No known treatment can stop or reverse the breakdown of nerve cells that causes Parkinson's disease. However, drugs can relieve many symptoms of the disease. Surgery also can be effective in a small number of people to treat symptoms of Parkinson's disease.
Treatment is different for every person, and the type of treatment you will need may change as the disease progresses. Your age, work status, family, and living situation can all affect decisions about when to begin treatment, what types of treatment to use, and when to make changes in treatment. As your medical condition changes, you may need regular adjustments in your treatment to balance quality-of-life issues, side effects of treatment, and treatment costs.
Parkinson's disease causes a wide range of symptoms and complications. This topic covers the overall management of the disease. This topic does not discuss managing specific symptoms.
Initial treatment
If your symptoms are mild, you may not need treatment for Parkinson's disease. Your doctor may wait to prescribe treatment with drugs until your symptoms begin to interfere with your daily activities. Additional treatment methods (such as exercise, physical therapy, and occupational therapy) can be helpful at all stages of Parkinson's disease to help you maintain your strength, mobility, and independence.
If you do need drugs at this point, there are several options. Levodopa is considered the "gold standard" of treatment for Parkinson's disease. But levodopa can have negative effects when used long-term. Because of this, dopamine agonists such as pramipexole and ropinirole often are used first. Other non-dopamine drugs may be used early in the course of the disease. These include amantadine, monoamine oxidase inhibitors (such as selegiline), and anticholinergics (such as trihexyphenidyl). As the disease progresses, levodopa will likely need to be added.
Early in the disease, it might be helpful to take pills with food to help with nausea, which may be caused by some medicines taken for Parkinson's disease. Later in the disease, taking the medicines at least one hour before meals (and at least two hours after meals) may help them work better.
Your doctor, other health professionals, or Parkinson's disease support groups can help you get emotional support and education about the illness. This is important both early and throughout the course of the disease.
Ongoing treatment
As Parkinson's disease progresses, the symptoms usually become more disabling. Most people develop mild to moderate tremor. Movement is often slow and limited due to muscular rigidity and the slowing down and loss of automatic and spontaneous movement (bradykinesia). Treatment in this stage is determined by weighing the severity of the symptoms against the side effects of drugs.
The symptoms of Parkinson's disease change as the disease progresses. Because of this, your doctor will adjust your drugs to deal with the symptoms as they appear. Levodopa is the most commonly used drug for Parkinson's disease. However, it may cause side effects with prolonged use or high dosages. Your doctor may prescribe dopamine agonists such as pramipexole or ropinirole to delay the point at which you need to begin taking levodopa. Studies have suggested that this may delay the onset of levodopa's side effects.234 Your doctor may also prescribe levodopa along with a dopamine agonist.
Monday, July 20, 2009
Monday, July 13, 2009
Oxford Biomedica says study of ProSavin Parkinson’s treatment progressing well
Gene therapy group Oxford Biomedica PLC (AIM: OXB) said the Phase I/II study of its novel gene therapy, ProSavin, for the treatment of Parkinson's disease is progressing well.
Patients treated at the first dose level have maintained their improvement in motor function for one year, with an average improvement of 29 percent. Analogous investigator assessments of patients in the second cohort treated at a higher dose level have achieved similar benefit at three months, and the first patient to reach their six-month assessment has demonstrated further improvement.
The independent data monitoring committee supported Oxford BioMedica's proposal to proceed to a third dose level incorporating the company's new administration technology.
The ongoing Phase I/II study is designed to evaluate the safety and efficacy of ProSavin in patients with mid-stage Parkinson's disease who are experiencing reduced benefit on L-DOPA 'equivalent' therapy.
ProSavin is administered directly into the striatum of the brain using a well established surgical technique. The first stage of the study is a dose escalation in cohorts of three patients at each dose level and, to date, six patients have been treated.
ProSavin has been safe and well tolerated in all patients, with no serious adverse events and no evidence of immunotoxicity. All patients have reduced or maintained their PD medication relative to baseline.
The monitoring committee supports the company's proposal to proceed directly to a third dose level that is five-fold higher than the first dose level. Oxford Biomedica will incorporate its new delivery technology for the administration of the 5x dose level of ProSavin.
The new technique reduces the surgical time, facilitates higher dosing and has the potential to provide better reproducibility as study centres expand and thus accelerate clinical development timelines. A protocol amendment for the new technology is being prepared, which it plans to submit to French healthcare regulatory agency, AFSSAPS, before the end of the third quarter of 2009.
Patients treated at the first dose level have maintained their improvement in motor function for one year, with an average improvement of 29 percent. Analogous investigator assessments of patients in the second cohort treated at a higher dose level have achieved similar benefit at three months, and the first patient to reach their six-month assessment has demonstrated further improvement.
The independent data monitoring committee supported Oxford BioMedica's proposal to proceed to a third dose level incorporating the company's new administration technology.
The ongoing Phase I/II study is designed to evaluate the safety and efficacy of ProSavin in patients with mid-stage Parkinson's disease who are experiencing reduced benefit on L-DOPA 'equivalent' therapy.
ProSavin is administered directly into the striatum of the brain using a well established surgical technique. The first stage of the study is a dose escalation in cohorts of three patients at each dose level and, to date, six patients have been treated.
ProSavin has been safe and well tolerated in all patients, with no serious adverse events and no evidence of immunotoxicity. All patients have reduced or maintained their PD medication relative to baseline.
The monitoring committee supports the company's proposal to proceed directly to a third dose level that is five-fold higher than the first dose level. Oxford Biomedica will incorporate its new delivery technology for the administration of the 5x dose level of ProSavin.
The new technique reduces the surgical time, facilitates higher dosing and has the potential to provide better reproducibility as study centres expand and thus accelerate clinical development timelines. A protocol amendment for the new technology is being prepared, which it plans to submit to French healthcare regulatory agency, AFSSAPS, before the end of the third quarter of 2009.
Saturday, June 13, 2009
Treatments and drugs
Your initial response to Parkinson's treatment can be dramatic. Over time, however, the benefits of drugs frequently diminish or become less consistent, although symptoms can usually still be fairly well controlled. Your doctor may recommend lifestyle changes, such as physical therapy, a healthy diet and exercise, in addition to medications. In some cases, surgery may be helpful.
Medications
Medications can help manage problems with walking, movement and tremor by increasing the brain's supply of dopamine. Taking dopamine itself is not helpful, because it is unable to enter your brain.
*
Levodopa. The most effective Parkinson's drug is levodopa, which is a natural substance that we all have in our body. When taken by mouth in pill form, it passes into the brain and is converted to dopamine. Levodopa is combined with carbidopa to create the combination drug Sinemet. The carbidopa protects levodopa from premature conversion to dopamine outside the brain; in doing that, it also prevents nausea. In Europe, levodopa is combined with a similar substance, benserazide, and is marketed as Madopar.
As the disease progresses, the benefit from levodopa may become less stable, with a tendency to wax and wane ("wearing off"). This then requires medication adjustments. Levodopa side effects include confusion, delusions and hallucinations, as well as involuntary movements called dyskinesia. These resolve with dose reduction, but sometimes at the expense of reduced parkinsonism control.
*
Dopamine agonists. Unlike levodopa, these drugs aren't changed into dopamine. Instead, they mimic the effects of dopamine in the brain and cause neurons to react as though dopamine is present. They are not nearly as effective in treating the symptoms of Parkinson's disease. However, they last longer and are often used to smooth the sometimes off-and-on effect of levodopa.
This class includes pill forms of dopamine agonists, pramipexole (Mirapex) and ropinirole (Requip), as well as a patch form, rotigotine (Neupro). Pergolide (Permax) has been withdrawn from the market because of its association with heart valve problems. A short-acting injectable dopamine agonist, apomorphine (Apokyn), is used for quick relief.
The side effects of dopamine agonists include those of carbidopa-levodopa, although they're less likely to cause involuntary movements. However, they are substantially more likely to cause hallucinations, sleepiness or swelling. These medications may also increase your risk of compulsive behaviors such as hypersexuality, compulsive gambling and compulsive overeating. If you are taking these medications and start behaving in a way that's out of character for you, talk to your doctor.
* MAO B inhibitors. These types of drugs, including selegiline (Eldepryl) and rasagiline (Azilect), help prevent the breakdown of both naturally occurring dopamine and dopamine formed from levodopa. They do this by inhibiting the activity of the enzyme monoamine oxidase B (MAO B) — the enzyme that metabolizes dopamine in the brain. Side effects are rare but can include serious interactions with other medications, including drugs to treat depression and certain narcotics.
* Catechol O-methyltransferase (COMT) inhibitors. These drugs prolong the effect of carbidopa-levodopa therapy by blocking an enzyme that breaks down levodopa. Tolcapone (Tasmar) has been linked to liver damage and liver failure, so it's normally used only in people who aren't responding to other therapies. Entacapone (Comtan) doesn't cause liver problems and is now combined with carbidopa and levodopa in a medication called Stalevo.
* Anticholinergics. These drugs have been used for many years to help control the tremor associated with Parkinson's disease. A number of anticholinergic drugs, such as trihexyphenidyl and benztropine (Cogentin), are available. However, their modest benefits may be offset by side effects such as confusion and hallucinations, particularly in people over the age of 70. Other side effects include dry mouth, nausea, urine retention — especially in men with an enlarged prostate — and severe constipation.
* Antivirals. Doctors may prescribe amantadine (Symmetrel) alone to provide short-term relief of mild, early-stage Parkinson's disease. It also may be added to carbidopa-levodopa therapy for people in the later stages of Parkinson's disease, especially if they have problems with involuntary movements (dyskinesia) induced by carbidopa-levodopa. Side effects include swollen ankles and a purple mottling of the skin.
Physical therapy
Exercise is important for general health, but especially for maintaining function in Parkinson's disease. Physical therapy may be advisable and can help improve mobility, range of motion and muscle tone. Although specific exercises can't stop the progress of the disease, improving muscle strength can help you feel more confident and capable. A physical therapist can also work with you to improve your gait and balance. A speech therapist or speech pathologist can improve problems with speaking and swallowing.
Surgery
Deep brain stimulation is the most common surgical procedure to treat Parkinson's disease. It involves implanting an electrode deep within the parts of your brain that control movement. The amount of stimulation delivered by the electrode is controlled by a pacemaker-like device placed under the skin in your upper chest. A wire that travels under your skin connects the device, called a pulse generator, to the electrode.
Deep brain stimulation is most often used for people who have advanced Parkinson's disease who have unstable medication (levodopa) responses. It can stabilize medication fluctuations and reduce or eliminate involuntary movements (dyskinesias). Tremor is especially responsive to this therapy. Deep brain stimulation doesn't help dementia and may make that worse.
Like any other brain surgery, this procedure has risks — such as brain hemorrhage or stroke-like problems. Infection also may occur, requiring parts of the device to be replaced. In addition, the unit's battery beneath the skin of the chest wall must be surgically replaced every few years. Deep brain stimulation isn't beneficial for people who don't respond to carbidopa-levodopa.
Medications
Medications can help manage problems with walking, movement and tremor by increasing the brain's supply of dopamine. Taking dopamine itself is not helpful, because it is unable to enter your brain.
*
Levodopa. The most effective Parkinson's drug is levodopa, which is a natural substance that we all have in our body. When taken by mouth in pill form, it passes into the brain and is converted to dopamine. Levodopa is combined with carbidopa to create the combination drug Sinemet. The carbidopa protects levodopa from premature conversion to dopamine outside the brain; in doing that, it also prevents nausea. In Europe, levodopa is combined with a similar substance, benserazide, and is marketed as Madopar.
As the disease progresses, the benefit from levodopa may become less stable, with a tendency to wax and wane ("wearing off"). This then requires medication adjustments. Levodopa side effects include confusion, delusions and hallucinations, as well as involuntary movements called dyskinesia. These resolve with dose reduction, but sometimes at the expense of reduced parkinsonism control.
*
Dopamine agonists. Unlike levodopa, these drugs aren't changed into dopamine. Instead, they mimic the effects of dopamine in the brain and cause neurons to react as though dopamine is present. They are not nearly as effective in treating the symptoms of Parkinson's disease. However, they last longer and are often used to smooth the sometimes off-and-on effect of levodopa.
This class includes pill forms of dopamine agonists, pramipexole (Mirapex) and ropinirole (Requip), as well as a patch form, rotigotine (Neupro). Pergolide (Permax) has been withdrawn from the market because of its association with heart valve problems. A short-acting injectable dopamine agonist, apomorphine (Apokyn), is used for quick relief.
The side effects of dopamine agonists include those of carbidopa-levodopa, although they're less likely to cause involuntary movements. However, they are substantially more likely to cause hallucinations, sleepiness or swelling. These medications may also increase your risk of compulsive behaviors such as hypersexuality, compulsive gambling and compulsive overeating. If you are taking these medications and start behaving in a way that's out of character for you, talk to your doctor.
* MAO B inhibitors. These types of drugs, including selegiline (Eldepryl) and rasagiline (Azilect), help prevent the breakdown of both naturally occurring dopamine and dopamine formed from levodopa. They do this by inhibiting the activity of the enzyme monoamine oxidase B (MAO B) — the enzyme that metabolizes dopamine in the brain. Side effects are rare but can include serious interactions with other medications, including drugs to treat depression and certain narcotics.
* Catechol O-methyltransferase (COMT) inhibitors. These drugs prolong the effect of carbidopa-levodopa therapy by blocking an enzyme that breaks down levodopa. Tolcapone (Tasmar) has been linked to liver damage and liver failure, so it's normally used only in people who aren't responding to other therapies. Entacapone (Comtan) doesn't cause liver problems and is now combined with carbidopa and levodopa in a medication called Stalevo.
* Anticholinergics. These drugs have been used for many years to help control the tremor associated with Parkinson's disease. A number of anticholinergic drugs, such as trihexyphenidyl and benztropine (Cogentin), are available. However, their modest benefits may be offset by side effects such as confusion and hallucinations, particularly in people over the age of 70. Other side effects include dry mouth, nausea, urine retention — especially in men with an enlarged prostate — and severe constipation.
* Antivirals. Doctors may prescribe amantadine (Symmetrel) alone to provide short-term relief of mild, early-stage Parkinson's disease. It also may be added to carbidopa-levodopa therapy for people in the later stages of Parkinson's disease, especially if they have problems with involuntary movements (dyskinesia) induced by carbidopa-levodopa. Side effects include swollen ankles and a purple mottling of the skin.
Physical therapy
Exercise is important for general health, but especially for maintaining function in Parkinson's disease. Physical therapy may be advisable and can help improve mobility, range of motion and muscle tone. Although specific exercises can't stop the progress of the disease, improving muscle strength can help you feel more confident and capable. A physical therapist can also work with you to improve your gait and balance. A speech therapist or speech pathologist can improve problems with speaking and swallowing.
Surgery
Deep brain stimulation is the most common surgical procedure to treat Parkinson's disease. It involves implanting an electrode deep within the parts of your brain that control movement. The amount of stimulation delivered by the electrode is controlled by a pacemaker-like device placed under the skin in your upper chest. A wire that travels under your skin connects the device, called a pulse generator, to the electrode.
Deep brain stimulation is most often used for people who have advanced Parkinson's disease who have unstable medication (levodopa) responses. It can stabilize medication fluctuations and reduce or eliminate involuntary movements (dyskinesias). Tremor is especially responsive to this therapy. Deep brain stimulation doesn't help dementia and may make that worse.
Like any other brain surgery, this procedure has risks — such as brain hemorrhage or stroke-like problems. Infection also may occur, requiring parts of the device to be replaced. In addition, the unit's battery beneath the skin of the chest wall must be surgically replaced every few years. Deep brain stimulation isn't beneficial for people who don't respond to carbidopa-levodopa.
Saturday, June 6, 2009
Creatine and Possible Benefits to Parkinson’s Disease Victims
Creatine, also known as creatine monohydrate, creatine phosphate or creatine citrate, is a naturally occurring amino acid compound in your body that is made by your liver and facilitates the production of energy in your body. Most of the creatine is stored in your skeletal muscles and the rest is found in your brain, heart and testes. You can eat foods that have creatine, such as red meat and fish. However, creatine is also available in supplement form through health food and drug stores.
Promoted in supplement form as an energy enhancement, creatine use is encouraged by the exercise and bodybuilding industries to increase exercise performance. It is this long-standing benefit that has lead scientists to organize large-scale national clinical trials of the product to determine if creatine can have a beneficial effect on symptoms of Parkinson’s disease. Classified by the Food and Drug Administration (FDA) as a nutritional supplement, creatine is widely used by professional athletes and is considered safe for daily supplemental use.
Researchers have also concluded that creatine increases the available energy for brain nerve cells and that this process helps prevent the loss of mitochondria. As a result it has positive effect on the health and survival of your nerve cell. Recognizing that an increase in cellular energy is beneficial to the health of your nerve cells, researchers believe that the addition of creatine to the diet will prevent injury and the premature death of the neurotransmitters and cells of your brain that are affected by Parkinson’s disease.
The symptoms of Parkinson’s, progressively uncontrollable shaking of the limbs and degeneration in the ability to speak, result from a reduction of dopamine in the brain. Dopamine is a neurotransmitter, which helps control movement. It is the hope of researchers that the introduction of creatine will increase the neurological response between brain cells and result in a potential treatment for the sufferers of Parkinson’s disease.
In prior 18 month clinical trials of several potential Parkinson’s treatments, in which the trials were designed to eliminate those that are proven to be futile, results indicated that creatine being noted as warranting of further large scale clinical study for efficacy. Researchers also noted that creatine was well tolerated by test subjects. Prior research on creatine, unrelated to study of Parkinson’s disease or its treatment, have also resulted in no long term or serious side effects.
The research studies to determine whether creatine will be instrumental in arresting the progression of Parkinson’s disease will last for 5 to 7 years. The subjects will be those that have been diagnosed with Parkinson’s in the last five years and have been treated for two years or less with drugs that increase the levels of dopamine in the brain. Additional benefits of creatine, which have researchers optimistic in the study outcome, include its antioxidant properties that have been shown to prevent brain cell loss in laboratory mice that are affected with Parkinson’s disease. Researchers are encouraged by this revelation, and hope to prove the same effects of creatine to be present in human test subjects.
Promoted in supplement form as an energy enhancement, creatine use is encouraged by the exercise and bodybuilding industries to increase exercise performance. It is this long-standing benefit that has lead scientists to organize large-scale national clinical trials of the product to determine if creatine can have a beneficial effect on symptoms of Parkinson’s disease. Classified by the Food and Drug Administration (FDA) as a nutritional supplement, creatine is widely used by professional athletes and is considered safe for daily supplemental use.
Researchers have also concluded that creatine increases the available energy for brain nerve cells and that this process helps prevent the loss of mitochondria. As a result it has positive effect on the health and survival of your nerve cell. Recognizing that an increase in cellular energy is beneficial to the health of your nerve cells, researchers believe that the addition of creatine to the diet will prevent injury and the premature death of the neurotransmitters and cells of your brain that are affected by Parkinson’s disease.
The symptoms of Parkinson’s, progressively uncontrollable shaking of the limbs and degeneration in the ability to speak, result from a reduction of dopamine in the brain. Dopamine is a neurotransmitter, which helps control movement. It is the hope of researchers that the introduction of creatine will increase the neurological response between brain cells and result in a potential treatment for the sufferers of Parkinson’s disease.
In prior 18 month clinical trials of several potential Parkinson’s treatments, in which the trials were designed to eliminate those that are proven to be futile, results indicated that creatine being noted as warranting of further large scale clinical study for efficacy. Researchers also noted that creatine was well tolerated by test subjects. Prior research on creatine, unrelated to study of Parkinson’s disease or its treatment, have also resulted in no long term or serious side effects.
The research studies to determine whether creatine will be instrumental in arresting the progression of Parkinson’s disease will last for 5 to 7 years. The subjects will be those that have been diagnosed with Parkinson’s in the last five years and have been treated for two years or less with drugs that increase the levels of dopamine in the brain. Additional benefits of creatine, which have researchers optimistic in the study outcome, include its antioxidant properties that have been shown to prevent brain cell loss in laboratory mice that are affected with Parkinson’s disease. Researchers are encouraged by this revelation, and hope to prove the same effects of creatine to be present in human test subjects.
Saturday, May 30, 2009
Deep Brain Stimulation
Under the skin, a battery is surgically implanted -- generally within the upper chest. From the battery, wires snake up to the head, to tickle different targets deep inside the brain.
Such is the hardware for deep brain stimulation -- the equivalent of a cardiac pacemaker for the mind.
Until recently, deep brain stimulation was approved in the U.S. only to treat certain movement disorders, primarily those of Parkinson's disease, for which it diminishes tremors and rigidity and improves mobility. To date, more than 60,000 patients worldwide have had the devices implanted.
But now use of the technique seems set to mushroom.
This year, the Food and Drug Administration granted a so-called humanitarian device exemption for the treatment to be used in severe cases of obsessive-compulsive disorder -- the first approval of deep brain stimulation therapy for any psychiatric condition.
Large clinical trials are also in the works for use of deep brain stimulation for epilepsy and depression, and experimental studies in the U.S. and elsewhere -- still in their early stages -- are exploring the treatment for obesity, traumatic brain injury, severe chronic pain, Alzheimer's disease, anorexia, tinnitus and addiction.
There are discussions too on the possible use of deep brain stimulation to treat hypertension.
"The field is taking off," says Dr. Ali Rezai, director of functional neurosurgery at the Cleveland Clinic, who has been involved in research on movement disorders, traumatic brain injury, obsessive-compulsive disorder and severe depression, among others.
Some researchers warn, however, that with all this activity -- pushed in part by the industry that makes the brain-stimulation devices -- the field may be moving too fast.
"There is so much progress that's been made and so much potential -- you would hate to lose that potential," says Dr. Joseph Fins, chief of the division of medical ethics and a professor at Weill Cornell Medical College in New York.
Here's a look at deep brain stimulation as it moves beyond Parkinson's disease. (See the related story about reservations scientists have about the growth of the field, and go online at latimes.com/health for a look at less-explored applications such as traumatic brain injury and obesity.)
Obsessive- compulsive disorder
In studies with a total of 26 patients with severe obsessive-compulsive disorder, 60% of those whose device was turned on demonstrated "very much improved" symptoms after months of deep brain stimulation as measured by interviews and questionnaires, says Dr. Benjamin Greenberg, an associate professor at Brown University Medical School and Butler Hospital in Providence, R.I., who was one of the study researchers.
The patients had previously failed on medicines as well as behavioral cognitive therapy.
Yet the data, published last year in Molecular Psychiatry, can't really nail the effect of the treatment, Greenberg says, because the patients for the most part knew whether their devices were turned on or off. Thus, researchers can't rule out that some of the observed improvements were due to a placebo effect.
Patients were stimulated in an area called ventral capsule/ventral striatum, chosen, in part, because removal of nerve fibers in that area is known to cause improvement in obsessive-compulsive symptoms.
Based largely on these findings, the FDA recently granted a limited humanitarian device exemption that permits the device to be used in as many as 4,000 of the country's most severe cases of obsessive compulsive disorder per year.
To get this kind of exemption, Medtronic -- makers of the only deep brain stimulation device that is FDA-approved -- needed only to show its safety and probable benefit.
Greenberg is now doing a randomized, double-blinded trial with 30 patients, some of whom have devices turned on right away and some who have them turned on after a delay. No one will know whose device is turned on for the first several months of the trial.
Medtronic has conducted a large-scale randomized trial for deep brain stimulation on epilepsy. Data will be submitted to the FDA this year, says Paul Stypulkowski, senior director of therapy research of Medtronic.
The device was turned on, for three months, in half of the 110 volunteers, stimulating -- and thereby, paradoxically, inhibiting-- an area called the anterior nucleus of the thalamus. That area is believed to influence a circuit involved in seizures.
The data, presented in December at a meeting in Seattle, show that deep brain stimulation reduced the number of seizures by 38% compared with what was seen before implanting the device.
That is slightly better than improvement seen with vagus nerve stimulation, another FDA-approved electrical stimulation treatment, which reduces seizures by about 25%.
The control group whose device was kept turned off, also improved, by 14.5%. That could be due to a placebo effect. Or it might be because people who join trials are usually at their worst -- and often tend to improve somewhat on their own, says trial researcher Dr. Douglas Labar, of the Weill Cornell Medical College in New York.
If deep brain stimulation is approved, Labar says, patients will have the choice between a more efficient but also more risky treatment and the slightly less efficient but also less risky vagus nerve stimulation.
Depression
Medtronic and a second company, St. Paul, Minn.-based St. Jude Medical, have two large-scale randomized trials underway for severe, treatment-resistant depression. (St. Jude Medical recently received approval to sell its device for the treatment of Parkinson's disease in Europe and is now completing studies aimed at securing FDA approval for treating Parkinson's and another movement disorder in the U.S.)
Medtronic's depression trial will follow about 200 patients stimulated in an area called the anterior limb of the internal capsule for at least one year.
This brain target for depression was identified by accident: When obsessive-compulsive disorder patients who also had depression were stimulated in this area, their depression also improved.
In one case, a patient produced a one-sided smile when stimulated on one side of the brain and also expressed feelings of happiness, says study researcher Dr. Wayne Goodman of the National Institute of Mental Health.
In a recently published unblinded study, about half of 15 patients showed at least a 50% improvement in severe depression symptoms a year or more after surgery when the anterior limb of the internal capsule was stimulated, says Rezai, who was involved in the study.
St. Jude Medical chose a different brain target, area 25, for its depression trial, which will enroll more than 100 patients. Brain imaging studies have shown that area 25 is more active in depressed people.
In a study of 20 patients, 55% still responded to treatment as late as one year after surgery, says study author Dr. Helen Mayberg, professor of psychiatry and neurology at Emory University. That is an "unheard-of response rate" given that these patients had tried and failed every other treatment, including several medications and electroconvulsive therapy, Mayberg says.
By comparison, Mayberg says, stimulation of the vagus nerve in the neck, approved by the FDA for depression, has only a 15% response rate at 10 weeks in similarly severely depressed patients.
Dr. Thomas Schlaepfer, vice chairman of the department of psychiatry of the University of Bonn in Germany, has been treating severely depressed patients by stimulating yet a third brain target, the nucleus accumbens.
The nucleus accumbens doesn't show normal activity in depressed patients, which could explain why they are less able to experience pleasure.
Last year, Schlaepfer showed that deep brain stimulation in this area led to acute improvements in three severely depressed patients. He says he has extended the work to 10 patients, half of whom showed an improvement when examined a year later.
With deep brain stimulation now being tried in at least three brain areas for depression, the question is, which target is the best? All agree that it's too early to tell.
Such is the hardware for deep brain stimulation -- the equivalent of a cardiac pacemaker for the mind.
Until recently, deep brain stimulation was approved in the U.S. only to treat certain movement disorders, primarily those of Parkinson's disease, for which it diminishes tremors and rigidity and improves mobility. To date, more than 60,000 patients worldwide have had the devices implanted.
But now use of the technique seems set to mushroom.
This year, the Food and Drug Administration granted a so-called humanitarian device exemption for the treatment to be used in severe cases of obsessive-compulsive disorder -- the first approval of deep brain stimulation therapy for any psychiatric condition.
Large clinical trials are also in the works for use of deep brain stimulation for epilepsy and depression, and experimental studies in the U.S. and elsewhere -- still in their early stages -- are exploring the treatment for obesity, traumatic brain injury, severe chronic pain, Alzheimer's disease, anorexia, tinnitus and addiction.
There are discussions too on the possible use of deep brain stimulation to treat hypertension.
"The field is taking off," says Dr. Ali Rezai, director of functional neurosurgery at the Cleveland Clinic, who has been involved in research on movement disorders, traumatic brain injury, obsessive-compulsive disorder and severe depression, among others.
Some researchers warn, however, that with all this activity -- pushed in part by the industry that makes the brain-stimulation devices -- the field may be moving too fast.
"There is so much progress that's been made and so much potential -- you would hate to lose that potential," says Dr. Joseph Fins, chief of the division of medical ethics and a professor at Weill Cornell Medical College in New York.
Here's a look at deep brain stimulation as it moves beyond Parkinson's disease. (See the related story about reservations scientists have about the growth of the field, and go online at latimes.com/health for a look at less-explored applications such as traumatic brain injury and obesity.)
Obsessive- compulsive disorder
In studies with a total of 26 patients with severe obsessive-compulsive disorder, 60% of those whose device was turned on demonstrated "very much improved" symptoms after months of deep brain stimulation as measured by interviews and questionnaires, says Dr. Benjamin Greenberg, an associate professor at Brown University Medical School and Butler Hospital in Providence, R.I., who was one of the study researchers.
The patients had previously failed on medicines as well as behavioral cognitive therapy.
Yet the data, published last year in Molecular Psychiatry, can't really nail the effect of the treatment, Greenberg says, because the patients for the most part knew whether their devices were turned on or off. Thus, researchers can't rule out that some of the observed improvements were due to a placebo effect.
Patients were stimulated in an area called ventral capsule/ventral striatum, chosen, in part, because removal of nerve fibers in that area is known to cause improvement in obsessive-compulsive symptoms.
Based largely on these findings, the FDA recently granted a limited humanitarian device exemption that permits the device to be used in as many as 4,000 of the country's most severe cases of obsessive compulsive disorder per year.
To get this kind of exemption, Medtronic -- makers of the only deep brain stimulation device that is FDA-approved -- needed only to show its safety and probable benefit.
Greenberg is now doing a randomized, double-blinded trial with 30 patients, some of whom have devices turned on right away and some who have them turned on after a delay. No one will know whose device is turned on for the first several months of the trial.
Medtronic has conducted a large-scale randomized trial for deep brain stimulation on epilepsy. Data will be submitted to the FDA this year, says Paul Stypulkowski, senior director of therapy research of Medtronic.
The device was turned on, for three months, in half of the 110 volunteers, stimulating -- and thereby, paradoxically, inhibiting-- an area called the anterior nucleus of the thalamus. That area is believed to influence a circuit involved in seizures.
The data, presented in December at a meeting in Seattle, show that deep brain stimulation reduced the number of seizures by 38% compared with what was seen before implanting the device.
That is slightly better than improvement seen with vagus nerve stimulation, another FDA-approved electrical stimulation treatment, which reduces seizures by about 25%.
The control group whose device was kept turned off, also improved, by 14.5%. That could be due to a placebo effect. Or it might be because people who join trials are usually at their worst -- and often tend to improve somewhat on their own, says trial researcher Dr. Douglas Labar, of the Weill Cornell Medical College in New York.
If deep brain stimulation is approved, Labar says, patients will have the choice between a more efficient but also more risky treatment and the slightly less efficient but also less risky vagus nerve stimulation.
Depression
Medtronic and a second company, St. Paul, Minn.-based St. Jude Medical, have two large-scale randomized trials underway for severe, treatment-resistant depression. (St. Jude Medical recently received approval to sell its device for the treatment of Parkinson's disease in Europe and is now completing studies aimed at securing FDA approval for treating Parkinson's and another movement disorder in the U.S.)
Medtronic's depression trial will follow about 200 patients stimulated in an area called the anterior limb of the internal capsule for at least one year.
This brain target for depression was identified by accident: When obsessive-compulsive disorder patients who also had depression were stimulated in this area, their depression also improved.
In one case, a patient produced a one-sided smile when stimulated on one side of the brain and also expressed feelings of happiness, says study researcher Dr. Wayne Goodman of the National Institute of Mental Health.
In a recently published unblinded study, about half of 15 patients showed at least a 50% improvement in severe depression symptoms a year or more after surgery when the anterior limb of the internal capsule was stimulated, says Rezai, who was involved in the study.
St. Jude Medical chose a different brain target, area 25, for its depression trial, which will enroll more than 100 patients. Brain imaging studies have shown that area 25 is more active in depressed people.
In a study of 20 patients, 55% still responded to treatment as late as one year after surgery, says study author Dr. Helen Mayberg, professor of psychiatry and neurology at Emory University. That is an "unheard-of response rate" given that these patients had tried and failed every other treatment, including several medications and electroconvulsive therapy, Mayberg says.
By comparison, Mayberg says, stimulation of the vagus nerve in the neck, approved by the FDA for depression, has only a 15% response rate at 10 weeks in similarly severely depressed patients.
Dr. Thomas Schlaepfer, vice chairman of the department of psychiatry of the University of Bonn in Germany, has been treating severely depressed patients by stimulating yet a third brain target, the nucleus accumbens.
The nucleus accumbens doesn't show normal activity in depressed patients, which could explain why they are less able to experience pleasure.
Last year, Schlaepfer showed that deep brain stimulation in this area led to acute improvements in three severely depressed patients. He says he has extended the work to 10 patients, half of whom showed an improvement when examined a year later.
With deep brain stimulation now being tried in at least three brain areas for depression, the question is, which target is the best? All agree that it's too early to tell.
Sunday, May 10, 2009
Mayo Clinic Study Finds Anemia Might be Associated With Development of Parkinson's Disease
Mayo Clinic Study Finds Anemia Might be Associated With Development of Parkinson's Disease
ROCHESTER, Minn. — Results of a new Mayo Clinic study support an association between anemia experienced early in life and the development of Parkinson's disease many years later. The findings will be presented at the American Academy of Neurology Annual Meeting in Seattle on April 30, 2009.
"We were surprised to discover that chronic anemia or low levels of hemoglobin were linked to the risk of Parkinson's disease 20-30 years later," says Walter Rocca, M.D. an author of the study and a neurologist at Mayo Clinic.
Hemoglobin is the protein that transports oxygen in the blood, an essential element for life. "We looked at both anemia as diagnosed by a physician and low hemoglobin values," Dr. Rocca says. "Both were associated with an increased risk of Parkinson's disease. This might indicate that Parkinson's disease actually starts 20--30 years before we see any motor changes in the body."
The case-control study included 196 people who developed Parkinson's disease in Olmsted County, Minn., from 1976 through 1995. Each case was matched by age and sex to a general population control subject who was not affected by Parkinson's disease. The medical records of cases and controls were reviewed using the resources of the Rochester Epidemiology Project to determine if there was a link between anemia or low hemoglobin levels and the risk of developing Parkinson's disease many years later. Anemia was significantly more common in the history of cases than in the history of controls.
Dr. Rocca and his team hope to replicate these results in another population group. "We first need to confirm the study results. If the findings are replicated, we will try to understand what are the underlying mechanisms. Understanding the mechanisms may lead to new ways to prevent or treat Parkinson's disease," Dr. Rocca says.
Other members of the Mayo Clinic research team included Rodolfo Savica, M.D.; Justin Carlin; Brandon Grossardt; James Bower, M.D.; and Demetrius Maraganore, M.D.
ROCHESTER, Minn. — Results of a new Mayo Clinic study support an association between anemia experienced early in life and the development of Parkinson's disease many years later. The findings will be presented at the American Academy of Neurology Annual Meeting in Seattle on April 30, 2009.
"We were surprised to discover that chronic anemia or low levels of hemoglobin were linked to the risk of Parkinson's disease 20-30 years later," says Walter Rocca, M.D. an author of the study and a neurologist at Mayo Clinic.
Hemoglobin is the protein that transports oxygen in the blood, an essential element for life. "We looked at both anemia as diagnosed by a physician and low hemoglobin values," Dr. Rocca says. "Both were associated with an increased risk of Parkinson's disease. This might indicate that Parkinson's disease actually starts 20--30 years before we see any motor changes in the body."
The case-control study included 196 people who developed Parkinson's disease in Olmsted County, Minn., from 1976 through 1995. Each case was matched by age and sex to a general population control subject who was not affected by Parkinson's disease. The medical records of cases and controls were reviewed using the resources of the Rochester Epidemiology Project to determine if there was a link between anemia or low hemoglobin levels and the risk of developing Parkinson's disease many years later. Anemia was significantly more common in the history of cases than in the history of controls.
Dr. Rocca and his team hope to replicate these results in another population group. "We first need to confirm the study results. If the findings are replicated, we will try to understand what are the underlying mechanisms. Understanding the mechanisms may lead to new ways to prevent or treat Parkinson's disease," Dr. Rocca says.
Other members of the Mayo Clinic research team included Rodolfo Savica, M.D.; Justin Carlin; Brandon Grossardt; James Bower, M.D.; and Demetrius Maraganore, M.D.
Saturday, May 2, 2009
Parkinson's Disease: More Than Shaking Going On Researchers discovering non-motor symptoms may happen first
Parkinson's Disease: More Than Shaking Going On Researchers discovering non-motor symptoms may happen first
(live-PR.com) - TORONTO, ONTARIO -- (Marketwire) -- 04/21/09 -- Parkinson's is much more than a tremor. That's a message Parkinson Society Canada hopes to drive home this April during Parkinson's Awareness Month.
In Parkinson's, the most common symptoms are movement-related: tremor, slowness, muscle stiffness and balance problems. However, by the time Parkinson's is diagnosed, people have already lost 60 to 70 percent of the dopamine-producing cells. Now researchers are discovering that non-motor symptoms such as sleep problems, depression and smell loss may represent the earliest signs of Parkinson's, for some people, and may appear years before the diagnosis.
In research at Montreal's Sacre-Coeur Hospital, Dr. Ronald Postuma, assistant professor of neurology at McGill University found that people with a rare sleep disorder where they physically acted out their dreams had a 50% risk of developing Parkinson's disease or dementia within 12 years. The patients had REM-sleep behaviour disorder, which Postuma describes as "punching and yelling or kicking out while asleep. It mostly affects people in their 60s and 70s, almost always men." Not all will develop a neurodegenerative disease but Postuma says, "Patients with true REM-sleep behaviour disorder have a considerable risk of developing Parkinson's disease."
Depression and anxiety can surface early in Parkinson's. "Many people, as they're starting to lose their dopamine, may not yet have developed a tremor, slowness or trouble walking, but may feel anxious and depressed," says Dr. Susan Fox, assistant professor of neurology at University of Toronto. "Depression is also part of Parkinson's disease itself and not just a reaction to having a chronic neurological disorder." Fox notes untreated depression can reduce quality of life.
Smell loss is a common occurrence. "The general consensus is that the changes in olfaction (sense of smell) occur about five years before the Parkinson's diagnosis." says Dr. Harold Robertson, a professor in the Brain Repair Centre and Department of Pharmacology at Dalhousie University in Halifax. "That could give us enough lead time to try to stop the process."
Joyce Gordon, Parkinson Society Canada President and CEO says "The more dollars we can put towards Parkinson's research, the sooner we may be able to establish if there is a definite link to Parkinson's when a person has sleep problems, depression or loss of smell. This would lay the groundwork for developing treatments to delay or stop this debilitating disease in its tracks. The answers can't come soon enough for the 100,000 Canadians who have Parkinson's disease and those who are unknowingly at risk."
In the meantime, the first step for anyone experiencing difficulties with sleep or mood is to see a doctor for a proper diagnosis. REM sleep behaviour disorder and depression are treatable. Smell loss is not currently treatable but is worth mentioning to the doctor, during a routine visit, as it may be due to a variety of causes.
Parkinson's is a progressive neurological disease for which there is no known cause or cure. When cells in the brain that normally produce a chemical called "dopamine" die, symptoms of Parkinson's appear. The most common symptoms are: tremor (shaking), slowness in movements, muscle stiffness and problems with balance. Other symptoms that may also occur for some people include fatigue, difficulties with speech and writing, sleep disorders, depression and cognitive changes.
For over 40 years, Parkinson Society Canada (PSC) has been the national voice of people living with Parkinson's disease. PSC has over 230 chapters and support groups. PSC's mission is to fund research, support services, advocacy and education.
For more information on Parkinson's disease and Parkinson Society Canada, visit the PSC website at www.parkinson.ca : www.parkinson.ca or call 1-800-565-3000.
Contacts:
Parkinson Society Canada
John Provenzano
416-227-3399 or 1-800-565-3000 ext 3399
John.provenzano@parkinson.ca : John.provenzano@parkinson.ca
(live-PR.com) - TORONTO, ONTARIO -- (Marketwire) -- 04/21/09 -- Parkinson's is much more than a tremor. That's a message Parkinson Society Canada hopes to drive home this April during Parkinson's Awareness Month.
In Parkinson's, the most common symptoms are movement-related: tremor, slowness, muscle stiffness and balance problems. However, by the time Parkinson's is diagnosed, people have already lost 60 to 70 percent of the dopamine-producing cells. Now researchers are discovering that non-motor symptoms such as sleep problems, depression and smell loss may represent the earliest signs of Parkinson's, for some people, and may appear years before the diagnosis.
In research at Montreal's Sacre-Coeur Hospital, Dr. Ronald Postuma, assistant professor of neurology at McGill University found that people with a rare sleep disorder where they physically acted out their dreams had a 50% risk of developing Parkinson's disease or dementia within 12 years. The patients had REM-sleep behaviour disorder, which Postuma describes as "punching and yelling or kicking out while asleep. It mostly affects people in their 60s and 70s, almost always men." Not all will develop a neurodegenerative disease but Postuma says, "Patients with true REM-sleep behaviour disorder have a considerable risk of developing Parkinson's disease."
Depression and anxiety can surface early in Parkinson's. "Many people, as they're starting to lose their dopamine, may not yet have developed a tremor, slowness or trouble walking, but may feel anxious and depressed," says Dr. Susan Fox, assistant professor of neurology at University of Toronto. "Depression is also part of Parkinson's disease itself and not just a reaction to having a chronic neurological disorder." Fox notes untreated depression can reduce quality of life.
Smell loss is a common occurrence. "The general consensus is that the changes in olfaction (sense of smell) occur about five years before the Parkinson's diagnosis." says Dr. Harold Robertson, a professor in the Brain Repair Centre and Department of Pharmacology at Dalhousie University in Halifax. "That could give us enough lead time to try to stop the process."
Joyce Gordon, Parkinson Society Canada President and CEO says "The more dollars we can put towards Parkinson's research, the sooner we may be able to establish if there is a definite link to Parkinson's when a person has sleep problems, depression or loss of smell. This would lay the groundwork for developing treatments to delay or stop this debilitating disease in its tracks. The answers can't come soon enough for the 100,000 Canadians who have Parkinson's disease and those who are unknowingly at risk."
In the meantime, the first step for anyone experiencing difficulties with sleep or mood is to see a doctor for a proper diagnosis. REM sleep behaviour disorder and depression are treatable. Smell loss is not currently treatable but is worth mentioning to the doctor, during a routine visit, as it may be due to a variety of causes.
Parkinson's is a progressive neurological disease for which there is no known cause or cure. When cells in the brain that normally produce a chemical called "dopamine" die, symptoms of Parkinson's appear. The most common symptoms are: tremor (shaking), slowness in movements, muscle stiffness and problems with balance. Other symptoms that may also occur for some people include fatigue, difficulties with speech and writing, sleep disorders, depression and cognitive changes.
For over 40 years, Parkinson Society Canada (PSC) has been the national voice of people living with Parkinson's disease. PSC has over 230 chapters and support groups. PSC's mission is to fund research, support services, advocacy and education.
For more information on Parkinson's disease and Parkinson Society Canada, visit the PSC website at www.parkinson.ca : www.parkinson.ca or call 1-800-565-3000.
Contacts:
Parkinson Society Canada
John Provenzano
416-227-3399 or 1-800-565-3000 ext 3399
John.provenzano@parkinson.ca : John.provenzano@parkinson.ca
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