The following is a close to verbatim transcript of the March 7th Satellite Symposium Question and Answer portion of the program. Dr. Dee Silver, from San Diego, California, moderated the question and answer period. Q. What can a Parkinson's patient do to sleep better at night? D Silver: I think that there are a combination of things that are helpful. 1. Have plenty of exercise and activities during the day. 2. Don't take lots of naps during the day. 3. Don't take Eldepryl after Noon or 1 p.m. 4. Sleep in a quiet place, free of noises 5. Use some of the tricyclates or anti-histamines Benedryl low dose at bedtime Elavil If you have nocturnal symptomology, meaning tremor or rigidity, that wakes you up at night, it is important to consider how to change your medication. Tailor your individual treatment. If you have urinary problems, that require you to be up many times during the night, consult with your doctor about the possibility of the cause being a Neurogenic bladder and its treatment which can be complex but helpful. ******** Editors Note # 4 ************************** A document discussing Neurogenic bladder and its treatment is in the parkinsn archives. To receive the document, send a message to: [log in to unmask] Paste into the body of the message: //DBlook JOB Echo=No Database Search DD=Rules //Rules DD * select * in parkinsn print all 4349 ****************************************************** Fort Myers Florida Q. Do Parkinson's disease patients ever regain their loss of brain cells or is this the very best day of their lives? Dr. Tatton: Well, they don't recover brain cells if they have died but it is not necessarily the best day of their lives. People like Galen Finch and other people, and we are beginning to think this way as well. The death process is probably a prolonged process, in which the cells are first damaged and the 'end of the road' is likely to be the apoptosis process, as I talked about. In between, some proportion of the cells become dysfunctional so when you gave the numbers of 20 to 40 percent, before we started to see the disease, maybe there are 5 to 10 percent of the cells that are not dead but dysfunctional. We have an opportunity to recover or get back those cells so that you may have a better day. Grand Rapids, Minnesota Q. Some recent reports, suggest selegiline's (Eldepryl, deprenyl) benefit may not last for a number of years. Dr. Olanow: It's a very difficult question to answer, because, in order to determine if selegiline benefit lasts for years, you would have to have controlled groups that were follow for that length of time and compare them with what is happening to them with their Parkinson's. One of the things that we know is that selegiline does not stop the progression of Parkinson's disease, the question is whether it slows it down. To my mind, the study that most closely looks at that from a specific point of view is that which I described for you earlier and that only looks out about 14 or 16 months. I think that for now that there is just not information to say what happens several years down the road. Tucson, Arizona Q. Does Deep Brain Stimulation (DBS) produce the same results clinical that the ablative surgical procedures? Dr. Kordower: In terms of the Stimulation of the VIM of the thalamus, the constellation of symptoms that are improved are different than pallidotomy or transplantation. Tremor control is effective when the VIM of the thalamus is stimulated. There may be other brain regions that may be sensitive to deep brain stimulation such as the globus pallidus, or the subthalmic nucleus and remains to be determined if these nuclei which are much more located in the direct main circuitry of the basal ganglia. Stimulation in these regions may give a more widespread and efficacious relief to more parkinsonian symptoms. Ridgecrest, California Q. What new medications are on the horizon and can you group them into specific types, giving the names if possible? Dr. Olanow: There are fortunately a lot of new medications that are being evaluated. Some are in the process of being assessed by the FDA, for the use in the treatment of Parkinson's disease. Dopamine Agonists Ropinerole Pramipexole These dopamine agonists are potent, D2 receptor stimulants, in some ways similar with Pergolide (bromocriptine). They are being tested predominately in early stage disease to see if they can be used to delay the start of levodopa, and also to see if they could reduce the likelihood of adverse effects. Cabergoline A long lasting, one dose a day agonist. Apomorphine A drug used in Europe for advanced patients in which freezing is a problem. May be injected and used as a rescue drug for those who freeze in the middle of a crosswalk on a busy street. It is also valuable in a post operative setting in which patients may not be able to swallow. COMT Inhibitors COMT inhibitors prolong the effective dose period and in some cases will turn "On" those patients whose levodopa dosage is not enough. Fort Myers, Florida Q. Is melatonin of any benefit, or could it have side-effects? Dr. Tatton: Melatonin is an agent that resets part of the brain that controls our sleep and awake cycles. It's been an experimental agent for some time. I don't think that there have been wide-spread trials in relation to Parkinson's disease benefit. Cape Coral, Florida Q. When do you begin Sinemet treatment and when is more dosage, too much? Dr. Silver: I use Sinemet CR in the younger and Sinemet regular in the older patient when functional impairment occurs. When Activities of Daily Living (ADL) are significantly affected. Without question, levodopa (Sinemet) is the biggest, most powerful drug we have for the treatment of parkinsonism, today. How much is too much? Too much is always determined by monitoring side effects/benefits. Q. If Parkinson's disease is genetic, is there any evidence that it is only passed down to one gender? Dr. Olanow: At the present time there is some evidence that at least in some families, Parkinson's disease is genetically transmitted, but they are few and far between. Probably only 5% of cases follow an autosomal dominate pattern. That doesn't mean that the other cases don't have a genetic component, but what is likely a genetic component that is brought into play by circumstances that involve another form of stress, such as exposure to a toxin. For example if you were born with the inability to metabolize a particular toxin, if you don't get exposed to that toxin, then you don't get the disease. On the other hand, if you don't have the defect, and you are exposed to the toxin, you don't get the disease. What you need is what was referred to previously, you need a "Double Hit", you need to have the defect and also be exposed to the toxin. That's becoming a very popular theory. With respect to cases where there is proven Autosomal Dominate inheritance, there is no evidence because it is autosomal rather than X-linked, that it specifically affects one sex member more than the other. With respect to the other, it is not yet proven what role genetics plays, only interests in the possibility that it contributes to risk nothing to suggest more that one sex, however it is noteworthy to note that Parkinson's disease seems to effect males more. Alberta, Canada Q. How is dopamine production, in the brain, measured in humans and animals? Dr. Tatton: There are a number of ways in doing that. One can do it indirectly by looking in the cerebrospinal fluid, in humans, and looking at the break-down products of dopamine and getting some idea of the dopamine productions. This is not a great way of doing it. In animals, or with post-mortem brain tissue, one can literally remove specific areas of the brain and measure dopamine and its break-down products with techniques like hplc and other techniques. Look at enzymes or proteins directly with ink stains or aminocytochemistry. Lastly you can get some ideas of dopamine by using PET scans. San Diego Q. How can you tell if you are over-medicated? Dr. Silver: There are a number of ways to determine if you are over-medicated and to understand that concept of over-medication, we have to think about the toxic features that we see. The ones that I am more concerned about are the involuntary movement disorders, the dyskinesias. Peak dyskinesias are those that occur between doses. That usually means toxicity. Another important area, is the neuropsychiatric manifestations that occur, especially those who have memory difficulty. Side-effects that are early warning signs of over-medication are: Early personality changes Nightmares Hallucinations Confusion Disorientation Delusions Now we have clozapine (Clozaril) that is of significant benefit. Waco, Texas Q. Is there evidence of a specific toxin, such as MSG or some other toxin, that is present in the environment today that causes Parkinson's disease? Dr. Olanow: About 10 years ago when Bill Langston and his colleagues identified MPTP injections as associated with Parkinson's, there was considerable interest in the possibility that there were MPTP-like toxins in the environment. Outside of MPTP there have been no toxins identified that produce Parkinson's syndrome. There are several toxins that can produce parkinsonian feature and have some aspects that resemble Parkinson's disease, such as manganese, carbon monoxide, carbon disulfide, but these are indeed different and probably not the same. There are a number of toxins that are being investigated, which could eventually have effects on dopamine, but as yet none of them have been directly linked to Parkinson's disease or Parkinson's disease-like syndrome other than MPTP itself. Q. Is pallidotomy a routine procedure and who should be selected to do that procedure? Dr. Olanow: I think that this is an important question and I think that it is an appropriate question in a forum like this. I think that there are many opinions what I'm going to say should be taken in context that I am just giving you my own personal opinion. Pallidotomy is a procedure that has been done since 1940 or since 1950, so that a lot of people have done pallidotomy. There have been claims of benefit from pallidotomy dating back to that time. The big advance came in the 70s or 80s when Laitenen, using the Leiksell technique, reported that if you did the pallidotomy in a slightly different location, which was called posteroventral, the quality of the results were improved. Pallidotomy is also done targeting something lying between the internal capsule and the optic region so it is possible during the lesioning, damage could be done to the optic region. Therefore, one has to take into consideration the improvement versus the adversity that could pursue. What has really triggered the resurgence of pallidotomy aside from improvements in stereotactic technique and MRImagery, is increased insight into the organization of the basal ganglia which provides a scientific reason why a lesion in this area might be expected to be helpful. Refined techniques, like microelectrode recordings permit very precise detection where exactly you are. I tell you all of this because the pallidotomy that is being done today in the highly academic centers is not the same being done routinely in neurosurgical operations in non-academic environments. There are many questions that remain to be answered like what is the best site for the lesion, is microelectrode technology essential to get the best results, how long do the improvements last, what are the side-effects, who are the very best patients for the pallidotomy. I think that these kinds of questions need to be answered. You must look at that in the context that there are very encouraging reports, particularly with dyskinesia that suggest that pallidotomy is a wonderful procedure and very beneficial for the appropriate patient. Taking all of that together, I would encourage one to think of pallidotomy as a procedure that still should be performed by those skilled in stereotactic surgery, expertise in neurology and expertise in neurophysiology, with expertise in clinical trials. In an effort to come to a conclusion that answers these questions in the best possible way, so that we can offer this procedure in the most effective way to our largest possible population. I personally don't think that we have reached the point where all pallidotomies can be considered the same and that just anyone should be doing the pallidotomy without concern for assertainment, full reporting of results, and full investigation of associated factors that might influence results. Houston, Texas & Alberta, Canada Q. What is the best times to take your medicines and do meals have any effect on Sinemet, Eldepryl and a dopamine agonist? Dr. Silver: Eldepryl, take in the morning and around noontime. Meals by and large do not effect the absorption of Eldepryl. Sinemet on the otherhand, can be blocked by the large proteins. Not only does the amino acids block the absorption in the stomach but the transport of the levodopa across the blood-brain barrier is affected. The other important concept is that dopamine agonists, are not affected by meals. Q. Would you please explain again what a free-radical is and the aspect of anti-oxidants in vitamin E? Dr. Tatton: Atoms that are stable have two electrons in orbit around them. Unstable atoms have one electron in their orbit. These unstable atoms are called free-radicals. If the free-radical is able to 'steal' an electron from a stable electron, it is called oxidation. Atoms that have an even number of electrons in their orbit and have the ability to change or absorb those atoms with only one, are called anti-oxidants. Vitamin E is such an anti-oxidant. As Dr. Olanow, it was used in the DATATOP study compared with deprenyl. In that study, it was shown to have no benefits in terms of the Parkinson's patients studied. Savannah, Georgia Q. Could you tell us what a Lewy body is, what is its significance and what role does it play in Parkinson's disease? Dr. Kordower: It is the defining feature of Parkinson's disease. Inside the cell there is an occlusion which histologically is seen preferentially and also exclusively with patients with Parkinson's disease. It is found in regions know to degenerate, such as the substantia nigra and the locus cerolious and again it is used as the hallmark histological diagnostic feature of Parkinson's disease. San Diego, California Q. Please explain a reason for freezing that occurs suddenly and unpredictably. Dr. Olanow: That is one of the troublesome features of Parkinson's disease, especially as they advance. Some can have freezing while in the 'On' stage, that is while they are responding to levodopa. Some can have freezing during the 'Off' stage, that is the period after the dose has lost its effectiveness. Characteristically, it occurs suddenly. The patients stop in the middle of a movement, and when they are changing from one environment to another like they are walking through a doorway. They stand for seconds or minutes at a time before they are able to restore function. It is different than the 'On' or 'Off' response that we talk about relative to levodopa. It does not respond relatively well to levodopa. For the most part, we do not have an effective treatment for it and do not fully understand it pathophysiology. Tacoma, Washington Q. Do nutritional supplements combat free-radicals and can they interfere with the aspects of Parkinson's disease? Dr. Tatton: Clearly, it is an attractive idea that dietary changes can reduce the destruction of free-radicals. The jury is still out on this. There are a number of supplements that are out, that claim to do this. There haven't been any studies that support the idea that simple dietary supplements will reduce free-radicals in the brain, especially the parts of the brain effected by Parkinson's disease. Fort Myers, Florida Q. Give me a simple treatment format for orthostatic hypotension. Dr. Olanow: Orthostatic Hypotension refers to a drop in blood pressure upon standing. This can be mild and innocent found on blood pressure taking as one changes from lying to standing positions, but it can also be extremely troublesome and be associated with syncope episodes (light-headedness, fainting) and literally prevent a patient from rising to their feet and being able to walk, so it can be very disabling. It usually results in autonomic dysfunction in parkinsonian patients. It is not rare to occur in Parkinson's disease, but is usually very mild. If it is present to a severe degree, it suggests that it is not Parkinson's disease but rather a more wide spread degenerative disease called, Multiple System Atrophy (MSA) in which autonomic involvement is prominent. When patients have autonomic dysfunction, there are a few things that can be done to treat them symptomatically. One thing is to increase their salt intake always bearing in mind that that may have an adverse effect on blood pressure. Patients can also take a drug called Fluorinef which is a form of steroid that retains salt and control blood pressure. 0.1 to 0.2 mg/day is usually sufficient. If you need more than that it is not particularly helpful. In the most severe cases, one could wear stockings which are like an antigravity stocking that wraps up all the way to your waist. If you wear stockings only to the thigh, it is not particularly helpful. They have to be worn to the waist to be effective. In regions like Florida where it is hot and humid, you can imagine that this is not a particularly popular therapy. Patients in this environment, even though they need them, will not take them. Dr. Silver: When I do not see a patient who has orthostatic hypotension for a while, I check their medicines that their HMOs may have prescribed since I saw them last. I especially look for anti-hypertensives and see if we can adjust their dosage. Charleston, West Virginia Q. With regards to recent reports, smokers have a lower prevalence of Parkinson's disease. Can you shed any light on why that may be so? Is there any protection from being a smoker? Dr. Tatton: There have been an number of reasons suggested for this. People who smoke have fairly high levels of carbon monoxide in their blood. Carbon monoxide can serve as an antioxidant and can reduce free-radical damage. It is like taking one poison to benefit, another. Dr. Olanow: People with Parkinson's disease were compared to non-smokers. People who smoke are risk takers. It has also been suggested that people who smoke, may not live long enough to get Parkinson's disease.....:) Florida Q. Could you please shed some light on the concepts in trophic factors and in transplantation, please? Dr. Kordower: There are a number of ways that trophic factors and transplants work independently and together. I showed you that over 200 thousand cells survived in our transplant patient but in truth, that was only 6 to 7% of the ones we put in. There are a number of studies in the laboratory by my group and other groups demonstrating that substances called trophic factors. A trophic factor is defined as a substance which supports the viability or survival of a cell and which we can use to get larger numbers of cells to survive in the animal model of transplantation. That is one way that a trophic factor can help transplantation. The other very interesting area of research is to use the trophic factor to prevent the degeneration of the nigral neurons, much in the same way Drs. Olanow and Tatton have been describing anti-oxidants to try to prevent the degeneration of nigral neurons. Probably the most promising of the group is a trophic factor called a Glial Derived Neurotrophic Factor (GDNF). Some pioneering work, here in Denver by Dr. Barry Hopper and his colleagues have demonstrated that you can inject in GDNF and prevent the degeneration of nigral cell neurons in animal models of Parkinson's disease. What makes this trophic factor particularly exciting, relative to others is the lasting effect. A single injections of GDNF can last for weeks or months. Based on the success of recent work on animals and primates, a number of centers including Dr. Lang at the University of Toronto and our group headed by Dr. Goetz at Rush-Presbyterian Medical Center, will be soon be initiating a clinical trial as to whether the inter-cerebral administration GDNF will be able to slow the progression of Parkinson's disease and potentially have a symptomatic effect on the signs and symptoms of this disease. Dr. Tatton: It is probably worth mentioning one other aspect of trophic factor. Years ago to get them, they had to be extracted from brain tissue. It was very expensive and the yield was only very small amounts. Recombiant-DNA methods now allow making the trophic factors very simply. This is a big factor in the possibility that these may be effective therapeutic tools. Florida Q. Are dopamine agonists an effective treatment by themselves or do they always have to be in combination with Sinemet? Dr. Silver: Dopamine agonists can be used in the concept of 'dopamine sparing' strategies. In early Parkinson's, Eldepryl and then an agonist may be used...keeping a close eye on the motor functions and then later adding Sinemet. Oxford, Ohio Q. For many parkinsonians who experience cognitive and memory problems, is there any drug that can be of benefit? Dr. Olanow: In the older parkinsonian, this is common. It has been estimated that 1/3 will develop a dementia at some stage. At pathology, approximately 50% of Parkinson's disease patients have changes in their brain consistent with Alzheimer's disease change. One of the arguments suggesting at least an overlap between these two conditions. In addition, Parkinson's patients also get Lewy bodies in their cortex giving rise to a syndrome called Lewy body dementia. This can be a very troublesome problem to deal with and to be quite candid, if we are dealing with dementia per se, difficulty with confusion, thinking and memory there are very few things one can do. One of the things you could do is make sure that the patient is not taking other drugs which interfere with mental function. Another thing is to make sure that the patient is not taking other anti-parkinson drugs that aren't particularly effective but have mental side-effects like artane or Symmetrel(amantadine). Thirdly, one could consider reducing the amount of levodopa necessary to control the Parkinson's disease. If the patient has hallucinations, not dementia, One can look at clozapine, the atypical neuroleptic or ECT. These drugs may control hallucinations and at the same time allow the increase of Sinemet to better control the Parkinson's symptoms. John Cottingham "The parkinsn list brings Knowledge, Comfort, Hope, and Homeboy Friendship to the parkinsonian world." 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