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Chronic Care Programme
Treatment guidelines
Parkinson’s Disease
Chronic condition
Consultations protocols
Preferred treating provider
Notes
 preferred as indicated by option
 referral protocols apply
Maximum consultations per annum
 Initial consultation
 Follow-up consultation
Tariff codes
ICD 10 coding
Provider
Option/plan
GMHPP
Gold Options
G1000, G500 and
G200.
Blue Options
B300 and B200.
GMISHPP
ONE LEVEL
General Practitioner
Physician
Neurologist
Psychiatrist
New Patient
1
5
0183; 0142; 0187; 0108
Existing patient
1
3
G20.-G21.
General
Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the
central nervous system that often impairs the sufferer's motor skills and speech, as well as other
functions.[1]
Parkinson's disease belongs to a group of conditions called movement disorders. It is
characterized by muscle rigidity, tremor, a slowing of physical movement (bradykinesia) and, in
extreme cases, a loss of physical movement (akinesia). The primary symptoms are the results of
decreased stimulation of the motor cortex by the basal ganglia, normally caused by the
insufficient formation and action of dopamine, which is produced in the dopaminergic neurons of
the brain. Secondary symptoms may include high level cognitive dysfunction and subtle language
problems. PD is both chronic and progressive.
PD is the most common cause of chronic progressive parkinsonism, a term which refers to the
syndrome of tremor, rigidity, bradykinesia and postural instability. PD is also called "primary
parkinsonism" or "idiopathic PD" (classically meaning having no known cause although this term
is not strictly true in light of the plethora of newly discovered genetic mutations). While many
forms of parkinsonism are "idiopathic", "secondary" cases may result from toxicity most notably
of drugs, head trauma, or other medical disorders. The disease is named after English physician
James Parkinson; who made a detailed description of the disease in his essay: "An Essay on the
Shaking Palsy" (1817).
Classification
"Parkinson's disease" is the synonym of "primary parkinsonism", i.e. isolated parkinsonism due to
a neurodegenerative process without any secondary systemic cause. In some cases, it would be
inaccurate to say that the cause is "unknown", because a small proportion is caused by genetic
mutations. It is possible for a patient to be initially diagnosed with Parkinson's disease but then to
develop additional features, requiring revision of the diagnosis.[11]
There are other disorders that are called Parkinson-plus diseases. These include: multiple system
atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD).
Some include dementia with Lewy bodies (DLB) — while idiopathic Parkinson's disease patients
also have Lewy bodies in their brain tissue, the distribution is denser and more widespread in
DLB. Even so, the relationship between Parkinson disease, Parkinson disease with dementia
(PDD), and dementia with Lewy bodies (DLB) might be most accurately conceptualized as a
spectrum, with a discrete area of overlap between each of the three disorders. The natural history
and role of Lewy bodies is little understood.
These Parkinson-plus diseases may progress more quickly than typical idiopathic Parkinson
disease. If cognitive dysfunction occurs before or very early in the course of the movement
disorder then DLBD may be suspected. Early postural instability with minimal tremor especially
in the context of ophthalmoparesis should suggest PSP. Early autonomic dysfunction including
erectile dysfunction and syncope may suggest MSA. The presence of extreme asymmetry with
patchy cortical cognitive defects such dysphasia and apraxias especially with "alien limb"
phenomena should suggest CBD.
The usual anti-Parkinson's medications are typically either less effective or not effective at all in
controlling symptoms; patients may be exquisitely sensitive to neuroleptic medications like
haloperidol. Additionally, the cholinesterase inhibiting medications have shown preliminary
efficacy in treating the cognitive, psychiatric, and behavioral aspects of the disease, so correct
differential diagnosis is important.
Essential tremor may be mistaken for Parkinson's disease but lacks all other features besides
tremor, and has particular characteristics distinguishing it from Parkinson's, such as improvement
with beta blockers and alcoholic beverages.[1]
Wilson's disease (hereditary copper accumulation) may present with parkinsonistic features;
young patients presenting with parkinsonism or any other movement disorder are frequently
screened for this rare condition, because it may respond to medical treatment. Typical tests are
liver function, slit lamp examination for Kayser-Fleisher rings, and serum ceruloplasmin levels.
Pathology
Dopaminergic pathways of the human brain in normal condition (left) and Parkinson's disease
(right). Red Arrows indicate suppression of the target, blue arrows indicate stimulation of target
structure.
The symptoms of Parkinson's disease result from the loss of pigmented dopamine-secreting
(dopaminergic) cells in the pars compacta region of the substantia nigra (literally "black
substance"). These neurons project to the striatum and their loss leads to alterations in the activity
of the neural circuits within the basal ganglia that regulate movement, in essence an inhibition of
the direct pathway and excitation of the indirect pathway.
The direct pathway facilitates movement and the indirect pathway inhibits movement, thus the
loss of these cells leads to a hypokinetic movement disorder. The lack of dopamine results in
increased inhibition of the ventral anterior nucleus of the thalamus, which sends excitatory
projections to the motor cortex, thus leading to hypokinesia.
There are four major dopamine pathways in the brain; the nigrostriatal pathway, referred to
above, mediates movement and is the most conspicuously affected in early Parkinson's disease.
The other pathways are the mesocortical, the mesolimbic, and the tuberoinfundibular. These
pathways are associated with, respectively: volition and emotional responsiveness; desire,
initiative, and reward; and sensory processes and maternal behavior. Disruption of dopamine
along the non-striatal pathways likely explains much of the neuropsychiatric pathology associated
with Parkinson's disease.
The mechanism by which the brain cells in Parkinson's are lost may consist of an abnormal
accumulation of the protein alpha-synuclein bound to ubiquitin in the damaged cells. The alphasynuclein-ubiquitin complex cannot be directed to the proteosome. This protein accumulation
forms proteinaceous cytoplasmic inclusions called Lewy bodies. Latest research on pathogenesis
of disease has shown that the death of dopaminergic neurons by alpha-synuclein is due to a defect
in the machinery that transports proteins between two major cellular organelles — the
endoplasmic reticulum (ER) and the Golgi apparatus. Certain proteins like Rab1 may reverse this
defect caused by alpha-synuclein in animal models.[12]
Excessive accumulations of iron, which are toxic to nerve cells, are also typically observed in
conjunction with the protein inclusions. Iron and other transition metals such as copper bind to
neuromelanin in the affected neurons of the substantia nigra. Neuromelanin may be acting as a
protective agent. The most likely mechanism is generation of reactive oxygen species.[13] Iron
also induces aggregation of synuclein by oxidative mechanisms.[14] Similarly, dopamine and the
byproducts of dopamine production enhance alpha-synuclein aggregation. The precise
mechanism whereby such aggregates of alpha-synuclein damage the cells is not known. The
aggregates may be merely a normal reaction by the cells as part of their effort to correct a
different, as-yet unknown, insult. Based on this mechanistic hypothesis, a transgenic mouse
model of Parkinson's has been generated by introduction of human wild-type alpha-synuclein into
the mouse genome under control of the platelet-derived-growth factor-β promoter.[15]
Signs and symptoms
Parkinson disease affects movement (motor symptoms). Typical other symptoms include
disorders of mood, behavior, thinking, and sensation (non-motor symptoms). Patients' individual
symptoms may be quite dissimilar and progression of the disease is also distinctly individual.
Motor symptoms
The cardinal symptoms are (mnemonic "TRAP"):[1]

Tremor: normally 4-6 Hz tremor, maximal when the limb is at rest, and decreased with
voluntary movement. It is typically unilateral at onset. This is the most apparent and wellknown symptom, though an estimated 30% of patients have little perceptible tremor; these are
classified as akinetic-rigid.

rigidity: stiffness; increased muscle tone. In combination with a resting tremor, this produces
a ratchety, "cogwheel" rigidity when the limb is passively moved.

Bradykinesia/akinesia: respectively, slowness or absence of movement. Rapid, repetitive
movements produce a dysrhythmic and decremental loss of amplitude.

Postural instability: failure of postural reflexes, which leads to impaired balance and falls.
Other motor symptoms include:

Gait and posture disturbances:
o Shuffling: gait is characterized by short steps, with feet barely leaving the ground,
producing an audible shuffling noise. Small obstacles tend to cause the patient to trip.
o Decreased arm-swing.
o Turning "en bloc": rather than the usual twisting of the neck and trunk and pivoting on
the toes, PD patients keep their neck and trunk rigid, requiring multiple small steps to
accomplish a turn.
o Stooped, forward-flexed posture. In severe forms, the head and upper shoulders may
be bent at a right angle relative to the trunk (camptocormia). [2]
o Festination: a combination of stooped posture, imbalance, and short steps. It leads to a
gait that gets progressively faster and faster, often ending in a fall.
o Gait freezing: "freezing" is a manifestation of akinesia (an inability to move). Gait
freezing is characterized by an inability to move the feet which may worsen in tight,
cluttered spaces or when attempting to initiate gait.
o Dystonia (in about 20% of cases): abnormal, sustained, painful twisting muscle
contractions, often affecting the foot and ankle (mainly toe flexion and foot inversion)
which often interferes with gait.

Speech and swallowing disturbances.
o Hypophonia: soft speech. Speech quality tends to be soft, hoarse, and monotonous.
Some people with Parkinson's disease claim that their tongue is "heavy" or have
cluttered speech.[3]
o Monotonic speech.
o Festinating speech: excessively rapid, soft, poorly-intelligible speech.
o Drooling: most likely caused by a weak, infrequent swallow and stooped posture.
o Non-motor causes of speech/language disturbance in both expressive and receptive
language: these include decreased verbal fluency and cognitive disturbance especially
related to comprehension of emotional content of speech and of facial expression.[4]
o Dysphagia: impaired ability to swallow. Can lead to aspiration, pneumonia.
o Other motor symptoms:
o Fatigue (up to 50% of cases);
o Masked faces (a mask-like face also known as hypomimia), with infrequent
blinking;[5]
o Difficulty rolling in bed or rising from a seated position;
o Micrographia (small, cramped handwriting);
o Impaired fine motor dexterity and motor coordination;
o Impaired gross motor coordination;
o Poverty of movement: overall loss of accessory movements, such as decreased arm
swing when walking, as well as spontaneous movement;
o Akathisia.
Non-motor symptoms
Mood disturbances
Estimated prevalence rates of depression vary widely according to the population sampled and
methodology used. Reviews of depression estimate its occurrence in anywhere from 20-80% of
cases.[6] Estimates from community samples tend to find lower rates than from specialist centres.
Most studies use self-report questionnaires such as the Beck Depression Inventory, which may
overinflate scores due to physical symptoms. Studies using diagnostic interviews by trained
psychiatrists also report lower rates of depression. More generally, there is an increased risk for
any individual with depression to go on to develop Parkinson's disease at a later date.[7] Seventy
percent of individuals with Parkinson's disease diagnosed with pre-existing depression go on to
develop anxiety. Ninety percent of Parkinson's disease patients with pre-existing anxiety
subsequently develop depression; apathy or abulia.
Cognitive disturbances

Slowed reaction time; both voluntary and involuntary motor responses are significantly
slowed.

Executive dysfunction, characterized by difficulties in: differential allocation of attention,
impulse control, set shifting, prioritizing, evaluating the salience of ambient data, interpreting
social cues, and subjective time awareness. This complex is present to some degree in most
Parkinson's patients; it may progress to:

Dementia: a later development in approximately 20-40% of all patients, typically starting with
slowing of thought and progressing to difficulties with abstract thought, memory, and
behavioral regulation. Hallucinations, delusions and paranoia may develop.

Short term memory loss; procedural memory is more impaired than declarative memory.
Prompting elicits improved recall.

Medication effects: some of the above cognitive disturbances are improved by dopaminergic
medications, while others are actually worsened.[8]
Sleep disturbances

Excessive daytime somnolence

Initial, intermediate, and terminal insomnia

Disturbances in REM sleep: disturbingly vivid dreams, and REM Sleep Disorder,
characterized by acting out of dream content — can occur years prior to diagnosis
Sensation disturbances

Impaired visual contrast sensitivity, spatial reasoning, colour discrimination, convergence
insufficiency (characterized by double vision) and oculomotor control

Dizziness and fainting; usually attributable orthostatic hypotension, a failure of the autonomic
nervous system to adjust blood pressure in response to changes in body position

Impaired proprioception (the awareness of bodily position in three-dimensional space)

Reduction or loss of sense of smell (microsmia or anosmia) - can occur years prior to
diagnosis

pain: neuropathic, muscle, joints, and tendons, attributable to tension, dystonia, rigidity, joint
stiffness, and injuries associated with attempts at accommodation
Autonomic disturbances

Oily skin and seborrheic dermatitis[9]

Urinary incontinence, typically in later disease progression

Nocturia (getting up in the night to pass urine) — up to 60% of cases

Constipation and gastric dysmotility that is severe enough to endanger comfort and even
health

Altered sexual function: characterized by profound impairment of sexual arousal, behavior,
orgasm, and drive is found in mid and late Parkinson disease. Current data addresses male
sexual function almost exclusively.

Weight loss, which is significant over a period of ten years.
Diagnosis
18F PET scan shows decreased dopamine activity in the basal ganglia, a pattern which aids in
diagnosing Parkinson's disease.
There are currently no blood or laboratory tests that have been proven to help in diagnosing PD.
Therefore the diagnosis is based on medical history and a neurological examination. The disease
can be difficult to diagnose accurately. The Unified Parkinson's Disease Rating Scale is the
primary clinical tool used to assist in diagnosis and determine severity of PD. Indeed, only 75%
of clinical diagnoses of PD are confirmed at autopsy.[10] Early signs and symptoms of PD may
sometimes be dismissed as the effects of normal aging. The physician may need to observe the
person for some time until it is apparent that the symptoms are consistently present. Usually
doctors look for shuffling of feet and lack of swing in the arms. Doctors may sometimes request
brain scans or laboratory tests in order to rule out other diseases. However, CT and MRI brain
scans of people with PD usually appear normal.
Clinical practice guidelines introduced in the UK in 2006 state that the diagnosis and follow-up of
Parkinson's disease should be done by a specialist in the disease, usually a neurologist with an
interest in movement disorders.[11]
Causes
Most people with Parkinson's disease are described as having idiopathic Parkinson's disease
(having no specific cause). There are far less common causes of Parkinson's disease including
genetic, toxins, head trauma, cerebral anoxia, and drug-induced Parkinson's disease.
Genetic
In recent years, a number of specific genetic mutations causing Parkinson's disease have been
discovered, including in certain populations (Contursi, Italy). These account for a small minority
of cases of Parkinson's disease. Someone who has Parkinson's disease is more likely to have
relatives that also have Parkinson's disease. However, this does not mean that the disorder has
been passed on genetically.
Genetic forms that have been identified include (external links in this section are to Online
Mendelian Inheritance in Man):
Type
OMIM
Locus
Details
caused by mutations in the SNCA gene, which codes for the
protein alpha-synuclein. PARK1 causes autosomal dominant
PARK1 OMIM #168601 4q21
Parkinson disease. So-called PARK4 (OMIM #605543) is
probably caused by triplication of SNCA.[16]
caused by mutations in protein parkin. Parkin mutations may
be one of the most common known genetic causes of earlyonset Parkinson disease. In one study, of patients with onset
of Parkinson disease prior to age 40 (10% of all PD
patients), 18% had parkin mutations, with 5% homozygous
mutations.[17] Patients with an autosomal recessive family
6q25.2PARK2 OMIM *602544
history of parkinsonism are much more likely to carry parkin
q27
mutations if age at onset is less than 20 (80% vs. 28% with
onset over age 40).[18]Patients with parkin mutations
(PARK2) do not have Lewy bodies. Such patients develop a
syndrome that closely resembles the sporadic form of PD;
however, they tend to develop symptoms at a much younger
age.
PARK3 OMIM %602404 2p13
autosomal dominant, only described in a few kindreds.
caused by mutations in the UCHL1 gene which codes for the
PARK5 OMIM +191342 4p14
protein ubiquitin carboxy-terminal hydrolase L1
caused by mutations in PINK1 (OMIM *608309) which
PARK6 OMIM #605909 1p36
codes for the protein PTEN-induced putative kinase 1.
PARK7 OMIM #606324 1p36
caused by mutations in DJ-1 (OMIM 602533)
caused by mutations in LRRK2 which codes for the protein
PARK8 OMIM #607060 12q12 dardarin. In vitro, mutant LRRK2 causes protein aggregation
and cell death, possibly through an interaction with
PARK9 OMIM #606693 1p36
PARK10 OMIM %606852 1p
2q36PARK11 OMIM %607688
37
Xq21PARK12 OMIM %300557
q25
PARK13 OMIM #610297 2p12
parkin.[19] LRRK2 mutations, of which the most common is
G2019S, cause autosomal dominant Parkinson disease, with
a penetrance of nearly 100% by age 80.[20] G2019S is the
most common known genetic cause of Parkinson disease,
found in 1-6% of U.S. and European PD patients.[21] It is
especially common in Ashkenazi Jewish patients, with a
prevalence of 29.7% in familial cases and 13.3% in
sporadic.[22]
Caused by mutations in the ATP13A2 gene, and also known
as Kufor-Rakeb Syndrome. PARK9 may be allelic to
PARK6.
However, this gene locus has conflicting data, and may not
have significance.
Caused by mutations in the HTRA2 (HtrA serine peptidase
2) gene.
Toxins
One theory holds that the disease may result in many or even most cases from the combination of
a genetically determined vulnerability to environmental toxins along with exposure to those
toxins.[23] This hypothesis is consistent with the fact that Parkinson's disease is not distributed
homogeneously throughout the population; its incidence varies geographically. It appears that
incidence varies by time as well, for although the later stages of untreated PD are distinct and
readily recognizable, the disease was not remarked upon until the beginning of the Industrial
Revolution and not long thereafter became a common observation in clinical practice. The toxins
most strongly suspected at present are certain pesticides and transition-series metals such as
manganese or iron, especially those that generate reactive oxygen species,[13][24] and/or bind to
neuromelanin, as originally suggested by G.C. Cotzias.[25][26] In the Cancer Prevention Study II
Nutrition Cohort, a longitudinal investigation, individuals who were exposed to pesticides had a
70% higher incidence of PD than individuals who were not exposed.[27]
MPTP (pro-toxin N-methyl-4-phenyl-1,2,3,6-tetrahyropyidine) is used as a model for Parkinson's,
as it can rapidly induce parkinsonian symptoms in human beings and other animals of any age.
MPTP was notorious for a string of Parkinson's disease cases in California in 1982 when it
contaminated the illicit production of the synthetic opiate MPPP. Its toxicity likely comes from
generation of reactive oxygen species through tyrosine hydroxylation.[28]
Other toxin-based models employ PCBs,[29] paraquat[30] (a herbicide) in combination with maneb
(a fungicide),[31] rotenone[32] (an insecticide), and specific organochlorine pesticides including
dieldrin[33] and lindane.[34] Rotenone is an inhibitor of complex 1 of the electron transport chain. It
easily crosses membranes due to its extremely hydrophobic properties. Rotenone, therefore, does
not rely on the dopamine transporter to enter into the cytoplasm. Numerous studies have found an
increase in PD in persons who consume rural well water; researchers theorize that water
consumption is a proxy measure of pesticide exposure. In agreement with this hypothesis are
studies which have found a dose-dependent increase in PD in persons exposed to agricultural
chemicals.
Head trauma
Past episodes of head trauma are reported more frequently by sufferers than by others in the
population.[35][36][37] A methodologically strong recent study[35] found that those who have
experienced a head injury are four times more likely to develop Parkinson’s disease than those
who have never suffered a head injury. The risk of developing Parkinson’s increases eightfold for
patients who have had head trauma requiring hospitalization, and it increases 11-fold for patients
who have experienced severe head injury. The authors comment that since head trauma is a rare
event, the contribution to PD incidence is slight. They express further concern that their results
may be biased by recall, i.e., the PD patients because they reflect upon the causes of their illness,
may remember head trauma better than the non-ill control subjects. These limitations were
overcome recently by Tanner and colleagues,[38] who found a similar risk of 3.8, with increasing
risk associated with more severe injury and hospitalization.
Treatment
Parkinson's disease is a chronic disorder that requires broad-based management including patient
and family education, support group services, general wellness maintenance, physiotherapy,
exercise, and nutrition.[11] At present, there is no cure for PD, but medications or surgery can
provide relief from the symptoms.
Levodopa
Stalevo for treatment of Parkinson's disease
The most widely used form of treatment is L-dopa in various forms. L-dopa is transformed into
dopamine in the dopaminergic neurons by L-aromatic amino acid decarboxylase (often known by
its former name dopa-decarboxylase). However, only 1-5% of L-DOPA enters the dopaminergic
neurons. The remaining L-DOPA is often metabolised to dopamine elsewhere, causing a wide
variety of side effects. Due to feedback inhibition, L-dopa results in a reduction in the
endogenous formation of L-dopa, and so eventually becomes counterproductive.
Carbidopa and benserazide are dopa decarboxylase inhibitors. They help to prevent the
metabolism of L-dopa before it reaches the dopaminergic neurons and are generally given as
combination preparations of carbidopa/levodopa (co-careldopa) (e.g. Sinemet, Parcopa) and
benserazide/levodopa (co-beneldopa) (e.g. Madopar). There are also controlled release versions
of Sinemet and Madopar that spread out the effect of the L-dopa. Duodopa is a combination of
levodopa and carbidopa, dispersed as a viscous gel. Using a patient-operated portable pump, the
drug is continuously delivered via a tube directly into the upper small intestine, where it is rapidly
absorbed. There is also Stalevo (Carbidopa, Levodopa and Entacapone).
Tolcapone inhibits the COMT enzyme, thereby prolonging the effects of L-dopa, and so has been
used to complement L-dopa. However, due to its possible side effects such as liver failure, it's
limited in its availability.
A similar drug, entacapone, has similar efficacy and has not been shown to cause significant
alterations of liver function. A recent follow-up study by Cilia and colleagues[39] looked at the
clinical effects of long-term administration of entacapone, on motor performance and
pharmacological compensation, in advanced PD patients with motor fluctuations: 47 patients with
advanced PD and motor fluctuations were followed for six years from the first prescription of
entacapone and showed a stabilization of motor conditions, reflecting entacapone can maintain
adequate inhibition of COMT over time.[39]
Mucuna pruriens, is a natural source of therapeutic quantities of L-dopa, and has been under
some investigation.[40]
Dopamine agonists
The dopamine agonists bromocriptine, pergolide, pramipexole, ropinirole , cabergoline,
apomorphine, and lisuride are moderately effective. These have their own side effects including
those listed above in addition to somnolence, hallucinations and/or insomnia. Several forms of
dopamine agonism have been linked with a markedly increased risk of problem gambling.
Dopamine agonists initially act by stimulating some of the dopamine receptors. However, they
cause the dopamine receptors to become progressively less sensitive, thereby eventually
increasing the symptoms.
Dopamine agonists can be useful for patients experiencing on-off fluctuations and dyskinesias as
a result of high doses of L-dopa. Apomorphine can be administered via subcutaneous injection
using a small pump which is carried by the patient. A low dose is automatically administered
throughout the day, reducing the fluctuations of motor symptoms by providing a steady dose of
dopaminergic stimulation. After an initial "apomorphine challenge" in hospital to test its
effectiveness and brief patient and primary caregiver (often a spouse or partner), the latter of
whom takes over maintenance of the pump. The injection site must be changed daily and rotated
around the body to avoid the formation of nodules. Apomorphine is also available in a more acute
dose as an autoinjector pen for emergency doses such as after a fall or first thing in the morning.
Nausea and vomiting are common, any may require domperidone (an antiemetic).
MAO-B inhibitors
Selegiline and rasagiline reduce the symptoms by inhibiting monoamine oxidase-B (MAO-B),
which inhibits the breakdown of dopamine secreted by the dopaminergic neurons. Metabolites of
selegiline include L-amphetamine and L-methamphetamine (not to be confused with the more
notorious and potent dextrorotary isomers). This might result in side effects such as insomnia.
Use of L-dopa in conjunction with selegiline has increased mortality rates that have not been
effectively explained. Another side effect of the combination can be stomatitis. One report raised
concern about increased mortality when MAO-B inhibitors were combined with L-dopa;[41]
however subsequent studies have not confirmed this finding.[42] Unlike other non selective
monoamine oxidase inhibitors, tyramine-containing foods do not cause a hypertensive crisis.
Speech therapies
The most widely practiced treatment for the speech disorders associated with Parkinson's disease
is Lee Silverman Voice Treatment (LSVT). LSVT focuses on increasing vocal loudness.[43]
A study found that an electronic device providing frequency-shifted auditory feedback (FAF)
improved the clarity of Parkinson's patients' speech.[44]
Physical exercise
Regular physical exercise and/or therapy, including yoga, tai chi, and dance, can be beneficial to
the patient for maintaining and improving mobility, flexibility, balance, and range of motion.
Physicians and physical therapists often recommend basic exercises, such as bringing the toes up
with every step, carrying a bag with weight to decrease the bend on one side, and practicing
chewing hard and moving the food around the mouth.[45]
Surgery and deep brain stimulation
Illustration showing an electrode placed deep seated in the brain
Treating Parkinson's disease with surgery was once a common practice, but after the discovery of
levodopa, surgery was restricted to only a few cases. Studies in the past few decades have led to
great improvements in surgical techniques, and surgery is again being used in people with
advanced PD for whom drug therapy is no longer sufficient.
Deep brain stimulation is presently the most used surgical means of treatment, but other surgical
therapies that have shown promise include surgical lesion of the subthalamic nucleus[46] and of
the internal segment of the globus pallidus, a procedure known as pallidotomy.[47]
Methods undergoing evaluation
Gene therapy
Currently under investigation is gene therapy. This involves using a non-infectious virus to
shuttle a gene into a part of the brain called the subthalamic nucleus (STN). The gene used leads
to the production of an enzyme called glutamic acid decarboxylase (GAD), which catalyses the
production of a neurotransmitter called GABA.[48] GABA acts as a direct inhibitor on the
overactive cells in the STN.
GDNF infusion involves the infusion of GDNF (glial-derived neurotrophic factor) into the basal
ganglia using surgically implanted catheters. Via a series of biochemical reactions, GDNF
stimulates the formation of L-dopa. GDNF therapy is still in development.
Implantation of stem cells genetically engineered to produce dopamine or stem cells that
transform into dopamine-producing cells has already started being used. These could not
constitute cures because they do not address the considerable loss of activity of the dopaminergic
neurons. Initial results have been unsatisfactory, with patients still retaining their drugs and
symptoms.
Neuroprotective treatments
Neuroprotective treatments are at the forefront of PD research, but are still under clinical
scrutiny.[49] These agents could protect neurons from cell death induced by disease presence
resulting in a slower progression of disease. Agents currently under investigation as
neuroprotective agents include apoptotic drugs (CEP 1347 and CTCT346), lazaroids,
bioenergetics, antiglutamatergic agents and dopamine receptors.[50] Clinically evaluated
neuroprotective agents are the monoamine oxidase inhibitors selegiline[51] and rasagiline,
dopamine agonists, and the complex I mitochondrial fortifier coenzyme Q10.
Neural transplantation
The first prospective randomised double-blind sham-placebo controlled trial of dopamineproducing cell transplants failed to show an improvement in quality of life although some
significant clinical improvements were seen in patients below the age of 60.[52] A significant
problem was the excess release of dopamine by the transplanted tissue, leading to dystonias.[53]
Research in African green monkeys suggests that the use of stem cells might in future provide a
similar benefit without inducing dystonias.[54]
Nutrients
Nutrients have been used in clinical studies and are widely used by people with Parkinson's
disease in order to partially treat PD or slow down its deterioration. The L-dopa precursor Ltyrosine was shown to relieve an average of 70% of symptoms.[55] Ferrous iron, the essential
cofactor for L-dopa biosynthesis was shown to relieve between 10% and 60% of symptoms in
110 out of 110 patients.[56] [57]
More limited efficacy has been obtained with the use of THFA, NADH, and pyridoxine—
coenzymes and coenzyme precursors involved in dopamine biosynthesis.[58] Vitamin C and
vitamin E in large doses are commonly used by patients in order to theoretically lessen the cell
damage that occurs in Parkinson's disease. This is because the enzymes superoxide dismutase and
catalase require these vitamins in order to nullify the superoxide anion, a toxin commonly
produced in damaged cells. However, in the randomized controlled trial, DATATOP of patients
with early PD, no beneficial effect for vitamin E compared to placebo was seen.[51]
Coenzyme Q10 has more recently been used for similar reasons. MitoQ is a newly developed
synthetic substance that is similar in structure and function to coenzyme Q10.
Qigong
There have been two studies looking at qigong in Parkinson's disease. In a trial in Bonn, an openlabel randomised pilot study in 56 patients found an improvement in motor and non-motor
symptoms amongst patients who had undergone one hour of structured qigong exercise per week
in two 8-week blocks. The authors speculate that visualizing the flow of "energy" might act as an
internal cue and so help improve movement.[59]
The second study, however, found qigong to be ineffective in treating Parkinson's disease. In that
study, researchers used a randomized cross-over trial to compare aerobic training with qigong in
advanced Parkinson's disease. Two groups of PD patients were assessed, had 20 sessions of either
aerobic exercise or qigong, were assessed again, then after a 2-month gap were switched over for
another 20 sessions, and finally assessed again. The authors found an improvement in motor
ability and cardiorespiratory function following aerobic exercise, but found no benefit following
qigong. The authors also point out that aerobic exercise had no benefit for patients' quality of
life.[60]
Botox
Recently, Botox injections are being investigated as a non-FDA approved possible experimental
treatment.[61]
Medicine formularies
Plan or option
[Link to appropriate Mediscor formulary]
GMHPP
Gold Options
G1000, G500 and
G200
Blue Options
B300 and B200
GMISHPP
Blue Option B100
[Core]
n/a
Epidemiology
EPIDEMIOLOGY
· Predominant age: 60 years, with 5% between the ages of 21-39
· Predominant sex: Male > Female (1.4:1)
Incidence
In the US: 50,000 new cases per year
Prevalence
· In ages 55-64, 0.3%
· In ages 65-74, 1%
· In ages 75-84, 3.1%
· In ages 85-94, 4.3%
Prognosis
PD is not considered to be a fatal disease by itself, but it progresses with time. The average life
expectancy of a PD patient is generally lower than for people who do not have the disease.[62] In
the late stages of the disease, PD may cause complications such as choking, pneumonia, and falls
that can lead to death.
The progression of symptoms in PD may take 20 years or more. In some people, however, the
disease progresses more quickly. There is no way to predict what course the disease will take for
an individual person. With appropriate treatment, most people with PD can live productive lives
for many years after diagnosis.
In at least some studies, it has been observed that mortality was significantly increased, and
longevity decreased among nursing home patients as compared to community dwelling
patients.[63]
One commonly used system for describing how the symptoms of PD progress is called the Hoehn
and Yahr scale. Another commonly used scale is the Unified Parkinson's Disease Rating Scale
(UPDRS). This much more complicated scale has multiple ratings that measure motor function,
and also mental functioning, behavior, mood, and activities of daily living; and motor function.
Both the Hoehn and Yahr scale and the UPDRS are used to measure how individuals are faring
and how much treatments are helping them. It should be noted that neither scale is specific to
Parkinson's disease; that patients with other illnesses can score in the Parkinson's range.
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