INTRODUCTION
Parkinson’s disease (PD) is Central Nervous System disorder which affects movement. Parkinson’s disease is characterized by tremors and stiffness. It is a progressive disease, which means that it worsens with time. There is no cure available at present.
Parkinson’s disease is a progressive disorder that is caused by degeneration of nerve cells in the part of the brain called the substantia nigra, which controls movement. These nerve cells die or become impaired, losing the ability to produce an important chemical called dopamine. Studies have shown that symptoms of Parkinson's develop in patients with an 80 percent or greater loss of dopamine-producing cells in the substantia nigra.
Normally, dopamine operates in a delicate balance with other neurotransmitters to help coordinate the millions of nerve and muscle cells involved in movement. Without enough dopamine, this balance is disrupted, resulting in tremor (trembling in the hands, arms, legs and jaw); rigidity (stiffness of the limbs); slowness of movement; and impaired balance and coordination – the hallmark symptoms of Parkinson's.
STAGES OF PARKINSON’S DISEASE
Parkinson’s disease is a progressive disease. That means symptoms of the condition typically worsen over time.
Many doctors use the Hoehn and Yahr scale to classify its stages. This scale divides symptoms into five stages, and it helps healthcare providers know how advanced the disease signs and symptoms are.
Stage 1 Parkinson’s is the mildest form. It’s so mild, in fact, you may not experience symptoms that are noticeable. They may not yet interfere with your daily life and tasks. If you do have symptoms, they may be isolated to one side of your body.
The progression from stage 1 to stage 2 can take months, or even years. Each person’s experience will be different. At this moderate stage, you may experience symptoms such as:
Muscle stiffness can complicate daily tasks, prolonging how long it takes you to complete them. However, at this stage, you’re unlikely to experience balance problems. Symptoms may appear on both sides of the body. Changes in posture, gait, and facial expressions may be more noticeable.
At this middle stage, symptoms reach a turning point. While you’re unlikely to experience new symptoms, they may be more noticeable. They may also interfere with all of your daily tasks. Movements are noticeably slower, which slows down activities. Balance issues become more significant, too, so falls are more common. But people with stage 3 Parkinson’s can usually maintain their independence and complete activities without much assistance.
The progression from stage 3 to stage 4 brings about significant changes. At this point, you will experience great difficulty standing without a walker or assistive device. Reactions and muscle movements also slow significantly. Living alone can be unsafe, possibly dangerous.
In this most advanced stage, severe symptoms make around-the-clock assistance a necessity. It will be difficult to stand, if not impossible. A wheelchair will likely be required. Also, at this stage, individuals with Parkinson’s may experience confusion, delusions, and hallucinations. These complications of the disease can begin in the later stages. This is the most common Parkinson’s disease stage system, but alternative staging systems for Parkinson’s are sometimes used.
Some of the early symptoms of Parkinson’s can come before motor problems by several years. These earliest signs include:
The four major motor problems seen are:
Secondary symptoms include:
Other, more severe, symptoms may include:
Early signs of Parkinson’s disease may go unrecognized. Your body may try to alert you to the movement disorder many years before movement difficulties begin with these warning signs.
FOUR CARDINAL SYMPTOMS OF PARKINSON’S DISEASE
Following are considered to be the cardinal symptoms of Parkinson’s Disease:
1. Bradykinesia: slowness of movement
2. Tremor: most apparent, It is usually a rest tremor, maximal when the limb is at rest and disappearing with voluntary movement and sleep.
3. Rigidity: increased muscle tone which produces stiffness and resistance to movement in joints.
4. Postural instability (aka parkinsonism): impaired balance and frequent falls
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 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.
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. These changes include:
· The presence of Lewy bodies. Clumps of specific substances within brain cells are microscopic markers of Parkinson's disease. These are called Lewy bodies, and researchers believe these Lewy bodies hold an important clue to the cause of Parkinson's disease.
· Alpha-synuclein is found within Lewy bodies. Although many substances are found within Lewy bodies, scientists believe an important one is the natural and widespread protein called alpha-synuclein (a-synuclein). It's found in all Lewy bodies in a clumped form that cells can't break down. This is currently an important focus among Parkinson's disease researchers.
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.
It is not possible to prevent Parkinson’s disease, but research has shown that some lifelong habits may help to reduce the risk.
Turmeric: This spice contains curcumin, an antioxidant ingredient. It may help to prevent the clumping of a protein involved in Parkinson’s disease, at least one laboratory study has found.
Flavonoids: Consuming another type of antioxidant — flavonoids — may lower the risk of developing Parkinson’s disease, according to research. Flavonoids are present in berries, apples, some vegetables, tea, and red grapes.
Avoiding reheated cooking oils: Scientists have linked toxic chemicals, known as aldehydes, to Parkinson’s, Alzheimer’s and other neurodegenerative diseases, and some cancers.
Heating certain oils — such as sunflower oil — to a certain temperature, and then using them again can cause aldehydes to occur in those oils.
Avoiding toxins: Exposure to herbicides, pesticides, and other toxins may increase the risk of neurological diseases such as Parkinson’s disease. People should take precautions when using these types of product, for example, by using protective clothing.
A number of disorders can cause symptoms similar to those of Parkinson's disease. People with Parkinson's-like symptoms that result from other causes are sometimes said to have parkinsonism. While these disorders initially may be misdiagnosed as Parkinson's, certain medical tests, as well as response to drug treatment, may help to distinguish them from Parkinson's. Since many other diseases have similar features but require different treatments, it is important to make an exact diagnosis as soon as possible.
There are currently no blood or laboratory tests to diagnose nongenetic cases of Parkinson's disease. Diagnosis is based on a person's medical history and a neurological examination. Improvement after initiating medication is another important hallmark of Parkinson's disease.
The UPD rating scale is the most commonly used scale in the evaluation of Parkinson’s disease.
The UPDRS scale consists of five segments:
1. Mentation, Behavior, and Mood,
2. ADL,
3. Motor sections,
4. Modified Hoehn and Yahr Scale, and
5. Schwab and England ADL scale.
A total score of 199 indicates worst disability due to Parkinson’s and a total score of zero indicates no disability at all.
TREATMENT
The majority of Parkinson's patients are treated with medications to relieve the symptoms of the disease. These medications work by stimulating the remaining cells in the substantia nigra to produce more dopamine (levodopa medications) or by inhibiting some of the acetylcholine that is produced (anticholinergic medications), therefore restoring the balance between the chemicals in the brain. It is very important to work closely with the doctor to devise an individualized treatment plan. Side effects vary greatly by class of medication and patient.
Developed more than 30 years ago, levodopa is often regarded as the gold standard of Parkinson's therapy. Levodopa works by crossing the blood-brain barrier, the elaborate meshwork of fine blood vessels and cells that filter blood reaching the brain, where it is converted into dopamine. Since blood enzymes (called AADCs) break down most of the levodopa before it reaches the brain, levodopa is now combined with an enzyme inhibitor called carbidopa. The addition of carbidopa prevents levodopa from being metabolized in the gastroinstenal tract, liver and other tissues, allowing more of it to reach the brain. Therefore, a smaller dose of levodopa is needed to treat symptoms. This advance also helps reduce the severe nausea and vomiting often experienced as a side effect of levodopa. For most patients, levodopa reduces the symptoms of slowness, stiffness and tremor. It is especially effective for patients that have a loss of spontaneous movement and muscle rigidity. This medication, however, does not stop or slow the progression of the disease.
Levodopa is available as a standard (or immediate) release formula or a long-acting or "controlled-release" formula. Controlled release may provide a longer duration of action by increasing the time it takes for the gastrointestinal tract to absorb the medication.
Side effects may include nausea, vomiting, dry mouth and dizziness. Dyskinesias (abnormal movements) may occur as the dose is increased. In some patients, levodopa may cause confusion, hallucinations or psychosis.
Bromocriptine, pergolide, pramipexole and ropinirole are medications that mimic the role of chemical messengers in the brain, causing the neurons to react as they would to dopamine. They can be prescribed alone or with levodopa and may be used in the early stages of the disease or administered to lengthen the duration of effectiveness of levodopa. These medications generally have more side effects than levodopa, so that is taken into consideration before doctors prescribe dopamine agonists to patients.
Side effects may include drowsiness, nausea, vomiting, dry mouth, dizziness and feeling faint upon standing. While these symptoms are common when starting a dopamine agonist, they usually resolve over several days. In some patients, dopamine agonists may cause confusion, hallucinations or psychosis.
Entacapone and tolcapone are medications that are used to treat fluctuations in response to levodopa. COMT is an enzyme that metabolizes levodopa in the bloodstream. By blocking COMT, more levodopa can penetrate the brain and, in doing so, increase the effectiveness of treatment. Tolcapone is indicated only for patients whose symptoms are not adequately controlled by other medications, because of potentially serious toxic effects on the liver. Patients taking tolcapone must have their blood drawn periodically to monitor liver function.
Side effects may include diarrhea and dyskinesias.
This medication slows down the activity of the enzyme monoamine oxidase B (MAO-B), the enzyme that metabolizes dopamine in the brain, delaying the breakdown of naturally occurring dopamine and dopamine formed from levodopa. When taken in conjunction with levodopa, selegiline may enhance and prolong the effectiveness of levodopa.
Side effects may include heartburn, nausea, dry mouth and dizziness. Confusion, nightmares, hallucinations and headache occur less often and should be reported to the doctor.
Trihexyphenidyl, benztropine mesylate, biperiden HCL and procyclidine work by blocking acetylcholine, a chemical in the brain whose effects become more pronounced when dopamine levels drop. These medications are most useful in the treatment of tremor and muscle rigidity, as well as in reducing medication-induced parkinsonism. They are generally not recommended for extended use in older patients because of complications and serious side effects.
Side effects may include dry mouth, blurred vision, sedation, delirium, hallucinations, constipation and urinary retention. Confusion and hallucinations may also occur.
This is an antiviral medication that also helps reduce symptoms of Parkinson’s (unrelated to its antiviral components) and is often used in the early stages of the disease. It is sometimes used with an anticholinergic medication or levodopa. It may be effective in treating the jerky motions associated with Parkinson's.
Side effects may include difficulty in concentrating, confusion, insomnia, nightmares, agitation and hallucinations. Amantadine may cause leg swelling as well as mottled skin, often on the legs.
For many patients with Parkinson’s, medications are effective for maintaining a good quality of life. As the disorder progresses, however, some patients develop variability in their response to treatment, known as "motor fluctuations. During "on" periods, a patient may move with relative ease, often with reduced tremor and stiffness. During "off" periods, patients may have more difficulty controlling movements. Off periods may occur just prior to a patient taking their next dose of medication, and these episodes are called "wearing off." Uncontrolled writhing movements, called dyskinesias, may result. These problems can usually be managed with changes in medications. Based upon the type and severity of symptoms, the deterioration of a patient's quality of life and a patient’s overall health, surgery may be the next step. The benefits of surgery should always be weighed carefully against its risks, taking into consideration the patient’s symptoms and overall health.
Neurosurgeons relieve the involuntary movements of conditions like Parkinson's by operating on the deep brain structures involved in motion control – the thalamus, globus pallidus and subthalamic nucleus. To target these clusters, neurosurgeons use a technique called stereotactic surgery. This type of surgery requires the neurosurgeon to fix a metal frame to the skull under local anesthesia. Using diagnostic imaging, the surgeon precisely locates the desired area in the brain and drills a small hole, about the size of a nickel. The surgeon may then create small lesions using high frequency radio waves within these structures or may implant a deep brain stimulating electrode, thereby helping to relieve the symptoms associated with Parkinson's.
This procedure may be recommended for patients with aggressive Parkinson's or for those who do not respond to medication. Pallidotomy is performed by inserting a wire probe into the globus pallidus – a very small region of the brain, measuring about a quarter inch, involved in the control of movement. Most experts believe that this region becomes hyperactive in Parkinson’s patients due to the loss of dopamine. Applying lesions to the global pallidus can help restore the balance that normal movement requires. This procedure may help eliminate medication-induced dyskinesias, tremor, muscle rigidity and gradual loss of spontaneous movement.
Thalamotomy uses radiofrequency energy currents to destroy a small, but specific portion of the thalamus. The relatively small number of patients who have disabling tremors in the hand or arm may benefit from this procedure. Thalamotomy does not help the other symptoms of Parkinson's and is used more often and with greater benefit in patients with essential tremor, rather than Parkinson’s.
DBS offers a safer alternative to pallidotomy and thalamotomy. It utilizes small electrodes which are implanted to provide an electrical impulse to either the subthalamic nucleus of the thalamus or the globus pallidus, deep parts of the brain involved in motor function. Implantation of the electrode is guided through magnetic resonance imaging (MRI) and neurophysiological mapping, to pinpoint the correct location. The electrode is connected to wires that lead to an impulse generator or IPG (similar to a pacemaker) that is placed under the collarbone and beneath the skin. Patients have a controller, which allows them to turn the device on or off. The electrodes are usually placed on one side of the brain. An electrode implanted in the left side of the brain will control the symptoms on the right side of the body and vice versa. Some patients may need to have stimulators implanted on both sides of the brain.
This form of stimulation helps rebalance the control messages in the brain, thereby suppressing tremor. DBS of the subthalamic nucleus or globus pallidus may be effective in treating all of the primary motor features of Parkinson's and may allow for significant decreases in medication doses.