139

Parkinson Disease
NUTAN SHARMA, MD, PhD

SYNONYMS
Shaking palsy Idiopathic parkinsonism
Paralysis agitans

  
ICD-10 CODES
G20 Parkinson disease G90.3 Multisystem degeneration of the autonomic nervous
G25.0 Essential tremor system
G23.9 Degenerative disease of basal ganglia, unspecified G31.85 Corticobasal degeneration
G23.1 Progressive supranuclear palsy G31.8 Lewy body dementia

  
Definition alpha-synuclein, leucine-rich repeat kinase 2 (LRRK2),
Parkin, PTEN-induced putative kinase-1 (PINK1), DJ-1,
Parkinson disease (PD) is a chronic, progressive neurodegen- ATPase type 13A2 (ATP3A2), and glucocerebrosidase. To
erative disease. On pathologic examination, it is character- date, monogenic causes of PD account for about 5% of
ized by preferential degeneration of dopaminergic neurons all PD cases, inherited in either an autosomal-dominant
in the substantia nigra pars compacta and the presence of or autosomal-recessive pattern. The most common mono-
cytoplasmic inclusions known as Lewy bodies. Clinically, it genic cause of PD is mutations in the LRKK2 gene, which
is characterized by a resting tremor, bradykinesia, and rigid- have been associated with 1% of sporadic PD cases and 4%
ity. It is important to distinguish PD from the disorders that of hereditary parkinsonism cases.3 While the presence of
are known collectively as the Parkinson-plus syndromes. homozygous pathogenic mutations in the glucocerebrosi-
These are relatively rare disorders that share some of the fea- dase gene result in Gaucher disease, the presence of a hetero-
tures of PD, such as rigidity and bradykinesia. However, the zygous pathogenic mutation increases the risk of developing
Parkinson-plus syndromes do not respond to medical treat- PD.4
ment and have some unique clinical features as well. Environmental risk factors are also thought to play a role
The prevalence of PD has been estimated in greater than in the pathogenesis of PD. Numerous studies have focused
80 studies conducted around the world. The most consis- on the risk of pesticide and heavy metal exposure to the
tent finding is that PD is an age-related disease. Between development of PD. Whereas the methodology used varies
the ages of 50 and 59, the prevalence is estimated at 273 per in different studies, in those with an occupational exposure
100,000, whereas between 70 and 79 the prevalence is esti- to pesticides or heavy metals, the data have been mixed,
mated at 2700 per 100,000.1 Some studies have reported indicating either an increased risk of developing PD or no
a higher prevalence of PD in males, whereas other studies increased risk.1
have not.
The genetic contribution to the development of PD is Symptoms
an area of intense study. A family history of PD, in a first-
degree relative, is estimated to increase the risk of developing The most common initial manifestations of PD are uni-
PD by two- to threefold.2 A variety of gene mutations have lateral rest tremor and bradykinesia. The resting tremor is
been identified, in family studies, that can cause PD.1 Seven suppressed by either purposeful movement or sleep and
disease-causing mutations have been identified, including exacerbated by anxiety. The bradykinesia may produce a

915
916 PA RT 3 Rehabilitation

sensation of stiffness in the affected arm or leg. A common good at ameliorating the rest tremor and bradykinesia, par-
complaint is that the affected limb is “weak.” However, on ticularly in the early stages of the disease. Typically, the
objective testing there is no motor strength weakness, but rest tremor will subside for 1–3 hours after the last dose
typically bradykinesia, manifesting as a reduced speed and of medication. Other features, such as poor hand writing,
amplitude in finger tapping or toe tapping, is evident. Pain hypophonia, and loss of postural reflexes, do not respond to
is also a part of PD. An aching pain in the initially affected oral medication.
limb may first be attributed to bursitis or arthritis. Less
common presenting complaints include gait difficulty and Functional Limitations
fatigue. It is not uncommon for one of these features to be
present for months or even years before others develop. Functional limitations depend on which symptoms are
As the disease progresses, there is marked difficulty in most prominent in a particular patient. Early during PD,
both initiating and terminating movement. There is diffi- the sole limitation may be in one’s ability to write legibly.
culty in rising from a seated position, particularly when one Affected individuals are still able to perform activities of
is seated in a sofa or chair without armrests. The unilateral daily living, although they may prefer to use the unaffected
rest tremor and bradykinesia become bilateral. Handwrit- limb for tasks such as shaving and dressing. Although the
ing becomes smaller and more difficult to read. Friends and rest tremor may result in a feeling of self-consciousness or
family members often complain that the patient’s speech is embarrassment, it does not affect one’s independence, as it
more difficult to understand, particularly on the telephone. is suppressed with purposeful movement.
The symptom of a softer voice with a decline in enunciation As the disease progresses, the ability to perform fine
is known as hypophonia. motor skills declines, and difficulty with standing and gait
develops. An individual will have difficulty in buttoning
Physical Examination a shirt or tying shoelaces. More time will be required to
stand and initiate gait. Postural instability with a tendency
The most distinctive clinical feature is the rest tremor. It to retropulse develops. Thus, patients have difficulty in
is typically present in a single upper extremity early in the climbing stairs and walking safely and quickly. Slowed
course of the disease. As the disease progresses, the resting reaction times may also affect one’s ability to drive safely.
tremor may spread to both the ipsilateral lower limb and Decisions about whether someone should drive are often
the contralateral limbs. Examination of motor tone reveals difficult and must be made on an individual basis. Marked
cogwheel rigidity in the affected limb. Motor strength, how- hypophonia may make speaking on the telephone difficult
ever, remains unaffected. as well. As the voice becomes more affected, dysphagia is
Additional features that must be evaluated in an exami- likely to develop.
nation include rapid, repetitive limb movements and gait. One aspect of PD that has historically gotten little atten-
Examination of repetitive movements of the fingers, entire tion is the effect it has on sexual activity. Males may experi-
hand, or foot will reveal bradykinesia and decreased ampli- ence erectile dysfunction and difficulty with ejaculation as
tude and accuracy of finger tapping or toe tapping move- part of the autonomic dysfunction found in PD. Females
ments in the affected limb. Examination of gait will reveal may experience inadequate lubrication and a tendency to
decreased arm swing on the affected side, smaller steps, and urinate during sex secondary to autonomic dysfunction. In
an inability to pivot turn. Typically, patients make several both sexes, hypersexuality may be seen as a side effect of
steps to complete a turn because of some degree of pos- treatment with dopamine agonists.7
tural instability. Deep tendon reflexes and sensation are not In end-stage PD, limitations include marked dysphagia
affected in PD. and severe abnormalities of gait that require both devices
In advanced PD, loss of postural reflexes becomes evi- and one or two persons for assistance. At this stage, help is
dent. Individuals are unable to maintain balance when turn- necessary for all activities of daily living as well.
ing. Other manifestations of advanced PD include episodes
of frozen gait and dysphagia. There is also a spectrum of Diagnostic Studies
cognitive impairment in PD, extending from minimal cog-
nitive impairment (MCI) to PD with dementia (PDD). PD is a clinical diagnosis. Conventional laboratory investi-
MCI is defined as a gradual decline in cognitive function, gations do not contribute to the diagnosis or management
identified by the patient or caregiver, that does not inter- of PD. Computed tomography and magnetic resonance
fere significantly with functional independence.5 PDD imaging scans of the brain do not reveal any consistent
is dementia with a slowly progressive course of cognitive abnormalities. Recently a dopamine transporter radioligand
impairment that most prominently affects attention, execu- has become available for clinical use in single-photon emis-
tive, and visuospatial functions.6 sion computed tomography scanning to assist in the evalu-
In examination of someone who is taking medication ation of those with suspected PD. The scan is known as a
for PD, it is important to record the time at which the last DaTSCAN, and an analysis demonstrates that it does not
dose of medication was taken relative to the time at which provide greater accuracy than a clinical diagnosis, based on
the examination occurs. Medications for PD are particularly history and examination of a patient.8
 CHAPTER 139 Parkinson Disease 917

aromatic amino acid decarboxylase. To ensure that ade-

DIFFERENTIAL DIAGNOSIS
quate levels of levodopa reach the central nervous system,
The differential diagnosis includes essential tremor and several levodopa is administered simultaneously with a peripheral
diseases known collectively as the Parkinson-plus syndromes:
Lewy body dementia, progressive supranuclear palsy, multiple
decarboxylase inhibitor. In the United States, the most used
system atrophy, and corticobasal degeneration. peripheral decarboxylase inhibitor is carbidopa. Levodopa is
most effective in reducing tremor, rigidity, and akinesia. The
Condition Symptoms most common side effects, seen with the onset of treatment,
Essential tremor An involuntary, rhythmic tremor of are nausea, abdominal cramping, and diarrhea. Long-term
a body part, most commonly treatment with levodopa is associated with three types of
affecting arms and hands but complications: hourly fluctuations in motor state, dyskine-
can also involve head, voice, sias, and a variety of psychiatric complaints including hal-
tongue, trunk, or legs lucinations and confusion. However, it is not clear whether
Lewy body Motor symptoms of PD with the motor fluctuations are due to the levodopa treatment
dementia rapidly progressive dementia alone, the disease progression alone, or a complex interplay
within the first year; visual of imperfect dopamine replacement and the inexorable pro-
hallucinations are common gression of disease. In summary, current evidence supports
Progressive Bradykinesia, rigidity, frequent the use of dopamine replacement as soon as the symptoms
supranuclear falls early in disease course, of PD become troublesome to the individual patient. There
palsy rest tremor, and inability to is no evidence that supports withholding of treatment to
voluntarily move the eyes minimize long-term motor complications.
upward Two medications that are available for the amelioration
Multiple system Bradykinesia, rigidity, ataxia, of motor complications are delivered via different routes:
atrophy and autonomic dysfunction levodopa-carbidopa intestinal gel (LCIG) and subcutaneous
(flushing, palpitations, injections of apomorphine. LCIG is administered via a per-
nausea, vomiting) cutaneous endoscopic gastrostomy with a jejunal extension
Corticobasal Bradykinesia, rigidity, inability tube (PEG-J). The medication is then administered, via a
degeneration to coordinate purposeful pump, into the PEG-J, resulting in reduced time in the “off”
movements (apraxia), and stage without an increase in dyskinesias.9 Apomorphine, a
sense that limbs are not one’s D2 receptor agonist, is particularly helpful in the morning.
own (alien limb syndrome) A daily injection has been shown to reduce the time before
symptoms are ameliorated, allowing patients to move more
PD, Parkinson disease.
easily and perform the activities of daily living.10
Dopamine agonists, which directly stimulate dopamine
receptors, are also used in the treatment of PD. These agents
Treatment can be used either as an adjunct to levodopa therapy or as
Initial monotherapy. The older dopamine agonists, which are rela-
tively nonspecific and exert their effects at both D1 and D2
The decision to initiate medical treatment is based on the receptors, are bromocriptine and pergolide. In comparison
degree of disability and discomfort that the patient is expe- to the side effects seen with levodopa, there is a lower fre-
riencing. Six classes of drugs are used to treat PD (sum- quency of dyskinesias and a higher frequency of confusion
marized in Table 139.1). The selection of a particular drug and hallucinations. The newer dopamine agonists pramipex-
depends on the patient’s main complaint, which is usually ole and ropinirole are more specific for D2 receptors. These
either a rest tremor or bradykinesia. There is no evidence to newer agents have been reported to cause daytime somno-
suggest that expediting or delaying the onset of treatment lence, peripheral edema, and impulse control disorders.11
for PD has any effect on the overall course of the disease. All dopamine agonists can cause orthostatic hypotension,
However, those who do not receive treatment and are brady- particularly when they are first introduced. It is best to start
kinetic are at greater risk of falling and injuring themselves. with a small dose of medication in late afternoon or evening
Anticholinergic agents are the oldest class of medications and then slowly increase the total daily dose.
used in PD. They are most effective in reducing the rest Inhibitors of dopamine metabolism are also used in the
tremor and rigidity associated with PD. However, the side medical treatment of PD. Both selegiline and rasagiline
effects associated with anticholinergic agents typically limit inhibit monoamine oxidase B, which metabolizes dopamine
their usefulness. Amantadine is also used in the treatment of in the central nervous system. Thus, inhibitors of mono-
PD. Amantadine produces a limited improvement in akine- amine oxidase B are thought to improve an individual’s
sia, rigidity, and tremor. response to levodopa by alleviating the motor fluctuations
Dopamine replacement remains the cornerstone of anti- that are seen with long-term levodopa treatment. Another
parkinson therapy. Levodopa is the natural precursor to agent that inhibits the metabolism of dopamine is entaca-
dopamine and is converted to dopamine by the enzyme pone. Entacapone inhibits catechol O-methyltransferase
918

TABLE
139.1 Classes of Antiparkinson Medications, Mechanisms of Action, Beneficial Effects, and Side Effects
PA RT 3 Rehabilitation
  
Drug Class Specific Agents Mechanism of Action Effective For Side Effects
Anticholinergic Benztropine Muscarinic receptor Tremor, rigidity Dry mouth, blurred vision,
blocker constipation, urinary
retention, confusion,
hallucinations, impaired
concentration
Antiviral Amantadine Promotes synthesis and Tremor, rigidity, Leg edema, livedo reticularis,
release of dopamine akinesia confusion, hallucinations
Dopamine Levodopa (oral and Converted to dopamine Tremor, rigidity, Nausea, diarrhea, confusion,
replacement intestinal forms) akinesia, freezing hallucinations
Dopamine agonists Bromocriptine, Dopamine analogs that Rigidity, akinesia Leg edema, nausea,
(D1 and D2) pergolide, bind to D1 and D2 confusion, hallucinations
apomorphine receptors
Dopamine Ropinirole, Dopamine analogs that Rigidity, akinesia Leg edema, sleep attacks,
agonists (D2) pramipexole bind to D2 receptors nausea, confusion,
hallucinations
Monoamine Selegiline, rasagiline Inhibit the metabolism of Mild reduction in Nausea, hallucinations,
oxidase B inhibitors dopamine “wearing off” from confusion
levodopa
Catechol Entacapone Inhibits the metabolism of Mild reduction in Dyskinesia, nausea, diarrhea
O-methyltransferase dopamine “wearing off” from
inhibitor levodopa
Adenosine A2A Istradefylline Adenosine analog that Reduces the Dyskinesia, dizziness,
antagonist binds to A2A receptor wearing off time constipation, nausea,
from levodopa hallucinations, insomnia

in the periphery. Entacapone is administered in conjunc- Because the symptoms of PD gradually worsen over
tion with levodopa and, by inhibiting peripheral catechol time, individuals can benefit from periodic physical train-
O-methyltransferase activity, increases the amount of ing throughout the course of their illness. The training
levodopa that reaches the central nervous system. The ben- may take place either through community-based pro-
efits of entacapone treatment include a reduction in total grams that are more readily accessible for those who live
daily levodopa dose and an improvement in the length of far from an academic center or home-based programs for
time of maximum mobility.12 those who cannot easily travel. An emphasis on gait train-
Istradefylline, an adenosine receptor antagonist, is an ing is particularly helpful to prevent falls and injury. Gait
adjunct to levodopa. Istradefylline has been used in Japan training typically involves training an individual to be
since 2013 and became approved in the United States in conscious of taking a longer stride and putting the foot
2019. Istradefylline is helpful in increasing the time when down with each step. Another method is to use visual cues
an individual experiences maximum mobility.13 to maintain a regular size for each step. For example, one
can put strips of masking tape on the floor, at a regular
Rehabilitation interval that is comfortable for one’s height, weight, and
sex. As PD progresses, episodes of frozen gait, in which
The clinical pathologic process seen in PD reveals that the feet seem to be stuck to the floor, occur. Freezing
patients tend to become more passive, less active, and less episodes can be broken by multiple techniques, such as
motivated as the disease progresses. The benefits to physical visualizing that one is stepping over an imaginary line on
and occupational therapy are thus more far-reaching than a the floor, counting in a rhythmic cadence, or marching
simple improvement in motor function. The physical bene- in place.
fits include improvement in muscle strength and tone as well Occupational therapy is particularly helpful in recom-
as maintenance of an adequate range of motion in the joints. mending adaptive devices or establishing new routines that
The psychological benefits include enlistment of the patient allow people with PD to continue to live independently.
as an active participant in treatment and provision of a sense For example, the use of a long-handled shoehorn eliminates
of mastery over the effects of PD. Both physical therapy and the need to bend over and thus reduces the risk that a per-
occupational therapy focus on mobility, the use of adaptive son with PD will fall while getting dressed. Other examples
equipment, and safety in both the home and community. of adaptive equipment are a firmly secured grab bar in the
 CHAPTER 139 Parkinson Disease 919

bathtub and a relatively high toilet seat with armrests to unilateral pallidotomy are limited and varied in their find-
minimize the risk of freezing while on the toilet. ings.15,16 Thus, neuropsychological evaluation is recom-
Speech therapy plays a critical role for those PD patients mended in all patients both before and after surgery.
who suffer from communication difficulties. Although dys- Deep brain stimulation (DBS) for PD consists of high-
arthria is difficult to treat, hypophonia can be overcome frequency electrical stimulation in either the globus pallidus
with training. Specifically, the Lee Silverman Voice Treat- or the subthalamic nucleus. DBS requires surgery, in which
ment program has been shown to be effective in improving the source of electrical stimulation is placed subcutane-
both the volume and clarity of speech in those with PD.14 ously in the chest wall and the leads to which it is attached
Swallow evaluation and therapy are also helpful in the treat- are placed in one of the locations listed. The advantage
ment of dysphagia, which occurs as PD progresses. of DBS is that the degree of electrical stimulation can be
easily adjusted, externally, once the DBS unit is in place.
Procedures In contrast, both thalamotomy and pallidotomy result in
permanent, fixed lesions in the brain. DBS of the ventral
Feeding tubes are sometimes used in individuals who have intermediate nucleus of the thalamus is effective in the treat-
severe end-stage PD. Some patients elect hospice care, with- ment of a severe and disabling tremor that is unresponsive
out artificial feeding at that point. Individuals who do get to medical therapy, with reports of approximately 80%
feeding tubes may need to have medication doses adjusted improvement in tremor 5 years after DBS implantation.17
(e.g., carbidopa-levodopa will now bypass the esophagus DBS of the globus pallidus results in a marked reduction
and have a shortened time to onset of action). in dyskinesia. There are also improvements in bradykinesia,
speech, gait, rigidity, and tremor. DBS of the subthalamic
Technology nucleus also results in marked improvement in tremor, aki-
nesia, gait, and postural stability.18
A common source of frustration for those with PD is that
others cannot hear them easily. Fortunately, there are several Health Equity
methods for overcoming that problem. Applications, com-
monly known as “apps,” that can be downloaded onto por- Health equity, the state in which everyone has a fair
table electronic devices, such as cell phones and tablets, can opportunity to attain their highest level of health, has not
be utilized to convert text into speech. For those who prefer been achieved for those with PD. A recent report found
to use their natural voice, rather than an artificial voice, por- that the proportion of African American patients treated
table voice amplifiers are readily available. For those who at the Boston Medical Center (BMC) movement disorder
experience episodes of frozen gait, new walkers with a laser clinic, a tertiary center providing state-of-the-art care, was
beam provide a visual cue that allows patients to “step over” significantly lower than that found in the total popula-
the laser beam and resume walking. tion receiving general medical care at BMC.19 These data
indicate that access to specialized neurologic care is not
Surgery equally available to all racial groups. Consistent with this
finding, an analysis of DBS utilization rates demonstrates
Although many medications are available for the treatment that African American patients are five times less likely
of early and moderately advanced PD, they are of limited to undergo DBS than White patients.20 While research
efficacy in those with advanced PD. Several surgical proce- focusing on health equity in PD is in its infancy, initial
dures are currently available for those with advanced PD. reports indicate that significant disparities exist between
These procedures consist of either creation of a permanent different racial groups.
lesion or insertion of an electrical stimulator in a specific
nucleus of the brain. Potential Disease Complications
Thalamotomy consists of introduction of a lesion in the
ventral intermediate nucleus of the thalamus. Thalamotomy Depression is found in approximately 35% of those with
has been reported to produce a reduction in tremor of the PD.21 It may be difficult to distinguish true depression from
contralateral limb in 85% of the patients who were treated. the apathy associated with PD. The crucial factor is to deter-
Thalamotomy is recommended in PD patients with an mine whether the patient has a true disturbance of mood,
asymmetric, severe, medically intractable tremor. with loss of interest, sleep disturbance, and sometimes
Unilateral pallidotomy consists of introduction of a suicidal thoughts. The reasons for depression in PD are a
lesion in the globus pallidus. The most striking benefits subject of debate. There is a suspicion that the pathologic
are a reduction in contralateral drug-induced dyskinesias, process of PD itself may predispose to depression. Regardless
contralateral tremor, bradykinesia, and rigidity. Unilateral of the cause, recognition and treatment of depression may
pallidotomy is recommended in PD patients with brady- have a significant impact on the overall disability caused by
kinesia, rigidity, and tremor who experience significant the illness. Many PD patients have been treated safely and
drug-induced dyskinesia despite optimal medical therapy. effectively with selective serotonin reuptake inhibitors, such
However, data regarding the long-term cognitive effects of as fluoxetine and paroxetine. Tricyclic antidepressants can
920 PA RT 3 Rehabilitation

be used, although their anticholinergic properties may limit The complete list of references is available in the eBook
their effectiveness. (see inside front cover for access details).
Gastrointestinal complications also occur in PD. Dys-
phagia is typically due to poor control of the muscles of
both mastication and the oropharynx. Soft food is easier Selected References
to eat, and antiparkinson medication improves swallowing. 1. Wirdefeldt K, Adami H, Cole P, et al. Epidemiology and etiology
Constipation is a frequent complaint in those with PD.


of Parkinson’s disease: a review of the evidence. Eur J Epidemiol.
Treatment includes increase in physical activity, discontinu- 2011;26:S1–S58.
ation of anticholinergic drugs, and maintenance of a diet 2. Balestrino R, Schapira AHV. Parkinson disease. Eur J Neurol.


with intake of adequate fluids, fruit, vegetables, fiber, and 2020;27:27–42.
lactulose (10 to 20 g daily). 3. Lee A, Gilbert RM. Epidemiology of Parkinson disease. Neurol


Clin. 2016:955–965.
4. Smith LJ, Lee CY, Menozzi E, Schapira AHV. Genetic varia-
Potential Treatment Complications


tions in GBA1 and LRRK2 genes: Biochemical and clinical con-
The motor complications seen with pharmacologic treat- sequences in Parkinson disease. Front Neurol. 2022;13:971252.
[Link]
ment are divided into two categories: fluctuations (off state)
5. Goldman JG, Sieg E. Cognitive Impairment and dementia in
and levodopa-induced dyskinesias. The off state consists of


Parkinson disease. Clin Geriatr Med. 2020;36:365–377.
a return of the signs and symptoms of PD: bradykinesia, 7. Gunduz A, Çiftçi T, Erbil AC, Senoglu G, Ser MH, Apaydın H.
tremor, and rigidity. Patients may also experience anxiety,


Impulse control disorders in Parkinson’s disease: A retrospective
dysphoria, or panic during an off state. analysis of 1824 patients in a 12-year period. Neurol Sci. 2023.
The development of levodopa-induced dyskine- [Link]
sias appears to be related to the degree of dopamine 8. de la Fuente-Fernandez. Role of DaTSCAN and clinical diagno-

receptor supersensitivity. As PD progresses, there is an sis in Parkinson disease. Neurology. 2012;78:696–701.
increasing loss of dopamine receptors. This results in an 9. Wirdefeldt K, Odin P, Nyholm D. Levodopa-carbidopa intesti-

increased sensitivity of the remaining dopamine recep- nal gel in patients with Parkinson’s disease: a systematic review.
tors to dopamine itself. Thus, there is a greater chance for CNS Drugs. 2016;30:381–404.
10. Isaacson S, Lew M, Ondo W, Hubble J, Clinch T, Pagan F. Apo-
development of dyskinesias at a given dose of levodopa.

morphine subcutaneous injection for management of morning aki-
Treatment options are to lower each dose of levodopa nesia in Parkinson’s disease. Mov Disord Clin Pract. 2017;4:78–83.
but with an increase in the frequency with which it is 12. Fabbri M, Ferreira JJ, Rascol O. COMT inhibitors in the man-
taken; to add or to increase the dose of a dopamine ago-

agement of Parkinson’s disease. CNS Drugs. 2022;36:261–282.
nist while the dose of levodopa is decreased; and to add 13. Kondo T, Mizuno Y, Japanese Istradefylline Study Group. A

amantadine, which has been shown to be an antidyski- long-term study of istradefylline safety and efficacy in patients
netic agent in some patients.22 There are potential com- with Parkinson disease. Clin Neuropharmacol. 2015;38(2):41.
plications to each of these solutions; reducing each dose 19. Branson C, Quehl L, Weinberg J, et al. Racial disparities in Par-

of levodopa while increasing the frequency of doses (e.g., kinsons disease at a tertiary movement disorders center. Neurol-
once every 2 hours) is a difficult schedule for a patient ogy. 2017;88(16 suppl).
to maintain; adding or increasing the dose of dopamine 20. Cramer SW, Do TH, Palzer EF, et al. Persistent racial disparities

in deep brain stimulation for Parkinson’s disease. Annals of Neu-
agonist may result in compulsive behaviors (shopping,
rol. 2022;92:246–254.
gambling, hypersexuality), excessive daytime sleepiness, 21. Aarsland D, Pahlhagen S, Ballard CG, et al. Depression in Par-
and peripheral edema; amantadine may cause confusion.

kinson’s disease – epidemiology, mechanisms and management.
An alternative is to treat those who continue to experi- Nat Rev Neurol. 2011;8:35–47.
ence an improvement in their mobility with levodopa but 22. Hubsher G, Haider M, Okun MS. Amantadine: the journey from

develop dyskinesias that become more pronounced as the fighting flu to treating Parkinson disease. Neurol. 2012;78:1096–
day progresses with DBS. 1099.
 CHAPTER 139 Parkinson Disease 920.e1

Complete List of References 12. Fabbri M, Ferreira JJ, Rascol O. COMT inhibitors in the man-


agement of Parkinson’s disease. CNS Drugs. 2022;36:261–282.
1. Wirdefeldt K, Adami H, Cole P, et al. Epidemiology and etiology 13. Kondo T, Mizuno Y, Japanese Istradefylline Study Group. A



of Parkinson’s disease: a review of the evidence. Eur J Epidemiol. long-term study of istradefylline safety and efficacy in patients
2011;26:S1–S58. with Parkinson disease. Clin Neuropharmacol. 2015;38(2):41.
2. Balestrino R, Schapira AHV. Parkinson disease. Eur J Neurol. 14. Sapir S, Spielman JL, Ramig LO, Story BH, Fox C. Effects of



2020;27:27–42. intensive voice treatment (the Lee Silverman Voice Treatment
3. Lee A, Gilbert RM. Epidemiology of Parkinson disease. Neurol [LSVT]) on vowel articulation in dysarthric individuals with

Clin. 2016:955–965. idiopathic Parkinson disease: acoustic and perceptual findings. J
4. Smith LJ, Lee CY, Menozzi E, Schapira AHV. Genetic varia- Speech Lang Hear Res. 2007;50:899–912.

tions in GBA1 and LRRK2 genes: Biochemical and clinical con- 15. Alegret M, Valldeoriola F, Tolosa E, et al. Cognitive effects of


sequences in Parkinson disease. Front Neurol. 2022;13:971252. unilateral posteroventral pallidotomy: a 4-year follow-up study.
[Link] Mov Disord. 2003;18(3):323–328.
5. Goldman JG, Sieg E. Cognitive Impairment and dementia in 16. Strutt AM, Lai EC, Jankovic J, et al. Five year follow-up of unilat-



Parkinson disease. Clin Geriatr Med. 2020;36:365–377. eral posteroventral pallidotomy in Parkinson’s disease. Surg Neu-
6. Goetz CG, Emre M, Dubois B. Parkinson’s disease dementia: rol. 2009;71:551–558.

definitions, guidelines and research perspectives in diagnosis. Ann 17. Pahwa R, Lyons KE, Wilkinson SB, et al. Long-term evalua-


Neurol. 2008;64:S81–S92. tion of deep brain stimulation of the thalamus. J Neurosurg.
7. Gunduz A, Çiftçi T, Erbil AC, Senoglu G, Ser MH, Apaydın H. 2006;104:506–512.

Impulse control disorders in Parkinson’s disease: a retrospective 18. Walter BL, Vitek JL. Surgical treatment for Parkinson’s disease.


analysis of 1824 patients in a 12-year period. Neurol Sci. 2023. Lancet Neurol. 2004;3:719–728.
[Link] 19. Branson C, Quehl L, Weinberg J, et al. Racial disparities in Par-


8. la Fuente-Fernandez de. Role of DaTSCAN and clinical diagno- kinsons disease at a tertiary movement disorders center. Neurol-

sis in Parkinson disease. Neurology. 2012;78:696–701. ogy. 2017;88(16 suppl).
9. Wirdefeldt K, Odin P, Nyholm D. Levodopa-carbidopa intesti- 20. Cramer SW, Do TH, Palzer EF, et al. Persistent racial disparities


nal gel in patients with Parkinson’s disease: a systematic review. in deep brain stimulation for Parkinson’s disease. Annals of Neu-
CNS Drugs. 2016;30:381–404. rol. 2022;92:246–254.
10. Isaacson S, Lew M, Ondo W, Hubble J, Clinch T, Pagan F. 21. Aarsland D, Pahlhagen S, Ballard CG, et al. Depression in Par-


Apomorphine subcutaneous injection for management of kinson’s disease – epidemiology, mechanisms and management.
morning akinesia in Parkinson’s disease. Mov Disord Clin Pract. Nat Rev Neurol. 2011;8:35–47.
2017;4:78–83. 22. Hubsher G, Haider M, Okun MS. Amantadine: the journey from

11. Antonini A, Tolosa E, Mizuno Y, Yamamoto M, Poewe WH. A fighting flu to treating Parkinson disease. Neurol. 2012;78:1096–

reassessment of risks and benefits of dopamine agonists in Parkin- 1099.
son’s disease. Lancet Neurol. 2009;8:929–937.