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Parkinson's Disease Consultation and Treatment- Neurology, Neurosurgery

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Parkinson’s disease is a neurological disorder characterized by degeneration of dopamine-producing neurons in the part of the brain which is crucial for controlling body movements (substantia nigra pars compacta), leading to related problems. It is the second most frequently observed neurodegenerative disease after Alzheimer’s disease. Older individuals are at a higher risk of Parkinson’s disease.

Epidemiology:

It affects ~0.3 % of the entire population and ~1% of individuals over 60 years of age. Globally, more than 10 million people are currently living with Parkinson’s disease.

Etiology: 

Parkinson’s disease is caused due to loss of dopamine-producing neurons and accumulation of proteins (Lewy bodies) within neurons in the brain. There are multiple factors involved in the occurrence of the disease.

  • In ~95 % of individuals the disease is caused by environmental factors (sporadic).
  • In ~5% of individuals the disease is caused by genetic factors.

Environmental factors influencing occurrence of Parkinson’s disease:

Scientists are working to better understand the broad range of environmental exposures linked to Parkinson's disease. Some articles have mentioned the following types of environmental factors,  but much research still has to be done on this.

  • Pesticides, herbicides and heavy metals: Exposure to toxins from pesticides (such as MPTP 1‐methyl‐4‐phenyl‐ 1,2,3,6‐tetrahydropyridine), herbicides (e.g., rotenone and paraquat), and heavy metals (e.g., iron, manganese, copper, lead, aluminium) can cause Parkinson’s disease.
  • Fat and fatty acids: Diets with high lipid content increase oxidative stress (increase in the free radicals that damage cells and tissues) and may increase the risk of Parkinson’s disease.
  • Vitamins: There is some research that has shown that the intake of antioxidants such as Vitamin E and C can help reduce the risk of developing Parkinson’s disease. They reduce the oxidative stress (increase in the free radicals that damage cells and tissues), which is responsible for causing the disease. Intake of Vitamin B12, B6, and folic acids are also known to reduce the incidence of disease.

Genetic factors:

In ~5% of individuals with Parkinson’s disease, the disease is caused due to genetic factors, evidenced by mutations in genes (α‐synuclein: SCNA).

Clinical features:

Key features of the disease include tremors at rest, rigidity, bradykinesia (slowness of voluntary movement), postural instability and freezing (temporary inability to move). In addition to this, individuals may develop decreased arm swing, inability to swallow, reduced facial expressions, difficulty in turning in bed, arising from chair, and overall delay in performing day to day tasks.

Other non-motor symptoms include impairment of cognitive functions, depression, loss of interest, psychiatric issues, fatigue, decreased sense of smell, disturbed sleep, weight loss, inability to stand for long, sexual dysfunction, and restless leg syndrome.

Stages in Parkinson’s disease:

Stage 1

Mild symptoms are observed. Tremors are experienced in one side of the body. Day to day activities are not affected but changes in gait, posture, and expressions on face are observed.

Stage 2

Rigidity and tremors are experienced in both sides of the body. Posture and walking related problems are more evident. Individuals may find it difficult to perform day to day activities.

Stage 3

Motor functions are affected. Sudden falls while walking due to loss of balance is common. All motor movements (muscle function) become very slow. The individual may have difficulty in eating or dressing up.

Stage 4

Motor movements are impaired, and assistance is needed to perform day to day activities.

Stage 5

The affected individual has difficulty in standing up, walking, and shifting side to side on the bed. The motor function is completely impaired. The individual may suffer from hallucinations, sleep disturbance, or develop dementia as the disease progresses.

Diagnosis:

There are no definite tests to diagnose Parkinson’s disease. Diagnosis mainly depends on clinical symptoms. To diagnose Parkinson’s disease, at least two of the four cardinal signs such as tremors at rest, bradykinesia, rigidity, and postural imbalance should be present.

The sudden and asymmetric onset of symptoms and response to levodopa medications can help in differentiating Parkinson’s disease from other disorders.

Research suggests that presence of Lewy bodies (protein) during autopsy (after death) is the only definitive way to diagnose the disease.

Differential Diagnosis:

Disorders which resemble symptoms of Parkinson’s disease along with additional disorders are called Parkinsonism syndrome. These include:

  • Progressive supranuclear palsy (brain disorder which affects movement, balance, gait, speech, and swallowing).
  • Multiple system atrophy (disorder affecting the involuntary movements of the body).
  • Vascular Parkinsonism (Symptoms resemble Parkinson’s disease but are caused by defects in blood vessels of the brain).
  • Diffuse Lewy body disease (Accumulation of proteins in the brain).
  • Corticobasal degeneration (Neurological disorder, affecting motor movements).

Management

There is no definitive treatment for the disease. In most individuals, a palliative treatment is recommended.

  • Levodopa treatment: It is a gold standard treatment for Parkinson’s disease. It is an efficient drug therapy for the disease. It replenishes the decreased dopamine levels in the brain. However, long-term usage of the medication can cause dyskinesia (uncontrolled involuntary movements).
  • Dopamine agonist treatment: This category of drug aids in stimulation of neurons to produce dopamine. These include bromocriptine, pergolide, cabergoline, and lisuride. However, prolonged use can exhibit side effects such as hallucination, confusion, leg edema, and orthostatic hypotension.
  • Monoamine oxidase-B (MAO-B) inhibitors: MAO-B chemicals cause breakdown of dopamine released in the brain. The use of MAO-B inhibitors inhibits the action of MAO-B chemicals and increase the concentration of dopamine.
  • Catechol-O-methyltransferase (COMT) inhibitors: The COMT chemical is responsible for metabolism of dopamine. The use of COMT inhibitors prevent the metabolism of dopamine and increase their availability. When used with levodopa, they prolong the duration of anti-Parkinson’s action (e.g., entacapone, tolcapone).
  • Others: Anticholinergics and psychiatric drugs (e.g., clozapine) help overcome the additional symptoms of the disease such as hallucinations, psychosis, paranoia, and sleep-related disorders. In affected individuals, physical and psychosocial treatment and speech therapy are also recommended.
  • Surgery (deep brain surgery): In rare cases, surgery is recommended in individuals with symptoms that are not manageable by medications.

Sources:

  • De Lau LM, Breteler MM. Epidemiology of Parkinson's disease. The Lancet Neurology. 2006 Jun 1;5(6):525-35.
  • Jankovic J. Parkinson’s disease: clinical features and diagnosis. Journal of Neurology, Neurosurgery & Psychiatry 2008;79:368-376
  • Modi P, Mohamad A, Phom L, Koza Z, Das A, Chaurasia R, Samadder S, Achumi B, Pukhrambam RS, Yenisetti SC. Understanding Pathophysiology of Sporadic Parkinson's Disease in Drosophila Model: Potential Opportunities and Notable Limitations. InChallenges in Parkinson's Disease 2016 Aug 24 (p. 217). IntechOpen.
  • Dauer W, Przedborski S. Parkinson's disease: mechanisms and models. Neuron. 2003 Sep 11;39(6):889-909.
  •  Davie CA. A review of Parkinson's disease. British medical bulletin. 2008 Jun 1;86(1):109-27.
  • Tarakad A, Jankovic J. Diagnosis and management of Parkinson's disease. InSeminars in neurology 2017 Apr (Vol. 37, No. 02, pp. 118-126). Thieme Medical Publishers.
  • Guttman M, Kish SJ, Furukawa Y. Current concepts in the diagnosis and management of Parkinson's disease. Cmaj. 2003 Feb 4;168(3):293-301.
  • Ciulla M, Marinelli L, Cacciatore I, Stefano AD. Role of dietary supplements in the management of Parkinson’s disease. Biomolecules. 2019 Jul;9(7):271.
  • Salawu F, Olokoba A, Danburam A. Current management of Parkinson's disease. Annals of African medicine. 2010;9(2).
  • Cutson TM, Laub KC, Schenkman M. Pharmacological and nonpharmacological interventions in the treatment of Parkinson's disease. Physical therapy. 1995 May 1;75(5):363-73.
  • Wendy Henderson, 5 stages of Parkinson’s disease, parkinsonsnewstoday.com, Jine 15, 2017. https://parkinsonsnewstoday.com/2017/06/15/5-stages-parkinsons-disease/
About the Author:
Dr. Shilpy Bhandari is an experienced dental surgeon, with specialization in periodontics and implantology. She received her graduate and postgraduate education from Rajiv Gandhi University of Health Sciences in India. Besides her private practice, she enjoys writing on medical topics. She is also interested in evidence-based academic writing and has published several articles in international journals.
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