AAN Annual Meeting

NEW ORLEANS – The total defined daily dose of antiepileptic drugs was the best predictor of medication side effects in a clinical prediction rule developed from a single-center, cross-sectional study of 801 patients with epilepsy.

The finding stands in contrast to a previous study that found overall antiepileptic drug (AED) burden, also calculated by defined daily dose (DDD), was not a significant predictor of the risk of side effects (Epilepsia 2010;51:797-804).

But the lead author of the current study, Jonathan Dykeman, and his associates used recursive partitioning to develop a clinical decision model that classifies patients into subgroups based on their risk of side effects, whereas the earlier report used standard multivariate linear progression to model patients’ scores on the Adverse Event Profile questionnaire. Disentangling the number of AEDs a person used from the overall AED burden on standard linear regression is not easy because the two are highly correlated, he said.

The investigators aim to help guide therapy and clinical decision making with their clinical prediction rule. "To our knowledge, there isn’t a clinical prediction rule that’s used because a lot of the focus is on reduction of seizures," said Mr. Dykeman, an MD/PhD student in the department of clinical neurosciences at the University of Calgary (Alta.) at the annual meeting of the American Academy of Neurology.

Drug burden was high in the group of 801 patients; they took 17 different AEDs, and there were 132 possible combinations of drugs. Instead of modeling that complex scenario, Mr. Dykeman and his colleagues converted AED burden into the World Health Organization’s definition of DDD, which is the average total that a person would take in 1 day for the drug’s main indication. The investigators also included a number of other characteristics that broadly fit into the categories of AED type, sociodemographic factors, and clinical factors. Patients reported side effects during clinical interviews.

The recursive partitioning method hierarchically organized the risk factors associated with side effects from strongest to weakest. Overall, 18% of the cohort experienced side effects. A DDD of greater than 3.5 was the best predictor of side effects. Of 46 patients with a DDD greater than 3.5, 33% reported side effects, compared with 17% of 755 patients with a lower DDD.

A history of psychiatric treatment with medication or counseling also carried about a threefold higher risk for side effects than did the absence of such history. Among patients with the higher DDD, side effects occurred in 8 (57%) of 14 patients with a history of psychiatric treatment, compared with 22% of low DDD patients without a history of psychiatric treatment.

"We have a side study going that’s going to try to tease out whether that’s an interaction with the psychiatric drugs or the fact that they have a psychiatric illness," Mr. Dykeman said in an interview.

Also, side effects reportedly occurred significantly less often among patients on a low DDD with a history of a learning disability (9% of 111) than in patients without such history (18% of 644). "We highly suspect this is related more to the reporting of side effects than actually the occurrence of side effects," said Mr. Dykeman. It might have been more difficult to convey that the patients were having side effects because of their learning disorders as opposed to not actually having them, he said.

The group of patients without learning disabilities could be further partitioned for side-effect risk based on whether they used topiramate (35% of 37) or not (17% of 607). Age was used to further refine the risk for side effects among patients who did not take topiramate. Patients aged 45 years or younger (6 of 27, or 22%) had a lower risk for side effects, compared with patients older than 45 years (7 of 10, or 70%).

Mr. Dykeman said the conclusions that can be drawn from the study are limited by the lack of ascertainment of self-reported side effects, the cross-sectional nature of the data, and the small sizes of subgroups used in comparisons.

Next, the researchers plan to validate their ascertainment of side effects against the Adverse Event Profile questionnaire and conduct the same analysis in a larger, external set of patients at another tertiary referral center before testing it in the general epilepsy population.

None of the authors had relevant disclosures.

NEW ORLEANS – The total defined daily dose of antiepileptic drugs was the best predictor of medication side effects in a clinical prediction rule developed from a single-center, cross-sectional study of 801 patients with epilepsy.

The finding stands in contrast to a previous study that found overall antiepileptic drug (AED) burden, also calculated by defined daily dose (DDD), was not a significant predictor of the risk of side effects (Epilepsia 2010;51:797-804).

But the lead author of the current study, Jonathan Dykeman, and his associates used recursive partitioning to develop a clinical decision model that classifies patients into subgroups based on their risk of side effects, whereas the earlier report used standard multivariate linear progression to model patients’ scores on the Adverse Event Profile questionnaire. Disentangling the number of AEDs a person used from the overall AED burden on standard linear regression is not easy because the two are highly correlated, he said.

The investigators aim to help guide therapy and clinical decision making with their clinical prediction rule. "To our knowledge, there isn’t a clinical prediction rule that’s used because a lot of the focus is on reduction of seizures," said Mr. Dykeman, an MD/PhD student in the department of clinical neurosciences at the University of Calgary (Alta.) at the annual meeting of the American Academy of Neurology.

Drug burden was high in the group of 801 patients; they took 17 different AEDs, and there were 132 possible combinations of drugs. Instead of modeling that complex scenario, Mr. Dykeman and his colleagues converted AED burden into the World Health Organization’s definition of DDD, which is the average total that a person would take in 1 day for the drug’s main indication. The investigators also included a number of other characteristics that broadly fit into the categories of AED type, sociodemographic factors, and clinical factors. Patients reported side effects during clinical interviews.

The recursive partitioning method hierarchically organized the risk factors associated with side effects from strongest to weakest. Overall, 18% of the cohort experienced side effects. A DDD of greater than 3.5 was the best predictor of side effects. Of 46 patients with a DDD greater than 3.5, 33% reported side effects, compared with 17% of 755 patients with a lower DDD.

A history of psychiatric treatment with medication or counseling also carried about a threefold higher risk for side effects than did the absence of such history. Among patients with the higher DDD, side effects occurred in 8 (57%) of 14 patients with a history of psychiatric treatment, compared with 22% of low DDD patients without a history of psychiatric treatment.

"We have a side study going that’s going to try to tease out whether that’s an interaction with the psychiatric drugs or the fact that they have a psychiatric illness," Mr. Dykeman said in an interview.

Also, side effects reportedly occurred significantly less often among patients on a low DDD with a history of a learning disability (9% of 111) than in patients without such history (18% of 644). "We highly suspect this is related more to the reporting of side effects than actually the occurrence of side effects," said Mr. Dykeman. It might have been more difficult to convey that the patients were having side effects because of their learning disorders as opposed to not actually having them, he said.

The group of patients without learning disabilities could be further partitioned for side-effect risk based on whether they used topiramate (35% of 37) or not (17% of 607). Age was used to further refine the risk for side effects among patients who did not take topiramate. Patients aged 45 years or younger (6 of 27, or 22%) had a lower risk for side effects, compared with patients older than 45 years (7 of 10, or 70%).

Mr. Dykeman said the conclusions that can be drawn from the study are limited by the lack of ascertainment of self-reported side effects, the cross-sectional nature of the data, and the small sizes of subgroups used in comparisons.

Next, the researchers plan to validate their ascertainment of side effects against the Adverse Event Profile questionnaire and conduct the same analysis in a larger, external set of patients at another tertiary referral center before testing it in the general epilepsy population.

None of the authors had relevant disclosures.

NEW ORLEANS – The total defined daily dose of antiepileptic drugs was the best predictor of medication side effects in a clinical prediction rule developed from a single-center, cross-sectional study of 801 patients with epilepsy.

The finding stands in contrast to a previous study that found overall antiepileptic drug (AED) burden, also calculated by defined daily dose (DDD), was not a significant predictor of the risk of side effects (Epilepsia 2010;51:797-804).

But the lead author of the current study, Jonathan Dykeman, and his associates used recursive partitioning to develop a clinical decision model that classifies patients into subgroups based on their risk of side effects, whereas the earlier report used standard multivariate linear progression to model patients’ scores on the Adverse Event Profile questionnaire. Disentangling the number of AEDs a person used from the overall AED burden on standard linear regression is not easy because the two are highly correlated, he said.

The investigators aim to help guide therapy and clinical decision making with their clinical prediction rule. "To our knowledge, there isn’t a clinical prediction rule that’s used because a lot of the focus is on reduction of seizures," said Mr. Dykeman, an MD/PhD student in the department of clinical neurosciences at the University of Calgary (Alta.) at the annual meeting of the American Academy of Neurology.

Drug burden was high in the group of 801 patients; they took 17 different AEDs, and there were 132 possible combinations of drugs. Instead of modeling that complex scenario, Mr. Dykeman and his colleagues converted AED burden into the World Health Organization’s definition of DDD, which is the average total that a person would take in 1 day for the drug’s main indication. The investigators also included a number of other characteristics that broadly fit into the categories of AED type, sociodemographic factors, and clinical factors. Patients reported side effects during clinical interviews.

The recursive partitioning method hierarchically organized the risk factors associated with side effects from strongest to weakest. Overall, 18% of the cohort experienced side effects. A DDD of greater than 3.5 was the best predictor of side effects. Of 46 patients with a DDD greater than 3.5, 33% reported side effects, compared with 17% of 755 patients with a lower DDD.

A history of psychiatric treatment with medication or counseling also carried about a threefold higher risk for side effects than did the absence of such history. Among patients with the higher DDD, side effects occurred in 8 (57%) of 14 patients with a history of psychiatric treatment, compared with 22% of low DDD patients without a history of psychiatric treatment.

"We have a side study going that’s going to try to tease out whether that’s an interaction with the psychiatric drugs or the fact that they have a psychiatric illness," Mr. Dykeman said in an interview.

Also, side effects reportedly occurred significantly less often among patients on a low DDD with a history of a learning disability (9% of 111) than in patients without such history (18% of 644). "We highly suspect this is related more to the reporting of side effects than actually the occurrence of side effects," said Mr. Dykeman. It might have been more difficult to convey that the patients were having side effects because of their learning disorders as opposed to not actually having them, he said.

The group of patients without learning disabilities could be further partitioned for side-effect risk based on whether they used topiramate (35% of 37) or not (17% of 607). Age was used to further refine the risk for side effects among patients who did not take topiramate. Patients aged 45 years or younger (6 of 27, or 22%) had a lower risk for side effects, compared with patients older than 45 years (7 of 10, or 70%).

Mr. Dykeman said the conclusions that can be drawn from the study are limited by the lack of ascertainment of self-reported side effects, the cross-sectional nature of the data, and the small sizes of subgroups used in comparisons.

Next, the researchers plan to validate their ascertainment of side effects against the Adverse Event Profile questionnaire and conduct the same analysis in a larger, external set of patients at another tertiary referral center before testing it in the general epilepsy population.

None of the authors had relevant disclosures.

NEW ORLEANS – Higher vitamin D levels are associated with slightly less disability and greater preservation of gray matter in patients with multiple sclerosis, according to a 5-year observational study.

The researchers assessed 25-hydroxyvitamin D levels, clinical disability, and MRI brain volumes annually in 469 patients with relapsing-remitting multiple sclerosis (MS) or clinically isolated syndrome, all members of a longitudinal MS cohort study at the University of California, San Francisco.

They found that for every 10-ng/mL increase in 25-hydroxyvitamin D levels, subsequent EDSS (Expanded Disability Status Scale) scores were 0.05 points lower (95% confidence interval –0.091 to –0.003; P = .037), and subsequent normalized gray matter volume was 7 cc higher (95% CI 2.4, 11.5; P = .003). The results were adjusted for age, sex, ethnicity, smoking status, body mass index, and use of MS treatments.

Based on the results and a growing body of literature suggesting a role for vitamin D in MS, lead investigator Dr. Ellen Mowry, an assistant professor of neuroimmunology at Johns Hopkins University, Baltimore, often supplements her patients to a vitamin D level of 40-60 ng/mL, which usually takes 2,000-4,000 international units a day.

"The preponderance of the observational evidence is in favor of supplementing, and I think those levels are the most strongly supported by the data. Above 60 ng/mL, there are very few data to say whether or not the effect remains the same," she said at the annual meeting of the American Academy of Neurology.

Dr. Mowry said she is careful to tell her MS patients that although observational studies suggest vitamin D is safe and helpful, ongoing randomized trials may prove otherwise.

The average age of patients in her study was 42 years; their median disease duration was 5 years, and about two-thirds were women. Their baseline vitamin D levels were low at around 28 ng/mL.

Mean EDSS scores were about 1.5 at the start of the study, and about 2 at its end. Mean normalized gray matter volumes were 985 cc at baseline and 964 cc at the end of 4 years. Only 9% of the subjects took vitamin D supplements at the start of the study, but almost half (43%) took them at its end.

Trends were favorable for an association between vitamin D levels and preservation of brain parenchymal volume, but the results were not statistically significant.

The results are in line with a 2006 study that found an inverse association between vitamin D levels and the risk for developing MS (JAMA 2006;296:2832-8).

Previously, Dr. Mowry and other researchers have demonstrated that vitamin D levels are inversely associated with MS relapse risk in both children and adults (Ann. Neurol. 2010;67:618-24; Ann. Neurol. 2010;68:193-203).

Dr. Mowry is the principal investigator in a randomized treatment trial that will assess the impact of high- and low-dose vitamin D supplementation on attack rates, numbers of new lesions, and changes in brain volume in relapsing-remitting MS.

The study was funded by a grant from the National Institutes of Health and by GlaxoSmithKline and Biogen Idec. Dr. Mowry reported receiving research support from Teva Pharmaceuticals.

NEW ORLEANS – Higher vitamin D levels are associated with slightly less disability and greater preservation of gray matter in patients with multiple sclerosis, according to a 5-year observational study.

The researchers assessed 25-hydroxyvitamin D levels, clinical disability, and MRI brain volumes annually in 469 patients with relapsing-remitting multiple sclerosis (MS) or clinically isolated syndrome, all members of a longitudinal MS cohort study at the University of California, San Francisco.

They found that for every 10-ng/mL increase in 25-hydroxyvitamin D levels, subsequent EDSS (Expanded Disability Status Scale) scores were 0.05 points lower (95% confidence interval –0.091 to –0.003; P = .037), and subsequent normalized gray matter volume was 7 cc higher (95% CI 2.4, 11.5; P = .003). The results were adjusted for age, sex, ethnicity, smoking status, body mass index, and use of MS treatments.

Based on the results and a growing body of literature suggesting a role for vitamin D in MS, lead investigator Dr. Ellen Mowry, an assistant professor of neuroimmunology at Johns Hopkins University, Baltimore, often supplements her patients to a vitamin D level of 40-60 ng/mL, which usually takes 2,000-4,000 international units a day.

"The preponderance of the observational evidence is in favor of supplementing, and I think those levels are the most strongly supported by the data. Above 60 ng/mL, there are very few data to say whether or not the effect remains the same," she said at the annual meeting of the American Academy of Neurology.

Dr. Mowry said she is careful to tell her MS patients that although observational studies suggest vitamin D is safe and helpful, ongoing randomized trials may prove otherwise.

The average age of patients in her study was 42 years; their median disease duration was 5 years, and about two-thirds were women. Their baseline vitamin D levels were low at around 28 ng/mL.

Mean EDSS scores were about 1.5 at the start of the study, and about 2 at its end. Mean normalized gray matter volumes were 985 cc at baseline and 964 cc at the end of 4 years. Only 9% of the subjects took vitamin D supplements at the start of the study, but almost half (43%) took them at its end.

Trends were favorable for an association between vitamin D levels and preservation of brain parenchymal volume, but the results were not statistically significant.

The results are in line with a 2006 study that found an inverse association between vitamin D levels and the risk for developing MS (JAMA 2006;296:2832-8).

Previously, Dr. Mowry and other researchers have demonstrated that vitamin D levels are inversely associated with MS relapse risk in both children and adults (Ann. Neurol. 2010;67:618-24; Ann. Neurol. 2010;68:193-203).

Dr. Mowry is the principal investigator in a randomized treatment trial that will assess the impact of high- and low-dose vitamin D supplementation on attack rates, numbers of new lesions, and changes in brain volume in relapsing-remitting MS.

The study was funded by a grant from the National Institutes of Health and by GlaxoSmithKline and Biogen Idec. Dr. Mowry reported receiving research support from Teva Pharmaceuticals.

NEW ORLEANS – Higher vitamin D levels are associated with slightly less disability and greater preservation of gray matter in patients with multiple sclerosis, according to a 5-year observational study.

The researchers assessed 25-hydroxyvitamin D levels, clinical disability, and MRI brain volumes annually in 469 patients with relapsing-remitting multiple sclerosis (MS) or clinically isolated syndrome, all members of a longitudinal MS cohort study at the University of California, San Francisco.

They found that for every 10-ng/mL increase in 25-hydroxyvitamin D levels, subsequent EDSS (Expanded Disability Status Scale) scores were 0.05 points lower (95% confidence interval –0.091 to –0.003; P = .037), and subsequent normalized gray matter volume was 7 cc higher (95% CI 2.4, 11.5; P = .003). The results were adjusted for age, sex, ethnicity, smoking status, body mass index, and use of MS treatments.

Based on the results and a growing body of literature suggesting a role for vitamin D in MS, lead investigator Dr. Ellen Mowry, an assistant professor of neuroimmunology at Johns Hopkins University, Baltimore, often supplements her patients to a vitamin D level of 40-60 ng/mL, which usually takes 2,000-4,000 international units a day.

"The preponderance of the observational evidence is in favor of supplementing, and I think those levels are the most strongly supported by the data. Above 60 ng/mL, there are very few data to say whether or not the effect remains the same," she said at the annual meeting of the American Academy of Neurology.

Dr. Mowry said she is careful to tell her MS patients that although observational studies suggest vitamin D is safe and helpful, ongoing randomized trials may prove otherwise.

The average age of patients in her study was 42 years; their median disease duration was 5 years, and about two-thirds were women. Their baseline vitamin D levels were low at around 28 ng/mL.

Mean EDSS scores were about 1.5 at the start of the study, and about 2 at its end. Mean normalized gray matter volumes were 985 cc at baseline and 964 cc at the end of 4 years. Only 9% of the subjects took vitamin D supplements at the start of the study, but almost half (43%) took them at its end.

Trends were favorable for an association between vitamin D levels and preservation of brain parenchymal volume, but the results were not statistically significant.

The results are in line with a 2006 study that found an inverse association between vitamin D levels and the risk for developing MS (JAMA 2006;296:2832-8).

Previously, Dr. Mowry and other researchers have demonstrated that vitamin D levels are inversely associated with MS relapse risk in both children and adults (Ann. Neurol. 2010;67:618-24; Ann. Neurol. 2010;68:193-203).

Dr. Mowry is the principal investigator in a randomized treatment trial that will assess the impact of high- and low-dose vitamin D supplementation on attack rates, numbers of new lesions, and changes in brain volume in relapsing-remitting MS.

The study was funded by a grant from the National Institutes of Health and by GlaxoSmithKline and Biogen Idec. Dr. Mowry reported receiving research support from Teva Pharmaceuticals.

NEW ORLEANS – It is a good idea to cast a wide net when asking patients with facioscapulohumeral muscular dystrophy about their symptoms because many problems go unrecognized, and some are at least partially treatable, according to a survey of 328 patients in the National Registry of Myotonic Dystrophy and FSHD Patients and Family Members.

For example, patients said not being able to play sports with their children, family, and friends was important. "Dancing is important in this population, too. I would never have guessed it, but it is," said lead investigator Dr. Chad Heatwole, an assistant professor of neurology at the University of Rochester (N.Y.).

For some, not being able to ski or play golf was more important than was difficulty walking.

It might take some creativity to help with such problems, but emotional problems – mostly depression and anxiety – were reported by about 75% of patients, and are readily treated with counseling and medication. These problems "are highly prevalent and an issue we didn’t expect," Dr. Heatwole said at the annual meeting of the American Academy of Neurology.

Usually all we ask is, "How strong are you? Can you go up the stairs?" he said. "These aren’t very amenable to therapy. But pain, fatigue, depression, anxiety, and the different types of emotional problems – you wouldn’t think to ask about these – they’re important but not that addressed."

The roots of the survey were extensive interviews of 20 patients with FSHD (facioscapulohumeral muscular dystrophy) that revealed 250 symptoms and 14 symptom categories of likely importance to the FSHD community. The 328 surveyed patients with FSHD from 46 states had a mean age of 55 years (range, 23-86 years). About half had a job.

More than 90% reported a variety of symptoms and limitations:

• An inability to do previous activities.

• Physical, emotional, or cognitive fatigue.

• Back, chest, or abdominal weakness.

• Mobility or walking limitations.

• Shoulder and arm problems.

• Disease-related changes in body image to the point that patients didn’t like to go swimming because of it.

Shoulder weakness, leg fatigue, decreased range of motion, and inability to exercise were common, as were difficulty lifting objects and reaching overhead items.

Patients said their lives were at least moderately affected by such problems, as well as by difficulty with stairs, inability to run, difficulty thinking, pain, decreased satisfaction in social situations, decreased performance in social situations, and inability to do specific activities. Emotional and communication issues, as well as hand or finger difficulties, also significantly affected patients’ lives. Fatigue and impaired social performance affected women more than men.

Ninety-four percent of patients said they were aware that their disease was getting worse; about 94% also said they feared the progression. About 14% had had their symptoms mistaken for drunkenness, and 64% for another disease; 37% said they try to hide their condition from friends, and 35% reported they have a hard time getting information about FSHD. "We need to do better providing information," Dr. Heatwole said.

Overall, patients were less likely to get further in school if they had difficulty thinking and communicating, or if they had emotional or hand-use problems. Patients with mobility, hand-use, or eating problems were less likely to be employed.

The findings have been turned into a quality of life assessment tool for upcoming FSHD trials, he said.

Dr. Heatwole said that he had no disclosures.

NEW ORLEANS – It is a good idea to cast a wide net when asking patients with facioscapulohumeral muscular dystrophy about their symptoms because many problems go unrecognized, and some are at least partially treatable, according to a survey of 328 patients in the National Registry of Myotonic Dystrophy and FSHD Patients and Family Members.

For example, patients said not being able to play sports with their children, family, and friends was important. "Dancing is important in this population, too. I would never have guessed it, but it is," said lead investigator Dr. Chad Heatwole, an assistant professor of neurology at the University of Rochester (N.Y.).

For some, not being able to ski or play golf was more important than was difficulty walking.

It might take some creativity to help with such problems, but emotional problems – mostly depression and anxiety – were reported by about 75% of patients, and are readily treated with counseling and medication. These problems "are highly prevalent and an issue we didn’t expect," Dr. Heatwole said at the annual meeting of the American Academy of Neurology.

Usually all we ask is, "How strong are you? Can you go up the stairs?" he said. "These aren’t very amenable to therapy. But pain, fatigue, depression, anxiety, and the different types of emotional problems – you wouldn’t think to ask about these – they’re important but not that addressed."

The roots of the survey were extensive interviews of 20 patients with FSHD (facioscapulohumeral muscular dystrophy) that revealed 250 symptoms and 14 symptom categories of likely importance to the FSHD community. The 328 surveyed patients with FSHD from 46 states had a mean age of 55 years (range, 23-86 years). About half had a job.

More than 90% reported a variety of symptoms and limitations:

• An inability to do previous activities.

• Physical, emotional, or cognitive fatigue.

• Back, chest, or abdominal weakness.

• Mobility or walking limitations.

• Shoulder and arm problems.

• Disease-related changes in body image to the point that patients didn’t like to go swimming because of it.

Shoulder weakness, leg fatigue, decreased range of motion, and inability to exercise were common, as were difficulty lifting objects and reaching overhead items.

Patients said their lives were at least moderately affected by such problems, as well as by difficulty with stairs, inability to run, difficulty thinking, pain, decreased satisfaction in social situations, decreased performance in social situations, and inability to do specific activities. Emotional and communication issues, as well as hand or finger difficulties, also significantly affected patients’ lives. Fatigue and impaired social performance affected women more than men.

Ninety-four percent of patients said they were aware that their disease was getting worse; about 94% also said they feared the progression. About 14% had had their symptoms mistaken for drunkenness, and 64% for another disease; 37% said they try to hide their condition from friends, and 35% reported they have a hard time getting information about FSHD. "We need to do better providing information," Dr. Heatwole said.

Overall, patients were less likely to get further in school if they had difficulty thinking and communicating, or if they had emotional or hand-use problems. Patients with mobility, hand-use, or eating problems were less likely to be employed.

The findings have been turned into a quality of life assessment tool for upcoming FSHD trials, he said.

Dr. Heatwole said that he had no disclosures.

NEW ORLEANS – It is a good idea to cast a wide net when asking patients with facioscapulohumeral muscular dystrophy about their symptoms because many problems go unrecognized, and some are at least partially treatable, according to a survey of 328 patients in the National Registry of Myotonic Dystrophy and FSHD Patients and Family Members.

For example, patients said not being able to play sports with their children, family, and friends was important. "Dancing is important in this population, too. I would never have guessed it, but it is," said lead investigator Dr. Chad Heatwole, an assistant professor of neurology at the University of Rochester (N.Y.).

For some, not being able to ski or play golf was more important than was difficulty walking.

It might take some creativity to help with such problems, but emotional problems – mostly depression and anxiety – were reported by about 75% of patients, and are readily treated with counseling and medication. These problems "are highly prevalent and an issue we didn’t expect," Dr. Heatwole said at the annual meeting of the American Academy of Neurology.

Usually all we ask is, "How strong are you? Can you go up the stairs?" he said. "These aren’t very amenable to therapy. But pain, fatigue, depression, anxiety, and the different types of emotional problems – you wouldn’t think to ask about these – they’re important but not that addressed."

The roots of the survey were extensive interviews of 20 patients with FSHD (facioscapulohumeral muscular dystrophy) that revealed 250 symptoms and 14 symptom categories of likely importance to the FSHD community. The 328 surveyed patients with FSHD from 46 states had a mean age of 55 years (range, 23-86 years). About half had a job.

More than 90% reported a variety of symptoms and limitations:

• An inability to do previous activities.

• Physical, emotional, or cognitive fatigue.

• Back, chest, or abdominal weakness.

• Mobility or walking limitations.

• Shoulder and arm problems.

• Disease-related changes in body image to the point that patients didn’t like to go swimming because of it.

Shoulder weakness, leg fatigue, decreased range of motion, and inability to exercise were common, as were difficulty lifting objects and reaching overhead items.

Patients said their lives were at least moderately affected by such problems, as well as by difficulty with stairs, inability to run, difficulty thinking, pain, decreased satisfaction in social situations, decreased performance in social situations, and inability to do specific activities. Emotional and communication issues, as well as hand or finger difficulties, also significantly affected patients’ lives. Fatigue and impaired social performance affected women more than men.

Ninety-four percent of patients said they were aware that their disease was getting worse; about 94% also said they feared the progression. About 14% had had their symptoms mistaken for drunkenness, and 64% for another disease; 37% said they try to hide their condition from friends, and 35% reported they have a hard time getting information about FSHD. "We need to do better providing information," Dr. Heatwole said.

Overall, patients were less likely to get further in school if they had difficulty thinking and communicating, or if they had emotional or hand-use problems. Patients with mobility, hand-use, or eating problems were less likely to be employed.

The findings have been turned into a quality of life assessment tool for upcoming FSHD trials, he said.

Dr. Heatwole said that he had no disclosures.

NEW ORLEANS – When Parkinson’s disease patients are admitted to hospitals, they often end up on incorrect doses of levodopa during their stay – if it’s prescribed at all – and sometimes inappropriately get metoclopramide or neuroleptics, dopamine-blocking agents that could make their disease worse, according to a study from the University of Calgary (Alta.).

That’s what researchers from the university’s Movement Disorders Clinic found when they compared what 44 of their Parkinson’s patients took at home with what they were given after being admitted to Calgary hospitals.

There were medication problems in 44 (80%) of the 55 hospitalizations those patients had in 2010, said lead author Dr. Katie Wiltshire, a neurology resident at the university.

"Our study identifies deficiencies in the in-hospital prescribing of medications for patients with PD [Parkinson’s disease]. This includes a failure to seamlessly continue usual PD medications when patients are admitted, and perhaps of even greater concern, the inappropriate addition of dopamine-blocking agents during their hospital stay," she said at the annual meeting of the American Academy of Neurology.

Similar problems have been found at hospitals in the United States and Britain, perhaps because some hospital services are unfamiliar with PD treatment. "Widespread education of providers and safe-prescribing protocols are urgently needed to address these unsafe care issues," Dr. Wiltshire said.

Patients in her study came in on stable levodopa doses in 53 of the 55 admissions (96.4%); there were subsequent problems with levodopa administration in 26 (49%) of those hospital stays.

During three hospitalizations (5.7%), levodopa was not ordered for people who been on it at home. In 15 of the 53 admissions (28.3%), doses ordered were too high or too low. Dose schedules were off during 8 hospital stays (15.1%). In another12 stays (22.6%), patients were put on either immediate or extended-release levodopa when they had been on the alternate formulation before coming to the hospital. Metoclopramide or neuroleptics were ordered in 24 (43.6%) of the overall 55 admissions.

Dr. Wilshire and her colleagues don’t know yet if the discrepancies hurt patients, but other studies have found that they do, and that many PD patients report bad hospital experiences related to medication mismanagement (Parkinsonism Relat. Disord. 2007;13:539-40; Postgrad. Med. J. 2010;86:334-7). "This is a sobering report," said Dr. Christopher Goetz, director of the Parkinson’s Disease and Movement Disorders program at Rush University in Chicago, who moderated her presentation.

The National Parkinson Foundation is trying to address the problem with an Aware in Care campaign that helps patients and physicians overcome medication challenges during PD hospitalizations.

In Calgary, Dr. Wiltshire and her colleagues are working with the electronic health records system to give admitting physicians access to notes from the Movement Disorders Clinic. "Ideally, we would like to be able to [write the medication orders] and have them sent directly into the admitting orders," Dr. Wiltshire said.

They’ve already put a warning flag in the system that pops up when people order metoclopramide for patients on antiparkinson drugs. They’ve also made sure that immediate-release levodopa comes up first on drug ordering screens. Extended-release levodopa "was coming up first, so that’s what people were clicking," Dr. Wiltshire said.

The team also hopes to give PD patients more control over when they get their medications, perhaps by keeping them on bedside tables, and involve pharmacy staff "right at admission, so that they can work to get the [medication] reconciliation done," she said.

Dr. Wiltshire said she has no disclosures. Dr. Goetz reported personal compensation from several pharmaceutical and medical companies, none of them involved in the study.

NEW ORLEANS – When Parkinson’s disease patients are admitted to hospitals, they often end up on incorrect doses of levodopa during their stay – if it’s prescribed at all – and sometimes inappropriately get metoclopramide or neuroleptics, dopamine-blocking agents that could make their disease worse, according to a study from the University of Calgary (Alta.).

That’s what researchers from the university’s Movement Disorders Clinic found when they compared what 44 of their Parkinson’s patients took at home with what they were given after being admitted to Calgary hospitals.

There were medication problems in 44 (80%) of the 55 hospitalizations those patients had in 2010, said lead author Dr. Katie Wiltshire, a neurology resident at the university.

"Our study identifies deficiencies in the in-hospital prescribing of medications for patients with PD [Parkinson’s disease]. This includes a failure to seamlessly continue usual PD medications when patients are admitted, and perhaps of even greater concern, the inappropriate addition of dopamine-blocking agents during their hospital stay," she said at the annual meeting of the American Academy of Neurology.

Similar problems have been found at hospitals in the United States and Britain, perhaps because some hospital services are unfamiliar with PD treatment. "Widespread education of providers and safe-prescribing protocols are urgently needed to address these unsafe care issues," Dr. Wiltshire said.

Patients in her study came in on stable levodopa doses in 53 of the 55 admissions (96.4%); there were subsequent problems with levodopa administration in 26 (49%) of those hospital stays.

During three hospitalizations (5.7%), levodopa was not ordered for people who been on it at home. In 15 of the 53 admissions (28.3%), doses ordered were too high or too low. Dose schedules were off during 8 hospital stays (15.1%). In another12 stays (22.6%), patients were put on either immediate or extended-release levodopa when they had been on the alternate formulation before coming to the hospital. Metoclopramide or neuroleptics were ordered in 24 (43.6%) of the overall 55 admissions.

Dr. Wilshire and her colleagues don’t know yet if the discrepancies hurt patients, but other studies have found that they do, and that many PD patients report bad hospital experiences related to medication mismanagement (Parkinsonism Relat. Disord. 2007;13:539-40; Postgrad. Med. J. 2010;86:334-7). "This is a sobering report," said Dr. Christopher Goetz, director of the Parkinson’s Disease and Movement Disorders program at Rush University in Chicago, who moderated her presentation.

The National Parkinson Foundation is trying to address the problem with an Aware in Care campaign that helps patients and physicians overcome medication challenges during PD hospitalizations.

In Calgary, Dr. Wiltshire and her colleagues are working with the electronic health records system to give admitting physicians access to notes from the Movement Disorders Clinic. "Ideally, we would like to be able to [write the medication orders] and have them sent directly into the admitting orders," Dr. Wiltshire said.

They’ve already put a warning flag in the system that pops up when people order metoclopramide for patients on antiparkinson drugs. They’ve also made sure that immediate-release levodopa comes up first on drug ordering screens. Extended-release levodopa "was coming up first, so that’s what people were clicking," Dr. Wiltshire said.

The team also hopes to give PD patients more control over when they get their medications, perhaps by keeping them on bedside tables, and involve pharmacy staff "right at admission, so that they can work to get the [medication] reconciliation done," she said.

Dr. Wiltshire said she has no disclosures. Dr. Goetz reported personal compensation from several pharmaceutical and medical companies, none of them involved in the study.

NEW ORLEANS – When Parkinson’s disease patients are admitted to hospitals, they often end up on incorrect doses of levodopa during their stay – if it’s prescribed at all – and sometimes inappropriately get metoclopramide or neuroleptics, dopamine-blocking agents that could make their disease worse, according to a study from the University of Calgary (Alta.).

That’s what researchers from the university’s Movement Disorders Clinic found when they compared what 44 of their Parkinson’s patients took at home with what they were given after being admitted to Calgary hospitals.

There were medication problems in 44 (80%) of the 55 hospitalizations those patients had in 2010, said lead author Dr. Katie Wiltshire, a neurology resident at the university.

"Our study identifies deficiencies in the in-hospital prescribing of medications for patients with PD [Parkinson’s disease]. This includes a failure to seamlessly continue usual PD medications when patients are admitted, and perhaps of even greater concern, the inappropriate addition of dopamine-blocking agents during their hospital stay," she said at the annual meeting of the American Academy of Neurology.

Similar problems have been found at hospitals in the United States and Britain, perhaps because some hospital services are unfamiliar with PD treatment. "Widespread education of providers and safe-prescribing protocols are urgently needed to address these unsafe care issues," Dr. Wiltshire said.

Patients in her study came in on stable levodopa doses in 53 of the 55 admissions (96.4%); there were subsequent problems with levodopa administration in 26 (49%) of those hospital stays.

During three hospitalizations (5.7%), levodopa was not ordered for people who been on it at home. In 15 of the 53 admissions (28.3%), doses ordered were too high or too low. Dose schedules were off during 8 hospital stays (15.1%). In another12 stays (22.6%), patients were put on either immediate or extended-release levodopa when they had been on the alternate formulation before coming to the hospital. Metoclopramide or neuroleptics were ordered in 24 (43.6%) of the overall 55 admissions.

Dr. Wilshire and her colleagues don’t know yet if the discrepancies hurt patients, but other studies have found that they do, and that many PD patients report bad hospital experiences related to medication mismanagement (Parkinsonism Relat. Disord. 2007;13:539-40; Postgrad. Med. J. 2010;86:334-7). "This is a sobering report," said Dr. Christopher Goetz, director of the Parkinson’s Disease and Movement Disorders program at Rush University in Chicago, who moderated her presentation.

The National Parkinson Foundation is trying to address the problem with an Aware in Care campaign that helps patients and physicians overcome medication challenges during PD hospitalizations.

In Calgary, Dr. Wiltshire and her colleagues are working with the electronic health records system to give admitting physicians access to notes from the Movement Disorders Clinic. "Ideally, we would like to be able to [write the medication orders] and have them sent directly into the admitting orders," Dr. Wiltshire said.

They’ve already put a warning flag in the system that pops up when people order metoclopramide for patients on antiparkinson drugs. They’ve also made sure that immediate-release levodopa comes up first on drug ordering screens. Extended-release levodopa "was coming up first, so that’s what people were clicking," Dr. Wiltshire said.

The team also hopes to give PD patients more control over when they get their medications, perhaps by keeping them on bedside tables, and involve pharmacy staff "right at admission, so that they can work to get the [medication] reconciliation done," she said.

Dr. Wiltshire said she has no disclosures. Dr. Goetz reported personal compensation from several pharmaceutical and medical companies, none of them involved in the study.

Results from new studies of the investigational imaging agents florbetaben and flutemetamol indicate that they may help to support a diagnosis of Alzheimer’s disease or rule it out, with the potential to improve both clinical management and research.

Comparisons of the radioactive imaging agents against the diagnostic standard of histopathology at autopsy in two studies, as well as against the results of brain biopsy in another, showed that the compounds have high sensitivity and specificity for detecting the presence of beta-amyloid plaques.

In a phase III trial, 204 patients from Japan, Australia, France, and the United States underwent PET imaging with florbetaben. The study group included 194 individuals with dementia and 10 healthy volunteers. All of the participants were near the end of life.

Patients underwent both MR and PET imaging 90-110 minutes after an intravenous infusion of florbetaben. The investigators coregistered the MRI and PET scans to more precisely track beta-amyloid deposits in each of the brain regions examined – the first time such a technique has been employed in amyloid imaging studies, said Dr. Marwan N. Sabbagh, lead author and the director of Banner Sun Health Research Institute in Sun City, Ariz.

The investigators then compared the imaging results with postmortem findings in 31 of the patients whose brains came to autopsy, for a total of 186 brain regions. They analyzed another 60 regions from the 10 participants without dementia whose brains also were autopsied. Three readers who analyzed the imaging data and three neuropathologists who scored the autopsy results were blinded to all clinical and autopsy data. They evaluated the presence of beta-amyloid plaques in six prespecified brain regions.

In the six brain regions, florbetaben detected beta-amyloid with an overall sensitivity of 77% and a specificity of 94%. Visual scoring of the entire brain for the presence of beta-amyloid plaques concurred with the autopsy results with 100% sensitivity and 92% specificity.

The inter-reader agreement for the presence of beta-amyloid plaques on imaging within each brain "was almost perfect, with a kappa value of 0.88," said one of the coauthors of the study, Dr. Cornelia Reininger, global clinical leader of the florbetaben development program at Bayer Pharma AG, in an interview. "This is important because a robust and reliable method for assessing the PET scans is also a prerequisite for approval of tracers of this type."

"These results confirm that florbetaben is able to detect beta-amyloid plaques in the brain during life with great accuracy and is a suitable biomarker," Dr. Sabbagh said in a written statement. "This is an easy, non-invasive way to assist an Alzheimer’s diagnosis at an early stage. Also exciting is the possibility of using florbetaben as tool in future therapeutic clinical research studies where therapy goals focus on reducing levels of beta-amyloid in the brain.

With a half-life of 10 hours, florbetaben could be much more clinically useful than the first amyloid imaging agent developed, Pittsburgh Compound B, which has a 20-minute half-life, making it much more difficult to obtain quality images in anything but a research setting.

(Bayer recently sold the rights to florbetaben and other in vivo imaging agents to Piramal Imaging SA, based in India. Piramal said it will seek Food and Drug Administration approval for florbetaben by the end of the year.)

Two separate studies of flutemetamol suggest that the drug not only binds strongly to beta-amyloid plaques, but that such binding also correlates with cognitive status.

Dr. David Wolk, assistant director of the Penn Memory Center at the University of Pennsylvania, Philadelphia, and his colleagues analyzed the results of flutemetamol PET imaging in 180 patients who were near the end of life and 49 patients who had a presumed diagnosis of normal pressure hydrocephalus (NPH).

NPH is a form of dementia characterized by enlarged cerebral ventricles, a specific gait imbalance, and urinary incontinence, Dr. Wolk said in an interview. "It also turns out that a significant proportion of these patients seem to have evidence of concomitant Alzheimer’s pathology. It’s thought that these are either coexistent diagnoses or that the NPH was an incorrect diagnosis and the patient actually has Alzheimer’s."

Placement of a cerebrospinal fluid shunt into a brain ventricle is the typical NPH treatment and, in true cases, can actually reverse some of the symptoms. Many neurosurgeons who perform the procedure take a biopsy of the tissue removed, and it was these samples that allowed Dr. Wolk and his associates to conduct their study.

In patients with suspected NPH, the investigators compared biopsy histopathology to PET scans of flutemetamol beta-amyloid binding. For the 69 end-of-life subjects who eventually came to autopsy, the investigators compared brain histopathology with the results of imaging.

Compared against autopsy results, five readers of the PET scans who were blinded to clinical data reported an overall sensitivity and specificity of 86% and 92%, respectively. In comparison against biopsy, the sensitivity and specificity of flutemetamol imaging by three separate readers who were blinded to clinical data were 93% and 100%.

The results not only confirm flutemetamol’s proclivity for beta-amyloid plaques, but also suggest the possibility that imaging could someday improve diagnostic accuracy and help pinpoint treatment decisions.

"In a prior study, we found that people with NPH and concomitant Alzheimer’s have a poor response to shunting," Dr. Wolk said. "If a patient gets a shunt and doesn’t get better, we typically do another shunt. But in someone who also has Alzheimer’s, we would be less inclined to do another procedure."

In a separate study of 11 community-dwelling older adults, Dustin Hammers, Ph.D., and his colleagues compared the relationship between flutemetamol uptake and cognitive status. All of the participants (eight women and three men with a mean age of 76 years) had a prior complaint of memory loss.

In these subjects, flutemetamol uptake was significantly related to several cognitive domains, including auditory delayed memory, processing speed, mental flexibility, and semantic fluency. Cognitive performance worsened with greater uptake of flutemetamol.

"Flutemetamol uptake was highly related to worse cognitive performance on tasks traditionally impaired in patients with Alzheimer’s disease, but not in others," said Dr. Hammers, a neuropsychologist at the University of Utah’s Center for Alzheimer’s Care, Imaging, and Research in Salt Lake City.

"What we found really interesting is that this was a population of normal, elderly adults who had no cognitive problems except for a prior complaint of some memory issue," he said in an interview. "The results clearly fall in the direction of what we would expect to see in Alzheimer’s, although clearly they were in a preclinical state."

The florbetaben study was sponsored by Bayer Pharma AG. Dr. Sabbagh said that he had no financial disclosures. Dr. Wolk’s study was sponsored by GE Healthcare. He has received personal compensation from the company for consulting activities. GE Healthcare partly sponsored Dr. Hammer’s study. Dr. Hammer had no financial disclosures.

Results from new studies of the investigational imaging agents florbetaben and flutemetamol indicate that they may help to support a diagnosis of Alzheimer’s disease or rule it out, with the potential to improve both clinical management and research.

Comparisons of the radioactive imaging agents against the diagnostic standard of histopathology at autopsy in two studies, as well as against the results of brain biopsy in another, showed that the compounds have high sensitivity and specificity for detecting the presence of beta-amyloid plaques.

In a phase III trial, 204 patients from Japan, Australia, France, and the United States underwent PET imaging with florbetaben. The study group included 194 individuals with dementia and 10 healthy volunteers. All of the participants were near the end of life.

Patients underwent both MR and PET imaging 90-110 minutes after an intravenous infusion of florbetaben. The investigators coregistered the MRI and PET scans to more precisely track beta-amyloid deposits in each of the brain regions examined – the first time such a technique has been employed in amyloid imaging studies, said Dr. Marwan N. Sabbagh, lead author and the director of Banner Sun Health Research Institute in Sun City, Ariz.

The investigators then compared the imaging results with postmortem findings in 31 of the patients whose brains came to autopsy, for a total of 186 brain regions. They analyzed another 60 regions from the 10 participants without dementia whose brains also were autopsied. Three readers who analyzed the imaging data and three neuropathologists who scored the autopsy results were blinded to all clinical and autopsy data. They evaluated the presence of beta-amyloid plaques in six prespecified brain regions.

In the six brain regions, florbetaben detected beta-amyloid with an overall sensitivity of 77% and a specificity of 94%. Visual scoring of the entire brain for the presence of beta-amyloid plaques concurred with the autopsy results with 100% sensitivity and 92% specificity.

The inter-reader agreement for the presence of beta-amyloid plaques on imaging within each brain "was almost perfect, with a kappa value of 0.88," said one of the coauthors of the study, Dr. Cornelia Reininger, global clinical leader of the florbetaben development program at Bayer Pharma AG, in an interview. "This is important because a robust and reliable method for assessing the PET scans is also a prerequisite for approval of tracers of this type."

"These results confirm that florbetaben is able to detect beta-amyloid plaques in the brain during life with great accuracy and is a suitable biomarker," Dr. Sabbagh said in a written statement. "This is an easy, non-invasive way to assist an Alzheimer’s diagnosis at an early stage. Also exciting is the possibility of using florbetaben as tool in future therapeutic clinical research studies where therapy goals focus on reducing levels of beta-amyloid in the brain.

With a half-life of 10 hours, florbetaben could be much more clinically useful than the first amyloid imaging agent developed, Pittsburgh Compound B, which has a 20-minute half-life, making it much more difficult to obtain quality images in anything but a research setting.

(Bayer recently sold the rights to florbetaben and other in vivo imaging agents to Piramal Imaging SA, based in India. Piramal said it will seek Food and Drug Administration approval for florbetaben by the end of the year.)

Two separate studies of flutemetamol suggest that the drug not only binds strongly to beta-amyloid plaques, but that such binding also correlates with cognitive status.

Dr. David Wolk, assistant director of the Penn Memory Center at the University of Pennsylvania, Philadelphia, and his colleagues analyzed the results of flutemetamol PET imaging in 180 patients who were near the end of life and 49 patients who had a presumed diagnosis of normal pressure hydrocephalus (NPH).

NPH is a form of dementia characterized by enlarged cerebral ventricles, a specific gait imbalance, and urinary incontinence, Dr. Wolk said in an interview. "It also turns out that a significant proportion of these patients seem to have evidence of concomitant Alzheimer’s pathology. It’s thought that these are either coexistent diagnoses or that the NPH was an incorrect diagnosis and the patient actually has Alzheimer’s."

Placement of a cerebrospinal fluid shunt into a brain ventricle is the typical NPH treatment and, in true cases, can actually reverse some of the symptoms. Many neurosurgeons who perform the procedure take a biopsy of the tissue removed, and it was these samples that allowed Dr. Wolk and his associates to conduct their study.

In patients with suspected NPH, the investigators compared biopsy histopathology to PET scans of flutemetamol beta-amyloid binding. For the 69 end-of-life subjects who eventually came to autopsy, the investigators compared brain histopathology with the results of imaging.

Compared against autopsy results, five readers of the PET scans who were blinded to clinical data reported an overall sensitivity and specificity of 86% and 92%, respectively. In comparison against biopsy, the sensitivity and specificity of flutemetamol imaging by three separate readers who were blinded to clinical data were 93% and 100%.

The results not only confirm flutemetamol’s proclivity for beta-amyloid plaques, but also suggest the possibility that imaging could someday improve diagnostic accuracy and help pinpoint treatment decisions.

"In a prior study, we found that people with NPH and concomitant Alzheimer’s have a poor response to shunting," Dr. Wolk said. "If a patient gets a shunt and doesn’t get better, we typically do another shunt. But in someone who also has Alzheimer’s, we would be less inclined to do another procedure."

In a separate study of 11 community-dwelling older adults, Dustin Hammers, Ph.D., and his colleagues compared the relationship between flutemetamol uptake and cognitive status. All of the participants (eight women and three men with a mean age of 76 years) had a prior complaint of memory loss.

In these subjects, flutemetamol uptake was significantly related to several cognitive domains, including auditory delayed memory, processing speed, mental flexibility, and semantic fluency. Cognitive performance worsened with greater uptake of flutemetamol.

"Flutemetamol uptake was highly related to worse cognitive performance on tasks traditionally impaired in patients with Alzheimer’s disease, but not in others," said Dr. Hammers, a neuropsychologist at the University of Utah’s Center for Alzheimer’s Care, Imaging, and Research in Salt Lake City.

"What we found really interesting is that this was a population of normal, elderly adults who had no cognitive problems except for a prior complaint of some memory issue," he said in an interview. "The results clearly fall in the direction of what we would expect to see in Alzheimer’s, although clearly they were in a preclinical state."

The florbetaben study was sponsored by Bayer Pharma AG. Dr. Sabbagh said that he had no financial disclosures. Dr. Wolk’s study was sponsored by GE Healthcare. He has received personal compensation from the company for consulting activities. GE Healthcare partly sponsored Dr. Hammer’s study. Dr. Hammer had no financial disclosures.

Results from new studies of the investigational imaging agents florbetaben and flutemetamol indicate that they may help to support a diagnosis of Alzheimer’s disease or rule it out, with the potential to improve both clinical management and research.

Comparisons of the radioactive imaging agents against the diagnostic standard of histopathology at autopsy in two studies, as well as against the results of brain biopsy in another, showed that the compounds have high sensitivity and specificity for detecting the presence of beta-amyloid plaques.

In a phase III trial, 204 patients from Japan, Australia, France, and the United States underwent PET imaging with florbetaben. The study group included 194 individuals with dementia and 10 healthy volunteers. All of the participants were near the end of life.

Patients underwent both MR and PET imaging 90-110 minutes after an intravenous infusion of florbetaben. The investigators coregistered the MRI and PET scans to more precisely track beta-amyloid deposits in each of the brain regions examined – the first time such a technique has been employed in amyloid imaging studies, said Dr. Marwan N. Sabbagh, lead author and the director of Banner Sun Health Research Institute in Sun City, Ariz.

The investigators then compared the imaging results with postmortem findings in 31 of the patients whose brains came to autopsy, for a total of 186 brain regions. They analyzed another 60 regions from the 10 participants without dementia whose brains also were autopsied. Three readers who analyzed the imaging data and three neuropathologists who scored the autopsy results were blinded to all clinical and autopsy data. They evaluated the presence of beta-amyloid plaques in six prespecified brain regions.

In the six brain regions, florbetaben detected beta-amyloid with an overall sensitivity of 77% and a specificity of 94%. Visual scoring of the entire brain for the presence of beta-amyloid plaques concurred with the autopsy results with 100% sensitivity and 92% specificity.

The inter-reader agreement for the presence of beta-amyloid plaques on imaging within each brain "was almost perfect, with a kappa value of 0.88," said one of the coauthors of the study, Dr. Cornelia Reininger, global clinical leader of the florbetaben development program at Bayer Pharma AG, in an interview. "This is important because a robust and reliable method for assessing the PET scans is also a prerequisite for approval of tracers of this type."

"These results confirm that florbetaben is able to detect beta-amyloid plaques in the brain during life with great accuracy and is a suitable biomarker," Dr. Sabbagh said in a written statement. "This is an easy, non-invasive way to assist an Alzheimer’s diagnosis at an early stage. Also exciting is the possibility of using florbetaben as tool in future therapeutic clinical research studies where therapy goals focus on reducing levels of beta-amyloid in the brain.

With a half-life of 10 hours, florbetaben could be much more clinically useful than the first amyloid imaging agent developed, Pittsburgh Compound B, which has a 20-minute half-life, making it much more difficult to obtain quality images in anything but a research setting.

(Bayer recently sold the rights to florbetaben and other in vivo imaging agents to Piramal Imaging SA, based in India. Piramal said it will seek Food and Drug Administration approval for florbetaben by the end of the year.)

Two separate studies of flutemetamol suggest that the drug not only binds strongly to beta-amyloid plaques, but that such binding also correlates with cognitive status.

Dr. David Wolk, assistant director of the Penn Memory Center at the University of Pennsylvania, Philadelphia, and his colleagues analyzed the results of flutemetamol PET imaging in 180 patients who were near the end of life and 49 patients who had a presumed diagnosis of normal pressure hydrocephalus (NPH).

NPH is a form of dementia characterized by enlarged cerebral ventricles, a specific gait imbalance, and urinary incontinence, Dr. Wolk said in an interview. "It also turns out that a significant proportion of these patients seem to have evidence of concomitant Alzheimer’s pathology. It’s thought that these are either coexistent diagnoses or that the NPH was an incorrect diagnosis and the patient actually has Alzheimer’s."

Placement of a cerebrospinal fluid shunt into a brain ventricle is the typical NPH treatment and, in true cases, can actually reverse some of the symptoms. Many neurosurgeons who perform the procedure take a biopsy of the tissue removed, and it was these samples that allowed Dr. Wolk and his associates to conduct their study.

In patients with suspected NPH, the investigators compared biopsy histopathology to PET scans of flutemetamol beta-amyloid binding. For the 69 end-of-life subjects who eventually came to autopsy, the investigators compared brain histopathology with the results of imaging.

Compared against autopsy results, five readers of the PET scans who were blinded to clinical data reported an overall sensitivity and specificity of 86% and 92%, respectively. In comparison against biopsy, the sensitivity and specificity of flutemetamol imaging by three separate readers who were blinded to clinical data were 93% and 100%.

The results not only confirm flutemetamol’s proclivity for beta-amyloid plaques, but also suggest the possibility that imaging could someday improve diagnostic accuracy and help pinpoint treatment decisions.

"In a prior study, we found that people with NPH and concomitant Alzheimer’s have a poor response to shunting," Dr. Wolk said. "If a patient gets a shunt and doesn’t get better, we typically do another shunt. But in someone who also has Alzheimer’s, we would be less inclined to do another procedure."

In a separate study of 11 community-dwelling older adults, Dustin Hammers, Ph.D., and his colleagues compared the relationship between flutemetamol uptake and cognitive status. All of the participants (eight women and three men with a mean age of 76 years) had a prior complaint of memory loss.

In these subjects, flutemetamol uptake was significantly related to several cognitive domains, including auditory delayed memory, processing speed, mental flexibility, and semantic fluency. Cognitive performance worsened with greater uptake of flutemetamol.

"Flutemetamol uptake was highly related to worse cognitive performance on tasks traditionally impaired in patients with Alzheimer’s disease, but not in others," said Dr. Hammers, a neuropsychologist at the University of Utah’s Center for Alzheimer’s Care, Imaging, and Research in Salt Lake City.

"What we found really interesting is that this was a population of normal, elderly adults who had no cognitive problems except for a prior complaint of some memory issue," he said in an interview. "The results clearly fall in the direction of what we would expect to see in Alzheimer’s, although clearly they were in a preclinical state."

The florbetaben study was sponsored by Bayer Pharma AG. Dr. Sabbagh said that he had no financial disclosures. Dr. Wolk’s study was sponsored by GE Healthcare. He has received personal compensation from the company for consulting activities. GE Healthcare partly sponsored Dr. Hammer’s study. Dr. Hammer had no financial disclosures.

Patients with an apparent first demyelinating event who are treated early with subcutaneous interferon beta-1a experience a significantly longer time until progression to multiple sclerosis, compared with those whose treatment is initiated after diagnosis with clinically definite MS, according to 3-year results from the ongoing phase III, double-blind REFLEX extension trial.

The best results from the REFLEXION trial occurred in those treated early with a 44-mcg dose given three times weekly.

The findings provide additional evidence that treating early makes a difference in the long run, lead investigator Dr. Mark Freedman said in an interview. Dr. Freedman will present the results April 25 at the annual meeting of the American Academy of Neurology.

"What we saw at 2 years [in the REFLEXION trial] is definitely still there at 3 years. Treating early is the best opportunity for getting control of the disease," he said.

Not only do the findings show that early treatment matters, they show that the dose matters – even at the start of treatment, said Dr. Freedman, director of the multiple sclerosis research unit at the Ottawa (Ont.) Hospital and professor of neurology at the University of Ottawa. "The one question that remained after all the other interferon trials was the question about the dose," and now the answer is 44 mcg three times weekly.

In the REFLEX trial, 517 patients with a first demyelinating event were randomized to receive placebo; 44-mcg of interferon beta-1a three times weekly; or an off-label, 44-mcg dose of interferon beta-1a once weekly. They received treatment for 24 months or until they were diagnosed with clinically definite multiple sclerosis (CDMS), at which time they were switched to the three-times-weekly interferon dose. Both doses of interferon, when given early, significantly delayed CDMS and MS based on the more MRI-dependent McDonald criteria, compared with placebo. For MS diagnosed with the McDonald criteria, the three-times-weekly interferon dose was associated with significantly greater delay than the once-weekly dose.

All patients from the REFLEX trial were eligible for REFLEXION; 402 (78%) participated. All those originally on placebo who did not reach CDMS were switched to interferon three times weekly, and those in the initial interferon once- or three-times-weekly groups who did not reach CDMS remained in their original treatment group.

Integrated data from the two trials, analyzed by original group, showed that the 36-month cumulative probability of CDMS was 41.3% for the placebo/delayed-treatment group, 27.6% for the once-weekly interferon group, and 27.1% for the three-times-weekly interferon group. The 36-month probability of McDonald-criteria MS was 87% for placebo/delayed treatment, 79% for the once-weekly interferon group, and 67% for the three times weekly interferon group.

As in the REFLEX trial, the difference in time to progression was statistically significant for both interferon groups compared with placebo based on both clinical and MRI-based criteria, and for the three-times-weekly interferon group compared with the once-weekly interferon group based on McDonald criteria, Dr. Freedman said.

The REFLEX and REFLEXION trials were conducted using a human serum albumin-free formulation of interferon beta-1a that is available in numerous countries worldwide but not in the United States. Participants had a first clinical episode suggestive of a demyelinating event, including symptoms such as tingling, numbness, muscle weakness, or balance problems. They also had at least two clinically silent brain lesions detected on MRI.

CDMS was diagnosed in those experiencing a second clinical attack or a sustained increase of more than 1.5 in the Expanded Disability Status Scale score. Those who initially received placebo but who did not develop CDMS – and who therefore switched to interferon only after entering the REFLEXION trial – started interferon treatment an average of 58 days following their initial symptoms.

An added benefit of starting with this higher dose is that, compared with the lower dose, it was associated with a reduction in the persistent flulike symptoms known to be associated with interferon beta-1a, Dr. Freedman said.

The REFLEXION trial, which is sponsored by Merck Serono S.A., will continue for a total of 5 years, he said.

Dr. Freedman had no other disclosures to report.

Patients with an apparent first demyelinating event who are treated early with subcutaneous interferon beta-1a experience a significantly longer time until progression to multiple sclerosis, compared with those whose treatment is initiated after diagnosis with clinically definite MS, according to 3-year results from the ongoing phase III, double-blind REFLEX extension trial.

The best results from the REFLEXION trial occurred in those treated early with a 44-mcg dose given three times weekly.

The findings provide additional evidence that treating early makes a difference in the long run, lead investigator Dr. Mark Freedman said in an interview. Dr. Freedman will present the results April 25 at the annual meeting of the American Academy of Neurology.

"What we saw at 2 years [in the REFLEXION trial] is definitely still there at 3 years. Treating early is the best opportunity for getting control of the disease," he said.

Not only do the findings show that early treatment matters, they show that the dose matters – even at the start of treatment, said Dr. Freedman, director of the multiple sclerosis research unit at the Ottawa (Ont.) Hospital and professor of neurology at the University of Ottawa. "The one question that remained after all the other interferon trials was the question about the dose," and now the answer is 44 mcg three times weekly.

In the REFLEX trial, 517 patients with a first demyelinating event were randomized to receive placebo; 44-mcg of interferon beta-1a three times weekly; or an off-label, 44-mcg dose of interferon beta-1a once weekly. They received treatment for 24 months or until they were diagnosed with clinically definite multiple sclerosis (CDMS), at which time they were switched to the three-times-weekly interferon dose. Both doses of interferon, when given early, significantly delayed CDMS and MS based on the more MRI-dependent McDonald criteria, compared with placebo. For MS diagnosed with the McDonald criteria, the three-times-weekly interferon dose was associated with significantly greater delay than the once-weekly dose.

All patients from the REFLEX trial were eligible for REFLEXION; 402 (78%) participated. All those originally on placebo who did not reach CDMS were switched to interferon three times weekly, and those in the initial interferon once- or three-times-weekly groups who did not reach CDMS remained in their original treatment group.

Integrated data from the two trials, analyzed by original group, showed that the 36-month cumulative probability of CDMS was 41.3% for the placebo/delayed-treatment group, 27.6% for the once-weekly interferon group, and 27.1% for the three-times-weekly interferon group. The 36-month probability of McDonald-criteria MS was 87% for placebo/delayed treatment, 79% for the once-weekly interferon group, and 67% for the three times weekly interferon group.

As in the REFLEX trial, the difference in time to progression was statistically significant for both interferon groups compared with placebo based on both clinical and MRI-based criteria, and for the three-times-weekly interferon group compared with the once-weekly interferon group based on McDonald criteria, Dr. Freedman said.

The REFLEX and REFLEXION trials were conducted using a human serum albumin-free formulation of interferon beta-1a that is available in numerous countries worldwide but not in the United States. Participants had a first clinical episode suggestive of a demyelinating event, including symptoms such as tingling, numbness, muscle weakness, or balance problems. They also had at least two clinically silent brain lesions detected on MRI.

CDMS was diagnosed in those experiencing a second clinical attack or a sustained increase of more than 1.5 in the Expanded Disability Status Scale score. Those who initially received placebo but who did not develop CDMS – and who therefore switched to interferon only after entering the REFLEXION trial – started interferon treatment an average of 58 days following their initial symptoms.

An added benefit of starting with this higher dose is that, compared with the lower dose, it was associated with a reduction in the persistent flulike symptoms known to be associated with interferon beta-1a, Dr. Freedman said.

The REFLEXION trial, which is sponsored by Merck Serono S.A., will continue for a total of 5 years, he said.

Dr. Freedman had no other disclosures to report.

Patients with an apparent first demyelinating event who are treated early with subcutaneous interferon beta-1a experience a significantly longer time until progression to multiple sclerosis, compared with those whose treatment is initiated after diagnosis with clinically definite MS, according to 3-year results from the ongoing phase III, double-blind REFLEX extension trial.

The best results from the REFLEXION trial occurred in those treated early with a 44-mcg dose given three times weekly.

The findings provide additional evidence that treating early makes a difference in the long run, lead investigator Dr. Mark Freedman said in an interview. Dr. Freedman will present the results April 25 at the annual meeting of the American Academy of Neurology.

"What we saw at 2 years [in the REFLEXION trial] is definitely still there at 3 years. Treating early is the best opportunity for getting control of the disease," he said.

Not only do the findings show that early treatment matters, they show that the dose matters – even at the start of treatment, said Dr. Freedman, director of the multiple sclerosis research unit at the Ottawa (Ont.) Hospital and professor of neurology at the University of Ottawa. "The one question that remained after all the other interferon trials was the question about the dose," and now the answer is 44 mcg three times weekly.

In the REFLEX trial, 517 patients with a first demyelinating event were randomized to receive placebo; 44-mcg of interferon beta-1a three times weekly; or an off-label, 44-mcg dose of interferon beta-1a once weekly. They received treatment for 24 months or until they were diagnosed with clinically definite multiple sclerosis (CDMS), at which time they were switched to the three-times-weekly interferon dose. Both doses of interferon, when given early, significantly delayed CDMS and MS based on the more MRI-dependent McDonald criteria, compared with placebo. For MS diagnosed with the McDonald criteria, the three-times-weekly interferon dose was associated with significantly greater delay than the once-weekly dose.

All patients from the REFLEX trial were eligible for REFLEXION; 402 (78%) participated. All those originally on placebo who did not reach CDMS were switched to interferon three times weekly, and those in the initial interferon once- or three-times-weekly groups who did not reach CDMS remained in their original treatment group.

Integrated data from the two trials, analyzed by original group, showed that the 36-month cumulative probability of CDMS was 41.3% for the placebo/delayed-treatment group, 27.6% for the once-weekly interferon group, and 27.1% for the three-times-weekly interferon group. The 36-month probability of McDonald-criteria MS was 87% for placebo/delayed treatment, 79% for the once-weekly interferon group, and 67% for the three times weekly interferon group.

As in the REFLEX trial, the difference in time to progression was statistically significant for both interferon groups compared with placebo based on both clinical and MRI-based criteria, and for the three-times-weekly interferon group compared with the once-weekly interferon group based on McDonald criteria, Dr. Freedman said.

The REFLEX and REFLEXION trials were conducted using a human serum albumin-free formulation of interferon beta-1a that is available in numerous countries worldwide but not in the United States. Participants had a first clinical episode suggestive of a demyelinating event, including symptoms such as tingling, numbness, muscle weakness, or balance problems. They also had at least two clinically silent brain lesions detected on MRI.

CDMS was diagnosed in those experiencing a second clinical attack or a sustained increase of more than 1.5 in the Expanded Disability Status Scale score. Those who initially received placebo but who did not develop CDMS – and who therefore switched to interferon only after entering the REFLEXION trial – started interferon treatment an average of 58 days following their initial symptoms.

An added benefit of starting with this higher dose is that, compared with the lower dose, it was associated with a reduction in the persistent flulike symptoms known to be associated with interferon beta-1a, Dr. Freedman said.

The REFLEXION trial, which is sponsored by Merck Serono S.A., will continue for a total of 5 years, he said.

Dr. Freedman had no other disclosures to report.

Thrombolytic drugs appear to be as safe for children with acute ischemic stroke as they are for adults, based on an analysis of more than 9,000 patients in the Kids’ Inpatient Database.

Overall, 4% of the children in the database who got the clot-busting drugs had a brain hemorrhage, which was not significantly different than the 6% rate seen in adults with similar treatment, according to Dr. Amer Alshekhlee, a neurology fellow at the St. Louis University.

The Kids Inpatient Database contains data on 3 million pediatric hospital stays from 1997 through 2009. Dr. Alshekhlee identified 9,367 children who were treated in hospitals for acute ischemic stroke. Only 75 of those – less than 1% – received thrombolysis.

The rate was not unexpectedly low, Dr. Alshekhlee, said in an interview. In fact, he said, some reviews have suggested avoiding thrombolytic treatment for children altogether.

"Children are not getting the treatment because the treatment is not recommended for them. The rate of using thrombolysis is also low in adults, about 2%, but this rate in children is even lower."

In the database, treated children were significantly older than the untreated (mean 13 years vs. 8 years).There were no significant demographic differences in sex, race, or family income.

An unadjusted analysis showed that treated children had a significantly greater incidence of both intracranial hemorrhage (4.0% vs. 0.38 %) and intracranial hemorrhage and in-hospital mortality combined (12% vs. 6%).

In a fully adjusted model, children who received thrombolysis had significantly greater odds of developing a brain bleed than were untreated children (odds ratio, 4.3), and those who did have a bleed had almost three and a half times greater odds of dying (OR, 3.4). However, thrombolysis itself was not associated with any significant increase in mortality.

Dr. Alshekhlee’s review of the database didn’t examine functional outcomes among the children who received thrombolytic medications.

Although the data used in the review are several years old, Dr. Alshekhlee said they probably accurately reflect today’s thrombolytic treatment in children.

From a practical standpoint, the study shows that the drugs are relatively safe for children, but can’t be construed as a practice changer, coauthor Dr. Salvador Cruz-Flores said in an interview.

"In the absence of any other alternative therapy for kids with severe stroke, perhaps physicians facing the situation should consider using it, but that will require informing parents of the uncertainty of its efficacy in the population and acknowledging the gap in knowledge we have," said Dr. Cruz-Flores, director of the Souers Stroke Institute at Saint Louis University.

The investigators are scheduled to present the full results of the study in late April at the annual meeting of the American Academy of Neurology.

The review was conducted without outside funding. Neither investigator had any relevant financial disclosures.

Thrombolytic drugs appear to be as safe for children with acute ischemic stroke as they are for adults, based on an analysis of more than 9,000 patients in the Kids’ Inpatient Database.

Overall, 4% of the children in the database who got the clot-busting drugs had a brain hemorrhage, which was not significantly different than the 6% rate seen in adults with similar treatment, according to Dr. Amer Alshekhlee, a neurology fellow at the St. Louis University.

The Kids Inpatient Database contains data on 3 million pediatric hospital stays from 1997 through 2009. Dr. Alshekhlee identified 9,367 children who were treated in hospitals for acute ischemic stroke. Only 75 of those – less than 1% – received thrombolysis.

The rate was not unexpectedly low, Dr. Alshekhlee, said in an interview. In fact, he said, some reviews have suggested avoiding thrombolytic treatment for children altogether.

"Children are not getting the treatment because the treatment is not recommended for them. The rate of using thrombolysis is also low in adults, about 2%, but this rate in children is even lower."

In the database, treated children were significantly older than the untreated (mean 13 years vs. 8 years).There were no significant demographic differences in sex, race, or family income.

An unadjusted analysis showed that treated children had a significantly greater incidence of both intracranial hemorrhage (4.0% vs. 0.38 %) and intracranial hemorrhage and in-hospital mortality combined (12% vs. 6%).

In a fully adjusted model, children who received thrombolysis had significantly greater odds of developing a brain bleed than were untreated children (odds ratio, 4.3), and those who did have a bleed had almost three and a half times greater odds of dying (OR, 3.4). However, thrombolysis itself was not associated with any significant increase in mortality.

Dr. Alshekhlee’s review of the database didn’t examine functional outcomes among the children who received thrombolytic medications.

Although the data used in the review are several years old, Dr. Alshekhlee said they probably accurately reflect today’s thrombolytic treatment in children.

From a practical standpoint, the study shows that the drugs are relatively safe for children, but can’t be construed as a practice changer, coauthor Dr. Salvador Cruz-Flores said in an interview.

"In the absence of any other alternative therapy for kids with severe stroke, perhaps physicians facing the situation should consider using it, but that will require informing parents of the uncertainty of its efficacy in the population and acknowledging the gap in knowledge we have," said Dr. Cruz-Flores, director of the Souers Stroke Institute at Saint Louis University.

The investigators are scheduled to present the full results of the study in late April at the annual meeting of the American Academy of Neurology.

The review was conducted without outside funding. Neither investigator had any relevant financial disclosures.

Thrombolytic drugs appear to be as safe for children with acute ischemic stroke as they are for adults, based on an analysis of more than 9,000 patients in the Kids’ Inpatient Database.

Overall, 4% of the children in the database who got the clot-busting drugs had a brain hemorrhage, which was not significantly different than the 6% rate seen in adults with similar treatment, according to Dr. Amer Alshekhlee, a neurology fellow at the St. Louis University.

The Kids Inpatient Database contains data on 3 million pediatric hospital stays from 1997 through 2009. Dr. Alshekhlee identified 9,367 children who were treated in hospitals for acute ischemic stroke. Only 75 of those – less than 1% – received thrombolysis.

The rate was not unexpectedly low, Dr. Alshekhlee, said in an interview. In fact, he said, some reviews have suggested avoiding thrombolytic treatment for children altogether.

"Children are not getting the treatment because the treatment is not recommended for them. The rate of using thrombolysis is also low in adults, about 2%, but this rate in children is even lower."

In the database, treated children were significantly older than the untreated (mean 13 years vs. 8 years).There were no significant demographic differences in sex, race, or family income.

An unadjusted analysis showed that treated children had a significantly greater incidence of both intracranial hemorrhage (4.0% vs. 0.38 %) and intracranial hemorrhage and in-hospital mortality combined (12% vs. 6%).

In a fully adjusted model, children who received thrombolysis had significantly greater odds of developing a brain bleed than were untreated children (odds ratio, 4.3), and those who did have a bleed had almost three and a half times greater odds of dying (OR, 3.4). However, thrombolysis itself was not associated with any significant increase in mortality.

Dr. Alshekhlee’s review of the database didn’t examine functional outcomes among the children who received thrombolytic medications.

Although the data used in the review are several years old, Dr. Alshekhlee said they probably accurately reflect today’s thrombolytic treatment in children.

From a practical standpoint, the study shows that the drugs are relatively safe for children, but can’t be construed as a practice changer, coauthor Dr. Salvador Cruz-Flores said in an interview.

"In the absence of any other alternative therapy for kids with severe stroke, perhaps physicians facing the situation should consider using it, but that will require informing parents of the uncertainty of its efficacy in the population and acknowledging the gap in knowledge we have," said Dr. Cruz-Flores, director of the Souers Stroke Institute at Saint Louis University.

The investigators are scheduled to present the full results of the study in late April at the annual meeting of the American Academy of Neurology.

The review was conducted without outside funding. Neither investigator had any relevant financial disclosures.

A 2-year weight-lifting program improved physical symptoms of Parkinson’s disease – including tremor – and seemed to slow their progression.

The progressive resistance routine, which alternated between increasing strength and speed in weight-lifting, was significantly more effective than was an often-recommended program of strengthening, flexibility, and balance, according to Daniel Corcos, Ph.D., lead author of the comparative study. By the end of the study period, patients who were lifting weights maintained a significant level of improvement, but scores of the other group had fallen back to their baseline levels.

Photo courtesy kali9/iStockphoto.com

While weight lifting obviously benefits a patient by muscular strengthening, there seems to be a neuronal component as well, Dr. Corcos said in an interview.

"There is no question that part of the changes are related to what goes on in the brain. Every time you make a muscle contract, you involve the motor cortex and basal ganglia," he said. This repetitive experience appears to alter cortical excitability, improving the connection between brain and muscles, which deteriorates in Parkinson’s, said Dr. Corcos, a kinesiologist and professor of neurologic sciences at the University of Illinois, Chicago.

The investigation randomized 48 people with Parkinson’s disease to the progressive resistance program or to Fitness Counts, a program created by the National Parkinson’s Disease Foundation. Fitness Counts is performed without weights and includes 12 stretching exercises, 7 strengthening exercises, and a set of balancing exercises.

Patients in the weight-training program exercised upper and lower body muscle groups with ever-increasing weight. The initial step determined the heaviest weight a patient could tolerate. Resistance was set at 30%-40% of that maximum weight for the upper body exercises and 50%-60-% of the maximum for the lower body exercises. Weight was increased by at least 5% as soon as the exercise became easier. Every 8 weeks, the program alternated between strength training alone and the combination of strength and speed training, with emphasis on how quickly each repetition could be performed with good form.

The researchers expected each patient to complete 208 sessions by 24 months – usually 2 sessions each week. If they missed a two sessions in a row, the exercise study coordinator contacted the patient. The primary outcome was change on the Unified Parkinson’s Disease Rating Scale III (UPDRS-III) score off medication from baseline to the end of the study.

The patients’ mean age at study entry was 59 years. Most (38) completed the entire 2-year program.

Both the strength training and overall fitness programs had significantly reduced the UPDRS-III score at 6 months (by 6.42 and 5.38 points, respectively). But by the end of 2 years, the weight training group had maintained its improvement (7.3 points), while the fitness group’s score had dropped back to its baseline levels.

The study shows that patients with Parkinson’s can adhere to a sustained exercise regimen and reap valuable benefits from it, Dr. Corcos said. The average Parkinson’s patient experiences about a 30% decrease in normal activity, which provokes muscle deterioration even apart from disease progression. "Think about it. If you, a healthy person, stopped doing anything and laid up in bed for a year, you would still end up in a sorry state," Dr. Corcos said.

Depression probably contributes to reduced activity along with muscular problems. "Depression is part of Parkinson’s and although not every patient has it, it can be quite disabling. As it becomes harder and harder to move, people lose the motivation [to exercise]."

Patients also tend to put exercise at the bottom of their personal "to do" list, just as many healthy people do.

"As the medications lose effectiveness, patients have fewer periods during which they can get things done," Dr. Corcos said. "When it’s working well, they have so many things to do that they just don’t find the time for exercise. I hope this objective evidence may motivate patients to realize that exercise should be a top priority."

His is not the only study expanding the knowledge base in this area.

Fuzhong Li, Ph.D., of the Oregon Research Institute, Eugene, and his colleagues recently published the results of a randomized trial that explored the effect of a modified tai chi program on physical function in Parkinson’s patients. The study randomized 195 patients to tai chi, resistance training, or stretching for 24 weeks. The tai chi group experienced a significantly greater improvement in the UPDRS-III score than did the stretching group (but not the resistance training group), as well as significantly fewer falls than either of the other groups. They retained these benefits at 3 months after the intervention (N. Engl. J. Med. 2012;366:511-9).

Dr. Corcos is scheduled to present the full results of his study in late April at the annual meeting of the America Academy of Neurology.

The National Institutes of Health funded the study. Dr. Corcos had no financial disclosures.

A 2-year weight-lifting program improved physical symptoms of Parkinson’s disease – including tremor – and seemed to slow their progression.

The progressive resistance routine, which alternated between increasing strength and speed in weight-lifting, was significantly more effective than was an often-recommended program of strengthening, flexibility, and balance, according to Daniel Corcos, Ph.D., lead author of the comparative study. By the end of the study period, patients who were lifting weights maintained a significant level of improvement, but scores of the other group had fallen back to their baseline levels.

Photo courtesy kali9/iStockphoto.com

While weight lifting obviously benefits a patient by muscular strengthening, there seems to be a neuronal component as well, Dr. Corcos said in an interview.

"There is no question that part of the changes are related to what goes on in the brain. Every time you make a muscle contract, you involve the motor cortex and basal ganglia," he said. This repetitive experience appears to alter cortical excitability, improving the connection between brain and muscles, which deteriorates in Parkinson’s, said Dr. Corcos, a kinesiologist and professor of neurologic sciences at the University of Illinois, Chicago.

The investigation randomized 48 people with Parkinson’s disease to the progressive resistance program or to Fitness Counts, a program created by the National Parkinson’s Disease Foundation. Fitness Counts is performed without weights and includes 12 stretching exercises, 7 strengthening exercises, and a set of balancing exercises.

Patients in the weight-training program exercised upper and lower body muscle groups with ever-increasing weight. The initial step determined the heaviest weight a patient could tolerate. Resistance was set at 30%-40% of that maximum weight for the upper body exercises and 50%-60-% of the maximum for the lower body exercises. Weight was increased by at least 5% as soon as the exercise became easier. Every 8 weeks, the program alternated between strength training alone and the combination of strength and speed training, with emphasis on how quickly each repetition could be performed with good form.

The researchers expected each patient to complete 208 sessions by 24 months – usually 2 sessions each week. If they missed a two sessions in a row, the exercise study coordinator contacted the patient. The primary outcome was change on the Unified Parkinson’s Disease Rating Scale III (UPDRS-III) score off medication from baseline to the end of the study.

The patients’ mean age at study entry was 59 years. Most (38) completed the entire 2-year program.

Both the strength training and overall fitness programs had significantly reduced the UPDRS-III score at 6 months (by 6.42 and 5.38 points, respectively). But by the end of 2 years, the weight training group had maintained its improvement (7.3 points), while the fitness group’s score had dropped back to its baseline levels.

The study shows that patients with Parkinson’s can adhere to a sustained exercise regimen and reap valuable benefits from it, Dr. Corcos said. The average Parkinson’s patient experiences about a 30% decrease in normal activity, which provokes muscle deterioration even apart from disease progression. "Think about it. If you, a healthy person, stopped doing anything and laid up in bed for a year, you would still end up in a sorry state," Dr. Corcos said.

Depression probably contributes to reduced activity along with muscular problems. "Depression is part of Parkinson’s and although not every patient has it, it can be quite disabling. As it becomes harder and harder to move, people lose the motivation [to exercise]."

Patients also tend to put exercise at the bottom of their personal "to do" list, just as many healthy people do.

"As the medications lose effectiveness, patients have fewer periods during which they can get things done," Dr. Corcos said. "When it’s working well, they have so many things to do that they just don’t find the time for exercise. I hope this objective evidence may motivate patients to realize that exercise should be a top priority."

His is not the only study expanding the knowledge base in this area.

Fuzhong Li, Ph.D., of the Oregon Research Institute, Eugene, and his colleagues recently published the results of a randomized trial that explored the effect of a modified tai chi program on physical function in Parkinson’s patients. The study randomized 195 patients to tai chi, resistance training, or stretching for 24 weeks. The tai chi group experienced a significantly greater improvement in the UPDRS-III score than did the stretching group (but not the resistance training group), as well as significantly fewer falls than either of the other groups. They retained these benefits at 3 months after the intervention (N. Engl. J. Med. 2012;366:511-9).

Dr. Corcos is scheduled to present the full results of his study in late April at the annual meeting of the America Academy of Neurology.

The National Institutes of Health funded the study. Dr. Corcos had no financial disclosures.

A 2-year weight-lifting program improved physical symptoms of Parkinson’s disease – including tremor – and seemed to slow their progression.

The progressive resistance routine, which alternated between increasing strength and speed in weight-lifting, was significantly more effective than was an often-recommended program of strengthening, flexibility, and balance, according to Daniel Corcos, Ph.D., lead author of the comparative study. By the end of the study period, patients who were lifting weights maintained a significant level of improvement, but scores of the other group had fallen back to their baseline levels.

Photo courtesy kali9/iStockphoto.com

While weight lifting obviously benefits a patient by muscular strengthening, there seems to be a neuronal component as well, Dr. Corcos said in an interview.

"There is no question that part of the changes are related to what goes on in the brain. Every time you make a muscle contract, you involve the motor cortex and basal ganglia," he said. This repetitive experience appears to alter cortical excitability, improving the connection between brain and muscles, which deteriorates in Parkinson’s, said Dr. Corcos, a kinesiologist and professor of neurologic sciences at the University of Illinois, Chicago.

The investigation randomized 48 people with Parkinson’s disease to the progressive resistance program or to Fitness Counts, a program created by the National Parkinson’s Disease Foundation. Fitness Counts is performed without weights and includes 12 stretching exercises, 7 strengthening exercises, and a set of balancing exercises.

Patients in the weight-training program exercised upper and lower body muscle groups with ever-increasing weight. The initial step determined the heaviest weight a patient could tolerate. Resistance was set at 30%-40% of that maximum weight for the upper body exercises and 50%-60-% of the maximum for the lower body exercises. Weight was increased by at least 5% as soon as the exercise became easier. Every 8 weeks, the program alternated between strength training alone and the combination of strength and speed training, with emphasis on how quickly each repetition could be performed with good form.

The researchers expected each patient to complete 208 sessions by 24 months – usually 2 sessions each week. If they missed a two sessions in a row, the exercise study coordinator contacted the patient. The primary outcome was change on the Unified Parkinson’s Disease Rating Scale III (UPDRS-III) score off medication from baseline to the end of the study.

The patients’ mean age at study entry was 59 years. Most (38) completed the entire 2-year program.

Both the strength training and overall fitness programs had significantly reduced the UPDRS-III score at 6 months (by 6.42 and 5.38 points, respectively). But by the end of 2 years, the weight training group had maintained its improvement (7.3 points), while the fitness group’s score had dropped back to its baseline levels.

The study shows that patients with Parkinson’s can adhere to a sustained exercise regimen and reap valuable benefits from it, Dr. Corcos said. The average Parkinson’s patient experiences about a 30% decrease in normal activity, which provokes muscle deterioration even apart from disease progression. "Think about it. If you, a healthy person, stopped doing anything and laid up in bed for a year, you would still end up in a sorry state," Dr. Corcos said.

Depression probably contributes to reduced activity along with muscular problems. "Depression is part of Parkinson’s and although not every patient has it, it can be quite disabling. As it becomes harder and harder to move, people lose the motivation [to exercise]."

Patients also tend to put exercise at the bottom of their personal "to do" list, just as many healthy people do.

"As the medications lose effectiveness, patients have fewer periods during which they can get things done," Dr. Corcos said. "When it’s working well, they have so many things to do that they just don’t find the time for exercise. I hope this objective evidence may motivate patients to realize that exercise should be a top priority."

His is not the only study expanding the knowledge base in this area.

Fuzhong Li, Ph.D., of the Oregon Research Institute, Eugene, and his colleagues recently published the results of a randomized trial that explored the effect of a modified tai chi program on physical function in Parkinson’s patients. The study randomized 195 patients to tai chi, resistance training, or stretching for 24 weeks. The tai chi group experienced a significantly greater improvement in the UPDRS-III score than did the stretching group (but not the resistance training group), as well as significantly fewer falls than either of the other groups. They retained these benefits at 3 months after the intervention (N. Engl. J. Med. 2012;366:511-9).

Dr. Corcos is scheduled to present the full results of his study in late April at the annual meeting of the America Academy of Neurology.

The National Institutes of Health funded the study. Dr. Corcos had no financial disclosures.