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Parkinson's Disease

Parkinson's Disease

Parkinson's disease (PD) is an age-related deterioration of certain nerve systems, which affects your movement, balance, and muscle control.

 

  • Parkinson's disease is one of the most common movement disorders, affecting 1% of people older than 60 years. PD is about 1.5 times more common in men than in women, and it becomes more common as you age. 
  • The average age of onset is about 60 years. Onset before age 40 years is relatively uncommon, but the recent diagnosis of actor Michael J. Fox shows that younger people are also vulnerable. 
  • In PD, brain cells deteriorate (or degenerate) in an area of the brain called the substantia nigra. From the substantia nigra, specific nerve cell tracts connect to another part of the brain called the corpus striatum, where theneurotransmitter (a chemical messenger in the brain) called dopamine is released. Dopamine is an important neurotransmitter and alterations in its concentration can lead to different medical problems. 
  • The loss of these specific brain cells and decline in dopamine concentration are the cornerstone of signs and symptoms of PD as well as the target for treatment. The biological mechanism responsible for the braincell loss has not been identified.

Symptoms

The 3 key signs of Parkinson's disease aretremor (shaking) at rest, rigidity, and slowness in the initiation of movement (calledbradykinesia). Of these features, 2 are required to make the diagnosis. Postural instability is the fourth key sign, but it happens late in the disease, usually after having PD 8 years or more.

 

  • Tremor at rest 
  1. Tremor usually begins in one arm and may start and stop. 
  2. As with most tremors, it worsens when under stress and improves during rest or sleep. 
  3. After several months to a few years, both arms may become affected, but the beginning asymmetry (lopsidedness) is often maintained. 
  4. PD tremor may also involve the tongue,lips, or chin. 
  5. The characteristic PD tremor is present and most prominent with the limb at rest.
  6. The tremor may appear as a pill-rolling motion of the hand or a simple oscillation of the hand or arm.

 

  • Rigidity 
  1. Rigidity refers to an increase in resistance to someone else moving yourjoint. 
  2. The resistance can be either smooth (lead-pipe) or start and stop (cog wheeling). Cog wheeling is thought to be a tremor rather than rigidity.
  3. Having someone else flex and extend your relaxed wrists tests for rigidity. 
  4. Rigidity can be made more obvious with voluntary movement in the opposite limb.

 

  • Bradykinesia 
  1. Bradykinesia refers to slowness of movement but also includes a lessening of unplanned movements and decreased size of movement. 
  2. Bradykinesia is also expressed as micrographia (small handwriting), hypomimia (decreased facial expression), decreased blink rate, and hypophonia (soft speech).

 

  • Postural instability 
  1. Postural instability refers to imbalance and loss of reflexes used to keep you upright. 
  2. This symptom is an important milestone, because it is not easy to treat and a common source of disability in late disease.

 

  • Other symptoms 
  1. You may experience freezing when starting to walk (start-hesitation), during turning, or crossing a threshold such as going through a doorway. 
  2. Flexed postures of neck, trunk, and limbs may occur. 
  3. Altered mental status generally occurs late in PD and affects 15-30% of people with PD. 
  4. Short-term memory and visio-spacial function may be impaired. 
  5. The onset of PD is typically lopsided, with the most common initial finding being an asymmetric rest tremor in one arm. About 20% of people first experience clumsiness in 1 hand. 
  6. Over time, you will notice symptoms related to progressive bradykinesia, rigidity, and problems with walking (called gait disturbances).

 

  • The initial symptoms of PD may be nonspecific and include fatigue anddepression. 
  1. Some people experience a subtle decrease in dexterity and may notice a lack of coordination with activities such as golf, dressing, or climbing stairs. 
  2. Some people complain of aching or tightness in the calf or shoulderregion. 
  3. The first affected arm may not swing fully when walking, and the foot on the same side may scrape the floor. 
  4. Over time, posture becomes progressively flexed and your stride becomes shorter leading to a shuffling gait. 
  5.  Decreased swallowing may lead to excess saliva and ultimately drooling. 
  6. Symptoms of problems with your involuntary nervous system are common and may include constipation, sweating abnormalities, and sexual dysfunction. 
  7. Sleep disturbances are also common.

 

  • The best clinical predictors of a diagnosis of PD are asymmetry, the presence of rest tremor, and a good response to dopamine replacement therapy.

Causes

The challenge that remains is to discover how these neurons are destroyed to cause Parkinson's disease.

 

  • Many theories have been put forward, but most researchers believe that Parkinson's disease is not due to a single culprit but rather a combination of both geneticsusceptibility and environmental stresses causing brain cell death.

 

  • Studies have found that living in a rural area, drinking well water, or being exposed to pesticides, herbicides, or wood pulp mills may increase your risk for developing Parkinson's disease. 

 

  • It has been demonstrated that 5-10% of people with PD have a genetic tendency. A recent study identified a specific genemutation in a group of people who were related. Although this gene mutation is not responsible for all causes of PD, this finding may give scientists the opportunity to develop an animal model to gain insight into PD. 
  • Currently, one of the most promising theories is the oxidation hypothesis. 

 

  1. It is thought that free radicals may play a role in the development of Parkinson's disease. Free radicals are chemical compounds with a positive charge that are created when dopamine is broken down by combining it with oxygen. 
  2. This breakdown of dopamine by an enzyme called monoamine oxidase (MAO) leads to the formation of hydrogen peroxide. 
  3. A protein called glutathione normally breaks down the hydrogen peroxide quickly. If the hydrogen peroxide is not broken down correctly, it may lead to the formation of these free radicals that then can react with cell membranes to cause cell damage and something called lipid peroxidation (when the hydrogen peroxide interacts with lipids [fat soluble substances] in the cell membrane). 
  4. In PD, glutathione is reduced, which may mean that you have a loss of protection against the formation of these free radicals. 
  5. Also, iron is increased in the brain and may help form free radicals. 
  6. In addition, lipid peroxidation is increased in Parkinson's disease. 
  7. The association of Parkinson's disease with increased dopamine turnover, decreased mechanisms (glutathione) to protect against free radical formation, increased iron (which makes it easier to create free radicals), and increased lipid peroxidation helps support the oxidation hypothesis. 
  8. If this hypothesis turns out to be correct, it still does not explain why or how a loss of the protective mechanism occurs. An answer to this question may not be required. If the theory is correct, drugs may be developed to stop or delay these events.

 

  • Although the cause of Parkinson's disease is not known, some people have symptoms of PD that may have an identifiable cause. In this case, thesyndrome is known as Parkinsonism or secondary PD. 

 

  • It is thought that although primary Parkinson's, or Parkinson's disease, is the most common type seen by neurologists, Parkinson's that is caused by drugs is probably far more common than reported and accounts for about 4% of all cases of Parkinson's. 

 

  1. A change in the level of dopamine, whether by brain cell loss or drug use, can create the symptoms of PD. 
  2. Interestingly, people who experience drug-induced Parkinson's may actually have a higher risk of developing PD later in life. 
  3. A number of medications can cause Parkinson's by lowering dopamine levels. These are referred to as dopamine receptor antagonists or blockers. 
  4. Nearly all antipsychotic or neuroleptic medications such aschlorpromazine (Thorazine), haloperidol (Haldol), and thioridazine (Mellaril) can induce the symptoms of Parkinson's. 
  5. The medication valproic acid (Depakote), a widely use antiseizure medication, may also cause a reversible Parkinson's. 
  6. Medications such as metoclopramide (Octamide, Maxolon, Reglan), which is used to treat certain stomach disorders such as peptic ulcerdisease, are capable of causing Parkinson's or making it worse. 
  7. Antidepressants known as selective serotonin-reuptake inhibitors may cause symptoms similar to Parkinson's.

 

  • Central to all these medications is their ability to alter the concentration of dopamine in the central nervous system. 

 

  • Therefore a careful review of a medication list and ruling out of other causes such as brain tumors, stroke, infections, toxins, AIDS, and hydrocephalusmust occur before the absolute diagnosis of Parkinson's disease is made. 

Treatment

The decision to care for a family member with Parkinson's disease is very complex.

 

  • In the beginning, the symptoms are minimal. The person may continue carrying out the activities of daily living, for example, eating, bathing, dressing, taking medications, and toileting. In fact, the person may continue to work and excel in other areas of life. 

 

  • A time will come when the symptoms of the disease progress to the point of decline. It is, however, impossible to predict which symptoms will become most pronounced and debilitating. This makes it especially difficult in planning and arranging future care. Nevertheless, with adequate planning, providing for the person at home is feasible. 

 

  1. It must be determined what level of care is required and what financial and social resources will be available to accomplish home care. There will need to be a designated caregiver, preferably someone with few other family responsibilities. 
  2. With time, the needs of the person with Parkinson's disease will only increase. The demands on the caregiver will mount. In terms of living independence, the ability to safely cook, drive an automobile, or use public transportation will be lost. A caregiver will assume full responsibility. 
  3. The home should be large enough to accommodate the person's needs. Special medical equipment such as a walker, wheelchair, bedside commode, or chair lift may be required. In terms of added safety, dangerous and breakable objects will have to be removed. 
  4. Medications should not be accessible to the person once or if confusion becomes part of the symptoms. 
  5. As with all things in life, a spectrum in the level of needs will vary from person to person. One person may need only moderate assistance. Someone else might require full-time care.
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