Parkinson Disease (PD)

 What is PD?

Parkinson disease is a disorder of brain.  It may cause multiple physical problems including loss of facial expressions, decreased blinking, body rigidity or stiffness, slowing of movements, loss of dexterity, problem with handwriting or similar tasks, tremor, mumbling, loss of balance, stooped posture, slowed walking, shuffling gait, and falling. Not every patient may have all these problems, while many patients have several additional ones.

How common is PD?

It is a disease of later life. In the 45 years and older population, it affects about 500-600 persons out of every 100,000. 

What causes symptoms of PD?

Main symptoms of PD are caused by deficiency of a chemical called dopamine in brain, which happens due to deficiency of dopamine-producing cells in a particular area of the brain. A small area in the brainstem part of the brain, called substantia nigra compacta, has a collection of cells that make dopamine. In this disease, patients start losing these cells, and once they lose a significant amount, symptoms start to happen. As they lose more cells, symptoms increase in severity.

What is the underlying mechanism leading to PD?

It is not well understood what starts or leads to the changes in the nervous system leading to PD pathology. Autopsy studies have shown collection of some abnormal material (misfolded alpha-synuclein protein or Lewy bodies and Lewy neurites) in the substantia nigra, but also many other areas of brainstem, the limbic part of the brain, some parts of the cerebral cortex, and some parts of the autonomic nervous system outside the brain, including in the skin. 

Are there any known causes of PD?

Cause of PD can be divided into genetic and non-genetic types. There are some known genes that may trigger PD, some dominant and some recessive type, together involved in about 20% of cases. Having an abnormal gene does not lead to the disease in every case, it may increase its risk. Knowledge about PD and genetics is less well understood in non-white populations as most of this information is obtained through research involving European and white American population.

Following are some non-genetic causes of PD:

1. Pesticides: Paraquat, rotenone, 2,4-dichlorophenoxyacetic acid, organochlorines, and organophosphates.
2. Solvents: Trichloroethylene, perchloroethylene.
3. Higher consumption of dairy from animals exposed to excessive pesticides.
4. Head injury.
5. Multiple medications like anti-psychotics.
6. There may be more chemicals leading to PD or PD like illness, including some military and industrial exposures. Data for this type of analysis is either insufficient, not shared, or not easily available.

There are other exposures that seem to reduce the risk of PD, such as cigarette smoking, caffeine consumption, and higher level of physical activity.

What are symptoms of PD? 

Symptoms of PD can be divided into these categories. Not every patient has all these symptoms:

1. Motor symptoms: Decreased facial expressions and blinking, slowing of movements, rigidity, resting tremor (tremor when the limb is not in use), imbalance, loss of dexterity, difficulty walking, difficulty dressing or undressing, difficulty getting in and out of car, falls, difficulty using stairs, difficulty writing, or doing similar motor tasks.
2. Sleep disorders: Insomnia, restless leg syndrome, REM sleep disorders.
3. Psychiatric: Apathy, anxiety and depression. In conditions that look like PD, or the Parkinsonian syndromes, there can be numerous other behavioral and physical symptoms.
4. Cognitive: Forgetfulness, confusion, difficulty finding places, difficulty navigating an automobile, especially in tight spots like the garage, and dementia.
5. Sensory: Decreased sense of smell, body pain.
6. Autonomic: Dizziness, low blood pressure, constipation, urinary control problems, erectile dysfunction, dry or sweaty skin, impaired temperature control.
7. Systemic: Weight loss, constipation, decreased energy, fatigue.
8. Skin: Oily skin.
9. Speech: Soft speech, monotonous voice, mumbling, slurring, the so-called festination of speech (fast speech).
10. Eyes: Dry eyes, blurred vision.  
11. Others: Drooling, choking, coughing while eating or drinking.

How is Parkinson disease diagnosed?

It is diagnosed by its symptoms and signs on physical examination. So far, there is no lab test for PD. CT scan and MRI scan of the brain may be helpful but do not make the diagnosis. Some other brain imaging, like the SPECT or a PET scan, can be helpful in some cases, especially to differentiate between PD and atypical tremor.

How difficult is it to diagnose Parkinson disease?

For an experienced neurologist, especially the one with extra training in movement disorder, it is an easy and straightforward diagnosis to make, which is made based upon history and examination. Many times, observing the patient walking from the waiting room to the examination room provides enough information to make the diagnosis. But there are many conditions that look like PD, which must be considered to find the precise diagnosis.

What is parkinsonism?

There are medical conditions, other than PD, which have some of the same clinical features. Sometimes, to differentiate, neurologist used the term of parkinsonism or the parkinsonian syndromes for these conditions. In every case with PD-like symptoms and signs, it is important to make sure one is not dealing with one of these conditions, which may require different approach of treatment.

What other conditions may look like PD?

Following conditions may have PD like features:

. Progressive supranuclear palsy or PSP

. Multiple system atrophy or MSA

. Normal pressure hydrocephalus or NPH

. Corticobasal syndrome or CBS

. Side effect of some psychiatric medicines.

. Tardive dyskinesia or TD

. Multiple strokes.

. Traumatic brain injury.

. Dementias, especially dementia with Lewy bodies.

. Benign essential tremor or BET.

. Severe depression.

How is Parkinson disease treated?

There is no known medicine or a mean available to slow down, stop, or reverse this condition. On the other hand, regular exercise, healthy diet, avoidance of further brain injury (e.g., by avoiding alcohol and drugs of abuse), and staying physically and socially active in life can be helpful.

Symptoms of PD can be divided between motor and non-motor symptoms. Following medicines are available for motor symptoms of PD:  

1. Levodopa: It is helpful for slowing of movements, body stiffness, imbalance, and difficulty walking. It also helps with tremor but not as much. Levodopa can make people nauseous and to counter that a medicine called Carbidopa is added with it; so, the name, Carbidopa/Levodopa. It comes in multiple strengths and formulations. Each dose of Levodopa lasts for a few hours, though there are some long-acting versions that may last little longer. It usually works well in early stage of the disease but not as well after 4-5 years when its good effect, or the “on” stage, seem not to last long. This can be managed by either taking a higher dose, taking it more frequently, or adding another medicine to it.
2. Non-ergot dopamine agonists: Like ropinirole (Requip), pramipexole (Mirapex), rotigotine transdermal patch (Neupro), apomorphine HCl injectable (Apokyn).
3. MAO-B inhibitors: Selegiline (Eldepryl), rasagiline (Azilect), zonisamide (Zonegran), safinamide (Xadago).
4. COMT inhibitors: Entacapone (Comtan), opicapone (Ongentys)
5. Adenosine A2A methyltransferase antagonist: Istradefylline (Nourianz).
6. Anticholinergics: Trihexyphenidyl (Artane), benztropine (Cogentin).
7. NMDA receptor antagonist: Amantadine (Symmetrel, Gocovri).

Which of these medicines is best for me?

In early stages of PD, Levodopa alone can work well. If for some reason that is not a possibility, e.g., due to an allergy to it, a dopamine agonist drug can be tried. Problem with dopamine agonist drugs is that in comparison to Levodopa, they are not as effective, and may have more side effects. On the other hand, if tolerated well, their effect lasts longer.

My experience with prescribing medicines for PD is following, which can be divided in periods of 5 years: First few or five years of treatment is easy, medicines work well with minimal or no side effects. In the second 5-year period, combination of medicines is needed while side effects may increase. During the third 5-year period, medicines combinations may get complicated and with frequent dosing may cause more obvious side effects. In addition, overall physical and cognitive disability increases. This trend continues as the patient grow older with the disease. Management of PD is part science and part art (understanding and managing every individual’s social and physical situation, in addition to medical issues). Common side effects of medicines are fatigue, hypersomnia or excessive sleep, dyskinesias or abnormal movements, on/off phenomenon, behavioral issues, and sometimes compulsive behavior. This is compounded by progression of the disease leading to significant problem with walking and balancing, difficulty performing activities of daily living, abnormal posture, chronic fatigue, drooling, chronic back pain, cognitive dysfunction, difficulty chewing and swallowing, difficulty speaking, weight loss, chronic constipation, decreasing stamina, generalized weakness, and many more issues.

What medicines are available for non-motor symptoms of PD?

Non-motor symptoms and problems described in the above paragraph can be managed in the same manner as in any other patient. There is no specific medicine for non-motor symptoms of PD.

Is there a cure for Parkinson disease?

A permanent solution or a cure for Parkinson disease is currently not available. Scientists have been working to develop different solutions, including some ways to replace the lost dopamine producing cells.

Is there a surgical treatment for Parkinson disease?

For some patients and for some of their symptoms, surgery may help. Surgery does not replace what is lost, it helps in a different manner. The circuitry in the brain for control of physical movements is quite complex. With experimentation, scientists have figured out some of the detail. They also have figured out that if they knockout a small part of that circuit, or if they stimulate a different part, they can help patients with their symptoms. Both techniques, knocking out or stimulation have been used in surgical treatments. For knocking out, patients get a surgical procedure where the area to be knocked out is carefully selected, and then frozen or cauterized. In recent years, this technique has been mostly replaced by a different procedure called Deep Brain Stimulation. In this technique, patients get a similar procedure, but a wirelike structure is left in a particular area of the brain. Electrical signals are sent through the wire to stimulate that area by a controller placed under the skin. The controller is programmable, and its settings are changed from outside based upon patient’s response.

Who is the right candidate for surgical treatment for Parkinson disease?

Surgical treatment is mainly for a patient not responsive to medications or having excessive side effects from them. It is a brain surgical intervention and is avoided in a patient with mild symptoms, or anyone doing well on medicines. On the other hand, in carefully selected patients, it can be quite an effective treatment.

What is carbidopa/levodopa?

As stated above, Parkinson disease is caused by deficiency of dopamine in the brain. Levodopa is a chemical that gets converted to dopamine in the brain. When taken by mouth, levodopa may break down in the blood before it reaches the brain. A chemical called carbidopa is added to it, which prevents its breaking so that enough Levodopa may reach the brain, to be converted to dopamaine. Carbidopa also helps to decrease sided effects of levodopa.

What are common side effects of carbidopa/levodopa?

Common side effects of carbidopa/levodopa are nausea, low blood pressure, dizziness, and sedation. Most patients can tolerate it or have minimal side effects.

What are common side effects of dopamine agonist drugs?

Examples of dopamine agonist drugs are ropinorole and pramipaxole. Their side effects are like the side effects of carbidopa/levodopa. In addition, other common side effects are low blood pressure, sudden onset of sleep, confusion, hallucinations, or compulsive behavior.

What are anticholinergic drugs?

Anticholinergics are drugs like benztropine or trihexyphenidyl. This is a different type of medicine used to treat some symptoms of Parkinson disease. They are helpful in treating tremor of Parkinson disease. Their common side effects include dizziness, drowsiness, dry mouth, forgetfulness, and confusion. They are not used in a patient with glaucoma and are risky in elderly.

Why is it important to know if someone has Parkinson disease or a Parkinsonian Syndrome?

Patients with Parkinson disease have a predictable clinical course and usually a good response to medicines. Patients with Parkinsonian Syndromes on other hand, may not respond to medicines, may need different type of treatment, and have a different clinical course. In this regard, one should also be careful reading medical records as many times all these conditions are lumped under the term of Parkinson disease.

Does exercise help with Parkinson disease?

Strength and aerobic exercise on regular basis have significant positive impact on the wellbeing of a patient with Parkinson disease. Patient feels better, both emotionally and physically. One may not necessarily need a physical therapist but at least one or two formal consultations with a professional may help to figure out a plan of exercise that patients may continue. Many patients, who can afford this service, feel better with regular physical therapy or the service of a private therapist.

Is there a special diet plan for Parkinson disease?

In traditional literature there is recommendation of avoiding protein meal while taking levodopa. I do not consider this to be a significant issue. In general, there is no particular or specific diet that may improve or specifically worsen Parkinson disease. A healthy lifestyle and healthy well-balanced diet are recommended. Because constipation is a common problem with Parkinson disease, appropriate dietary changes (higher amount of fiber and ample hydration) are recommended to avoid it.

Does alcohol help with Parkinson disease?

Alcohol does not help. It is a chemical toxin for the brain. It has short-term effects for which people drink, but also long-term, which lead to degeneration or death of brain cells. No amount of alcohol is completely safe for human consumption. If one already has a brain disease, it is very important to avoid any other reason for brain injury.

Does marijuana help with Parkinson disease?

Answer to this question is somewhat like the one provided above for alcohol. Medically speaking, not enough information is available to make any claim of benefit. Also, unlike alcohol, marijuana is a complex product. It has thousands of chemicals, and their medical effects have not been formally studied. Some people provide anecdotal evidence that it is helpful, while ignoring that there is more than anecdotal evidence of its harmful effects on the nervous system. Better answers to this type of questions require changes at Federal level legislation leading to appropriate funding and medical research.

Is there a human stem cell treatment for Parkinson disease?

As Parkinson disease involves deficiency of dopamine producing cells, it is natural to consider treatment with cells that may manufacture dopamine. Currently, this type of thinking and treatment is experimental and not available in routine clinical settings.

What are different stages of Parkinson disease?

Staging of a condition like Parkinson disease is based upon patient’s clinical picture. One may divide it into mild, to moderate, and severe; and the stages in between like mild to moderate and moderate to severe.

For medical research, neurologists use many formal clinical scales to assess severity, such as Hoehn and Yahr Scale, or Unified Parkinson’s Disease Rating Scale (UPDRS), or Schwab and England Activities of Daily Living Scale. These types of scales are not much used or useful in day-to-day clinical settings.

How quickly Parkinson disease may progress?

Parkinson disease is not a rapidly progressive disease. Its progress is different in different patients but the first few years, may be 5, are relatively easy and patients have mild symptoms, which respond well to medicines. After a few more years, symptoms are noticeable, especially if patient skips medicines. Patient is still able to function without significant disability. After that period, patients may still respond to medicines, but may also have side effects, and finding a balance may be difficult. Working or employment may become difficult. At this point, one can figure out a progress curve and its direction for an individual patient, a slow and steady, or with significant difficulty. Part of this assessment depends upon some other factors, like if the patient has cognitive problems or not, and other medical issues.

How many medicines does a Parkinson patient take?

If symptoms are minimum and not impacting patient’s quality of life, there is no reason to take a medicine. In initial stages of the disease, patient might just be fine with one medicine, or may be two. In a few years of the disease, patients usually are better with combination of 2-3 meds, and in later stages more than that. The goal of medicine(s) is symptom control and improvement of patient’s quality of life.

Do patients with Parkinson disease have dementia?

Majority of patients with Parkinson disease develop dementia, especially after a few years into the disease. If you remember the cause of Parkinson described above, it is from deficiency of dopamine from loss of cells that produce dopamine. There is another finding of Lewy bodies in the brain that may be the main cause of dementia. Dementia of Parkinson disease may cause forgetfulness, loss of focus, difficulty making complex decisions or multi-tasking, and some behavioral issues. There is no specific medicine available to stop or reverse this process.

Is constipation common in Parkinson disease?

Constipation is a common problem in Parkinson disease. Patients are advised to have multi-dimensional approach to avoid this problem. Make sure diet is balanced with ample fibers, fruits, and vegetables. Keep yourself well hydrated. Check all the prescription and over-the-counter medicines, including any nutritional supplements, to avoid anything making this condition worse. Use stool softener if needed.

Where can I get more information about Parkinson disease?

American Academy of Neurology
Parkinson’s Foundation