Introduction

In 1817 a British doctor, Dr. James Parkinson, published a paper on what he called "shaking palsy". He described the common symptoms of shaking/trembling hands. Parkinson's disease was named after Dr. Parkinson since he first described the disease. Nearly 1 million people in the United States are affected by Parkinson's disease.

Parkinson's Disease (PD) is caused by a lack of production of dopamine in an area of the brain known as the substantia nigra, located deep in the base of the brain. There is a delicate balance between the effect of acetylcholine (a neurotransmitter that carries messages along the nerves) and dopamine. Acetylcholine inhibits motor activity, while dopamine facilitates motor activity. If dopamine is decreased, then the effect of acetylcholine is enhanced and motor activity becomes slower.

There are many processes which can cause a lack of dopamine. The process can be degenerative, viral, toxic, or traumatic in etiology. Strokes in the area of the substantia nigra can also produce a decrease in dopamine levels. PD is chronic and usually worsens over time.

Symptoms

Parkinson's disease can begin at any age. Several years prior to the onset of typical Parkinson’s symptoms, patients may experience violent dream reenactment which may be diagnosed as REM (rapid eye movement) behavioral disorder.  Patients may also, very early in the course of the disease, experience changes in taste and smell (dysgeusia and hyposmia).  The average age of diagnosis is around age 60. The four major symptoms are: rigidity (stiffness in arms, legs and neck, difficulty getting out of chairs), resting tremor (shakiness of hands), bradykinesia (slowness in initiating movement which may contribute to decreased facial expression, change in speech, shuffling gait, smaller-lettered handwriting, trouble with fine finger movements) and loss of postural reflexes (poor balance and coordination).

Secondary symptoms can include: depression, anxiety, memory and sleep problems, changes in speech patterns, urinary or bowel difficulties, low blood pressure upon standing, trouble swallowing, hallucinations or problems chewing or swallowing.

Disease progression varies among individuals. For some progression is slow, over 20-30 years, while others may progress more rapidly.

Diagnosis

Diagnosis is made from a complete medical history and physical exam. Laboratory tests and a CT scan or MRI of the brain are done to exclude other potential causes. In some cases a DaT scan may be recommended.

Treatment

Medications to replace dopamine can provide relief from Parkinsonian symptoms. Carbidopa Levodopa is the gold standard of treatment and is available in several different forms, including an immediate release, a continuous release and an extended release version (called Rytary). There are dopamine-sparing therapies available as well including dopamine agonists and MAOb inhibitors. In some cases, the use of levodopa can be delayed if Parkinson's patients are given dopamine agonists or MAOb inhibitors early during diagnosis. Other medication treatments exist for the other symptoms of Parkinson’s. To name a few, we often use SSRIs for anxiety, fludrocortisone/midodrine/droxidopa for low blood pressure, amantadine/Gocovri for dyskinesias, Nuplazid for hallucinations.

Medications for movement symptoms:

• MAOb inhibitors (3): rasagiline (Azilect), selegiline, safinamide (Xadago). These medications act by inhibiting the activity of an enzyme that breaks down dopamine in the brain and make dopamine available for longer. Rasagiline is the most potent. Safinamide has benefits for dyskinesias
  Side effects include but are not limited to: nausea, lightheadedness, fatigue, hallucinations
• Carbidopa Levodopa: Carbidopa levodopa IR, Carbidopa levodopa CR, Stalevo, Rytary. The levodopa in these medications is converted into dopamine in the brain. Carbidopa inhibits breakdown of this medication before it gets to the brain.
  Side effects include but are not limited to: nausea, lightheadedness, fatigue, hallucinations
• Dopamine Agonists: pramipexole (Mirapex), rotigotine (Neupro), ropinirole (Requip). These medications mimic the action of dopamine and bind to dopamine receptors. These are often used PRIOR to levodopa in order to delay time to starting levodopa. Pramipexole in particular is very helpful for tremor. Ropinorole is helpful for restless leg symptoms. Neupro comes as a patch and bypasses the gut so can be helpful in cases of constipation.
  Side effects include but are not limited to: hallucinations, impulse control disorders, sleep attacks, leg swelling

Medications for dyskinesias:

• Amantadine: can be taken once or twice a day to control dyskinesias
  Gocovri: this is a long acting amantadine taken once a day at night that also helps by increasing ON TIME during the day.
  Side effects include but are not limited to orthostasis, worsened cognition/hallucinations.

Medications for hallucinations:

• Seroquel: antipsychotic, typically used at low doses, can be used nightly or twice a day.
  Side effects include but are not limited to weight gain, drowsiness/sedation
• Clozapine: Antipsychotic, used rarely due to increased monitoring necessary on this medication. The first 6 months require weekly blood draws with regular blood draws subsequently to monitor for a reduction in neutrophil counts.  Side effects include but are not limited to weight gain.
• Nuplazid: Inverse agonist and agonist at serotonin receptors. Only FDA approved medication for delusions and hallucinations in Parkinson’s disease. On this medication, symptoms may get worse for the first two weeks before they improve.

Medications to help with WEARING OFF of Levodopa:

• Comtan: inhibits an enzyme that breaks down dopamine. Taken with each dosage of levodopa.
  Side effects include but are not limited to urine discoloration, nausea, diarrhea, dyskinesa
• Nourianz: adenosine A2A receptor antagonist, helps improve on time, taken once a day in the AM
  Side effects include but are not limited to dyskinesia
• Kynmobi: apomorphine which stimulates dopamine receptors. Taken sublingually, can be used up to 5x a day with two hours between doses.
  Side effects include but are not limited to mouth sores, dry mouth, nausea, vomiting
• Inbrija: levodopa inhalation powder, used by inhaler up to 5x per day, allows for levodopa absorption through the lungs, bypassing the gut, can be helpful in constipation.
  Side effects include but are not limited to coughing, choking, nausea, lightheadedness

Medications for REM (rapid eye movement) sleep behavior disorder:

• Clonazepam: benzodiazepine, taken in small doses nightly to prevent the acting out of dreams
  Side effects include but are not limited to sedation
• Melatonin: natural form of treatment used in dosage of 1-12mg taken before bed to prevent the acting out of dreams.
  Side effects include but are not limited to sedation.

Medications for neurogenic orthostatic hypotension:

• Fludrocortisone: taken once a day by mouth this is a mineralocorticoid that increases salt retention from the kidneys thereby increasing water retention to increase your circulating blood volume and target low blood pressure readings
  Side effects include but are not limited to salt and water retention
• Midodrine: this is an alpha-1-agonist that can be taken up to 3 times a day in doses that range from 2.5-10mg at a time to raise your blood pressure
  Side effects include but are not limited to supine hypertension.
• Northera: this is a precursor of norepinephrine that works to raise the blood pressure and can be taken up to 3 times in a day in doses that range from 100mg to 600mg at a time
  Side effects include but are not limited to supine hypertension

There are surgical options for managing Parkinson’s currently available: we offer management of Deep Brain Stimulation and Duopa. Another more recently approved option is focused ultrasound treatment.

Exercise and healthy lifestyle decisions make a big difference in the quality of life of people with Parkinson’s. We often recommend BIG physical therapy - a program created specifically to tackle the challenges of Parkinson’s. We also offer botulinum toxin treatment for conditions like excess salivation, limb dystonia (abnormal involuntary muscle contractions which result in repetitive or twisting movements) or cervical dystonia which can present in Parkinson’s disease.