Parkinson's Disease

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Parkinson's Disease

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Parkinson's disease is a progressive, degenerative disorder that affects the motor and non-motor components of the nervous system. It occurs in 1% of individuals older than 60 years. The motor symptoms of the disease are due to the degeneration/depigmentation of neurons in the substantia nigra, a region of the midbrain. This region contains dopaminergic neurons and its degeneration results in dopamine deficiency. Dopamine is a neurotransmitter involved in motor control and in regulating the release of various hormones. Its shortage impairs the control of movements. Around 80% of dopaminergic neurons are lost prior to the onset of motor signs of Parkinson disease.

Apart from the degeneration of dopaminergic neurons, there is a build-up of alpha-synuclein protein in the brain in the form of Lewy bodies (similar to those seen in Lewy body dementia).

Parkinson's disease versus Parkinsonism

Parkinson's disease (also called as idiopathic or primary Parkinson's disease) is the most common cause of Parkinsonism, which is a clinical syndrome with the cardinal features of resting tremors, rigidity, bradykinesia, and postural instability.

A variety of conditions can secondarily produce a parkinsonian syndrome. Some of these include:

  • Alzheimer's disease
  • Drug-induced parkinsonism
  • Diffuse Lewy body disease
  • Parkinson-plus syndromes such as progressive supranuclear palsy and multiple system atrophy
  • MPTP (a contaminant used in street drugs)

Clinical Presentation

A) Motor Symptoms

An asymmetric resting tremor in an upper limb extremity is an initial presentation in most cases. This is followed by bradykinesia (slowness of movements), rigidity, and gait abnormalities.

Limb bradykinesia: Reduced arm swinging on one side and fatigability on performing similar actions are noticed in the initial stages.

Facial bradykinesia: Masked facial expression, decreased blink rate, speech becomes slow and indistinct.

Rigidity is a state of stiffness and resistance to limb movement secondary to increased muscle tone. The rigidity can be uniform (lead-pipe rigidity) or ratchety (cogwheel rigidity).

B) Non-Motor Symptoms

1) Autonomic: Orthostatic hypotension, nocturnal hypertension, constipation, delayed gastric emptying, nausea, excessive salivation, urinary urgency, and sexual dysfunction

2) Neuropsychiatric: like REM sleep behavioral disorder, depression, slowness in thinking, perceptual problems and hallucinations, and cognitive impairment and dementia in later stages

3) Sensory: Loss of taste or smell


At this time, there is no proven cure for Parkinson's disease. The treatment is directed towards improving the symptomatology and modifying the disease.

Symptomatic treatment


Levodopa is administered coupled with carbidopa or benserazide. Most of the levodopa is metabolized by dopa decarboxylase in the periphery to dopamine, and only 5–10% of L-DOPA is able to cross the blood–brain barrier to produce its effects. Therefore, carbidopa or benserazide are given along with L-DOPA. Carbidopa and benserazide are dopa decarboxylase inhibitors that do not cross the blood–brain barrier and help prevent the unwanted side effects (like nausea and vomiting and dyskinesias) resulting from the peripheral conversion of L-DOPA to dopamine. In the long-term, the effects of L-DOPA wear-off contributing to the relapse of fluctuations and dyskinesias.

Entacapone - a COMT inhibitor is sometimes administered to complement L-DOPA.

Dopamine agonists

Pramipexole, ropinirole, cabergoline, pergolide offer moderate symptomatic benefit but may delay the motor complications of treatment in contrast to L-DOPA.

MAO-B inhibitors

Selegiline and rasagiline block MAO-B enzyme that metabolizes dopamine and thus, augment the levels of dopamine in the basal ganglia. These may modify the disease process in Parkinson's disease.


Unfortunately, despite the optimal medical therapy, several patients go on to develop long-term complications like fluctuations and dyskinesias.

FDA Approved Medicines

  • FDA approved ropinirole hydrochloride, sold as Requip, manufactured by SmithKline Beecham for the treatment of Parkinson's Disease ( Parkinson's Disease ) in year 1997.
  • FDA approved carbidopa and levodopa, sold as Duopa, manufactured by Abbvie for the treatment of motor fluctuations in patients with advanced Parkinson's disease ( Parkinson's Disease ) in year 2015.
  • FDA approved apomorphine hydrochloride, sold as Apokyn, manufactured by Mylan Laboratories for the treatment of acute, intermittent hypomobility episodes associated with advanced Parkinson�s disease ( Parkinson's Disease ) in year 2004.
  • FDA approved carbidopa and levodopa, sold as Rytary, manufactured by Impax Labs for the treatment of Parkinson's disease ( Parkinson's Disease ) in year 2015.