POSSIBLE CAUSES OF PARKINSONISM

Introduction
Parkinsonism is a clinical syndrome presenting with any combination of bradykinesia, rest tremor, rigidity, and postural instability. The most common form of parkinsonism is Parkinson's disease (PD), a chronic, progressive disorder caused by a degenerative loss of dopaminergic neurons in the brain and characterized clinically by asymmetric parkinsonism and a clear, dramatic, and sustained benefit from dopaminergic therapy. 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.

Causes
Scientists believe a combination of genetic and environmental factors is the cause of Parkinson’s disease (PD). PD is an extremely diverse disorder. While no two people experience Parkinson’s the same way, there are some commonalities. PD affects about one million people in the United States and ten million worldwide. The main finding in the brains of people with PD is the loss of dopaminergic neurons in the area of the brain known as the substantia nigra. Parkinson's disease is caused by a loss of nerve cells in the part of the brain called the substantia nigra. Nerve cells in this part of the brain are responsible for producing a chemical called dopamine. Dopamine acts as a messenger between the parts of the brain and nervous system that help control and coordinate body movements. If these nerve cells die or become damaged, the amount of dopamine in the brain is reduced. This means the part of the brain controlling movement cannot work as well as normal, causing movements to become slow and abnormal. The loss of nerve cells is a slow process. The symptoms of Parkinson's disease usually only start to develop when around 80% of the nerve cells in the substantia nigra have been lost. 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 impaired movement and other symptoms of Parkinson's disease.
The cause of Parkinson's disease is unknown, but several factors appear to play a role, including:
Genes. Researchers have identified specific 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 disease but with a relatively small risk of Parkinson's disease for each of these genetic markers.
Environmental triggers. Exposure to certain toxins or environmental factors may increase the risk of later Parkinson's disease, but the risk is relatively small.

Lewy bodies are abnormal clumps of proteins found in the brain stem of people with Parkinson’s disease. These clumps contain a protein that cells are unable to break down. They surround cells in the brain and, in the process, interrupt the way the brain functions. Clusters of Lewy bodies cause the brain to degenerate over time. This results in decreased motor coordination in people with Parkinson’s disease.
Loss of dopamine. Dopamine is a neurotransmitter chemical that aids in passing messages between different sections of your brain. In people with Parkinson’s, the cells that produce dopamine are impaired. Without an adequate supply of dopamine, your brain is unable to properly send and receive messages. This disruption affects the body’s ability to coordinate movement and results in trouble with walking and balance.
Medication (drug-induced parkinsonism) – where symptoms develop after taking certain medications, such as some types of antipsychotic medication, and usually improve once the medication is stopped
Other progressive brain conditions – such as progressive supranuclear palsy, multiple- systems atrophy, and corticobasal degeneration
Cerebrovascular disease – where a series of small strokes cause several parts of the brain to die
Age. Since it mostly affects people 60 and older, your risk goes up as the years go by.
Gender. Men get it more than women. Doctors aren't sure why.
Race. It shows up more often in white people than in other groups.
Serious head injury. If you hit your head hard enough to lose consciousness or forget things as a result of it, you may be more likely to get Parkinson's later in life.
Family history. If your parent, brother, or sister has it, you're a little more likely to get it.
Job. Some types of work, like farming or factory jobs, can cause you to have contact with chemicals linked to Parkinson's.
Where you live. People in rural areas seem to get it more often, which may be tied to chemicals used in farming.
Diagnosis
General approach — The diagnosis of PD during life is based upon its distinctive clinical features discerned from the history and neurologic examination. At a minimum, bradykinesia plus either tremor or rigidity must be present in order to consider the diagnosis of PD. In addition, unequivocal, beneficial response to dopaminergic therapy is an important supportive feature of the diagnosis, while the absence of an observable response to high-dose levodopa therapy (>1000 mg daily) in patients with at least a moderate severity of parkinsonism makes the diagnosis of PD extremely unlikely. Postural instability is also a feature of PD but
usually does not appear until later in the course of the disease. Thus, patients with parkinsonian signs who exhibit postural instability early in the course of the illness most likely have another form of parkinsonism.
Symptoms of Parkinson's disease
The 4 main symptoms of Parkinson's disease are:
• Shaking or tremor: Called resting tremor, a trembling of a hand or foot that happens when the patient is at rest and typically stops when he or she is active or moving
• Bradykinesia: Slowness of movement in the limbs, face, walking, or overall body
• Rigidity: Stiffness in the arms, legs, or trunk
• Posture instability: Trouble with balance and possible falls person with Parkinson's disease can also experience a wide range of other physical and psychological symptoms.
These include:
depression and anxiety
balance problems (this may increase the chances of a fall)
loss of sense of smell (anosmia)
problems sleeping (insomnia)
memory problems
Treatment:
Drugs That Make Dopamine. Parkinson's affects nerve cells in your brain that make a chemical called dopamine. As a result, levels of the chemical fall. Doctors usually start treatment with levodopa (L-dopa). Your brain turns it into dopamine. But it can make you sick to your stomach, so you’ll probably take it with another medicine called carbidopa to control these side effects. The combination drug is called carbidopa-levodopa (Parcopa, Rytary)
Treatment: Boosting Dopamine’s Effects
Your doctor might give you one of these, alone or with another drug:
Dopamine agonists: They act like dopamine but don’t raise levels of it in your brain. You can take them with any drug that has levodopa. You might try pramipexole (Mirapex) or ropinirole (Requip).
COMT Inhibitors: They help levodopa last longer. You might get entacapone (Comtan) or tolcapone (Tasmar).
MAO-B inhibitors: These stop your brain from breaking down levodopa. You could get selegiline (Eldepryl, Zelapar) or rasagiline (Azilect).

The doctor may also give you something to treat the tremors that come with Parkinson’s. These medications are called anticholinergics, and they put the brakes on a chemical in your brain
that controls movement. You might take benztropine mesylate (Cogentin) or trihexyphenidyl (Artane).
If medicine doesn’t work well enough, your doctor may suggest deep brain stimulation (DBS). In DBS, your doctor implants electrodes deep in the brain. A device connected to them delivers electrical pulses. Those pulses can help control the tremors caused by Parkinson's. In the past, doctors sometimes used other operations to damage the brain in ways to help with movement symptoms. But they rarely use those surgeries now.
These Therapies Also May Help
Physical therapy can teach you exercises to improve strength and balance and help you stay independent. Occupational therapy shows you new ways to manage daily tasks. Speech therapy can help with slurred or unclear speech.
Food and Exercises
Eating healthy foods can help you feel better. It may also help with certain Parkinson’s symptoms, such as constipation. Getting regular exercise will also boost strength, flexibility, and balance.
What Else Helps
Along with your regular medical care, these approaches may help with mood, energy, and how you feel day today:
Massage
Yoga
Meditation
Outlook
As the condition progresses, the symptoms of Parkinson's disease can get worse and it can become increasingly difficult to carry out everyday activities without help. Many people respond well to treatment and only experience mild to moderate disability, whereas the minority may not respond as well and can, in time, become more severely disabled. Parkinson's disease does not directly cause people to die, but the condition can place great strain on the body and can make some people more vulnerable to serious and life-threatening infections. But with advances in treatment, most people with Parkinson's disease now have a normal or near-normal life expectancy.

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