Excerpt from the Young Parkinson's Handbook (full content available at youngparkinsons.org)
Parkinson's disease (PD) is a movement disorder that is caused by the defi-
ciency of a substance in the brain called dopamine. Dopamine is a neurotrans-
mitter that is produced by cells (neurons) in a region of the brain known as the
substantia nigra. When approximately 60-80% of the dopamine neurons are lost,
motor symptoms of PD begin to emerge. Although we know that PD symptoms
are caused by a depletion of dopamine in the brain, we do not as yet fully under-
stand what mechanisms or conditions cause the degeneration to occur.
The diagnosis of Parkinson's disease is made on clinical grounds, meaning that
the person is examined by a physician who determines whether the following
cardinal features of the disease are present:
Tremor at rest (tremor when the limb is not in use)
Loss of postural reflexes (balance problems)
Not all of these features need to be present to make the diagnosis. Currently,
there is no definitive test for Parkinson's disease. Instead, there are a series of
physical and cognitive assessments used by your healthcare team to determine
the diagnosis and rule out the existence of other conditions that may have
It is now known that Parkinson's disease can encompass more than just motor
symptoms. In some people these non-motor symptoms may affect quality of life
more than the motor symptoms. They can include sleep problems, pain, loss of
sense of smell, cognitive and psychiatric symptoms, and problems with blood
pressure, bowel and bladder function, and sexual functioning. In a recent neu-
ropathological study, it appears that changes in other par ts of the brain may
predate the loss of dopamine neurons in the substantia nigra. This could possi-
bly explain the fact that many patients may have loss of sense of smell, sleep
disorders, depression and other symptoms well before their motor symptoms
begin. Currently, these changes often associated with Parkinson's disease are
being fur ther investigated in the hope of discovering ways to predict who is
Excerpt from the Young Parkinson's Handbook (full content available at youngparkinsons.org)
Although the neuropathology and most clinical symptoms are the same at what-
ever age PD develops, there are some unique characteristics and treatment
strategies that require consideration when PD occurs at an early age.
What is Young Onset Parkinson's Disease?
When Parkinson's disease is seen in individuals under the age of 40, it is called
"young onset" Parkinson's disease (YOPD). However, the age range considered
young onset varies somewhat depending on the source.
It is estimated that approximately 10% of the 1.5 to 2 million people with PD
in the United States fall into the YOPD categor y, strictly defined as occurring
between the ages of 21-40. The number of cases may actually be much higher
than 10% of the PD population because Parkinson's disease is often overlooked
as a possible diagnosis in younger patients. As a result, many young people
travel a circuitous route in order to attain eventual diagnosis. Although the
diagnosis is not a welcome one, for many young people it ends a lengthy
process of referrals to a variety of medical specialists searching for the cause
of their symptoms. Once the diagnosis is made, some express relief that this
was "not just all in my head," and that they now have a name and medical treat-
ment for what they have been experiencing.
Although both environmental and genetic causes for YOPD have been implicat-
ed, it appears genetics may play a greater role in the development of PD in
those with young onset than in those with later onset. A number of genes have
been identified as possible players in the development of PD, but more research
is needed to determine how each of these genes specifically functions (see
Excerpt from the Young Parkinson's Handbook (full content available at youngparkinsons.org)
There are some physical, emotional, and social characteristics as well as
medical management implications that are unique to YOPD:
Dystonia Symptoms in up to half of those with YOPD begin with dystonia, an
uncontrollable stiffness or cramping of a muscle group or limb. A cramp or ache
in a specific area of the body, commonly in the foot or shoulder, is a ver y com-
mon initial symptom of young onset PD. Individuals often repor t "early morning
dystonia" which may interrupt sleep.
Dyskinesia and Motor Fluctuation There is a greater tendency in young people
to develop dyskinesias (involuntar y body movements) and fluctuations in move-
ment over time when taking the PD medication levodopa.
Disease Progression Recent data has shown that those with young onset
PD tend to have a more slowly progressive course and a smoother course of the
illness than their older counterpar ts.
Cognition (Thinking) Problems with dementia appear to occur less frequently
Emotional and Social Issues YOPD occurs at a time when young people already
have a ver y full life. Managing career and family obligations along with the
stress associated with the presence of a chronic disease can prove to be a
challenge to all members of the family. For some, the most difficult aspect of
YOPD is an uncer tain future. Questions abound, such as: Will I be able to con-
tinue working? What kind of medical bills can I expect? Will I still be able to
function as a nur turing parent and spouse? For tunately, due to its typically
slower progression and the considerable number of medications now available
for the control of symptoms, many young people find they are able to continue
the work, social, and recreational activities they enjoy for many years.
Coming to terms with the diagnosis and challenges of the disease over a life-
time can be difficult. The patient and his or her family members are likely to
experience a wide range of emotions as they tr y to manage this unexpected
change in their lives. Many find a sense of suppor t when they are able to
communicate with others who are living with YOPD. Young onset PD suppor t
groups, online discussion groups, and various programs offered by the APDA
and other Parkinson's organizations offer the oppor tunity to meet and to share
Excerpt from the Young Parkinson's Handbook (full content available at youngparkinsons.org)
information and resources with other young people and their families.
Professional counseling can also be ver y beneficial. Individual counseling can
provide a private place to talk about the impact PD may be having on you and
your family, and family counseling can facilitate better communication between
all family members and help ever yone develop healthy ways of adapting.
Currently, no treatment has been shown to definitively slow or stop the progres-
sion of PD. Instead, therapy is directed at managing the symptoms of the
disease. Treatment typically includes the use of medications and surgical inter-
vention. Other treatment approaches include physical therapy, occupational
therapy, speech therapy, and general lifestyle modifications such as diet and
Principles to be considered with regard to the medical management of
Treatment usually begins when the person with
YOPD feels that his or her symptoms are affecting motor or social functioning
to the extent that the ability to enjoy a meaningful quality of life or maintain
employment is being compromised. Treatment is typically focused on the most
bothersome symptoms, and medications can often be targeted to par ticular
symptoms, such as management of tremor.
Levodopa Currently, levodopa is considered the most effective drug for control-
ling the symptoms of Parkinson's disease. Levodopa is modified by brain
enzymes to produce the chemical dopamine, which the brain needs to properly
control muscle movement. When there is a deficiency of dopamine, it negatively
affects motor functioning and results in the symptoms of PD. While almost all
people with PD will be taking levodopa at some point, its use should be delayed
for as long as possible, par ticularly in young people. This is because the length
of time levodopa is taken has been shown to be related to the development of
motor complications, such as excessive movements (dyskinesias) and motor
fluctuations. Once introduced, levodopa should be utilized at the lowest doses
possible when: 1) an inadequate response is obtained with other medications,
or 2) side effects are encountered with other medications at doses required to
Excerpt from the Young Parkinson's Handbook (full content available at youngparkinsons.org)
Because long-term use of levodopa at high dosages
often leads to movement complications that can be difficult to manage, many
doctors are now using a number of other medications which can be used alone
or in combination with levodopa to treat PD symptoms. MAO-B inhibitors, anti-
cholinergics, amantadine, and dopamine receptor agonists (such as Mirapex®
and Requip®) may be used prior to the introduction of levodopa, and are often
adequate to treat the early stages of PD for a number of years. Dopamine recep-
tor agonists behave like dopamine but are not as potent as levodopa and are
not conver ted into dopamine as is levodopa.
For tunately, we are witnessing the continual development of new drug thera-
pies for the treatment of both the motor and non-motor symptoms of PD. For the
most up-to-date information on available medications, contact APDA's National
Regular Exercise A consistent exercise program, based on one's ability level,
should be incorporated into the treatment regimen of each patient in order to
maintain flexibility, mobility, and general well-being. Patients can develop an
exercise program on their own or with a physical therapist. Many find that
attending general or PD-specific exercise classes is also helpful.
Adjunct therapies, such as physical therapy, can
address gait and balance issues. Speech therapy (such as the Lee Silverman
Voice Treatment) can be used when symptoms are troublesome or as an early
For most people with Parkinson disease, levodopa and other medications are
effective for maintaining a good quality of life. However, when medication
adjustments do not continue to improve mobility or if PD medications cause
significant side effects, surgical treatment may be considered. Many people
with YOPD have experienced a positive response with Deep Brain Stimulation
(DBS) surger y. This procedure involves inser ting a thin metal lead into a target-
ed area of the brain. The lead contains four electrodes. A wire, attached to the
lead, runs down the neck under the skin to a computerized pulse generator. This
computerized device is implanted under the skin in the chest, much like a pace-
maker for the hear t. Electrical impulses from the electrode silence the par ts of
the brain that produce movement problems resulting from dopamine loss, and
can decrease motor fluctuations and markedly reduce dyskinesias. DBS surger y
Excerpt from the Young Parkinson's Handbook (full content available at youngparkinsons.org)
does not destroy brain tissue; therefore, if newer, more promising treatments
develop in the future, the DBS procedure can be reversed. Although most
patients still need to take medication after undergoing DBS, many find that
they are able to significantly reduce the amount of medication they are taking
because of the decrease in PD symptoms. The amount of symptom reduction
The availability of DBS represents a major milestone in the treatment options
for Parkinson's disease. When choosing a center for DBS surger y, look for one
with an experienced DBS team. There is a learning cur ve in successfully
implanting the DBS device, and you should seek a center that has per formed
the surger y many times (contact APDA's National Young Onset Center for local
resources). Criteria for patient selection may var y somewhat from center to
center. Although the procedure is not without some small risk, appropriate
patients can gain significant improvement. Research has shown that earlier
inter vention provides a more robust benefit, and that activities of daily living
and quality of life can be measurably improved. Fur thermore, it appears that
younger patients may benefit more from DBS than older patients.
As with any treatment decision, it is impor tant to discuss the potential risks
and benefits of DBS with your doctor.
When seeking neurological care, it is best to seek a physician who has an
understanding of the unique requirements of the young PD patient. This usual-
ly means a neurologist who has pursued specialized training in movement dis-
orders. Movement disorders specialists work extensively with PD and other
Parkinson's-like illnesses. Having someone who has this knowledge base as
your treating physician will help you maximize symptom control while minimiz-
ing complications of treatment which ultimately translates into long-term main-
Center For Drug Evaluation and Research List of Guidance Documents Guidance documents represent the Agency's current thinking on a particular subject. They do not create or confer any rights for or on any person and do not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statutes, regulations, or both. For i
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