Parkinson’s Disease: Etiology, Symptoms and Treatment

Abstract
The paper illustrates that Parkinson’s disease is a chronic neurodegenerative disorder. It can be caused due to genetic or various environmental factors. The classical clinical features of parkinsonism is associated with the loss of dopaminergic neurons in the substantia nigra, part of the midbrain. Non-motor symptoms have drawn more attention in recent years compared to motor symptoms where non-motor symptoms can be diagnosed approximately 10 years before the diagnosis of Parkinson disease. Furthermore, there are no such treatments to halt or control parkinsons, but the introduction to levodopa and deep brain surgery have reduced the non-motor symptoms have provided a better quality of life to the patients.
Keywords: Parkinson’s disease (PD), Substantia Nigra,  Dopaminergic, Neurons, Levodopa, deep brain stimulation
Introduction to Parkinson’s Disease
Parkinson’s disease (PD) is a common and a complex neurodegenerative disorder that affects the movement, muscle control, motor system as well as other numerous functions of the body. It is called a progessive disorder as the symptoms get worse over time. It is a neurologic disorder as it affects the specific dopaminergic neurons in the substantia nigra (SNpc), a part of the brain. The deficiency of the dopaminergic neurons in the basal ganglia further results in the movement disorder classified by the motor symptoms where motor symptoms can be classified as tremors, slowing and stiffening in different parts of the body. Parkinson’s disease is named after British apothecary James Parkinson in 1817, who first described the illness through his paper An Essay on the Shaking Palsy. His paper explains how the disease progresses over time and explains the characteristics like resting tremor, diminished muscle strength and abnormal posture.

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Parkinson’s disease is a diverse and chronic disorder. The signs and symptoms of PD can be experienced differently by everyone. The hallmark symptoms of the parkinsons are rigid muscles, tremor, slowed movement, impaired posture and imbalance, speech changes and writing changes. There is no definite cure or treatment for the disease but medications can be slightly effective on the symptoms of the disease. According to the American Parkinson Association, nearly 60,000 people are diagnosed with Parkinsons every year. Approximately 1.5 million people in the US are living with PD and 10 million people world wide. Men are 1.5 times more commonly affected than women.
Etiology of the disease
Parkinson’s disease (PD) is the second most common disorder after Alzheimer’s disease. The common age of onset of PD is 60- 80 years. Scientists are not sure what causes PD but is believed to involve both environmental and genetic factors. People who are exposed to pesticides or have had prior head injuries are more likely to be diagnosed with the disease.
An important contribution was made by a neuroanatomist, Braak. He conducted his research on the postmortem brains of the people with PD using microscopic examination. He identified that lewy bodies can affect the patients without the signs of PD representing the primary stage of PD. Lewy bodies are the abnormal development of proteins in the nerve cells. Based on his research, Braak proposes a staging scheme of lewy pathology in Parkinson’s disease. In the earliest stage limited regions of the nervous system like lower brain stem, autonomic nervous system and olfactory brain regions (small sense) are affected. Dopaminergic substantia nigra is affected in the midway of the course. The later stages present the spread of the lewy bodies beyond the non-dopaminergic areas especially the cortex. This rapid increase of the lewy pathology later correlates with the development of dementia and refractory movement symptoms. The factors involved in Parkinsosn varies from person to person. Sometimes, PD appears to run in families. Genetic testing can be a powerful tool to uncover key molecular mechanisms that cause PD. About 10-15% of the individuals with PD are associated with a family history of the disease or tremor.
Scientists have studied the DNA of people with Parkinson’s and compared it to their genes. It is believed that dozens of gene mutations are linked to parkinsons. SNCA gene encodes the protein alpha-synuclein which was the first and important protein to be associated with the inheritance of the PD (Kalia & Lang, 2015). Inherited genetics, lifestyle choices and environmental factors collectively determine the cause of Parkinson’s disease.
Symptoms and course
The clinical features of Parkinson’s disease are the motor disorders in which Parkinsonism is defined by the presence of bradykinesia in addition to one motor sign, rest tremor, rigidity or abnormal posture. In the recent decades physicians have noticed the increase in frequency of nonmotor symptoms along with the motor symptoms (Rektorova, Aarsland, Chaudhuri, & Strafella, 2011).
Non-motor symptoms include excessive sweating, fatigue, mood disorders, sexual problems, sleep disorders, weight loss, gastrointestinal disorders, rapid eye movement and urinary disorders.
People might be confused by the early signs of parkinsons as normal signs of aging. Symptoms like depression, constipation, loss of smell , sleep disorders can occur years before the diagnosis of PD. Anxiety and depression can also occur years before the diagnosis of PD is made (Chen et al. 2013).  However, approximately 50% of the neurologists do not discuss non motor symptoms with their patients and 62% of the patients do not discuss nonmotor symptoms with their doctors because of the embarrassment or unawareness (Goyal & Radhakrishnan, 2018).
As disease gets worse the nonmotor symptoms can be more troublesome for the patients than the motor symptoms(Ahlskog, J. E. 2015). Nonmotor symptoms can be classified as disturbances in autonomic function, sleep disturbances, cognitive and psychiatric disturbances and sensory symptoms.
Disturbances in Autonomic Function: The autonomic dysfunction is the disturbance in both the central and peripheral postganglionic autonomic nervous system. Orthostatic hypotension is the fall in systolic blood pressure >20 mm Hg or in diastolic blood pressure > 10 mm Hg and affects 30-40% of the patients. In elderly PD patients this may occur after food intake (Sveinbjornsdottir, S.2016). Autonomic dermatological symptoms such as excessive sweating (hyperhidrosis) may also be found.
Sleep Disturbances: Fractionated sleep is the most common symptom of the patients diagnosed with PD. Some studies show that patients have frequent awakenings and more shallow sleep at night (Sveinbjornsdottir, S.2016). Fractionated sleep may be due to other symptoms of PD like difficulty in turning around, depression, frequent nocturia and nocturnal tremor. Excessive daytime sleepiness is found in approximately 50% of the patients and it seems that almost all the dopaminergic drugs may induce sleep attacks (Sveinbjornsdottir, S.2016).
Neuropsychiatry symptoms and dementia: Visual hallucinations and illusions are the common symptoms experienced by 40% of the patients diagnosed with PD. It is believed that all anti-parkinsonian medications induce hallucinations and psychosis. Visual hallucinations can be seen before the drug treatment(Sveinbjornsdottir, S.2016)
Sensory symptoms: Sensory symptoms like loss of smell and limb pain are the most common symptoms found in 80% of the patients in PD. Musculoskeletal pain is very common and reported by almost half of the patients. This pain may not always be related to PD (Sveinbjornsdottir, S.2016).
There are four motor symptoms that are considered cardinal in Parkinson’s Disease: Bradykinesia, rigidity, abnormal posture or instability and tremor.
Bradykinesia (slowness of movement) is the most common motor symptom and can be found in every case of PD. The patients may find difficulty or are not able to perform daily routine tasks like bathing, dressing and feeding.
Rigidity is the stiffness and resistance to the limb movement due to excessive contraction of muscles. As the disease progresses rigidity affects the whole body and reduces the ability to move. In the early stages the neck and the shoulder muscles are most affected.
Postural instability is often absent in the earlier stages and can be found in the later stages of PD. The patient might have problems balancing themselves and experience falls. The number of falls suggest the severity of PD.
Tremor or shaking usually begins in limbs, hands or fingers. It starts from one side of the body and as the disease progresses it eventually affects both sides. Pill-rolling tremor is the tendency to rub thumb and index finger back and forth performing a circular movement. 80% of the dopaminergic neurons are lost before the clinical motor features of PD can be observed. Bradykinesia and an additional symptom i.e. muscle rigidity, tremor or abnormal posture must be present for the diagnosis of PD (Sveinbjornsdottir, S. 2016).  
Treatment
Parkinson’s disease has no standard treatment or medications that can halt or stop the progression of the disease. The treatment of PD is based on the symptoms of the patients. Available therapies and medications can only treat the symptoms of the disease. The treatments include dopaminergic medication, non-dopaminergic medications and surgical treatment. Other non pharmacological treatments like lifestyle modification, yoga, education support groups,  taking more rest and exercise can also be beneficial.
Dopaminergic Therapy: The American Academy of Neurology (AAN) suggests to initiate any one of the following available drug therapies when the patient develops functional disability. The medical therapies for the treatment of motor symptoms include levodopa/carbidopa which is highly effective in  bradykinesia and rigidity and monamone MAO B inhibitors are moderately effective on the motor symptoms. There are other medications available which have near or no effect on the symptoms (Goyal & Radhakrishnan, 2018).
Non-dopaminergic pharmacological targets: Motor and nonmotor symptoms respond less to dopaminergic therapies due to abnormalities in the other non-dopaminergic neurotransmitters. Motor symptoms like feeling of gait, postural instability, swallowing and speech disturbances require non dopaminergic treatment. To treat the orthostatic hypotension the use of mineralocorticoid, fludrocortisone and adrenergic agents (midodrine and etilefrine); anti-muscarinics (oxybutynin, tolterodine or trospium chloride) to treat urinary disorders and pro-kinetic drugs to improve constipation was directed by the pharmacological therapy (Goyal & Radhakrishnan, 2018).
Surgical treatment: Deep brain stimulation (DBS) either on the subthalamic nucleus is the well known treatment for the motor symptoms of Parkinson’s disease. DBS is also effective in some non-motor symptoms like sleep disorders and behavioral disorders.
Findings of the multicultural randomized control trial, the EARLYSTIM trial, showed that DBS of the subthalamic nuleus in the early course of the disease is the best available medical therapy and could improve quality of life of the patients (Kalia & Lang, 2015).
Parkinson’s Disease is the most common and progressive neurodegenerative disease characterized by both motor and nonmotor symptoms which dramatically impairs the quality of life. It is important to be aware while understanding the proper management and treatment to reduce the symptoms of the disease as it can be caused due to both genetics and environmental factors. There is no such treatment to control Parkinson’s but the best effective treatment to control the symptoms are levodopa or dopaminergic medications and deep brain stimulation.
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