PARKINSON'S DISEASE
Philip A. Hanna, MD
Parkinson's Disease and Movement Disorders Center
New Jersey Neuroscience Institute
Edison, New Jersey
What is Parkinson's disease?
Parkinson's disease (PD) is a very common neurological disorder due to
loss of dopamine-producing cells in a part of the brain named the
substantia nigra. While the cause is unknown, genetic predisposition
and environmental factors are believed to play a role. The primary
features of the disease include rigidity (stiffness of muscles),
bradykinesia (slowness of movement), postural instability and tremor
(mainly at rest). A number of other symptoms may be present including
fatigue, lowering of blood pressure when assuming an upright position,
changes in bowel and bladder function, pain (often in the shoulder
area), swallowing difficulty, mild decline in memory and depression.
Diagnosis is based on the clinical presentation (evaluation of a
neurology specialist) as laboratory testing and imaging are generally
not helpful. The disease often primarily affects one side of the body
initially. The mean age of onset is the sixth decade of life, but in
5% of cases onset is prior to the age of 40. PD does not alter life
expectancy and progresses at a variable rate over several decades.
Good prognositic features include slow initial progression and having
tremor as the main symptom. Early difficulty with walking signals a
relatively poor outcome.
What is the treatment for PD?
There have never been so many options with regards to the treatment of
this condition. Medications including amantadine, selegiline (Eldepryl®,
Deprenyl®), anti-cholinergics including trihexephenidyl (Artane®),dopamine
agonists (pergolide (Permax®), bromocriptine (Parlodel®),
pramipexole (Mirapex®), and ropinirole (Requip®)) as well as various
preparations of carbidopa/levodopa (Sinemet®) provide significant
benefit for patients. Newer agents include catechol-0-methyl
transferase (COMT) inhibitors, such as tolcapone (Tasmar®) and
entacapone. Recent surgical advances in pallidotomy and deep brain
stimulation (DBS)) have significantly improved patients' symptoms and
even newer techniques such as transplantation and growth factors may
eventually reverse the underlying disease process.
What is the role of dopamine agonists?
Currently four dopamine agonists are commercially available in the
USA: (pergolide (Permax®), bromocriptine (Parlodel®), pramipexole (Mirapex®),
and ropinirole (Requip®)) and all provide significant relief against
all the main features of PD. Most specialists advocate the use of
dopamine agonists early in the disease and along with carbidopa/levodopa
later in the disease. These medications are much easier to use than
carbidopa/levodopa and have good long term effectiveness.
What is the role of Sinemet, and what are the possible side effects of
this agent?
Carbidopa/levodopa (L-dopa) [Sinemet®] has been the most potent
pharmacologic treatment for PD. Yet, experts continues to debate the
timing of beginning this agent. Some laboratory and indirect clinical
evidence suggests that extended L-dopa use may accelerate cell death,
and result in clinical fluctuations/unpredictable response, and
tolerance. Conversely, L-dopa clearly improves symptoms and has
reduced mortality, so the decision to begin L-dopa must be
individualized. An ongoing, multicenter clinical trial is designed to
help determine when to begin Sinemet.
The most common initial side effects of L-dopa are nausea and
hypotension. Higher doses may result in confusion, sedation and visual
hallucinations. Dyskinesias (irregular involuntary movements) and
fluctuations (wearing off, "on"/"off" periods at
times unpredictable) may be seen typically after 5 years or so on
L-dopa.
What surgical options are available?
Surgical procedures such as pallidotomy and deep brain stimulation
(DBS) are being increasingly used in PD. Pallidotomy is typically
reserved for patients whose condition is unsatisfactorily controlled
on conventional treatment. The procedure is safe (overall, less than
2% incidence of serious complications) with sustained long term
benefits. Prognostic factors for a good outcome include responsiveness
to L-dopa, particularly those with L-dopa induced dyskinesias, and
young age. Relative poor predictors include older age, multiple
medical problems, impaired cognition and marked freezing of gait.
Reduction in dyskinesias is the most dramatic benefit followed by
reduction in tremor, rigidity and bradykinesia. Gait improves
moderately but freezing of gait, speech and swallowing often respond
less dramatically.
For pallidotomy, the surgeon identifies the globus pallidus (an area
fairly deep in the brain) via the guidance of MRI and electrical
recordings. Then, an electrode is inserted through a small burr hole,
and the target is heated resulting in a small lesion. Results are
almost immediate, and the recovery time is brief and typically
uncomplicated.
Thalamotomy (making a lesion in the thalamus) and thalamic stimulation
(DBS) are effective against the tremor component of PD. Deep brain
stimulation (DBS) of other sites (subthalamic nucleus or globus
pallidus) are showing promise as sites for relief of many of the
cardinal symptoms of PD. Transplant studies are ongoing, including the
use of fetal pig transplants to avoid the numerous difficulties with
human fetal research. The placement of growth factors into the brain
is another exciting area of active research. At the NJ Neuroscience
Institute, gamma knife radiosurgery is a future area of investigation
in the treatment of PD.
National Parkinson Foundation, Inc. (NPF)
1501 N.W. 9th Ave./Bob Hope Rd.
Miami FL 33136-1494
1-800-327-4545 in U.S. except Florida & California
1-800-433-7022 in Florida, 1-800-400-8448 in California, 305-547-6666
in Miami, 310-203-8448 in LA.
Hanna PA, Cardoso F, Jankovic J. Basal Ganglia and Movement Disorders.
In: Rolak LA, ed. Neurology Secrets, 2nd ed. New York: Hanley and
Belfus, 1998:137-169.
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