decarboxylase. It inhibits the decarboxylation of Levodopa to dopamine in the systemic circulation thereby making Levodopa more available for distribution into the central nervous system. The greatest benefit that Levodopa provides is the anti Parkinsonism effect it has for the motor signs and symptoms. In the short term, the side effects are few. However, long term use will lead to fluctuations in the symptoms which are described as the "wearing off" effect. There is also the reappearance of dyskinesia. It is said that once dyskinesia appears, it is problematic to resolve (Hauser, 2013).
A group of drugs, called Monoamine oxidase inhibitors have also been considered to be used in the initial treatment of the early stage of the disease. These drugs provide some symptomatic benefit. They also have fewer side effects (SIGN, 2010), (Lee et al, 2009).
A group of drugs known as Dopamine agonists provide moderate symptomatic benefit. They also slow down the development of dyskinesia when compared to Levodopa (SIGN 2010).
Current Research and prospects
Neuroprotective therapy is aimed at blocking or even reversing progression of the disease. If this materializes, it will be the ultimate cure for the disease as individuals who have developed symptoms of the disease will receive cure. This is the focus of current research (Stower & Watt, 2008).
Another prospect is the transplantation of dopamine neurons into the Putamen region of individuals with Parkinson’s disease. Results of the research showed that there was good clinical improvement in individuals younger than 60 years of age as opposed to subjects over 60 years of age. (Freed et al, 2001)
Moreover, in younger patients, the clinician needs to place a lot of emphasis on long-term treatment of the patient (Lee et al, 2009).
Non-motor symptoms are equally as important as motor symptoms in Parkinsonism. These symptoms include depression, hallucinations, orthostatic hypotension. Dementia, numbness, pain, erectile dysfunction, restless-legs syndrome and akathisia to mention just a few. Symptomatic treatment is given if any of these symptoms are noticed in the individual.
In conclusion, Parkinsonism is a common neurological disorder that essentially affects the elderly. The symptoms are progressive and they cause significant reduction in the quality of life of the individual. However, the disease can be alleviated by the administration of some drugs that provide symptomatic treatment. It is also important to note that the non-motor symptoms are equally as important as the motor symptoms (Hauser, 2013).
References
R Hauser (2013). Parkinson’s Disease. Medscape Reference. Retrieved on 2nd December, 2013 from <http://emedicine.medscape.com/article/1831191-overview>
A lee et al (2009). Parkinson’s Disease. Lancet Vol 373: 2055 - 66. Retrieved from http://doursat.free.fr/docs/HSS512F_F10/Lees_Hardy_Revesz_2009_Parkinson’s.pdf
S Heyn & M Stoppler (2013). Parkinson’s Disease. http://www.medicinenet.com/Parkinson’ss_disease/article.htm
SIGN (2010). Diagnosis and pharmacological Management of Parkinson’s disease. Scottish Intercollegiate Guidelines Network. Retrieved from < http://www.sign.ac.uk/pdf/sign113.pdf>
PDF (2013). What Causes Parkinson's?. Parkinson's Disease Foundation. <http://www.pdf.org/en/causes>
N Stower & R Watts (2008). Spheramine for Treatment of Parkinson’s Disease. Neurotherapeutics: The Journal of the American Society for Experimental NeuroTherapeutics. http://download.springer.com/static/pdf/406/art%253A10.1016%252Fj.nurt.2008.02.006.pdf?auth66=1386206244_db4e333100e249475d90e6d24bc5e41c&ext=.pdf
C Freed et al (2001). Transplantation of Embryonic Dopamine Neurons for Severe Parkinson's Disease. http://www.nejm.org/doi/full/10.1056/NEJM200103083441002#t=articleTop
