Parkinson's Disease is a sporadic disorder, with a probable genetic predisposition in ~16% of  families. 2% of the population develop Parkinson's by age 80. The average age of onset of symptoms is 63. The range of age of onset is quite wide, with "young onset" Parkinsons occurring not infrequently. 8% of patients have the onset of their symptoms before age 40.

There are no blood tests or X-rays that will confirm the diagnosis. although PET scans are capable of detecting a deficiency in some Parkinsonisms. The diagnosis is based on meeting motor criteria. (See United Kingdom Brain Bank Criteria) made on finding 2 of the 3 cardinal features of the disorder on neurologic exam and ruling out other possible causes includung several conditions that can mimic Parkinson's Disease but often have additional features (Atypical Parkinsonisms or Parkinsn's "Plus" syndromes).

Cardinal Features

1) Tremor:

This is present in 80% of cases. It is usually manifest by a tremor at rest (at a time when the body part is relaxed). It may affect the hands, feet, chin, and tongue. It can be brought out by distraction such as mental arithmetic as per the video example. It doesn't affect the head. Classically when it affects the hand it creates a "pill rolling" tremor. The thumb slides back and forth on the index finger.  30% of patients will also have a component of this tremor with action (movement induced tremor). This tremor like all tremors will be worse after physical exertion, or with good or bad emotional excitement.

2) Rigidity (stiffness):

Rigidity or stiffness in muscles leads to a characteristic loss of arm swing with walking, loss of facial expression, fatigue, and a variety of muscle pain syndromes (e.g. frozen shoulder). This is identified on examination by the examiner passively manipulating the limb while the patient is relaxed. Getting the patient to perform movements with the opposite side of the body will  accentuate the abnormality in the tone of the limb. There is  a classically described "cog wheel" type of rigidity in Parkinson's Disease. Without regular exercise, physiotherapy, and/or medication this rigidity can lead to progressively increased problems with immobility and muscular pain.

3) Bradykinesia (slow movement):

A general slowing down of movement will occur. The features that should be looked for include slowness of speed, loss of amplitude over time and a disruption in a smooth rhythm. Eventually there may be arrests in ongoing movements. These features are all evident in the video. This together with the rigidity causes the  many other symptoms, and signs of Parkinson's. The walking slows, the feet start to shuffle, the voice softens, and losses its expression. Fine coordinated tasks like buttoning and cutting food become difficult. Writing becomes messy, and gets smaller, and increasingly illegible.

Other motor symptoms:

There is a typical gait disorder (Click on the underlined words to link to an excellent youtube video example) that starts with loss of arm swing on one side then the step length shortens and walking speed slows down. The body becomes more stooped or flexed and the arms bend more at the elbows and gradually this worsens with increasing difficulty getting started (gait initiation) and turning.

A stooped posture and a blank facial expression occurs as the result of immobility and rigidity.

Postural Instability (loss of balance) occurs later in this condition.

Freezing or sudden loss of movement, often occurring in doorways, or when attempting a  movement that requires more than one action (such as walking to a door and opening it) may trigger this. Cues such as seeing something to step over, hearing a beat to move with, or having someone touch the individual  may help the person to start moving. In addition to freezing of gait (FOG) patients can also experience freezing of arm movement.

Speech problems result from incoordination or reduced movements of the muscles involved in breathing, voice, pronunciation and prosody (rhythm, intonation and speaking rate). The first  change is usually a soft or fading voice.  Words may become slurred or unclear with the final sounds in words being omitted. Speech may become faster. Their may be difficulty beginning  conversations or sentences causing hesitations or uncontrolled repetitions of words or phrases. Drooling may cause muffled speech. Drooling is often an early symptom with the pillows being wet at night. This isn't due to increased salivation, but relates to decreased frequency of swallowing.

Difficulty swallowing affects approximately 50% of advanced Parkinsonians. It is caused by slow moving, poorly coordinated throat muscles.

Non-Motor Symptoms:

We now know in addition to the more often recognized motor symptoms, that a host of additional "non-motor" problems arise in this condition and in many of these are evident years before the motor symptoms become evident allowing the diagnosis to be made.

It is common for constipation, loss of sense of smell, sleep disorders and anxiety to precede the motor symptoms and have been reported to do so up to 20 years prior to the motor diagnosis. Many of these features are being studied as potential markers in patients at risk (those with a familial or genetic type of Parkinson's in their family).

Sleep disorders include:

REM (rapid eye movement) sleep behavior disorder, a condition during which patients while dreaming abnormally retain the ability to move and can be seen "acting out their dreams". This can be dangerous as it can lead to sleep related falling out of bed (SFOB) or unintentionally striking one's bed partner while dreaming.

Restless Leg syndrome (RLS) a condition where when the patient relaxes, typically while lying down at night to fall asleep they get an uncomfortable sensation in their legs associated with an urge to move the legs to obtain relief.

Sleep fragmentation, a result of frequent nocturnal wakening secondary to a variety of causes including; urge to go to the bathroom to urinate, muscular cramping, difficulty rolling over in bed, nightmares, REM sleep problems, nocturnal wearing off related to Parkinson medications not lasting through the night, early morning wakening (sometimes a sign of depression. This leads to or contributes to daytime sleepiness.

Sleep Apnea is a condition reported in up to 30% of patient's with Parkinson's disease. It results from a combination of either an obstructive component which occurs as a result of a relaxation of the jaw and throat muscles allowing the patient's airway to be obstructed, or a loss of the central drive to breath at certain stages of sleep. This causes frequent nocturnal sleep stage disruption and results in a failure of a normal amount of the deep restorative sleep that is required to feel awake during the day.

Constipation is often a major problem. It results from a combination of  immobility, dehydration slowing of digestion, and antiparkinson medication side effects.

Loss of the sense of thirst is common in Parkinson's disease and contributes to low blood pressure symptoms and constipation. Recommendations include consuming at least 8 to 10 servings of fluid (water, soup, jello, ice cream, juice, milk etc per day.

Sexual dysfunction is a frequent problem due to the autonomic nervous system involvement.   Impotence as well as hypersexuality may be a side effect of antiparkinson medications.

Easy fatigability is often the result of the effort and constant attention required to move. This is complicated by sleep disturbances including sleep initiation problems and early morning wakening that may result from depression. Insomnia may occur from antiparkinson medication, as can vivid dreams or night mares.  Parkinson patients are more likely to act out their dreams.

Seborrhea or excessive scalp, eyebrow or eyelash oiliness, reddness, or scaliness may occur.

Late in this condition problems with low blood pressure causing weakness or dizziness, neck pain, blurred vision and if severe enough, confusion and increased risk of falls as well as fainting.

Sweating, or an impaired sweating response may occur. Antiparkinson medications may aggravate this. It most commonly happens when the benefit of Parkinson medication runs out including the middle of the night.

Bladder problems occur in advanced parkinson's, and results from varying effects of the illness on sphincter muscle control.   Antiparkinson medication may cause retention of urine and constipation.

Mental changes including depression which occurs in approximately 30% of Parkinson patients may be aggravated by self-imposed social isolation. Fatigue may contribute to feelings of discouragement. Anxiety may also be evident.

Memory loss will occur in up to 30-50% of patients. This occurs late in the illness.

Progression:

The disorder progresses differently from one individual to the next. With treatment almost normal abilities can be maintained for 5 -10 years. Unfortunately there is no curative treatment  and the treatment options only help control the symptoms.

As the illness progresses the patients require more medications at a time when they are less able to tolerate their side effects. This can lead to fluctuating degrees of control of the symptoms. Variable degrees of disability start to break through the previous ability to maintain  consistent symptom control throughout the day.

Most of the ongoing research is investigating ways of pushing this problem further into the future, and to lengthen the time the symptoms can be adequately controlled.

Some problems unfortunately have no treatment (e.g. memory loss).

Cause:

The cause is unknown but assumed to be the result of a combination of environmental influences (toxins, infections) superimposed on a varying genetic predisposition/ susceptibility. Findings recently suggest the illness has its origins in the lower brainstem (vagal nerve controlling bowel function) and/or the olfactory nerves (loss of sense of smell) and either spread or gradually develop in adjacent regions (brainstem involvement likely contributes to anxiety and sleep disorders) until the substantia nigra in the midbrain is affected. At this stage the motor symptoms become evident. It is known that all Parkinson patients have a marked reduction in the number of nerve cells in the Substantia Nigra (black pigmented nerve cell in the brain stem). Some families are known to be have an inherited defect that is assumed to result in a failure of survival of these nerve cells. These cells are known to die off earlier than expected in Parkinson's Disease. This results in the chemical that these cells produce, dopamine, becoming deficient. Without dopamine the part of the brain that normally slows down excess movement becomes over active, resulting in the slowness and stiffness seen in this disorder.

Researchers still don't know why but there is increasing evidence that the variety of genetic and environmental insults leading to Parkinson's have in common, a collection of abnormal forms of a normal protein - Alpha synuclein - this seems to contribute to cell death. There are some who feel that this protein, when in an abnormal state, can spread from cell to cell causing further nerve cell loss. Research is exploring ways of controlling the production or improving the clearance of this protein.

Treatment:                                          

Work toward a healthy lifestyle:

There are currently several options to treat Parkinson's disease.

The first step is to make sure the patient becomes well informed about the disorder and has a doctor with experience in managing this condition. An interdisciplinary team approach can be valuable.

A healthy lifestyle with good eating, sleeping, and exercise habits is strongly encouraged.

Early assessment by a physiotherapist to initiate an appropriate regular exercise program is recommended.

The motor vehicle branch needs to be informed, but early on the illness should not interfere with safely driving a motor vehicle if the expected treatment response occurs.

Initial Treatment Options:

Slowing progression

The decision to start medications is a difficult one. To date (November 2011) there is no medication generally thought proven to be able to slow down the progressive nature of Parkinson's disease. If there was we would want to start it as soon as we know someone has or is at risk of having Parkinson's dissease. Exercise is recommended in hopes this may have that potential. 3 hours of cardiovascular fitness producing exercise per week is often recommended. This needs to be vigorous enough to cause an alteration in breathing enough that is would be difficult to carry on a conversation. Any such exercise program should be introduced slowly and with the advise of a physician or physiotherapist.

Rasagiline is a medication that is being researched due to a potential it is thought to have to slow disease progression. The most recent trial ( The ADAGIO trial) failed to demonstrate clear confirmation of this. A 1 mg dose met all end points required to confirm this potential but the study also assessed a 2 mg dose which didn't fill all the required endpoints. As a result without further research, the answer to this important need is still to be met. This study was published in the New England Journal of Medicine (C. Warren Olanow, M.D., Olivier Rascol, M.D.,  Ph.D., Robert Hauser, M.D., Paul D. Feigin, Ph.D., Joseph Jankovic, M.D., Anthony Lang, M.D., William Langston, M.D., Eldad Melamed, M.D., Werner Poewe, M.D., Fabrizio Stocchi, M.D., and Eduardo Tolosa, M.D., for the ADAGIO Study  Investigators. A Double-Blind, Delayed-Start  Trial of Rasagiline in Parkinson's Disease. N Engl J Med 2009;361:1268-78).

Treating symptoms

The 2 main options for treatment include replacing dopamine directly with Levodopa or using a chemical mimic of dopamine (a dopamine "agonist").

As Dopamine given directly is poorly absorbed, the medication Levodopa, a precursor of dopamine, which is well absorbed is used). Levodopa is metabolized quickly in the body preventing much of this medication from getting to the brain where it is needed. As a result it is combined with other medication (carbidopa or benzarazide) to allow an effective amount to get into the brain. These other chemicals also reduce the nausea and low blood pressure that would occur if Levodopa was given alone. These medications come under the trade names of Sinemet, Sinemet CR, and Prolopa. Common side effects include nausea, dizziness, and confusion. hallucinations, and abnormal involuntary movements. Domperidone is a medication available in Canada that is very effective at controlling the nausea or low blood pressure if these are persistent problems preventing a patient from tolerating the levodopa.

There are 3 dopamine agonists available in Canada, each varying in cost, duration of action, and side effects. In general the side effects are similar to levodopa but more frequent. The dopamine agonists available include: Bromocriptine, Ropinirole, and Pramipexole.

Dopamine agonists have the advantage over levodopa in younger patients of reducing the potential of producing dyskinesias and as a result are often suggested early on in management.

After the release of Ropinirole, and Pramipexole 2 newly recognized side effects became evident that are very important to watch for.

The first was excessive daytime sleepiness. In some cases this was associated with sudden onset of sleep and was associated with motor vehicle accidents due to falling asleep at the wheel. All patients need to be aware of this potential exists with all Parkinson Medications and should they be experiencing excessive sleepiness during the day (a score of greater than 7 on an Epworth scale) or have any experience of falling asleep in inappropriate circumstances (driving / while eating, or during a conversation) they should immediately stop driving and consult their doctor.

The next side effect of these medications to be identified relates to impulse control disorders. These include but are not limited to gambling, shopping addiction, eating binges with weight gain, and hypersexuality. Almost any activity that brings a reward can be accentuated and take over one's normal activities. Should a personality change occur relating to a patient seemingly driven to one or two activities at the exclusion of more normal life interests, their doctor should be notified. The offending medication often needs to be discontinued to resolve this problem.

Other medication options include some older medications including Amantadine (symmetryl) which, interestingly, is the only comoonly used Parkinson medication that can be used to treat dyskinesia. Amantadine will help symptoms 60% of the time. It's duration of benefit varies.

The anti-cholinergics (e.g. trihexyphenidyl, benztropine, ethoproprazine) can be helpful for refractory tremor, and tend to dry up saliva, so they  can reduced drooling. Overall these medications are less well tolerated particularly in older patients due to their tendency to reduce memory and worsen constipation.

Selegiline, like rasagiline is a medication that blocks the breakdown of  dopamine, and may prolong the benefit patients receive from l-dopa medications. There had been some suggestion that selegiline might slow the progression of Parkinson's disease in the late 1980's, but most neurologists consider this as unproven as a result of several trials that have shown inconsistent results.

Avoid Drugs that are Contraindicated in Parkinson's:

The term "contraindicated" essentially means that the drug in question should not be given to a patient. In the parkinsonian, the basic problem is the chemical nature of the disease itself. Many drugs alter the brain's dopamine system and may not be recognized as having the potential to markedly alter the symptoms of Parkinson's simply because the drugs are often used for the treatment of non-neurological conditions. Every patient with Parkinson's should have a list of these agents available for their physician's reference.

Drug Category Trade Name Generic Name Antipsychotic (used for agitated confusion) Haldol Haloperidol Trilafon Perphenazine Thorazine Chlorpromazine Stelazine Trifluoperazine Prolixin,     Permitil Flufenazine Navane Thiothixene Mellaril (high dosage) Thioridazine Antidepressant Triavil Combination of Perphenazine &  Amitriptyline Antivomiting Compazine Prochlorperazine Reglan, Maxeran Metoclopramide Torecan Thiethylperazine Miscellaneous Serpasil Reserpine Nitoman Tetrabenazine Possible /  Potential Contraindicated Meds Blood Pressure Meds Aldomet Alpha-methyldopa Anti-Seizure Medication Dilantin Phenytoin Mood Stabilizer Lithium Lithium Anti Anxiety Buspar Buspirone

Information in Table above taken from The Transmitter Vol. 7, No. 4, Oct 1990.

Surgical Options:

In addition to pills surgical treatments are now more frequently used to help control symptoms that become refractory to medications.

1) Steriotactic thalmotomy is a procedure that surgically destroys the very small area deep within the brain that causes the tremor (the thalamus).   This, if successful, will stop the tremor on the opposite side of the body.   There are, as with any surgery , possible side effects that need to be discussed and considered.

2) Another option is to implant a deep brain stimulator  (a small electrode usually implanted into the globus pallidus or more commonly the Subthalamic nucleus, that is connected to a programmable transmitter under the chest wall, like a pacemaker).  By electrically interfering with the natural firing pattern of the nerve cells in this area the tremor is electrically suppressed and in addition the rigidity and slowness of movement also improves.

On average with this type of surgery there is an average 50% reduction in medication and a smoothing out of the fluctuations in response to medication. There has now been > 16 year follow-up and many examples of maintained improvement over the long term.  There are, as with any surgery, possible side effects that need to be discussed and considered.

Surgical procedures directed to controlling other symptoms by operating on, transplanting, or stimulating other areas of the brain are continuing to produce exciting results.

Follow this link to more information on treatment links including Deep Brain Stimulation: