Parkinson’s disease (PD) is a chronic and progressive movement disorder, meaning that symptoms continue and worsen over time. Nearly one million people in the US are living with Parkinson’s disease. The cause is unknown, and although there is presently no cure, there are treatment options such as medication and surgery to manage its symptoms.

Parkinson’s involves the malfunction and death of vital nerve cells in the brain, called neurons. Parkinson’s primarily affects neurons in an area of the brain called the substantia nigra. Some of these dying neurons produce dopamine, a chemical that sends messages to the part of the brain that controls movement and coordination. As PD progresses, the amount of dopamine produced in the brain decreases, leaving a person unable to control movement normally.

The specific group of symptoms that an individual experiences varies from person to person. Primary motor signs of Parkinson’s disease include the following.

1.tremor of the hands, arms, legs, jaw and face

2.bradykinesia or slowness of movement

3.rigidity or stiffness of the limbs and trunk

4.postural instability or impaired balance and coordination

Scientists are also exploring the idea that loss of cells in other areas of the brain and body contribute to Parkinson’s. For example, researchers have discovered that the hallmark sign of Parkinson’s disease — clumps of a protein alpha-synuclein, which are also called Lewy Bodies — are found not only in the mid-brain but also in the brain stem and the olfactory bulb.

These areas of the brain correlate to nonmotor functions such as sense of smell and sleep regulation. The presence of Lewy bodies in these areas could explain the nonmotor symptoms experienced by some people with PD before any motor sign of the disease appears. The intestines also have dopamine cells that degenerate in Parkinson’s, and this may be important in the gastrointestinal symptoms that are part of the disease.

SYMPTOMS

The diagnosis of PD depends upon the presence of one or more of the four most common motor symptoms of the disease. In addition, there are other secondary and nonmotor symptoms that affect many people and are increasingly recognized by doctors as important to treating Parkinson’s.

Each person with Parkinson’s will experience symptoms differently. For example, many people experience tremor as their primary symptom, while others may not have tremors, but may have problems with balance. Also, for some people the disease progresses quickly, and in others it does not.

PRIMARY MOTOR SYMPTOMS

Almost 200 years after Parkinson’s was first discovered and after many new discoveries about the biology of the disease, a diagnosis still depends on identifying the core features — tremor, slowness and stiffness — described by James Parkinson. The diagnosis of Parkinson’s does not come from a test, but instead requires a careful medical history and a physical examination to detect the cardinal signs of the disease, including:

Resting Tremor: In the early stages of the disease, about 70 percent of people experience a slight tremor in the hand or foot on one side of the body, or less commonly in the jaw or face. A typical onset is tremor in one finger. The tremor consists of a shaking or oscillating movement, and usually appears when a person’s muscles are relaxed, or at rest, hence the term “resting tremor.” The affected body part trembles when it is not performing an action. Typically, the fingers or hand will tremble when folded in the lap, or when the arm is held loosely at the side, i.e., when the limb is at rest. The tremor usually ceases when a person begins an action. Some people with PD have noticed that they can stop a hand tremor by keeping the hand in motion or in a flexed grip. The tremor of PD can be exacerbated by stress or excitement, sometimes attracting unwanted notice. The tremor often spreads to the other side of the body as the disease progresses, but usually remains most apparent on the initially affected side. Although tremor is the most noticeable outward sign of the disease, not all people with PD will develop tremor.

Bradykinesia:Bradykinesia means “slow movement.” A defining feature of Parkinson’s, bradykinesia also describes a general reduction of spontaneous movement, which can give the appearance of abnormal stillness and a decrease in facial expressivity. Bradykinesia causes difficulty with repetitive movements, such as finger tapping. Due to bradykinesia, a person with Parkinson’s may have difficulty performing everyday functions, such as buttoning a shirt, cutting food or brushing his or her teeth. People who experience bradykinesia may walk with short, shuffling steps. The reduction in movement and the limited range of movement caused by bradykinesia can affect a person’s speech, which may become quieter and less distinct as Parkinson’s progresses.
Rigidity: Rigidity causes stiffness and inflexibility of the limbs, neck and trunk. Muscles normally stretch when they move, and then relax when they are at rest. In Parkinson’s rigidity, the muscle tone of an affected limb is always stiff and does not relax, sometimes contributing to a decreased range of motion. People with PD most commonly experience tightness of the neck, shoulder and leg. A person with rigidity and bradykinesia tends to not swing his or her arms when walking. Rigidity can be uncomfortable or even painful.

Postural Instability:One of the most important signs of Parkinson’s ispostural instability, a tendency to be unstable when standing upright. A person with postural instability has lost some of the reflexes needed for maintaining an upright posture, and may topple backwards if jostled even slightly. Some develop a dangerous tendency to sway backwards when rising from a chair, standing or turning. This problem is called retropulsion and may result in a backwards fall. People with balance problems may have particular difficulty when pivoting or making turns or quick movements. Doctors test postural stability by using the “pull test.” During this test, theneurologist gives a moderately forceful backwards tug on the standing individual and observes how well the person recovers. The normal response is a quick backwards step to prevent a fall; but many people with Parkinson’s are unable to recover, and would tumble backwards if the neurologist were not right there to catch him or her.

SECONDARY MOTOR SYMPTOMS

In addition to the cardinal signs of Parkinson’s, there are many other motor symptoms associated with the disease.

Freezing: Freezing of gait is an important sign of PD that is not explained by rigidity or bradykinesia. People who experience freezing will normally hesitate before stepping forward. They feel as if their feet are glued to the floor. Often, freezing is temporary, and a person can enter a normal stride once he or she gets past the first step. Freezing can occur in very specific situations, such as when starting to walk, when pivoting, when crossing a threshold or doorway, and when approaching a chair. For reasons unknown, freezing rarely happens on stairs. Various types of cues, such as an exaggerated first step, can help with freezing. Some individuals have severe freezing, in which they simply cannot take a step. Freezing is a potentially serious problem in Parkinson’s disease, as it may increase a person’s risk of falling forward.

Micrographia:This term is the name for a shrinkage in handwriting that progresses the more a person with Parkinson’s writes. This occurs as a result of bradykinesia, which causes difficulty with repetitive actions.

Mask-like Expression: This expression, found in Parkinson’s, meaning a person’s face may appear less expressive than usual, can occur because of decreased unconscious facial movements. The flexed posture of PD may result from a combination of rigidity and bradykinesia.
Unwanted Accelerations: It is worth noting that some people with Parkinson’s experience movements that are too quick, not too slow. These unwanted accelerations are especially troublesome in speech and movement. People with excessively fast speech, tachyphemia, produce a rapid stammering that is hard to understand. Those who experience festination, an uncontrollable acceleration in gait, may be at increased risk for falls.

Additional secondary motor symptoms include those below, but not all people with Parkinson’s will experience all of these.  

*Stooped posture, a tendency to lean forward

 *Dystonia

 *Impaired fine motor dexterity and motor coordination

 *Impaired gross motor coordination

 *Poverty of movement (decreased arm swing)

 *Akathisia

 *Speech problems, such as softness of voice or slurred speech caused by lack of muscle control

 *Difficulty swallowing

 *Sexual dysfunction

 *Cramping

 *Drooling and excess saliva resulting from reduced swallowing movements

NON MOTOR SYMPTOMS

Most people with Parkinson’s experience nonmotor symptoms, those that do not involve movement, coordination, physical tasks or mobility. While a person’s family and friends may not be able to see them, these “invisible” symptoms can actually be more troublesome for some people than the motor impairments of PD.

Early Symptoms

Many researchers believe that nonmotor symptoms may precede motor symptoms — and a Parkinson’s diagnosis — by years. The most recognizable early symptoms include:

*Loss of sense of smell, constipation 

*REM behavior disorder (a sleep disorder)

*Mood disorders

*Orthostatic hypotension (low blood pressure when standing up).

If a person has one or more of these symptoms, it does not necessarily mean that individual will develop Parkinson’s, but these markers are helping scientists to better understand the disease process.

Other Nonmotor Symptoms

Some of these important and distressing symptoms include:

*Sleep disturbances

*Constipation

*Bladder problems

*Sexual problems

*Excessive saliva

*Weight loss or gain

*Vision and dental problems

*Fatigue and loss of energy

*Depression

*Fear and anxiety

*Skin problems

*Cognitive issues, such as memory difficulties, slowed thinking, confusion and in some cases, dementia

*Medication side effects, such as impulsive behaviors

Making an accurate diagnosis of Parkinson’s — particularly in its early stages — is difficult, but a skilled practitioner can come to a reasoned conclusion that it is PD. You may have experienced this frustration. Perhaps it took years for you to receive a diagnosis. Perhaps you have been diagnosed, but with Parkinsonism, not Parkinson’s, and are confused about the implications.

How is Parkinson’s Diagnosed?

Often, the diagnosis of Parkinson’s is first made by an internist or family physician. Many people seek an additional opinion from a neurologist with experience and specific training in the assessment and treatment of Parkinson’s disease — referred to as a movement disorder specialist.

To diagnose Parkinson’s, the physician takes a careful neurological history and performs an examination. There are no standard diagnostic tests for Parkinson’s, so the diagnosis rests on the clinical information provided by the person with Parkinson’s and the findings of the neurological exam.

The doctor looks to see if your expression is animated.

Your arms are observed for tremor, which is present either when they are at rest, or extended

.
Is there stiffness in your limbs or neck?

Can you rise from a chair easily?

Do you walk normally or with short steps, and do your arms swing symmetrically? The doctor will pull you backwards.

How quickly are you able to regain your balance?

The main role of any additional testing is to exclude other diseases that imitate Parkinson’s disease, such as stroke or hydrocephalus. Very mild cases of PD can be difficult to confirm, even by an experienced neurologist. This is in part because there are many neurological conditions that mimic the appearance of Parkinson’s.

A person’s good response to levodopa (which temporarily restores dopamineaction in the brain) may support the diagnosis. But this is not relevant if your doctor thinks you do not need any medication at this time. If you are in doubt of your diagnosis or if you need further information, you may want to seek a second opinion.


 

Why Aren’t There Tests to Diagnose Parkinson’s?

There is no standard diagnostic test for Parkinson’s. Researchers are working to develop an accurate “biological marker,” such as a blood test or an imaging scan. To date, the best objective testing for PD consists of specialized brain scanning techniques that can measure the dopamine system and brain metabolism. But these tests are performed only in specialized imaging centers and can be very expensive.

To date, despite decades of intensive study, the causes of Parkinson’s remain unknown. Many experts think that the disease is caused by a combination of genetic and environmental factors, which may vary from person to person.

In some people, genetic factors may play a role; in others, illness, an environmental toxin or other event may contribute to PD. Scientists have identified aging as an important risk factor; there is a two to four percent riskfor Parkinson’s among people over age 60, compared with one to two percent in the general population.

The chemical or genetic trigger that starts the cell death process in dopamineneurons is the subject of intense scientific study. Many believe that by understanding the sequence of events that leads to the loss of dopamine cells, scientists will be able to develop treatments to stop or reverse the disease


Genetic Factors

The vast majority of Parkinson’s cases are not directly inherited. About 15 to 25 percent of people with Parkinson’s report having a relative with the disease. In large population studies, researchers have found that people with an affected first-degree relative, such as a parent or sibling, have a four to nine percent higher chance of developing PD, as compared to the general population. This means that if a person’s parent has PD, his or her chances of developing the disease are slightly higher than the risk among the general population.

Researchers have discovered several gene mutations that can cause the disease directly, but these affect only a small number of families. Some of these mutations involve genes that play a role in dopamine cell functions. Parkinson’s has developed at an early age in individuals with mutations in genes for parkin, PINK1, LRRK2, DJ-1, and glucocerebrosidase, among others.

Because genetic forms of a disease can be studied in great detail in the laboratory, and because understanding the rare genetic forms of Parkinson’s may help us to understand more common forms of the disease, genetics is currently the subject of intense research.

 

Environmental Factors

Some scientists have suggested that Parkinson’s disease may result from exposure to an environmental toxin or injury. Epidemiological research has identified several factors that may be linked to Parkinson’s, including rural living, well water, manganese and pesticides.

Some studies have demonstrated that prolonged occupational exposure to certain chemicals is associated with an elevated risk of PD. These include the insecticides permethrin and beta-hexachlorocyclohexane (beta-HCH), the herbicides paraquat and 2,4-dichlorophenoxyacetic acid and the fungicide maneb. In 2009, the US Department of Veterans Affairs added Parkinson’s to a list of diseases possibly associated with exposure to Agent Orange.

A synthetic neurotoxin agent called MPTP can also cause immediate and permanent parkinsonism. The compound was discovered in the 1980s in individuals who injected themselves with a synthetic form of heroin contaminated with MPTP. Cases of MPTP-induced Parkinson’s in the general population are exceedingly rare.

It is noted that a simple exposure to an environmental toxin is never enough to cause Parkinson’s. Most people exposed to a toxin do not develop the disease. In fact, there is no conclusive evidence that any environmental factor, alone, can be considered a cause of the disease.

However, environmental factors have been helpful in studying laboratory models of Parkinson’s. Scientists continue to pursue these clues to understand why Parkinson’s disease occurs.

The progression of Parkinson’s disease varies among different individuals.  Parkinson’s is chronic and slowly progressive, meaning that symptoms continue and worsen over a period of years.  Parkinson’s is not considered a fatal disease. And the way that it progresses is different for everyone:

Movement symptoms vary from person to person, and so does the rate at which they progress.

Some are more bothersome than others depending on what a person normally does during the day.

Some people with Parkinson’s live with mild symptoms for many years, whereas others develop movement difficulties more quickly.

Nonmotor symptoms also are very individualized, and they affect most people with Parkinson’s at all stages of disease.  Some people with Parkinson’s find that symptoms such as depression or fatigue interfere more with daily life than do problems with movement.

Rating Scales

That said, there are tools that your doctor may use to understand the progression of your Parkinson’s.  The stages of Parkinson’s correspond both to the severity of movement symptoms and to how much the disease affects a person’s daily activities.  The most commonly used rating scales are focused on the motor symptoms, but new scales include information on non-motor symptoms (such as problems with sense of smell).

1. The first, known as Hoehn and Yahr, will rate your symptoms on a scale of 1 to 5.  On this scale, depending on a person’s difficulties, 1 and 2 represent early-stage, 2 and 3 mid-stage, and 4 and 5 advanced-stage Parkinson’s.

2. Another scale commonly used to assess the progression of Parkinson’s is the United Parkinson’s Disease Rating Scale (UPDRS).  It is more comprehensive than the Hoehn and Yahr scale, which focuses on movement symptoms.  In addition to these, the UPDRS takes into account cognitive difficulties, ability to carry out daily activities, and treatment complications.

Severity of Parkinson’s

Below are some descriptions of mild, moderate and advanced Parkinson’s.  As disease progresses differently in different people, many do not progress to the advanced stage. 

Mild Parkinson’s

Movement symptoms may be inconvenient, but do not affect daily activities

Movement symptoms, often tremor, occur on one side of the body

Friends may notice changes in a person’s posture, walking ability or facial expression

Parkinson’s medications suppress movement symptoms effectively

Regular exercise improves and maintains mobility, flexibility, range of motion and balance, and also reduces depression and constipation
Moderate Parkinson’s

Movement symptoms occur on both sides of the body

The body moves more slowly

Trouble with balance and coordination may develop

“Freezing” episodes — when the feet feel stuck to the ground — may occur

Parkinson’s medications may “wear off” between doses

Parkinson’s medications may cause side effects, including dyskinesias (involuntary movements)

Regular exercise, perhaps with physical therapy, continues to be important for good mobility and balance

Occupational therapy may provide strategies for maintaining independence

Advanced Parkinson’s

Great difficulty walking; in wheelchair or bed most of the day

Not able to live alone

Assistance needed with all daily activities

Cognitive problems may be prominent, including hallucinations and delusions

Balancing the benefits of medications with their side effects becomes more challenging

At all stages of Parkinson’s, effective therapies are available to ease symptoms and make it possible for people with Parkinson’s to live well.

A healthy diet will improve your general health, reducing your risk of diabetes, heart disease and stroke. There is no specific diet for Parkinson’s; however, general recommendations for healthy eating do apply, and changes in you diet can help some of your symptoms. Avoid the many fad diets that carry promises of health or symptom control.

Choose a diet rich in fruits and vegetables. Local produce that ripens naturally on the vine contains more nutrients than a canned or “fresh” vegetables picked early and shipped from afar. Consider eating organic foods to reduce ingestion of pesticides, herbicides, or hormones that may be harmful to your health. The most recent dietary and lifestyle recommendations are published by the American Heart Association, the U.S. Department of Health and Human Services and the Institute of Medicine.

Dietary Recommendations for Certain Parkinson’s symptoms:

Constipation
Lightheadedness
Fatigue and Energy Loss
Sleep Problems
Protein Interference with Drug Performance
Nausea and Stomach Bloating
Drooling and Swallowing
Weight Loss
Vitamins and Supplements

Researchers at the Universities of Manchester and York found the enzyme in Aspergillus oryzae, a kind of fungus used for making soy sauce. The discovery, ‘A reductive aminase from Aspergillus oryzae’ was published in Nature Chemistry.

The enzyme’s greatest impact could be in a class of medications called monoamine oxidase (MAO) inhibitors. One such example of this kind of drug is Rasagiline. Rasagiline helps Parkinson sufferers by increasing a substance in the brain that affects motor function.

These substances help reduce the involuntary tremors that are associated with the condition. The medicine works in both early and advanced Parkinson’s, and is especially useful in dealing with non-motor symptoms of the condition, like fatigue.

The team, led by Professor Nick Turner, Professor of Chemical Biology from the Manchester Institute of Biotechnology (MIB), have identified a new biocatalyst (RedAm) that accelerates a process called reductive amination.

Reductive amination is one of the most important methods for the synthesis of chiral amines, which are important chemical building blocks in the production of pharmaceutical products.

The discovery of RedAms means more efficient routes for chiral amine synthesis, including medications such as Rasagiline. The application of RedAms will result in a dramatic reduction in time required for synthesis which will also have a positive impact on the costings and manpower needed to produce chiral amines.

A recent analysis of drugs approved by America’s Food and Drug Administration (FDA) found that approximately 40 percent of new chemical entities (NCEs) contain one or more chiral amine building blocks. This means this new enzyme could also be key to improving the manufacture of numerous other medications on the market treating multiple conditions.

There is currently no cure for Parkinson’s, but there are a range of treatments to control the symptoms. However, medication such as Rasagiline is the main treatment for Parkinson’s. Every hour, someone in the UK is told they have Parkinson’s. One person in every 500 has Parkinson’s. That’s about 127,000 people in the UK.