Bridgepoint Neurology


what causes parkinson's?



Parkinson’s disease is a disorder of the brain. Specifically, there is a small nucleus of cells deep in the brain called the substantia nigra (the dark substance) that gradually dies off, and this causes the main manifestations of Parkinson’s. These cells in the substantia nigra produce a substance called dopamine, and via their connections they release this dopamine at various areas in the brain to influence movement. When there is not enough dopamine, movement is impoverished. This can result in a variety of manifestations, including slowness of movement, stiffness, stooped posture, slow unsteady walking, an expressionless face, a poorly projecting voice, difficulty swallowing, and tremor. Although tremor is an increased movement, it actually reflects poor control of movement. Fortunately, there are medications that can restore some of the brain’s dopamine and improve some of these symptoms.


Although medical science knows the substantia nigra has to be damaged to cause Parkinson’s, we still don’t know why this structure gets damaged. There are a small number of cases of Parkinson’s that are caused by genetic defects, and these defects are commonly seen in people who develop Parkinson’s in their 30s or 40s. However, the vast majority of people with Parkinson’s develop it after the age of 60, and there are no clear genetic defects that cause this. In fact, if someone develops Parkinson’s after the age of 60, the chance that any son or daughter will develop it is less than 3%. There are some studies suggesting exposure to pesticides may create an increased risk, and certain genetic variations may increase the susceptibility to this disease, but the only consistently identified factor that increases the risk of elderly onset Parkinson’s is age itself.


When these cells in the substantia nigra are looked at under a microscope, little proteinaceous deposits are seen in the cells, and these are called Lewy Bodies. However, we still don’t know how these deposits form or how to prevent them from forming. A related disease, Lewy Body Dementia, is characterized by more widespread deposition of these same proteinaceous deposits.


As scientists develop a better understanding of the cause of Parkinson’s disease, we may be able to prevent it more effectively, treat it more effectively, and keep it from getting any worse once it develops.



which medications are best?



Because the motor manifestations of Parkinson's disease are due to an inadequate production of dopamine by a certain area of the brain, the substantia nigra, it should be no surprise that the most effective medication provides the brain with an abundant supply of the precursor it uses to make dopamine. This medication is known generically as carbidopa/levodopa, but has several brand names now, including the shorter acting SinemetTM and the longer acting RytariTM. The brain uses the levodopa in carbidopa/levodopa to make dopamine. The carbidopa is included to keep the body from converting levodopa to dopamine outside the brain, where it would cause severe nausea and possibly irregular heartbeats.


Carbidopa/levodopa also has the best side effect profile of the medications used for the motor manifestations of Parkinson's. However, some people may develop some nausea while taking it, especially at higher doses, and they may require the use of a different medication or additional strategies to reduce the nausea. Additionally, a small percentage of people with Parkinson's who take carbidopa/levodopa will experience a fall in blood pressure when they stand, a phenomena called orthostatic hypotension, and this can cause dizziness on standing.


The dopamine agonists are another class of medications that are widely used to treat Parkinson's. These medications look and act like dopamine in the brain, so are essentially an artificial dopamine substitute, but are not exactly dopamine. Examples of the dopamine agonists include NeuproTM (rotigotine), RequipTM (ropinirole), and MirapexTM (pramipexole). These medications are clearly effective, and for more advanced cased of Parkinson's often form part of the treatment regimen. They have a much higher rate of causing hallucinations than carbidopa/levodopa, and are also associated with an "impulse control" disorder, which affects around 9% of people taking them. This impulse control disorder manifests as such things as excessive gambling, excessive online shopping, or watching X rated movies. For these reasons, at Bridgepoint Neurology we virtually always start treatment for Parkinson's with some form of carbidopa/levodopa and slowly increase the dose to ensure tolerability. We usually switch to a dopamine agonist if there is an intolerable side effect to carbidopa/levodopa. Additionally, we may add one of these medications to an existing regimen of carbidopa/levodopa to improve symptom control.


Some patients with Parkinson's are prescribed amantadine, which now has a couple branded long acting forms, GocovriTM and Osmolex ERTM. This medication is modestly helpful for the motor manifestations, but also has a high frequency of hallucinations. However, it can be helpful at reducing dyskinesias, a form of fluctuation that is discussed in the section on fluctuations below.


AzilectTM is another medication approved for Parkinson's. It works by inhibiting one of the breakdown pathways of dopamine in the brain. Its beneficial effects are modest, but for some people it provides just the right amount of fine tuning without having increasing side effects from higher doses of carbidopa/levodopa or the dopamine agonists. It may also prolong the duration of effectiveness of each dose of carbidopa/levodopa a little bit.


Some patients with Parkinson's are still prescribed ArtaneTM (trihexyphenidyl), and this is an outdated and minimally effective medication for Parkinson's.



What are fluctuations?



When medications for Parkinson's are effective for the tremors, stiffness, slowness, speech or walking (the motor effects), this effect can wear off after the medication is no longer present in the body at an effective level. Early in the course of Parkinson's disease this is an uncommon problem, and the effect of the medication, when taken regularly, lasts all day. However, as the disease progresses the benefit of the medication may not last as long, and the effect may wear off before taking the next dose of medicine. This phenomena is called, simply enough, wearing off. This wearing off can be treated by taking the medication at shorter intervals, adding other medications that prolong the duration of the agents used for Parkinson's, or taking longer acting forms of the medications used for Parkinson's. For people who still have this phenomena of wearing off despite adjusting their medications, more advanced treatments such as deep brain stimulation and continuous medication infusions are available.


On the other hand, if the blood level of Parkinson's medications gets too high, it can cause another problem, in which patients experience ongoing involuntary movements that are reminiscent of a fish out of water. This problem is called dyskinesias. It can be treated by reducing the dose of the medication for Parkinson's, taking them less frequently, or adding other medications that reduce this phenomena. Both dyskinesia and wearing off are forms of fluctuations in the response to medication.


Treating Parkinson's disease consists of a delicate balancing act between having enough medication so the beneficial effect does not wear off, but not so much as to cause dyskinesias or other side effects. Because of the complexity, the treatment of more advanced forms of Parkinson's is best performed by a neurologist with expertise in movement disorders.


At Bridgepoint Neurology, our medical director spent several years at a dedicated movement disorders institute, under the mentorship of the current president of the International Association of Parkinson's and Movement Disorders, enjoys treating and has extensive experience with the management of advanced Parkinson's disease.



can i keep it from getting worse?



Parkinson's disease is, like aging, a slowly progressive condition. It can slowly worsen over 10, 15, 20 or more ears. Probably the most well-known person with Parkinson's, Michael J. Fox, began having symptoms in 1991 and was still giving interviews 25 years later. The natural progression is a slow worsening of walking ability, increased tremors, stiffness and slowness of movement. A certain amount of these symptoms can be mitigated by medication.


Because of its gradually progressive course, there is much interest in finding a way to slow down or stop the progression. To date, there have only been a few hints of possibly being able to slow the rate of functional loss down some, but no clear and obvious method of doing so. However, a large amount of research is being done in this area now, with the Michael J. Fox foundation raising a significant amount of money to do so.


Physical therapy may also help the functional capabilities in Parkinson's disease, and this is generally recommended for people who are at least moderately affected.


One of the leaders in the field of movement disorders, of which Parkinson's is one type of movement disorder, is Dr. Stanley Fahn at Columbia University. He did a small study in which giving people vitamin E and vitamin C appeared to prolong the time (by a few years) that they could go without needing medication for Parkinson's. Although a larger study looking at the ability of vitamin E to reduce the progression of Parkinson's was a failure, the effects of vitamin C have not been evaluated in a large study. Therefore, supplementation with a moderate amount of vitamin C, in addition to a healthy diet, seems reasonable in individuals with Parkinson's disease.



what else can i experience with parkinsons?



Although Parkinson's is typically recognized by the tremors, stiffness, slowness and walking difficulty people with this condition experience, there are a variety of other manifestations that can happen, and some of these have highly effective treatments.


Lightheadedness or a fuzzy headed feeling on standing is a common problem in Parkinson's, and this is different than the balance impairments that occur. This lightheadedness is due to the blood pressure dropping when someone with this condition stands up. Not too infrequently, someone presents to my clinic with dizziness, we find their blood pressure drops when they stand up, and after doing a more detailed neurologic examination I find they have Parkinson's. Quite often, these same people have been on the same medication to lower their blood pressure for years, and do not think that the medication is a problem. However, since they have developed Parkinson's disease, they have become much more susceptible to the effects of blood pressure medications and frequently have to be tapered off of these to resolve their dizziness. Sometimes, though, the problem is sufficiently severe we have to add medications that help keep the blood pressure up when someone with Parkinson's stands up.


People with Parkinson's also frequently act out their dreams in bed. Normally, when an individual dreams, their body is paralyzed. This is helpful, because if their body wasn't paralyzed when they dream they might wake up on the other side of the house badly bruised. In people with Parkinson's disease, the brain circuit responsible for maintaining this paralysis while dreaming is often dysfunctional, and it is common to observe such people talking, yelling, or hitting in their sleep. This condition is called REM sleep behavior disorder, and REM is the stage of sleep in which people dream. Fortunately, a low dose of the medication clonazepam at night will often resolve this problem. Some patients may respond to melatonin for this problem, but the results do not seem to be as consistent as with clonazepam.


Bladder control problems are frequent in individuals with Parkinson's also, and this usually takes the form of a frequent urgency to go to the bathroom. This can respond to medications for overactive bladder, but in men we generally have an initial urology consultation first to evaluate for other common causes of urinary urgency, such as an enlarged prostate. Additionally, some medications used for overactive bladder can worsen cognitive impairments that can occur in Parkinson's.


Memory, attention, mood and motivation can also be affected in Parkinson's. For each of these problems certain medications may be helpful.



BRIDGEPOINT NEUROLOGY



12062 Valley View Street
Suite 107
Garden Grove, CA 92845



Phone: 714-646-7040

info@bridgepointneurology.com