Perera thushara-parkinsons-disease

1. Name of Disorder: Parkinson’s Disease
Essay Title: An Introduction to Parkinson’s Disease
Authors: Dr Thushara Perera (BE, MBioE, PhD) and
Dr Wesley Thevathasan (MBBS, FRACP, CESR, PhD)
Institution: Bionics Institute of Australia
Date: 23/06/2014
Introduction
Parkinson’s disease (PD) is a progressive condition marked by a loss of nerve cells (neurons) in the
brain (known as neurodegeneration). The exact cause of neuronal loss in PD is unknown. However,
many of the symptoms of PD can be explained by the loss of cells that contain the neurotransmitter
‘dopamine’. Dopamine, like all neurotransmitters, is a chemical released by nerve cells to
communicate with other nerve cells. It has a variety of key functions in the brain, including important
roles in behaviour, cognition, voluntary movement, motivation, punishment and reward, sleep, mood,
attention, working memory, and learning. In the case of PD, the dopamine–producing neurons of the
‘substantia nigra’, a hub of nerve cells in the brainstem, slowly die. This reduction in dopamine levels
causes an imbalance with other neurotransmitters resulting in an array of both motor (movement) and
non-motor symptoms that become worse over time (Sethi 2002).
What triggers this fairly selective death of neurons is a point of debate, but several different
theories have been proposed. The most common theories are: environmental toxins (exposure to a
range of metals and chemicals); oxidative stress (cellular processes that are a natural part of aging);
genetic predisposition; and a combination of these factors.
PD is the second most common neurodegenerative condition after Alzheimer’s disease (de Lau
and Breteler 2006). More than 64,000 Australians have PD (Deloitte 2011) and as the major risk factor
is age, this number is expected to grow with the ageing population (Lees, Hardy et al. 2009).
Symptoms
Although considered to be a movement disorder, people with PD may experience a variety of motor
and non-motor symptoms. There is a great diversity in presentation of Parkinson symptoms.
Motor Symptoms
Motor symptoms include a "shuffling" gait, tremor of the arms and legs, muscle stiffness, slowed
movement and stooped posture. These can impact on many activities of daily living, for example,
eating, drinking and writing. Generally, these symptoms present on one side of the body (unilateral),
then over time move to both sides of the body (bilateral) (Klockgether 2004).
Slowness, reduction and absence of movement (Bradykinesia/Hypokinesia/Akinesia)
Changes in movements are one of the key characteristics of PD which implicates the ability to perform
involuntary movements (e.g. blinking and swallowing) as well as voluntary tasks (e.g. dressing). The
ability to communicate is also affected by soft monotonous vocal tone, reduced gestures, and a less
expressive face (Klockgether 2004).
Particularly in later stages of the disease, people may experience the sudden inability to walk,
typically lasting less than a minute, which patients have described as the sensation that their feet are
“glued to the ground”. This is called gait freezing and may lead to dangerous falls (Thevathasan and
Aziz 2010) and in some cases wheelchair dependency (Giladi, McDermott et. al. 2001).

2. Postural instability
Postural instability reflects an impairment of the reflexes to maintain an upright stance. This is
frequently disabling, creating difficulty maintaining balance during everyday tasks such as walking,
turning and standing up from sitting. Similar to gait freezing, this is a major cause of falls and tends to
occur later in the disease (Giladi, McDermott et al. 2001, Kerr, Worringham, et. al. 2010).
Muscle stiffness
Muscle stiffness (or rigidity) refers to the resistance felt in muscles when they are moved, for example
through massage or medical intervention, without purposefully activating muscles to perform the
movement. Muscle stiffness partially accounts for the sensory symptoms of neck and shoulder pain
sometimes experienced during early stages of PD.
Tremor
Tremor in PD is typically noticeable when the limb is at rest and may affect different limbs with a
variable severity. This “resting tremor” is found in over 70% of patients at disease onset and remains
the most characteristic feature of PD (Sethi 2004). Stress may cause a worsening of tremor possibly
due to increases in adrenaline (leading to further neurotransmitter imbalance).
Non-Motor Symptoms
Cognition
Cognitive problems (thinking, judgment, and memory) may also be present, particularly in the late
stages of the disease, with greater than 80% prevalence after 15 years (Hely, Reid et al. 2008). Sleep
disturbance is common and narcolepsy-like symptoms (excessive sleepiness and sleep attacks at an
inappropriate time) may also be experienced during later stages (Schenck, Bundlie et al. 1996).
Psychiatric
Depression, which may be triggered by the diagnosis of the disease or related to a chemical imbalance
within the brain, and anxiety, which can aggravate motor symptoms, are both commonly experienced
(Aarsland, Bronnick et al. 2007). Visual hallucinations and psychosis are also common, particularly at
later disease stages.
Autonomous System
The autonomic nervous system acts as a control system for involuntary functions such as heart
rate, digestion, respiratory rate, salivation, perspiration, pupillary dilation, urination and sexual
arousal. Autonomic dysfunction, including impotence, postural hypotension and constipation tend to
occur later in the disease course (Chaudhuri, Healy et al. 2006).
Diagnosis
The diagnosis of PD is usually made on clinical grounds by observing symptoms of impaired
movement, muscle stiffness, tremor and postural instability (Hughes, Daniel et al. 1992). In general,
changes in movement and other key symptoms are considered enough for a positive diagnosis
(Klogether 2004). A specialised brain scan (not available in Australia) can be used to distinguish non-
Parkinsonian mimics such as tremulous dystonia, essential tremor and drug-induced Parkinsonism
(Scherfler, Schwarz et al. 2007).

3. Treatment
Treatments at present only address the symptoms, and not the underlying neurodegenerative cause.
Drug Therapies
Dopamine replacement therapy (dopaminergic therapy) is the mainstay of treatment (Birkmayer an
Hornykiewicz 1961; Cotzias, Van Woert et al. 1967). The most common dopaminergic therapy is
levodopa, a pre-cursor, that unlike dopamine, is able to cross the protective blood–brain barrier. It is
most effective on motor symptoms although gait freezing and postural instability respond poorly
(Bloem 1992). Over time, levodopa can cause involuntary movements called ‘dyskinesias’. To spare
levodopa doses and limit this effect, another class of medications are often used called ‘dopamine
agonists’. However dopamine agonists are not quite as effective as levodopa and can cause a group of
symptoms called impulse control disorders including obsessions and compulsions regarding hobbies,
objects, sex, eating, gambling, and even with medication (Weintraub 2008). Thus, treatment must be
carefully monitored to optimise the reduction in motor symptoms whilst avoiding neuropsychiatric
complications.
Deep Brain Stimulation (DBS)
DBS uses a surgically implanted, battery-operated device to deliver electrical stimulation to targeted
areas in the brain that control movement, blocking the abnormal nerve signals that cause tremor and
other symptoms (Thevathasan and Gregory 2010).
Surgery
Lesioning (careful destruction of brain tissue) is still performed in many medical centres in specific
circumstances such as in elderly patients with a predominantly unilateral tremor (Thevathasan and
Gregory 2010). Since the potential of irreversible damage is high, this technique is usually the last
resort.
Other Therapies
Many therapies not currently available as clinical treatments are under investigation, including dietary
modification with ketone esters to enhance the function of mitochondria (subunits within nerve cells)
as well as stem cell treatments (Kashiwaya, Takeshima et al. 2000). Scientific research into PD is as
varied as the disease itself. Researchers continue to improve our understanding of the disease and help
to provide better treatments for the underlying causes of this highly debilitating condition.
Conclusion
Parkinson’s disease results from a gradual loss of neurons that produce dopamine. This causes an
imbalance in the brain leading to symptoms of tremor, gait problems and cognitive decline. Diagnosis
is made on clinical grounds and treatment is typically through oral medication intended to replace
dopamine. As disease severity worsens and side-effects of medication become exceedingly worse,
more radical therapies such as deep brain stimulation and surgical lesioning are explored. Continued
scientific research into Parkinson’s disease may reveal important clues to help find more effective
treatments in the near future.

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