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Parkinson's Disease

Parkinson's disease is a disorder of the central nervous system in which the brain does not produce enough of the neurotransmitter dopamine.  The result is a clinical syndrome of tremor typically involving the hands while they are at rest, which stops when engaged in movement or during sleepbut can also involve the arms, legs, jaw, and face; rigidity or stiffness; bradykinesia, or slowness of movement; and postural instability, or impaired balance, coordination, and other derangements of posture maintenance.  Other symptoms may include depression and other emotional changes; difficulty in swallowing, chewing, and speaking; urinary problems or constipation; skin problems; and sleep disruptions.  Early symptoms of Parkinson’s disease are subtle and occur gradually; as they become more pronounced, patients may have difficulty walking, talking, or completing other simple tasks.

Parkinson’s disease is named for the British physician James Parkinson, who published the first detailed description in 1817.  It usually affects people over the age of 60.  The cause is unknown, but some cases are genetic and run in families.  Smokers and those exposed to certain environmental toxins are more prone to develop the disease.  The motor symptoms of Parkinson's disease result from the death of dopamine-generating cells in the substantia nigra, a region of the midbrain.  “Substantia Nigra” means “black substance” and is named from the black appearance of region seen on brain autopsy.  The black pigment, called neuromelaninis actually a polymer made from L-DOPA, a precursor of dopamine.  Other features of the disorder are related to the appearance of “Lewy bodies” in the brain; these are accumulations of the protein alpha-synuclein.   

At present, there is no cure for Parkinson’s disease, but a variety of medications provide symptomatic relief.  The first approach is to supply what is lacking in the brain, dopamine, by administering its precursor L-DOPA in the form of a tablet.  However, very little L-DOPA makes its way into the brain, as it is broken down outside of the central nervous system, or “in the periphery.”  Fortunately, giving the L-DOPA along with carbidopa, which antagonizes its metabolism in the periphery, allows meaningful levels of L-DOPA to penetrate the brain.  The remaining functioning dopamine neurons use this L-DOPA to produce dopamine, thus relieving symptoms.  But L-DOPA does not stop the neurons from dying off, and soon the condition becomes less and less responsive to treatment. 

Although L-DOPA helps at least three-quarters of Parkinson’s disease sufferers, not all symptoms respond equally. Bradykinesia and rigidity respond best; tremor least. Problems with balance may not be helped at all.  Medications that antagonize the action of the neurotransmitter acetylcholine may help control tremor and rigidity.  Other drugs help by mimicking the action of dopamine in the brain (that is, are dopaminergic) such as pramipexole and ropinirole.  An antiviral drug, amantadinereduces symptoms through a number of mechanisms; it is particularly helpful for those occurring in the context of treatment with L-DOPA or dopaminergic drugs.  In some cases, surgery may be appropriate. Deep Brain Stimulation (DBS) involves electrodes implanted into the brain and connected to a pulse generator that can be externally programmed. DBS can reduce or delay the need for L-DOPA and dopaminergic drugs, which in turn decreases the involuntary movements called dyskinesias that are a common side effect of these treatments.    

Bibliography
 
NIH/Parkinsons , Parkinson Definition

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