Parkinson’s Disease

Condition

Definition
Parkinson’s disease is a progressive disorder of the nervous system that affects movement. It develops gradually, sometimes starting with a barely noticeable tremor in just one hand. But while a tremor may be the most well-known sign of Parkinson’s disease, 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, or 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 may markedly improve your symptoms. In occasional cases, your doctor may suggest surgery to regulate certain regions of your brain and improve your symptoms.

Symptoms

Parkinson’s disease symptoms and signs may vary from person to person. Early signs may be mild and may 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.

Parkinson’s signs and symptoms may include:

  • Tremor. A tremor, or shaking, usually begins in a limb, often your hand or fingers. You may notice a back-and-forth rubbing of your thumb and forefinger, known as a pill-rolling tremor. One characteristic of Parkinson’s disease is a tremor of your hand when it is relaxed (at rest).
  • Slowed movement (bradykinesia). Over time, Parkinson’s disease may reduce your ability to move and slow your movement, making simple tasks difficult and time-consuming. Your steps may become shorter when you walk, or you may find it difficult to get out of a chair. Also, you may drag your feet as you try to walk, making it difficult to move.
  • Rigid muscles. Muscle stiffness may occur in any part of your body. The stiff muscles can limit your range of motion and cause you pain.
  • Impaired posture and balance. Your posture may become stooped, or you may have balance problems as a result of Parkinson’s disease.
  • Loss of automatic movements. In Parkinson’s disease, you may have a decreased ability to perform unconscious movements, including blinking, smiling or swinging your arms when you walk.
  • Speech changes. You may have speech problems as a result of Parkinson’s disease. You may speak softly, quickly, slur or hesitate before talking. Your speech may be more of a monotone rather than with the usual inflections.
  • Writing changes. It may become hard to write, and your writing may appear small.

When to see a Doctor

See your doctor if you have any of the symptoms associated with Parkinson’s disease — not only to diagnose your condition but also to rule out other causes for your symptoms.

Causes

n 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 signs 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.

Treatments

Parkinson’s disease can’t be cured, but medications can help control your symptoms, often dramatically. In some later cases, surgery may be advised.

Your doctor may also recommend lifestyle changes, especially ongoing aerobic exercise. In some cases, physical therapy that focuses on balance and stretching also is important. A speech-language pathologist may help improve your speech problems.

Medications

Medications may help you manage problems with walking, movement and tremor. These medications increase or substitute for dopamine, a specific signaling chemical (neurotransmitter) in your brain.

People with Parkinson’s disease have low brain dopamine concentrations. However, dopamine can’t be given directly, as it can’t enter your brain.

You may have significant improvement of your symptoms after beginning Parkinson’s disease treatment. Over time, however, the benefits of drugs frequently diminish or become less consistent, although symptoms usually can continue to be fairly well-controlled.

Medications your doctor may prescribe include:

  • Carbidopa-levodopa. Levodopa, the most effective Parkinson’s disease medication, is a natural chemical that passes into your brain and is converted to dopamine.Levodopa is combined with carbidopa (Rytary, Sinemet), which protects levodopa from premature conversion to dopamine outside your brain, which prevents or lessens side effects such as nausea.Side effects may include nausea or lightheadedness (orthostatic hypotension).After years, as your disease progresses, the benefit from levodopa may become less stable, with a tendency to wax and wane (“wearing off”).Also, you may experience involuntary movements (dyskinesia) after taking higher doses of levodopa. Your doctor may lessen your dose or adjust the times of your doses to control these effects.
  • Carbidopa-levodopa infusion. The U.S. Food and Drug administration approved a drug called Duopa in 2015. This medication is made up of carbidopa and levodopa. However, it’s administered through a feeding tube that delivers the medication in a gel form directly to the small intestine.Duopa is for patients with more advanced Parkinson’s who still respond to carbidopa-levodopa, but who have a lot of fluctuations in their response. Because Duopa is continually infused, blood levels of the two drugs remain constant.Placement of the tube requires a small surgical procedure. Risks associated with having the tube include the tube falling out or infections at the infusion site.
  • Dopamine agonists. Unlike levodopa, dopamine agonists don’t change into dopamine. Instead, they mimic dopamine effects in your brain.They aren’t as effective as levodopa in treating your symptoms. However, they last longer and may be used with levodopa to smooth the sometimes off-and-on effect of levodopa.Dopamine agonists include pramipexole (Mirapex), ropinirole (Requip) and rotigotine (given as a patch, Neupro). A short-acting injectable dopamine agonist, apomorphine (Apokyn), is used for quick relief.Some of the side effects of dopamine agonists are similar to the side effects of carbidopa-levodopa, but also include hallucinations, sleepiness and compulsive behaviors such as hypersexuality, gambling and eating. If you’re taking these medications and you behave in a way that’s out of character for you, talk to your doctor.
  • MAO-B inhibitors. These medications include selegiline (Eldepryl, Zelapar) and rasagiline (Azilect). They help prevent the breakdown of brain dopamine by inhibiting the brain enzyme monoamine oxidase B (MAO-B). This enzyme metabolizes brain dopamine. Side effects may include nausea or insomnia.When added to carbidopa-levodopa, these medications increase the risk of hallucinations.These medications are not often used in combination with most antidepressants or certain narcotics due to potentially serious but rare reactions. Check with your doctor before taking any additional medications with a MAO-B inhibitor.
  • Catechol-O-methyltransferase (COMT) inhibitors. Entacapone (Comtan) is the primary medication from this class. This medication mildly prolongs the effect of levodopa therapy by blocking an enzyme that breaks down dopamine.Side effects, including an increased risk of involuntary movements (dyskinesias), mainly result from an enhanced levodopa effect. Other side effects include diarrhea or other enhanced levodopa side effects.Tolcapone (Tasmar) is another COMT inhibitor that is rarely prescribed due to a risk of serious liver damage and liver failure.
  • Anticholinergics. These medications were used for many years to help control the tremor associated with Parkinson’s disease. Several anticholinergic medications are available, including benztropine (Cogentin) or trihexyphenidyl.However, their modest benefits are often offset by side effects such as impaired memory, confusion, hallucinations, constipation, dry mouth and impaired urination.
  • Amantadine. Doctors may prescribe amantadine alone to provide short-term relief of symptoms of mild, early-stage Parkinson’s disease. It may also be given with carbidopa-levodopa therapy during the later stages of Parkinson’s disease to control involuntary movements (dyskinesias) induced by carbidopa-levodopa.Side effects may include a purple mottling of the skin, ankle swelling or hallucinations.

Surgical procedures

  • Deep brain stimulation. In deep brain stimulation (DBS), surgeons implant electrodes into a specific part of your brain. The electrodes are connected to a generator implanted in your chest near your collarbone that sends electrical pulses to your brain and may reduce your Parkinson’s disease symptoms.Your doctor may adjust your settings as necessary to treat your condition. Surgery involves risks, including infections, stroke or brain hemorrhage. Some people experience problems with the DBS system or have complications due to stimulation, and your doctor may need to adjust or replace some parts of the system.Deep brain stimulation is most often offered to people with advanced Parkinson’s disease who have unstable medication (levodopa) responses. DBS can stabilize medication fluctuations, reduce or halt involuntary movements (dyskinesias), reduce tremor, reduce rigidity, and improve slowing of movement.DBS is effective in controlling erratic and fluctuating responses to levodopa or for controlling dyskinesias that don’t improve with medication adjustments.However, DBS isn’t helpful for problems that don’t respond to levodopa therapy apart from tremor. A tremor may be controlled by DBS even if the tremor isn’t very responsive to levodopa.Although DBS may provide sustained benefit for Parkinson’s symptoms, it doesn’t keep Parkinson’s disease from progressing.

Source: Mayo Clinic

Staff

Risa Ravitz, MD
Neurology / Pain Medicine

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