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.

In Parkinson's Disease (PD), there is slow degeneration of dopamine-producing cells 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.

The cause of PD remains largely unknown. Scientists believe the combination of aging brain, environmental factors and genetics contribute to the development of PD. PD is chronic and worsens over time.

Symptoms

Parkinson's disease can begin at any age. The average age of diagnosis is around age 60. The cardinal features include 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).

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

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

Diagnosis

Parkinson’s disease is a clinical diagnosis which involves a complete medical history and neurological exam. Laboratory tests and brain imaging may be done to exclude other potential causes. In some cases, a dopamine transporter scan (DaTscan) may be recommended.

Management

Currently, there is no cure for Parkinson’s disease, however symptoms are managed with medications, lifestyle modification and surgery.

Medications for motor symptoms:

• Carbidopa/Levodopa is the gold standard of treatment and is available in several different forms, including tablets (Sinemet, Sinemet CR, Rytary, Parcopa, Stalevo), a gel form (Duopa) and an inhaled form (Inbrija). The levodopa in these medications is converted into dopamine in the brain. Carbidopa inhibits breakdown of levodopa before it gets to the brain. Side effects include but are not limited to: nausea, lightheadedness, fatigue, confusion, hallucinations and dyskinesia.
• Dopamine Agonists include Pramipexole, Rotigotine, and Ropinirole. These medications mimic the action of dopamine and bind to dopamine receptors. Rotigotine 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, and leg swelling.
• MAOB Inhibitors include Rasagiline, Selegiline, and Safinamide. These medications act by inhibiting the activity of an enzyme that breaks down dopamine in the brain and make dopamine available for longer. They can be taken as monotherapy or in combination with other dopaminergic agents. Side effects include but are not limited to: nausea, lightheadedness, fatigue, and hallucinations.

Medications for WEARING OFF symptoms:

• Entacapone inhibits an enzyme that breaks down dopamine. It is taken with each dosage of levodopa. Side effects include but are not limited to urine discoloration, nausea, diarrhea, and dyskinesia.
• Istradefylline is an adenosine A2A receptor antagonist that helps improve ON time. It is taken once a day. Side effects include but are not limited to dyskinesia.
• Apomorphine is a fast-acting dopamine agonist. Taken sublingually, it 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, and vomiting.
• Inbrija is levodopa in inhaled form. It is can be used up to 5x per day and allows for levodopa absorption through the lungs, bypassing the gut. Side effects include but are not limited to coughing, choking, nausea, and lightheadedness.

Medications for dyskinesias: 

• Amantadine can be taken once or twice a day to control dyskinesias. Side effects include but are not limited to ankle edema, skin rash, hypotension, worsened cognition and hallucinations.
• Gocovri is a long acting amantadine taken once a day at night; it can also help increase “ON TIME” during the day.

Medications for dystonia:

• Trihexyphenidyl is an anticholinergic agent used to treat dystonia and tremor. Side effects include but are not limited to: blurred vision, dry mouth, constipation, urinary retention, and confusion.
• Botulinum toxin (BTX) injection temporarily calms muscle contractions by blocking the transmission of nerve impulses. The injection is typically done every 3 months and helps treat dystonia. Side effects include but are not limited to muscle weakness. Of note, BTX is also useful for treating excessive salivation.

Medications for anxiety and depression:

Antidepressants and anxiolytics are commonly used in Parkinson’s disease to treat symptoms of anxiety and depression. Among several options, some common medications include Escitalopram, Bupropion, Sertraline, Mirtazapine and Venlafaxine. Side effects include but are not limited to weight gain, sexual dysfunction, and insomnia.

Medications for psychosis and hallucinations:

• Clozapine is an antipsychotic used rarely due to increased blood monitoring necessary on this medication given risk of reduction in white blood cell counts. Side effects include but are not limited to weight gain.
• Pimavanserin is a selective serotonin inverse agonist and antagonist tartgeting receptors believed to play an important role in psychosis. It is the only FDA approved medication for psychosis and hallucinations in Parkinson’s disease. On this medication, symptoms may get worse for the first two weeks before they improve.
• Quetiapine is an antipsychotic, typically used at low doses and can be used nightly or twice a day. Side effects include but are not limited to somnolence, dry mouth, and weight gain.

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

• Clonazepam is a benzodiazepine, taken in small doses nightly to prevent the acting out of dreams. Side effects include but are not limited to sedation, incoordination and memory impairment.
• Melatonin is a natural supplement that regulates sleep cycle; it is 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 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. It is typically taken once a day. Side effects include but are not limited to salt and water retention.
• Midodrine 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 blood pressure. Side effects include but are not limited to supine hypertension.
  Side effects include but are not limited to supine hypertension.
• Northera 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.
  Side effects include but are not limited to supine hypertension

Surgical treatments:

Deep brain stimulation (DBS) is a surgical therapy where electrodes are inserted into a targeted area of the brain, causing disruption of abnormal electrical activity in the area that cause the symptoms of Parkinson’s disease. An impulse generator, similar to a pacemaker is implanted in the chest wall and sends electrical stimulation to the electrodes via an insulated wire. DBS treats motor symptoms of PD including tremor, bradykinesia, rigidity, motor fluctuations and dyskinesia. Side effects include but are not limited to disturbances of speech, impaired postural stability, unpleasant sensory symptoms, and impaired cognition.

High intensity focused ultrasound is a non-invasive procedure where inaudible sound waves are emitted into the brain, destroying a very specific area in the brain connected to PD symptoms. Side effects include but are not limited to balance issues, numbness, and difficulties with speech.

Duopa is Carbidopa/Levodopa in gel form delivered through a tube connected to a pump. A surgery is necessary to make a small hole (called a "stoma") to place the tube directly to the small intestine. Given this, Duopa improves absorption and reduces “OFF” times. Side effects are the same as Carbidopa/Levodopa.

Exercise:

Animal data suggests exercise affects dopaminergic neurotransmission and neuroplasticity. Exercise also helps maintain balance, mobility and activities of daily living and makes a big difference in the quality of life of people with Parkinson’s disease. Exercise should include aerobic activity, strength training, balance training and stretching.

Physical, Occupational and Speech Therapies:

We recommend LSVT-BIG physical and occupational therapy - a program created specifically to tackle the challenges of Parkinson’s. Speech therapy can address speech or voice changes and swallowing issues. We recommend LSVT-LOUD - the most researched voice treatment for people with PD.