Parkinson’s disease

Definition
• Parkinson's disease is a progressive disorder of
the nervous system that affects movement.
• It develops gradually, sometimes starting with
a barely noticeable tremor in just one hand.
• Tremor may be the most well-known sign of
Parkinson's disease, the disorder also
commonly causes stiffness or slowing of
movement.
 Symptoms
• Tremor. A tremor, or shaking, usually begins in a limb, often
your hand or fingers. You may notice a back-and-forth rubbing
of your thumb and forefinger, known as a pill-rolling tremor.
One characteristic of Parkinson's disease is a tremor of your
hand when it is relaxed (at rest).
• Slowed movement (bradykinesia). Over time, Parkinson's
disease may reduce your ability to move and slow your
movement, making simple tasks difficult and time-consuming.
Your steps may become shorter when you walk, or you may
find it difficult to get out of a chair. Also, you may drag your
feet as you try to walk, making it difficult to move.
• Rigid muscles. Muscle stiffness may occur in any part of your
body. The stiff muscles can limit your range of motion and
cause you pain.
• Impaired posture and balance. Your posture may
become stooped, or you may have balance problems as a
result of Parkinson's disease.
• Loss of automatic movements. In Parkinson's disease,
you may have a decreased ability to perform unconscious
movements, including blinking, smiling or swinging your
arms when you walk.
• Speech changes. You may have speech problems as a
result of Parkinson's disease. You may speak softly,
quickly, slur or hesitate before talking. Your speech may
be more of a monotone rather than with the usual
inflections.
• Writing changes. It may become hard to write, and your
writing may appear small.
Substantia Nigra
 Causes
• A small area in the brain stem called the substantia
nigra controls movement. In Parkinson's disease, cells
in the substantia nigra stop making dopamine, a brain
chemical that helps nerve cells communicate. As these
dopamine-making cells die, the brain does not receive
the necessary messages about how and when to move.
• Gene mutations can cause the disease directly. Some of
these mutations involve genes that play a role in
dopamine cell functions.
• Parkinson’s develops at an early age in individuals with
mutations in genes for parkin, PINK1, LRRK2, DJ-1,
and glucocerebrosidase,
 Medication
• Medications may help you manage problems with
walking, movement and tremor. These medications
increase or substitute for dopamine, a specific signaling
chemical (neurotransmitter) in your brain.
• People with Parkinson's disease have low brain
dopamine concentrations. However, dopamine can't
be given directly, as it can't enter your brain.
• There are two general approaches to the treatment
of Parkinson's disease with medication. The first
approach attempts to increase the levels of dopamine in
the brain and the second approach attempts to improve
the symptoms of Parkinson's disease by other means.
 Sinemet (Levodopa/Carbidopa)
• Levodopa (also called L-dopa) controls the symptoms of
Parkinson's disease, particularly bradykinesia and
rigidity.
• It is transported to the nerve cells in the brain that
produce dopamine and then converted into dopamine
• It is made up of levodopa and another drug
called carbidopa.
• Levodopa enters the brain and is converted to dopamine
while carbidopa increases its effectiveness and prevents
or lessens many of the side effects of levodopa, such
as nausea, vomiting, and occasional heart rhythm
disturbances.
 Dopamine agonists
• Activate the dopamine receptor and mimic the function of
dopamine in the brain.
• They aren't as effective as levodopa in treating your
symptoms. However, they last longer and may be used with
levodopa to smooth the sometimes off-and-on effect of
levodopa.
• Dopamine agonists include pramipexole (Mirapex),
ropinirole (Requip) and rotigotine (given as a patch, Neupro).
A short-acting injectable dopamine agonist, apomorphine
(Apokyn), is used for quick relief.
• Similar to the side effects of carbidopa-levodopa, but also
include hallucinations, sleepiness and compulsive behaviors
such as hypersexuality, gambling and eating.
 MAO-B inhibitors.
• Medications include selegiline (Eldepryl, Zelapar)
and rasagiline (Azilect).
• They prevent the breakdown of brain dopamine by
inhibiting the brain enzyme monoamine oxidase B
(MAO-B). This enzyme metabolizes brain dopamine.
• Side effects may include nausea or insomnia.
• When added to carbidopa-levodopa, these
medications increase the risk of hallucinations.
• These medications are not often used in combination
with most antidepressants or certain narcotics due to
potentially serious but rare reactions.
Catechol-O-methyltransferase (COMT) inhibitors

• Entacapone (Comtan) is the primary medication from this

class. This medication mildly prolongs the effect of
levodopa therapy by blocking an enzyme that breaks down
dopamine.
• Side effects, including an increased risk of involuntary
movements (dyskinesias), mainly result from an enhanced
levodopa effect. Other side effects include diarrhea or other
enhanced levodopa side effects.
• Tolcapone (Tasmar) is another COMT inhibitor that is
rarely prescribed due to a risk of serious liver damage and
liver failure.
 Anticholinergics
• They help control the tremor associated with
Parkinson's disease.
• Benztropine (Cogentin) or trihexyphenidyl.
• However, their modest benefits are often offset
by side effects such as impaired memory,
confusion, hallucinations, constipation, dry
mouth and impaired urination.
Surgical Procedures
 Deep brain stimulation

• It inactivate parts of the brain that cause Parkinson's disease and its
associated symptoms without destroying the brain.
• Electrodes are placed in the thalamus (to treat essential tremor) or
in the globus pallidus and subthalamic nucleus (for Parkinson's
disease).
• Stimulation electrodes are connected by wires to a type
of pacemaker device (called an impulse generator, or IPG)
implanted under the skin of the chest, below the collarbone.
• Once activated, the device sends continuous electrical pulses to the
target areas in the brain, blocking the impulses that cause tremors.
• The IPG can easily be programmed using a computer that sends
radio signals to the device. Patients are given special magnets or
other devices so they can externally turn the IPG on or off.
• Depending on use, the stimulators may last three to five years
STEREOTACTIC BRAIN SURGERY A patient about to undergo deep-brain stimulation
first has a frame fixed to the scalp. The frame helps the surgeon navigate to the precise site
in the brain where electrodes are to be implanted.
 Pallidotomy and Thalamotomy
• These surgeries use radio-frequency energy to
destroy a pea-sized area in the globus pallidus
or the thalamus. These areas are associated
with tremor, rigidity, and bradykinesia, so
movement generally improves after surgery
with less reliance on levodopa. But because
these surgeries are irreversible, they have
become less common than deep brain
stimulation.