© 2019 JETIR March 2019, Volume 6, Issue 3 www.jetir.

org (ISSN-2349-5162)

A Short Review on Scales for Outcomes in

Parkinson’s disease
Dr.P.Lakshmaiah*, B. Hima saisree1, Ch.Siva sai2, L.Deepthi3, B.Sridevi4
* 1234
Vishwa bharathi colleges of Pharmaceutical Sciences. Perecherla, Guntur.

Abstract

Parkinson’s disease affects the nerve cells in the brain that produce dopamine. Parkinson’s
disease symptoms include muscle rigidity, tremors, and changes in speech and gait. The disorder
that affects predominately dopamine-producing ‘dopaminergic’neurons in a specific area of the
brain called substantial nigra. Symptoms generally develop slowly over years. The progression
of symptoms is often a bit different from one person to another due to the diversity of the
disease. People with Parkinson’s may experience tremor mainly at rest and described as pill
rolling tremor in hands. Other forms of tremor are possible like Bradykinesia, Limb rigidity,
Gait and balance problems. Prevalence rates of depressive disorders in Parkinson’s disease
(Parkinson’s) vary widely across studies. Using Medline on Pub med, a systematic literature
search was carried out for studies of depression in Parkinson’s disease. Some articles were
included and assessed for quality. Clinically significant depressive symptoms, irrespective of the
presence of a DSM (diagnostic and statistical manual) defined depressive disorder, In this study
using a (semi) structured interview to establish DSM criteria, the reported prevalence of major
depressive disorder was while in studies using DSM criteria without a structured interview, the
reported prevalence of major depressive disorder Population studies. The report lower prevalence
rates for both major depressive disorder and the clinically significant depressive symptoms than
studies in other settings. This systematic review suggests that the average prevalence of major
depressive disorder in Parkinson’s is substantial, but lower than generally assumed.

Key words: DSM, Tremor, Depression, Prevalence, Dopamine, levodopa.

Introduction

Parkinson’s disease is a progressive nervous system disorder that affects movement. Symptoms
start gradually, sometimes starting with a barely noticeable tremor in just one hand. Tremors are
common, but the disorder also commonly causes stiffness or slowing of movement. In the early
stages of Parkinson’s disease, your face may show little or no expression. Your arms may not
swing when you walk. Your speech may become soft or slurred. Parkinson’s disease symptoms
worsen as your condition progresses over time. Although Parkinson’s disease can't be cured,
medications might significantly improve your symptoms. Occasionally, your doctor may suggest
surgery to regulate certain regions of your brain and improve your symptoms.

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Parkinsonism is a progressive neurodegenerative disorder with cardinal motor features of tremor,

bradykinesia, and rigidity. Although initially effective, dopaminergic therapies are eventually
complicated by motor fluctuations, including off time (periods of return of Parkinson’s
symptoms when medication effect wears off) and dyskinesia (drug-induced involuntary
movements including chorea and dystonia) in most patients. These motor complications can
impair quality of life and cause significant disability. Risk factors for motor complications
include younger age at onset of Parkinson’s, disease severity, higher levodopa dosage, and
longer disease duration. These problems are often addressed with levodopa adjustments and the
addition of adjunctive medications. Motor fluctuations and dyskinesia can be resistant to medical
therapy. This, along with advances in the understanding of basal ganglia circuitry, surgical
techniques, neuroimaging, and intraoperative microelectrode recording, has led to resurgence in
surgical approaches for medically refractory disabilities. Initially, ablative procedures like
thalamotomy and pallidotomy were used to treat Parkinson’s symptoms. However, due to
concerns about morbidity, especially with bilateral procedures, deep brain stimulation (DBS) has
become the most commonly performed surgery for Parkinson’s in North America.DBS is a
stereotactic surgical procedure that uses an implanted electrode connected to an implantable
pulse generator (IPG) that delivers electrical current to a targeted nucleus in the brain (Zurowski
M et al 2006).

Methods:

Patients:

Patients with Parkinson’s disease were eligible for the study if they met the following inclusion
criteria: an age of 18 to 60 years; disease duration of 4 years or more; a disease severity rating
below stage 3 in the on medication condition, mild-to-moderate impairment in social and
occupational functioning .Exclusion criteria were dementia, major depression with suicidal
thoughts, acute psychosis, and any medical or psychological problem that would interfere with
the conduction of the study protocol ( Dickson D et al 2005).

Pathology, etiology and pathogenesis of Parkinson’s:

The pathological hallmark of Parkinson’s is cell loss within the substantia nigra particularly
affecting the ventral component of the pars compacta. By the time of death, this region of the
brain has lost 50–70% of its neurons compared with the same region in unaffected individuals.
The earliest documented pathological changes in Parkinson’s have been observed in the medulla
oblongata/pontine tegmentum and olfactory bulb. Finally, the pathological changes appear in the
neocortex. This pathological staging is based on the distribution of lewy bodies. Lewy bodies are
the pathological hallmark of Parkinson’s (N Engl J Med et al 1995).

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Patients assigned to neurostimulation underwent bilateral stereotactic surgery of the sub thalamic
nucleus with the implantation of electrodes and a pulse generator within 6 weeks after
randomization, according to operative standards that address local anesthesia, imaging, targeting,
microelectrode recording, and confirmation of the final electrode position. A levodopa challenge
test was performed at baseline and at 24 Blinded assessments were based on preoperative and
postoperative standardized video recordings obtained at baseline and at 24 months. Videos were
recorded for each motor condition (according to whether the patient was or was not receiving
medication or stimulation)( Siderowf A et al 2005).

Outcome Measures:

The primary end point was the between-group difference in mean change in quality of life from
baseline to 2 years, as assessed with the use of the summary index of the Parkinson’s Disease.We
obtained a significant result for quality of life, the following clinically relevant motor functions
were tested sequentially as major secondary outcomes: activities of daily living (uparkinson’srs-
ii score) severity of motor signs (uparkinson’srs-iii score), severity of treatment-related
complications (uparkinson’srs-iv score), and time with good mobility and no troublesome
dyskinesia, as recorded by patients in a diary(Richard IH et al 2004). Minor secondary outcomes
included scores on the Scales for Outcomes in Parkinson’s Disease–Psychosocial (SCOPA-PS)
questionnaire (on a scale from 0 to 33, with higher scores indicating worse functioning), the
Mattis Dementia Rating Scale (on a scale of 0 to 144, with higher scores indicating better
functioning). Brief Psychiatric Rating Scale (on a scale of 18 to 126, with higher scores
indicating worse functioning), the Montgomery and Asberg Depression Rating Scale (on a scale
of 0 to 60, with higher scores indicating worse functioning), the Beck Depression Inventory II
(on a scale of 0 to 63, with higher scores indicating worse functioning), and the Starkstein
Apathy Scale (on a scale of 0 to 42, with higher scores indicating worse functioning), as well as
the levodopa-equivalent daily dose The other minor secondary outcomes are listed in the
Supplementary .

Symptoms:

Parkinson’s disease signs and symptoms can be different for everyone. Early signs may be mild
and go unnoticed. Symptoms often begin on one side of your body and usually remain worse on
that side, even after symptoms begin to affect both sides. A tremor, or shaking, usually begins in
a limb, often your hand or fingers. You may rub your thumb and forefinger back-and-forth,
known as a pill-rolling tremor. Your hand may tremor when it's at rest. Over time, Parkinson’s
disease may slow your movement, making simple tasks difficult and time-consuming. Your steps
may become shorter when you walk. It may be difficult to get out of a chair. You may drag your
feet as you try to walk (Lozano AM et al 2000) .Muscle stiffness may occur in any part of your
body. The stiff muscles can be painful and limit your range of motion. Your posture may become
stooped, or you may have balance problems as a result of Parkinson’s disease. You may have a
decreased ability to perform unconscious movements, including blinking, smiling or swinging
your arms when you walk. You may speak softly, quickly, slur or hesitate before talking. Your
speech may be more of a monotone rather than with the usual inflections. It may become hard to
write, and your writing may appear small.

Causes:

In Parkinson’s disease, certain nerve cells (neurons) in the brain gradually break down or die.
Many of the symptoms are due to a loss of neurons that produce a chemical messenger in your
brain called dopamine. When dopamine levels decrease, it causes abnormal brain activity,
leading to symptoms of Parkinson’s disease. The cause of Parkinson’s disease is unknown, but
several factors appear to play a role, including: Your genes. Researchers have identified specific
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genetic mutations that can cause Parkinson’s disease. But these are uncommon except in rare
cases with many family members affected by Parkinson’s disease. However, certain gene
variations appear to increase the risk of Parkinson’s. Exposure to certain toxins or environmental
factors may increase the risk of later Parkinson’s disease, but the risk is relatively small.
Researchers have also noted that many changes occur in the brains of people with Parkinson’s
disease, although it's not clear why these changes occur.

Risk factors:

Risk factors for Parkinson’s disease include: Age. Young adults rarely experience Parkinson’s
disease. It ordinarily begins in middle or late life, and the risk increases with age. People usually
develop the disease around age 60 or older. Heredity: Having a close relative with Parkinson’s
disease increases the chances that you'll develop the disease. However, your risks are still small
unless you have many relatives in your family with Parkinson’s disease. Sex: Men are more
likely to develop Parkinson’s disease than are women. Exposure to toxins: Ongoing exposure to
herbicides and pesticides may slightly increase your risk of Parkinson’s disease (Eur J Neurol et
al 2003).

Complications:

Parkinson’s disease is often accompanied by these additional problems, which may be treatable:
Thinking difficulties: You may experience cognitive problems (dementia). These usually occur
in the later stages of Parkinson’s disease. Such cognitive problems aren't very responsive to
medications. Depression and emotional changes: You may experience depression, sometimes in
the very early stages. Receiving treatment for depression can make it easier to handle the other
challenges of Parkinson’s disease(Dooneief G et al 1992) You may also experience other
emotional changes, such as fear, anxiety or loss of motivation. Doctors may give you
medications to treat these symptoms. Swallowing problems: You may develop difficulties with
swallowing as your condition progresses. Saliva may accumulate in your mouth due to slowed
swallowing, leading to drooling. Chewing and eating problems: Late-stage Parkinson’s disease
affects the muscles in your mouth, making chewing difficult. This can lead to choking and poor
nutrition. Sleep problems and sleep disorders: People with Parkinson’s disease often have sleep
problems, including waking up frequently throughout the night, waking up early or falling asleep
during the day. People may also experience rapid eye movement sleep behavior disorder, which
involves acting out your dreams. Medications may help your sleep problems (Gagnon JF et al
2007) .Bladder problems: Parkinson’s disease may cause bladder problems, including being
unable to control urine or having difficulty urinating. Constipation: Many people with
Parkinson’s disease develop constipation, mainly due to a slower digestive tract.

Environmental factors:

Identifying environmental factors that predispose to the development of Parkinson’s has proved
elusive. Living in a rural environment appears to confer an increased risk of Parkinson’s, and
perhaps causally linked to this some but not all epidemiological studies have shown a correlation
between exposure to pesticide use and wood preservatives. The only consistent environmental
factor is a strong negative correlation between cigarette smoking and the development of the
disease. It is also possible that mitochondrial dysfunction in Parkinson’s is triggered by one or
more environmental toxins.

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Clinical diagnosis of Parkinson’s:

The characteristic features of Parkinson’s are bradykinesia, rigidity and rest tremor. These may
not all be present. Postural instability may be a feature, though early postural instability
backwards particularly with a history of falls is more suggestive of progressive supranuclear
palsy (PSP). The clinical findings are usually asymmetrical in Parkinson’s. The clinical diagnosis
may often appear straightforward, though it is worth noting that post-mortem studies have shown
an alternative diagnosis in up to a quarter of patients with Parkinson’s diagnosed by general
neurologists. of note, there is substantially less diagnostic error in patients diagnosed in expert
movement disorder clinics which strengthens the argument for early referral of patients to
specialists expert in movement disorders( Emre M et al 2005)

Management of early Parkinson’s:

First line levodopa treatment:

For 40 years, levodopa, combined with a peripheral decarboxylase inhibitor, has been regarded
as the gold standard for the treatment of Parkinson’s. It still remains in many respects the most
efficacious drug treatment. However, the benefits achieved often come at a price. Long-term
levodopa therapy frequently leads to disabling side effects like dyskinesia, motor fluctuations.
(Larsen JP et al1998)

First line dopamine agonist treatment:

There are six orally acting dopamine agonists available in the UK. Four are ergot derivatives:
bromocriptine, pergolide, cabergoline and lisuride; and two non-ergot drugs: ropinirole and
pramipexole(Frucht S et al 1999). Rotigotine is a non-ergot agonist available by transdermal
patch. These drugs all work by stimulation of the post-synaptic dopamine receptors. The
dopamine agonists were initially licensed for use in conjunction with levodopa in patients with
advanced Parkinson’s. Monotherapy trials have been undertaken comparing dopamine agonists
with levodopa. The first such trial using bromocriptine in the 1980s showed a delay in the onset
of dyskinesias with bromocriptine monotherapy compared with levodopa therapy, but no effect
with regards to the onset of motor fluctuations. , (Dizdar N et al 2005).

The treatment of late motor complications of Parkinson’s:

After some years of stable, sustained response to levodopa therapy, most patients with
PARKINSON’S experience fluctuations in motor performance, the effect of a single levodopa
dose becoming progressively shorter (wearing-off phenomenon). Also, periods of immobility
unrelated to times of levodopa supply occur in most advanced cases (on–off phenomenon).
Levodopa-induced dyskinesia occur with increasing duration of therapy, and more than 50% of
patients will begin to develop motor fluctuations and dyskinesias between 5 and 10 years after
commencing levodopa with 20–30% developing dyskinesias after 2 years. In younger patients,
the situation is worse, with almost all patients under the age of 40 developing motor
complications after 6 years from the introduction of levodopa. Treatment of levodopa-induced
dyskinesias remains unsatisfactory. Simply reducing the daily dose frequently renders patients
rigid and immobile.( Siden A et al 1998)

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COMT inhibitors:

Entacapone is a peripheral catechol-O-methyltransferase COMT inhibitor that complements the

action of amino acid de-carboxylase (AADC) inhibitors. Assuming that the volume of
distribution remains unchanged, the addition of entacapone increases the plasma half-life of
levodopa by 45% after each dose (The Parkinson’s Disease Research Group of the United
Kingdom 1995).

Prevention:

Because the cause of Parkinson’s is unknown, proven ways to prevent the disease also remain a
mystery. Some research has shown that regular aerobic exercise might reduce the risk of
Parkinson’s disease. Some other research has shown that people who drink caffeine — which is
found in coffee, tea and cola — get Parkinson’s disease less often than those who don't drink it.
However, it is still not known whether caffeine actually protects against getting Parkinson’s, or is
related in some other way. Currently there is not enough evidence to suggest drinking caffeinated
beverages to protect against Parkinson’s. Green tea is also related to a reduced risk of developing
Parkinson’s disease. The diagnosis of Parkinson’s remains essentially a clinical one, and it is
important to recognize the early features together with symptoms and signs suggesting other
causes of Parkinsonism. There has also been a rapid expansion in the treatment options both in
the early and in the later stages of the illness together with a greater awareness of non-motor
complications. Guidelines for the diagnosis and management of patients with Parkinson’s have
been published from the National Institute for Health and Clinical Excellence (NICE) in the UK.

Conclusion:

Parkinson’s is a common neurodegenerative illness. A combination of genetic and

environmental factors is likely to be important in producing abnormal protein aggregation within
select groups of neurons, leading to cell dysfunction and then death. The diagnosis remains a
clinical one, and there should be a high index of suspicion to exclude other causes of
Parkinsonism. A large number of agents together with surgical interventions are now available to
treat early and late complications of Parkinson’s. Increasing attention is being given to the
diagnosis and treatment of non-motor complications in Parkinson’s. Future developments in
Parkinson’s are likely to focus on the concept of disease modifying drugs which offer
neuroprotection.

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