Amy Rothman Schonfeld

CARLSBAD, Calif. – Women with cerebral aneurysms were less likely to have used oral contraceptives or hormone replacement therapy in their lifetime than controls, according to the results of a retrospective case-control study of 60 women with aneurysms.

“These findings suggest that our case group may have had not only lower levels of estrogen, but also more severe physiologic fluctuations in their estrogen level as compared to population averages. To take this one step further, therapies that mitigate the effects of low estrogen level and fluctuations may decrease the risk for cerebral aneurysms,” Dr. Michael Chen said at the annual meeting of the Society of NeuroInterventional Surgery.

The study included 21 women with ruptured aneurysms and 39 with unruptured aneurysms who were under the care of a single physician during 2008-2010. Their median age was 52 years, with a range of 31-80 years. Dr. Chen and his associates conducted telephone interviews with the patients to obtain detailed medical, social, family and gynecologic histories, including information about lifetime use and duration of use of oral contraceptives and hormone replacement therapy, as well as menstrual and reproductive history.

For the control group, the investigators spoke with 4,682 random American women from a publicly available data set (Ann. Epidemiol. 2002;12:213-22) that was generated as part of a National Institutes of Health–funded study exploring the use of oral contraceptives and hormone replacement therapy in breast cancer.

For each case, seven control patients matched for age and educational levels were selected, giving 420 control patients. Measures such as median age, body mass index (BMI), age of menarche, nulliparity, and age of first pregnancy were comparable between the case and control patients.

Significantly fewer women with an aneurysm reported lifetime use of oral contraceptives than did controls (60% vs. 77.6%, P = .003) as well as use of hormone replacement therapy (23.7% vs. 44.8%, P = .002). The median age of menopause for women with aneurysms was more than 2 years earlier than for the control group (44.5 vs. 46.9 years, P = .53) and 50% of cases had menopause before age 45, compared with 34% of controls (P = .18). “The patient group also had a high rate of early hysterectomies,” noted Dr. Chen, an interventional vascular neurologist affiliated with Rush University Medical Center, Chicago.

One of the limitations of the study is that the vasculature of the control group had not been evaluated, although it is assumed that 3%-4% of the general population harbors an unruptured cerebral aneurysm. Another limitation is that the control group data were generated during 1994-1998, before the use of hormone replacement therapy decreased substantially in 2002 following the publication of the Women’s Health Initiative Study on breast cancer, Dr. Chen said.

He hopes these findings will guide future research not only on the role of estrogen in aneurysm development, but also the role of the estrogen receptor specific to cerebral vasculature. “Understanding more about the effects of estrogen at the receptor level may allow us to find therapies that target that receptor in order to provide some protection for women at risk of developing aneurysms or harboring unruptured aneurysms.”

Dr. Chen reported no relevant disclosures.

CARLSBAD, Calif. – Women with cerebral aneurysms were less likely to have used oral contraceptives or hormone replacement therapy in their lifetime than controls, according to the results of a retrospective case-control study of 60 women with aneurysms.

“These findings suggest that our case group may have had not only lower levels of estrogen, but also more severe physiologic fluctuations in their estrogen level as compared to population averages. To take this one step further, therapies that mitigate the effects of low estrogen level and fluctuations may decrease the risk for cerebral aneurysms,” Dr. Michael Chen said at the annual meeting of the Society of NeuroInterventional Surgery.

The study included 21 women with ruptured aneurysms and 39 with unruptured aneurysms who were under the care of a single physician during 2008-2010. Their median age was 52 years, with a range of 31-80 years. Dr. Chen and his associates conducted telephone interviews with the patients to obtain detailed medical, social, family and gynecologic histories, including information about lifetime use and duration of use of oral contraceptives and hormone replacement therapy, as well as menstrual and reproductive history.

For the control group, the investigators spoke with 4,682 random American women from a publicly available data set (Ann. Epidemiol. 2002;12:213-22) that was generated as part of a National Institutes of Health–funded study exploring the use of oral contraceptives and hormone replacement therapy in breast cancer.

For each case, seven control patients matched for age and educational levels were selected, giving 420 control patients. Measures such as median age, body mass index (BMI), age of menarche, nulliparity, and age of first pregnancy were comparable between the case and control patients.

Significantly fewer women with an aneurysm reported lifetime use of oral contraceptives than did controls (60% vs. 77.6%, P = .003) as well as use of hormone replacement therapy (23.7% vs. 44.8%, P = .002). The median age of menopause for women with aneurysms was more than 2 years earlier than for the control group (44.5 vs. 46.9 years, P = .53) and 50% of cases had menopause before age 45, compared with 34% of controls (P = .18). “The patient group also had a high rate of early hysterectomies,” noted Dr. Chen, an interventional vascular neurologist affiliated with Rush University Medical Center, Chicago.

One of the limitations of the study is that the vasculature of the control group had not been evaluated, although it is assumed that 3%-4% of the general population harbors an unruptured cerebral aneurysm. Another limitation is that the control group data were generated during 1994-1998, before the use of hormone replacement therapy decreased substantially in 2002 following the publication of the Women’s Health Initiative Study on breast cancer, Dr. Chen said.

He hopes these findings will guide future research not only on the role of estrogen in aneurysm development, but also the role of the estrogen receptor specific to cerebral vasculature. “Understanding more about the effects of estrogen at the receptor level may allow us to find therapies that target that receptor in order to provide some protection for women at risk of developing aneurysms or harboring unruptured aneurysms.”

Dr. Chen reported no relevant disclosures.

CARLSBAD, Calif. – Women with cerebral aneurysms were less likely to have used oral contraceptives or hormone replacement therapy in their lifetime than controls, according to the results of a retrospective case-control study of 60 women with aneurysms.

“These findings suggest that our case group may have had not only lower levels of estrogen, but also more severe physiologic fluctuations in their estrogen level as compared to population averages. To take this one step further, therapies that mitigate the effects of low estrogen level and fluctuations may decrease the risk for cerebral aneurysms,” Dr. Michael Chen said at the annual meeting of the Society of NeuroInterventional Surgery.

The study included 21 women with ruptured aneurysms and 39 with unruptured aneurysms who were under the care of a single physician during 2008-2010. Their median age was 52 years, with a range of 31-80 years. Dr. Chen and his associates conducted telephone interviews with the patients to obtain detailed medical, social, family and gynecologic histories, including information about lifetime use and duration of use of oral contraceptives and hormone replacement therapy, as well as menstrual and reproductive history.

For the control group, the investigators spoke with 4,682 random American women from a publicly available data set (Ann. Epidemiol. 2002;12:213-22) that was generated as part of a National Institutes of Health–funded study exploring the use of oral contraceptives and hormone replacement therapy in breast cancer.

For each case, seven control patients matched for age and educational levels were selected, giving 420 control patients. Measures such as median age, body mass index (BMI), age of menarche, nulliparity, and age of first pregnancy were comparable between the case and control patients.

Significantly fewer women with an aneurysm reported lifetime use of oral contraceptives than did controls (60% vs. 77.6%, P = .003) as well as use of hormone replacement therapy (23.7% vs. 44.8%, P = .002). The median age of menopause for women with aneurysms was more than 2 years earlier than for the control group (44.5 vs. 46.9 years, P = .53) and 50% of cases had menopause before age 45, compared with 34% of controls (P = .18). “The patient group also had a high rate of early hysterectomies,” noted Dr. Chen, an interventional vascular neurologist affiliated with Rush University Medical Center, Chicago.

One of the limitations of the study is that the vasculature of the control group had not been evaluated, although it is assumed that 3%-4% of the general population harbors an unruptured cerebral aneurysm. Another limitation is that the control group data were generated during 1994-1998, before the use of hormone replacement therapy decreased substantially in 2002 following the publication of the Women’s Health Initiative Study on breast cancer, Dr. Chen said.

He hopes these findings will guide future research not only on the role of estrogen in aneurysm development, but also the role of the estrogen receptor specific to cerebral vasculature. “Understanding more about the effects of estrogen at the receptor level may allow us to find therapies that target that receptor in order to provide some protection for women at risk of developing aneurysms or harboring unruptured aneurysms.”

Dr. Chen reported no relevant disclosures.

TORONTO – Even after having a stroke, people who maintain a healthy lifestyle can reduce the risk of death, and the more healthy lifestyle practices they follow, the greater the benefit, according to data from 388 stoke survivors.

Those who did not smoke and exercised regularly were less likely to die, and those who ate fruits and vegetables routinely were less likely to die from cardiovascular causes, Dr. Amytis Towfighi said at the annual meeting of the American Academy of Neurology. “The benefits of five simple healthy lifestyle factors had been shown in the general population, but had not been shown before for the stroke survivor population,” said Dr. Towfighi, of the University of Southern California, Los Angeles.

Dr. Towfighi analyzed data from the National Health and Nutrition Examination Survey (NHANES) From an initial sample of more than 33,000, 649 subjects were identified who had a prevalent stroke during 1988-1994 and were followed through 2000.

In the final analysis, 388 stroke survivors met all criteria, including information on such covariates as age, sex, race, and prior myocardial infarction. The sample was 80% white and 53% female, with a mean age of 67 years. Of the 388 stroke patients, 206 died by 2000, with 126 deaths attributed to cardiovascular causes. Of the stroke survivors, 75% said they did not smoke, and 23% used alcohol moderately (although most did not drink).

Of the five healthy lifestyle factors, abstaining from smoking (hazard ratio, 0.57; confidence interval, 0.34-0.98) and regular exercise (HR, 0.66; CI, 0.44-0.99) were associated with a lower all-cause mortality. Eating at least five servings of fruits and vegetables was associated with lower risk of cardiovascular death (HR, 0.30; CI, 0.09-1.04).

Compared with those who did not report any of the healthy practices, the HR for all cause-mortality was 0.07 (CI 0.01-0.51) for five practices, 0.04 (CI 0.01-0.19) for four practices, and 0.13 (CI 0.03-0.55) for three practices.

Dr. Towfighi said she had no relevant conflicts.

TORONTO – Even after having a stroke, people who maintain a healthy lifestyle can reduce the risk of death, and the more healthy lifestyle practices they follow, the greater the benefit, according to data from 388 stoke survivors.

Those who did not smoke and exercised regularly were less likely to die, and those who ate fruits and vegetables routinely were less likely to die from cardiovascular causes, Dr. Amytis Towfighi said at the annual meeting of the American Academy of Neurology. “The benefits of five simple healthy lifestyle factors had been shown in the general population, but had not been shown before for the stroke survivor population,” said Dr. Towfighi, of the University of Southern California, Los Angeles.

Dr. Towfighi analyzed data from the National Health and Nutrition Examination Survey (NHANES) From an initial sample of more than 33,000, 649 subjects were identified who had a prevalent stroke during 1988-1994 and were followed through 2000.

In the final analysis, 388 stroke survivors met all criteria, including information on such covariates as age, sex, race, and prior myocardial infarction. The sample was 80% white and 53% female, with a mean age of 67 years. Of the 388 stroke patients, 206 died by 2000, with 126 deaths attributed to cardiovascular causes. Of the stroke survivors, 75% said they did not smoke, and 23% used alcohol moderately (although most did not drink).

Of the five healthy lifestyle factors, abstaining from smoking (hazard ratio, 0.57; confidence interval, 0.34-0.98) and regular exercise (HR, 0.66; CI, 0.44-0.99) were associated with a lower all-cause mortality. Eating at least five servings of fruits and vegetables was associated with lower risk of cardiovascular death (HR, 0.30; CI, 0.09-1.04).

Compared with those who did not report any of the healthy practices, the HR for all cause-mortality was 0.07 (CI 0.01-0.51) for five practices, 0.04 (CI 0.01-0.19) for four practices, and 0.13 (CI 0.03-0.55) for three practices.

Dr. Towfighi said she had no relevant conflicts.

TORONTO – Even after having a stroke, people who maintain a healthy lifestyle can reduce the risk of death, and the more healthy lifestyle practices they follow, the greater the benefit, according to data from 388 stoke survivors.

Those who did not smoke and exercised regularly were less likely to die, and those who ate fruits and vegetables routinely were less likely to die from cardiovascular causes, Dr. Amytis Towfighi said at the annual meeting of the American Academy of Neurology. “The benefits of five simple healthy lifestyle factors had been shown in the general population, but had not been shown before for the stroke survivor population,” said Dr. Towfighi, of the University of Southern California, Los Angeles.

Dr. Towfighi analyzed data from the National Health and Nutrition Examination Survey (NHANES) From an initial sample of more than 33,000, 649 subjects were identified who had a prevalent stroke during 1988-1994 and were followed through 2000.

In the final analysis, 388 stroke survivors met all criteria, including information on such covariates as age, sex, race, and prior myocardial infarction. The sample was 80% white and 53% female, with a mean age of 67 years. Of the 388 stroke patients, 206 died by 2000, with 126 deaths attributed to cardiovascular causes. Of the stroke survivors, 75% said they did not smoke, and 23% used alcohol moderately (although most did not drink).

Of the five healthy lifestyle factors, abstaining from smoking (hazard ratio, 0.57; confidence interval, 0.34-0.98) and regular exercise (HR, 0.66; CI, 0.44-0.99) were associated with a lower all-cause mortality. Eating at least five servings of fruits and vegetables was associated with lower risk of cardiovascular death (HR, 0.30; CI, 0.09-1.04).

Compared with those who did not report any of the healthy practices, the HR for all cause-mortality was 0.07 (CI 0.01-0.51) for five practices, 0.04 (CI 0.01-0.19) for four practices, and 0.13 (CI 0.03-0.55) for three practices.

Dr. Towfighi said she had no relevant conflicts.

TORONTO — Even after having a stroke, people who maintain a healthy lifestyle can reduce the risk of death, and the more healthy lifestyle practices they follow, the greater the benefit, according to data from 388 stoke survivors.

Those who did not smoke and exercised regularly were less likely to die, and those who ate fruits and vegetables routinely were less likely to die from cardiovascular causes, Dr. Amytis Towfighi said at the annual meeting of the American Academy of Neurology.

“The benefits of five simple healthy lifestyle factors had been shown in the general population, but had not been shown before for the stroke survivor population,” said Dr. Towfighi, assistant professor of neurology at the University of Southern California, Los Angeles.

Dr. Towfighi analyzed cross-sectional and prospective data from the National Health and Nutrition Examination Survey (NHANES). From an initial sample of more than 33,000 people, 649 subjects were identified who had a prevalent stroke in the years 1988-1994 and were followed through 2000.I

In the final analysis, 388 stroke survivors met all criteria, including information on such covariates as age, sex, race, and prior myocardial infarction. The sample was 80% white and 53% female, with a mean age of 67 years. Of the 388 stroke patients, 206 died by 2000, with 126 deaths attributed to cardiovascular causes.

Of the stroke survivors, 75% self-reported that they did not smoke, 23% used alcohol moderately (although most did not drink), and 40% ate five or more servings of fruits and vegetables daily when surveyed at baseline. About one-third said that they exercised more than 12 times per month and 70% had a body-mass index in the 18.5 to 29.9-kg/m

Of the five healthy lifestyle factors, abstaining from smoking (hazard ratio, 0.57; confidence interval, 0.34-0.98) and regular exercise (HR, 0.66; CI, 0.44-0.99) were associated with a lower all-cause mortality rate.

Eating at least five servings of fruits and vegetables was associated with lower risk of cardiovascular death (HR, 0.30).

There appeared to be a dose/response relationship. Compared with those who did not report any of the healthy practices, the HR for all cause-mortality was 0.07 for five practices, 0.04 for four practices, and 0.13 for three practices.

Dr. Towfighi said that she had no relevant conflicts.

TORONTO — Even after having a stroke, people who maintain a healthy lifestyle can reduce the risk of death, and the more healthy lifestyle practices they follow, the greater the benefit, according to data from 388 stoke survivors.

Those who did not smoke and exercised regularly were less likely to die, and those who ate fruits and vegetables routinely were less likely to die from cardiovascular causes, Dr. Amytis Towfighi said at the annual meeting of the American Academy of Neurology.

“The benefits of five simple healthy lifestyle factors had been shown in the general population, but had not been shown before for the stroke survivor population,” said Dr. Towfighi, assistant professor of neurology at the University of Southern California, Los Angeles.

Dr. Towfighi analyzed cross-sectional and prospective data from the National Health and Nutrition Examination Survey (NHANES). From an initial sample of more than 33,000 people, 649 subjects were identified who had a prevalent stroke in the years 1988-1994 and were followed through 2000.I

In the final analysis, 388 stroke survivors met all criteria, including information on such covariates as age, sex, race, and prior myocardial infarction. The sample was 80% white and 53% female, with a mean age of 67 years. Of the 388 stroke patients, 206 died by 2000, with 126 deaths attributed to cardiovascular causes.

Of the stroke survivors, 75% self-reported that they did not smoke, 23% used alcohol moderately (although most did not drink), and 40% ate five or more servings of fruits and vegetables daily when surveyed at baseline. About one-third said that they exercised more than 12 times per month and 70% had a body-mass index in the 18.5 to 29.9-kg/m

Of the five healthy lifestyle factors, abstaining from smoking (hazard ratio, 0.57; confidence interval, 0.34-0.98) and regular exercise (HR, 0.66; CI, 0.44-0.99) were associated with a lower all-cause mortality rate.

Eating at least five servings of fruits and vegetables was associated with lower risk of cardiovascular death (HR, 0.30).

There appeared to be a dose/response relationship. Compared with those who did not report any of the healthy practices, the HR for all cause-mortality was 0.07 for five practices, 0.04 for four practices, and 0.13 for three practices.

Dr. Towfighi said that she had no relevant conflicts.

TORONTO — Even after having a stroke, people who maintain a healthy lifestyle can reduce the risk of death, and the more healthy lifestyle practices they follow, the greater the benefit, according to data from 388 stoke survivors.

Those who did not smoke and exercised regularly were less likely to die, and those who ate fruits and vegetables routinely were less likely to die from cardiovascular causes, Dr. Amytis Towfighi said at the annual meeting of the American Academy of Neurology.

“The benefits of five simple healthy lifestyle factors had been shown in the general population, but had not been shown before for the stroke survivor population,” said Dr. Towfighi, assistant professor of neurology at the University of Southern California, Los Angeles.

Dr. Towfighi analyzed cross-sectional and prospective data from the National Health and Nutrition Examination Survey (NHANES). From an initial sample of more than 33,000 people, 649 subjects were identified who had a prevalent stroke in the years 1988-1994 and were followed through 2000.I

In the final analysis, 388 stroke survivors met all criteria, including information on such covariates as age, sex, race, and prior myocardial infarction. The sample was 80% white and 53% female, with a mean age of 67 years. Of the 388 stroke patients, 206 died by 2000, with 126 deaths attributed to cardiovascular causes.

Of the stroke survivors, 75% self-reported that they did not smoke, 23% used alcohol moderately (although most did not drink), and 40% ate five or more servings of fruits and vegetables daily when surveyed at baseline. About one-third said that they exercised more than 12 times per month and 70% had a body-mass index in the 18.5 to 29.9-kg/m

Of the five healthy lifestyle factors, abstaining from smoking (hazard ratio, 0.57; confidence interval, 0.34-0.98) and regular exercise (HR, 0.66; CI, 0.44-0.99) were associated with a lower all-cause mortality rate.

Eating at least five servings of fruits and vegetables was associated with lower risk of cardiovascular death (HR, 0.30).

There appeared to be a dose/response relationship. Compared with those who did not report any of the healthy practices, the HR for all cause-mortality was 0.07 for five practices, 0.04 for four practices, and 0.13 for three practices.

Dr. Towfighi said that she had no relevant conflicts.

Major Finding: Men had significantly higher rates of stroke caused by cardioembolism, hemorrhage, or substance abuse, whereas women had significantly higher rates of stroke with a vasculopathic etiology.

Data Source: A prospective study of 363 stroke patients aged 18-49 years.

Disclosures: Dr. Nakagawa had no relevant disclosures.

TORONTO — The etiology of first-time strokes in young to middle-aged adults differed according to sex in a prospective study of patients seen at one center.

Men tended to have a higher risk of strokes caused by cardioembolism, intracerebral hemorrhage, or substance abuse, whereas women had more strokes related to a vasculopathic etiology, Dr. Emily M. Nakagawa reported at the annual meeting of the American Academy of Neurology.

“When you have a young stroke patient, a lot of physicians tend to think of the etiology to be atherosclerotic disease or a cardioembolic event. If you have a patient who is a young woman, you have to start thinking about other etiologies to appropriately treat and avoid future strokes. At the same time, young women who have already been diagnosed with a vasculopathy need to be educated on their vulnerability to strokes and the signs of stroke to get immediate care, and discuss with their primary care physician about using traditionally known stroke preventions such as use of aspirin,” said Dr. Nakagawa, a resident in neurology at the University of South Florida, Tampa.

Dr. Nakagawa's sample consisted of 202 women and 161 men with a mean age of 40 years (ranging from 18 to 49 years) who presented during a 4-year period to Tampa General Hospital. Patients underwent MR imaging, angiography, echocardiography, and stroke blood investigations. Strokes were stratified using expanded TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification and neurological deficit was assessed using the NIH Stroke Scale (NIHSS).

The women tended to present with a better clinical picture than men, making the diagnosis of stroke in women more difficult. The mean NIHSS was significantly lower among women (4.7) than men (6.0).

Compared with women, men had significantly higher rates of stroke caused by cardioembolism (26 of 42 vs. 16 of 42), intracerebral hemorrhage (63 of 106 vs. 43 of 106), or substance abuse (26 of 41 vs. 15 of 41).

Women were significantly more likely than men to have strokes associated with cerebral venous thrombosis, vasculitis, migraine, or miscellaneous vasculopathy.

Knowing that there are differences between the sexes in stroke etiology can help guide treatment decisions, Dr. Nakagawa said. Female patients can have strokes due to causes that “neurologists do not traditionally think of first for stroke.”

Major Finding: Men had significantly higher rates of stroke caused by cardioembolism, hemorrhage, or substance abuse, whereas women had significantly higher rates of stroke with a vasculopathic etiology.

Data Source: A prospective study of 363 stroke patients aged 18-49 years.

Disclosures: Dr. Nakagawa had no relevant disclosures.

TORONTO — The etiology of first-time strokes in young to middle-aged adults differed according to sex in a prospective study of patients seen at one center.

Men tended to have a higher risk of strokes caused by cardioembolism, intracerebral hemorrhage, or substance abuse, whereas women had more strokes related to a vasculopathic etiology, Dr. Emily M. Nakagawa reported at the annual meeting of the American Academy of Neurology.

“When you have a young stroke patient, a lot of physicians tend to think of the etiology to be atherosclerotic disease or a cardioembolic event. If you have a patient who is a young woman, you have to start thinking about other etiologies to appropriately treat and avoid future strokes. At the same time, young women who have already been diagnosed with a vasculopathy need to be educated on their vulnerability to strokes and the signs of stroke to get immediate care, and discuss with their primary care physician about using traditionally known stroke preventions such as use of aspirin,” said Dr. Nakagawa, a resident in neurology at the University of South Florida, Tampa.

Dr. Nakagawa's sample consisted of 202 women and 161 men with a mean age of 40 years (ranging from 18 to 49 years) who presented during a 4-year period to Tampa General Hospital. Patients underwent MR imaging, angiography, echocardiography, and stroke blood investigations. Strokes were stratified using expanded TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification and neurological deficit was assessed using the NIH Stroke Scale (NIHSS).

The women tended to present with a better clinical picture than men, making the diagnosis of stroke in women more difficult. The mean NIHSS was significantly lower among women (4.7) than men (6.0).

Compared with women, men had significantly higher rates of stroke caused by cardioembolism (26 of 42 vs. 16 of 42), intracerebral hemorrhage (63 of 106 vs. 43 of 106), or substance abuse (26 of 41 vs. 15 of 41).

Women were significantly more likely than men to have strokes associated with cerebral venous thrombosis, vasculitis, migraine, or miscellaneous vasculopathy.

Knowing that there are differences between the sexes in stroke etiology can help guide treatment decisions, Dr. Nakagawa said. Female patients can have strokes due to causes that “neurologists do not traditionally think of first for stroke.”

Major Finding: Men had significantly higher rates of stroke caused by cardioembolism, hemorrhage, or substance abuse, whereas women had significantly higher rates of stroke with a vasculopathic etiology.

Data Source: A prospective study of 363 stroke patients aged 18-49 years.

Disclosures: Dr. Nakagawa had no relevant disclosures.

TORONTO — The etiology of first-time strokes in young to middle-aged adults differed according to sex in a prospective study of patients seen at one center.

Men tended to have a higher risk of strokes caused by cardioembolism, intracerebral hemorrhage, or substance abuse, whereas women had more strokes related to a vasculopathic etiology, Dr. Emily M. Nakagawa reported at the annual meeting of the American Academy of Neurology.

“When you have a young stroke patient, a lot of physicians tend to think of the etiology to be atherosclerotic disease or a cardioembolic event. If you have a patient who is a young woman, you have to start thinking about other etiologies to appropriately treat and avoid future strokes. At the same time, young women who have already been diagnosed with a vasculopathy need to be educated on their vulnerability to strokes and the signs of stroke to get immediate care, and discuss with their primary care physician about using traditionally known stroke preventions such as use of aspirin,” said Dr. Nakagawa, a resident in neurology at the University of South Florida, Tampa.

Dr. Nakagawa's sample consisted of 202 women and 161 men with a mean age of 40 years (ranging from 18 to 49 years) who presented during a 4-year period to Tampa General Hospital. Patients underwent MR imaging, angiography, echocardiography, and stroke blood investigations. Strokes were stratified using expanded TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification and neurological deficit was assessed using the NIH Stroke Scale (NIHSS).

The women tended to present with a better clinical picture than men, making the diagnosis of stroke in women more difficult. The mean NIHSS was significantly lower among women (4.7) than men (6.0).

Compared with women, men had significantly higher rates of stroke caused by cardioembolism (26 of 42 vs. 16 of 42), intracerebral hemorrhage (63 of 106 vs. 43 of 106), or substance abuse (26 of 41 vs. 15 of 41).

Women were significantly more likely than men to have strokes associated with cerebral venous thrombosis, vasculitis, migraine, or miscellaneous vasculopathy.

Knowing that there are differences between the sexes in stroke etiology can help guide treatment decisions, Dr. Nakagawa said. Female patients can have strokes due to causes that “neurologists do not traditionally think of first for stroke.”

Major Finding: No serious cardiovascular adverse events or clinically meaningful changes in QT interval were recorded.

Data Source: The STAR trial, a 12-week randomized, placebo-controlled trial of 326 patients with pseudobulbar affect, followed by a 12-week open-label extension phase.

Disclosures: The study was supported by Avanir Pharmaceuticals. Dr. Pioro has received personal compensation for serving as a consultant and scientific advisory board member for Avanir. Dr. Kaye is the chief medical officer of Avanir.

TORONTO — The combination of dextromethorphan and quinidine to treat pseudobulbar affect does not appear to cause serious cardiovascular adverse events or clinically meaningful changes in QT interval, according to a 12-week, randomized, placebo-controlled trial.

The analysis was undertaken to address safety concerns expressed in October 2006 by the Food and Drug Administration in an approvable letter that the agency sent to Avanir Pharmaceuticals Inc., the company seeking to bring the combination medication (Zenvia) to market.

At a press conference at the annual meeting of the American Academy of Neurology, Dr. Erik P. Pioro, director of the section of ALS and Related Disorders at the Cleveland Clinic, explained that one of the FDA's concerns was the potential for quinidine to have a proarrhythmic effect, even though the dose used for pseudobulbar affect (PBA) is lower than that recommended to treat dysrhythmias. This might be particularly problematic for patients taking higher quinidine doses or those having pre-existing conditions such as torsades de pointes.

“We found no red flags at all that were clinically significant [and] no indication of cardiovascular problems,” Dr. Pioro said.

PBA refers to a syndrome of disinhibition of emotional expression. Patients with neurologic conditions such as multiple sclerosis, amyotrophic lateral sclerosis, and Parkinson's disease sometimes display uncontrollable episodes of laughing, crying, or other emotions that have no apparent cause. Patients who have PBA can have more than 30 or more episodes per week.

No drugs are currently approved for the treatment of PBA in the United States. Dr. Pioro said antidepressants are commonly used off-label, with variable efficacy and a high side-effect profile.

Previous work has shown that dextromethorphan, an N-methyl-D-aspartate-receptor antagonist and sigma-1-receptor agonist, in combination with quinidine, can reduce the frequency and severity of PBA episodes (Neurology 2004;63:1364–70; Ann. Neurol. 2006;59:780–7). Quinidine is used to increase the bioavailability of dextromethorphan.

In the STAR trial, the investigators randomized 326 patients to receive 30 mg of dextromethorphan plus 10 mg of quinidine (DMq-30), 20 mg of dextromethorphan plus 10 mg of quinidine (DMq-20), or placebo for 12 weeks. During the first week of the study, patients ingested a single capsule of study drug in the morning, but this increased to twice-daily dosing during weeks 2 through 12. Twelve-lead electrocardiograms were performed at baseline and on days 15, 29, 57, and 84.

Almost 87% of patients completed the trial. Approximately 60% of the patients had ALS, and 40% had multiple sclerosis. Effectiveness was assessed using the Center for Neurologic Study Lability Scale; a minimum score of 13 was needed to enroll in the trial.

Changes in QT interval were considered small and not clinically meaningful, with a mean change of 6.6 msec and 8.3 msec for the DMq-20 and DMq-30 groups, respectively.

Corrected mean changes in QT interval showed changes of less than 5 msec from baseline. No subjects had QT or corrected QT intervals of more than 500 msec at day 84, according to Dr. Randall Kaye, who presented the results at the meeting.

There were few cardiac or vascular adverse events, and none were considered serious. “QT prolonged” was reported in 2 subjects, including one in the placebo group. Neither event was assessed as serious or clinically meaningful.

Eight reports of cardiac adverse events were noted in the treated groups, including sinus bradycardia (two), palpitations (one), AV block first degree (two), tachycardia (one), sinus tachycardia (one), and atrial fibrillation (one).

Dr. Pioro also reported safety and tolerability results of a 12-week open-label extension of the STAR trial that enrolled 253 of the 283 patients who completed the double-blind trial; all of these patients received the DMq-30 combination.

During this open-label extension, no treatment-related or cardiovascular serious adverse events were reported. A total of 74% of patients reported one or more adverse events, with similar rates reported no matter which group they had been in during the controlled trial.

Major Finding: No serious cardiovascular adverse events or clinically meaningful changes in QT interval were recorded.

Data Source: The STAR trial, a 12-week randomized, placebo-controlled trial of 326 patients with pseudobulbar affect, followed by a 12-week open-label extension phase.

Disclosures: The study was supported by Avanir Pharmaceuticals. Dr. Pioro has received personal compensation for serving as a consultant and scientific advisory board member for Avanir. Dr. Kaye is the chief medical officer of Avanir.

TORONTO — The combination of dextromethorphan and quinidine to treat pseudobulbar affect does not appear to cause serious cardiovascular adverse events or clinically meaningful changes in QT interval, according to a 12-week, randomized, placebo-controlled trial.

The analysis was undertaken to address safety concerns expressed in October 2006 by the Food and Drug Administration in an approvable letter that the agency sent to Avanir Pharmaceuticals Inc., the company seeking to bring the combination medication (Zenvia) to market.

At a press conference at the annual meeting of the American Academy of Neurology, Dr. Erik P. Pioro, director of the section of ALS and Related Disorders at the Cleveland Clinic, explained that one of the FDA's concerns was the potential for quinidine to have a proarrhythmic effect, even though the dose used for pseudobulbar affect (PBA) is lower than that recommended to treat dysrhythmias. This might be particularly problematic for patients taking higher quinidine doses or those having pre-existing conditions such as torsades de pointes.

“We found no red flags at all that were clinically significant [and] no indication of cardiovascular problems,” Dr. Pioro said.

PBA refers to a syndrome of disinhibition of emotional expression. Patients with neurologic conditions such as multiple sclerosis, amyotrophic lateral sclerosis, and Parkinson's disease sometimes display uncontrollable episodes of laughing, crying, or other emotions that have no apparent cause. Patients who have PBA can have more than 30 or more episodes per week.

No drugs are currently approved for the treatment of PBA in the United States. Dr. Pioro said antidepressants are commonly used off-label, with variable efficacy and a high side-effect profile.

Previous work has shown that dextromethorphan, an N-methyl-D-aspartate-receptor antagonist and sigma-1-receptor agonist, in combination with quinidine, can reduce the frequency and severity of PBA episodes (Neurology 2004;63:1364–70; Ann. Neurol. 2006;59:780–7). Quinidine is used to increase the bioavailability of dextromethorphan.

In the STAR trial, the investigators randomized 326 patients to receive 30 mg of dextromethorphan plus 10 mg of quinidine (DMq-30), 20 mg of dextromethorphan plus 10 mg of quinidine (DMq-20), or placebo for 12 weeks. During the first week of the study, patients ingested a single capsule of study drug in the morning, but this increased to twice-daily dosing during weeks 2 through 12. Twelve-lead electrocardiograms were performed at baseline and on days 15, 29, 57, and 84.

Almost 87% of patients completed the trial. Approximately 60% of the patients had ALS, and 40% had multiple sclerosis. Effectiveness was assessed using the Center for Neurologic Study Lability Scale; a minimum score of 13 was needed to enroll in the trial.

Changes in QT interval were considered small and not clinically meaningful, with a mean change of 6.6 msec and 8.3 msec for the DMq-20 and DMq-30 groups, respectively.

Corrected mean changes in QT interval showed changes of less than 5 msec from baseline. No subjects had QT or corrected QT intervals of more than 500 msec at day 84, according to Dr. Randall Kaye, who presented the results at the meeting.

There were few cardiac or vascular adverse events, and none were considered serious. “QT prolonged” was reported in 2 subjects, including one in the placebo group. Neither event was assessed as serious or clinically meaningful.

Eight reports of cardiac adverse events were noted in the treated groups, including sinus bradycardia (two), palpitations (one), AV block first degree (two), tachycardia (one), sinus tachycardia (one), and atrial fibrillation (one).

Dr. Pioro also reported safety and tolerability results of a 12-week open-label extension of the STAR trial that enrolled 253 of the 283 patients who completed the double-blind trial; all of these patients received the DMq-30 combination.

During this open-label extension, no treatment-related or cardiovascular serious adverse events were reported. A total of 74% of patients reported one or more adverse events, with similar rates reported no matter which group they had been in during the controlled trial.

Major Finding: No serious cardiovascular adverse events or clinically meaningful changes in QT interval were recorded.

Data Source: The STAR trial, a 12-week randomized, placebo-controlled trial of 326 patients with pseudobulbar affect, followed by a 12-week open-label extension phase.

Disclosures: The study was supported by Avanir Pharmaceuticals. Dr. Pioro has received personal compensation for serving as a consultant and scientific advisory board member for Avanir. Dr. Kaye is the chief medical officer of Avanir.

TORONTO — The combination of dextromethorphan and quinidine to treat pseudobulbar affect does not appear to cause serious cardiovascular adverse events or clinically meaningful changes in QT interval, according to a 12-week, randomized, placebo-controlled trial.

The analysis was undertaken to address safety concerns expressed in October 2006 by the Food and Drug Administration in an approvable letter that the agency sent to Avanir Pharmaceuticals Inc., the company seeking to bring the combination medication (Zenvia) to market.

At a press conference at the annual meeting of the American Academy of Neurology, Dr. Erik P. Pioro, director of the section of ALS and Related Disorders at the Cleveland Clinic, explained that one of the FDA's concerns was the potential for quinidine to have a proarrhythmic effect, even though the dose used for pseudobulbar affect (PBA) is lower than that recommended to treat dysrhythmias. This might be particularly problematic for patients taking higher quinidine doses or those having pre-existing conditions such as torsades de pointes.

“We found no red flags at all that were clinically significant [and] no indication of cardiovascular problems,” Dr. Pioro said.

PBA refers to a syndrome of disinhibition of emotional expression. Patients with neurologic conditions such as multiple sclerosis, amyotrophic lateral sclerosis, and Parkinson's disease sometimes display uncontrollable episodes of laughing, crying, or other emotions that have no apparent cause. Patients who have PBA can have more than 30 or more episodes per week.

No drugs are currently approved for the treatment of PBA in the United States. Dr. Pioro said antidepressants are commonly used off-label, with variable efficacy and a high side-effect profile.

Previous work has shown that dextromethorphan, an N-methyl-D-aspartate-receptor antagonist and sigma-1-receptor agonist, in combination with quinidine, can reduce the frequency and severity of PBA episodes (Neurology 2004;63:1364–70; Ann. Neurol. 2006;59:780–7). Quinidine is used to increase the bioavailability of dextromethorphan.

In the STAR trial, the investigators randomized 326 patients to receive 30 mg of dextromethorphan plus 10 mg of quinidine (DMq-30), 20 mg of dextromethorphan plus 10 mg of quinidine (DMq-20), or placebo for 12 weeks. During the first week of the study, patients ingested a single capsule of study drug in the morning, but this increased to twice-daily dosing during weeks 2 through 12. Twelve-lead electrocardiograms were performed at baseline and on days 15, 29, 57, and 84.

Almost 87% of patients completed the trial. Approximately 60% of the patients had ALS, and 40% had multiple sclerosis. Effectiveness was assessed using the Center for Neurologic Study Lability Scale; a minimum score of 13 was needed to enroll in the trial.

Changes in QT interval were considered small and not clinically meaningful, with a mean change of 6.6 msec and 8.3 msec for the DMq-20 and DMq-30 groups, respectively.

Corrected mean changes in QT interval showed changes of less than 5 msec from baseline. No subjects had QT or corrected QT intervals of more than 500 msec at day 84, according to Dr. Randall Kaye, who presented the results at the meeting.

There were few cardiac or vascular adverse events, and none were considered serious. “QT prolonged” was reported in 2 subjects, including one in the placebo group. Neither event was assessed as serious or clinically meaningful.

Eight reports of cardiac adverse events were noted in the treated groups, including sinus bradycardia (two), palpitations (one), AV block first degree (two), tachycardia (one), sinus tachycardia (one), and atrial fibrillation (one).

Dr. Pioro also reported safety and tolerability results of a 12-week open-label extension of the STAR trial that enrolled 253 of the 283 patients who completed the double-blind trial; all of these patients received the DMq-30 combination.

During this open-label extension, no treatment-related or cardiovascular serious adverse events were reported. A total of 74% of patients reported one or more adverse events, with similar rates reported no matter which group they had been in during the controlled trial.

TORONTO — The National Multiple Sclerosis Society is assuming a leadership role in disseminating information and mobilizing research on the role of chronic cerebrospinal venous insufficiency in the etiology and treatment of multiple sclerosis. The move comes in response to mounting pressure from patients and the scientific community questioning the hypothesis.

The society and the American Academy of Neurology jointly organized a Web forum during the annual meeting of the AAN that was open to thousands of off-site patients, family members, researchers, and members of the press.

The forum featured two of the investigators whose research on chronic cerebrospinal venous insufficiency (CCSVI) has sparked so much interest. In addition, the society has implemented an expedited research program to see whether scientific results can be replicated and further avenues explored.

“I know the MS Society shares the public's sense of urgency in advancing any lead that may help us understand the cause, provide the cure, or change the course of MS,” said Dr. Aaron E. Miller, the society's chief medical officer. Dr. Miller, who is also professor of neurology and director of the MS Center at the Mount Sinai School of Medicine, New York, participated in the forum.

“The MS Society suggested holding a cosponsored educational Web forum on the CCSVI and MS … because of the extent of misinformation and general confusion we were observing both on the Internet and in the media. We also felt the timing to be apropos because of the number of experts who would be [at the AAN meeting],” Arney Rosenblat, the society's vice president of public affairs, said in an interview.

More than 5,000 people were preregistered for the forum, and more than 1,000 questions were submitted.

The speakers included Dr. Paolo Zamboni, director of the Vascular Diseases Center at the University of Ferrara, Italy, whose team was instrumental in hypothesizing a link between cerebrovascular insufficiency and MS.

In June last year, he and his colleagues described evidence of slowed and obstructed drainage in cerebrospinal veins in 100% of patients with MS, a condition that they called CCSVI (J. Neurol. Neurosurg. Psychiatry 2009;80:392–9). They also suggested that blood flow is detoured around obstructions and that reversed blood flow might initiate the inflammation and immune-mediated brain damage characteristic of MS.

The investigators had used advanced ultrasound techniques to evaluate blood outflow in 65 people with MS and in 235 controls who were either healthy or had other neurologic disorders.

Later last year, in December, the group reported on the safety and preliminary outcomes of surgical intervention using percutaneous transluminal angioplasty in 35 patients with relapsing-remitting, secondary progressive, and primary progressive multiple sclerosis (J. Vasc. Surg. 2009;50:1348–58).

Some positive effects were described—significant reduction of relapses and active lesions, improved function and quality of life, and less fatigue—although a high rate of restenosis was reported. The group issued a call for larger, controlled trials.

Dr. Robert Zivadinov, director of the Buffalo (N.Y.) Neuroimaging Analysis Center, was another featured speaker. He and his group are exploring the prevalence of venous obstruction in 1,700 children and adults with MS, healthy controls, autoimmune-vascular disorders, and other neurologic diseases using a combination of transcranial and extracranial venous Doppler methods.

They released their preliminary results earlier this year, and Dr. Zivadinov unveiled the results of phase I of the Combined Transcranial and Extracranial Venous Doppler Evaluation Study during the forum. In these first 500 patients, 62.5% of MS patients met CCSVI diagnostic criteria, compared with 25.5% of healthy controls and 45.8% of those with other neurologic diseases. Although there was an increased likelihood that MS patients would meet the criteria for CCSVI (odds ratio, 4.85; P less than 0.001), compared with healthy controls, CCSVI seemed to be present in a proportion of healthy controls as well—in contradiction to Dr. Zamboni's hypothesis.

By late 2009, patients and their families began asking for more information about CCSVI as a possible cause of MS, and endovascular stent treatment as a possible cure. At Stanford (Calif.) University, vascular specialist Dr. Michael D. Dake embarked on a program to insert stents into the internal jugular veins of MS patients based on Dr. Zamboni's reports—a program that was terminated in December because the procedure was deemed experimental.

Complications included the death of one of Dr. Dake's patients who had been on coumadin and a dislodged stent that required surgical removal in another patient.

With research reports published in reputable medical publications and calls from patients for more information, the MS Society decided to take an active role in evaluating “this interesting hypothesis that needed to be further explored: whether there is an association between CCSVI and MS,” said Patricia A. O'Looney, Ph.D., the vice president of biomedical research for the society.

She cited previous research programs in gender differences in MS, genetics, and myelin repair mechanisms, as examples of the society's role in encouraging research in “underexplored” areas.

On Dec. 16, 2009, the society invited researchers worldwide to submit applications for funding and proposals for further research on CCSVI in MS. The deadline for submissions was Feb. 9, and decisions are expected mid-June.

In an interview, Dr. O'Looney declined to specify how much money has been allocated by the society. She said that she expects more than one project to be funded and that the hope is that definitive information about the CCSVI-MS association would be available within 2 years.

“We felt that answering this question was critical before patients underwent interventional treatment, which carries its own risks,” Dr. O'Looney said.

Dr. Zivadinov (left), Dr. Miller (third from left), and Dr. Zamboni (standing) discuss CCSVI in a forum held at the AAN meeting.

Source Courtesy National MS Society

TORONTO — The National Multiple Sclerosis Society is assuming a leadership role in disseminating information and mobilizing research on the role of chronic cerebrospinal venous insufficiency in the etiology and treatment of multiple sclerosis. The move comes in response to mounting pressure from patients and the scientific community questioning the hypothesis.

The society and the American Academy of Neurology jointly organized a Web forum during the annual meeting of the AAN that was open to thousands of off-site patients, family members, researchers, and members of the press.

The forum featured two of the investigators whose research on chronic cerebrospinal venous insufficiency (CCSVI) has sparked so much interest. In addition, the society has implemented an expedited research program to see whether scientific results can be replicated and further avenues explored.

“I know the MS Society shares the public's sense of urgency in advancing any lead that may help us understand the cause, provide the cure, or change the course of MS,” said Dr. Aaron E. Miller, the society's chief medical officer. Dr. Miller, who is also professor of neurology and director of the MS Center at the Mount Sinai School of Medicine, New York, participated in the forum.

“The MS Society suggested holding a cosponsored educational Web forum on the CCSVI and MS … because of the extent of misinformation and general confusion we were observing both on the Internet and in the media. We also felt the timing to be apropos because of the number of experts who would be [at the AAN meeting],” Arney Rosenblat, the society's vice president of public affairs, said in an interview.

More than 5,000 people were preregistered for the forum, and more than 1,000 questions were submitted.

The speakers included Dr. Paolo Zamboni, director of the Vascular Diseases Center at the University of Ferrara, Italy, whose team was instrumental in hypothesizing a link between cerebrovascular insufficiency and MS.

In June last year, he and his colleagues described evidence of slowed and obstructed drainage in cerebrospinal veins in 100% of patients with MS, a condition that they called CCSVI (J. Neurol. Neurosurg. Psychiatry 2009;80:392–9). They also suggested that blood flow is detoured around obstructions and that reversed blood flow might initiate the inflammation and immune-mediated brain damage characteristic of MS.

The investigators had used advanced ultrasound techniques to evaluate blood outflow in 65 people with MS and in 235 controls who were either healthy or had other neurologic disorders.

Later last year, in December, the group reported on the safety and preliminary outcomes of surgical intervention using percutaneous transluminal angioplasty in 35 patients with relapsing-remitting, secondary progressive, and primary progressive multiple sclerosis (J. Vasc. Surg. 2009;50:1348–58).

Some positive effects were described—significant reduction of relapses and active lesions, improved function and quality of life, and less fatigue—although a high rate of restenosis was reported. The group issued a call for larger, controlled trials.

Dr. Robert Zivadinov, director of the Buffalo (N.Y.) Neuroimaging Analysis Center, was another featured speaker. He and his group are exploring the prevalence of venous obstruction in 1,700 children and adults with MS, healthy controls, autoimmune-vascular disorders, and other neurologic diseases using a combination of transcranial and extracranial venous Doppler methods.

They released their preliminary results earlier this year, and Dr. Zivadinov unveiled the results of phase I of the Combined Transcranial and Extracranial Venous Doppler Evaluation Study during the forum. In these first 500 patients, 62.5% of MS patients met CCSVI diagnostic criteria, compared with 25.5% of healthy controls and 45.8% of those with other neurologic diseases. Although there was an increased likelihood that MS patients would meet the criteria for CCSVI (odds ratio, 4.85; P less than 0.001), compared with healthy controls, CCSVI seemed to be present in a proportion of healthy controls as well—in contradiction to Dr. Zamboni's hypothesis.

By late 2009, patients and their families began asking for more information about CCSVI as a possible cause of MS, and endovascular stent treatment as a possible cure. At Stanford (Calif.) University, vascular specialist Dr. Michael D. Dake embarked on a program to insert stents into the internal jugular veins of MS patients based on Dr. Zamboni's reports—a program that was terminated in December because the procedure was deemed experimental.

Complications included the death of one of Dr. Dake's patients who had been on coumadin and a dislodged stent that required surgical removal in another patient.

With research reports published in reputable medical publications and calls from patients for more information, the MS Society decided to take an active role in evaluating “this interesting hypothesis that needed to be further explored: whether there is an association between CCSVI and MS,” said Patricia A. O'Looney, Ph.D., the vice president of biomedical research for the society.

She cited previous research programs in gender differences in MS, genetics, and myelin repair mechanisms, as examples of the society's role in encouraging research in “underexplored” areas.

On Dec. 16, 2009, the society invited researchers worldwide to submit applications for funding and proposals for further research on CCSVI in MS. The deadline for submissions was Feb. 9, and decisions are expected mid-June.

In an interview, Dr. O'Looney declined to specify how much money has been allocated by the society. She said that she expects more than one project to be funded and that the hope is that definitive information about the CCSVI-MS association would be available within 2 years.

“We felt that answering this question was critical before patients underwent interventional treatment, which carries its own risks,” Dr. O'Looney said.

Dr. Zivadinov (left), Dr. Miller (third from left), and Dr. Zamboni (standing) discuss CCSVI in a forum held at the AAN meeting.

Source Courtesy National MS Society

TORONTO — The National Multiple Sclerosis Society is assuming a leadership role in disseminating information and mobilizing research on the role of chronic cerebrospinal venous insufficiency in the etiology and treatment of multiple sclerosis. The move comes in response to mounting pressure from patients and the scientific community questioning the hypothesis.

The society and the American Academy of Neurology jointly organized a Web forum during the annual meeting of the AAN that was open to thousands of off-site patients, family members, researchers, and members of the press.

The forum featured two of the investigators whose research on chronic cerebrospinal venous insufficiency (CCSVI) has sparked so much interest. In addition, the society has implemented an expedited research program to see whether scientific results can be replicated and further avenues explored.

“I know the MS Society shares the public's sense of urgency in advancing any lead that may help us understand the cause, provide the cure, or change the course of MS,” said Dr. Aaron E. Miller, the society's chief medical officer. Dr. Miller, who is also professor of neurology and director of the MS Center at the Mount Sinai School of Medicine, New York, participated in the forum.

“The MS Society suggested holding a cosponsored educational Web forum on the CCSVI and MS … because of the extent of misinformation and general confusion we were observing both on the Internet and in the media. We also felt the timing to be apropos because of the number of experts who would be [at the AAN meeting],” Arney Rosenblat, the society's vice president of public affairs, said in an interview.

More than 5,000 people were preregistered for the forum, and more than 1,000 questions were submitted.

The speakers included Dr. Paolo Zamboni, director of the Vascular Diseases Center at the University of Ferrara, Italy, whose team was instrumental in hypothesizing a link between cerebrovascular insufficiency and MS.

In June last year, he and his colleagues described evidence of slowed and obstructed drainage in cerebrospinal veins in 100% of patients with MS, a condition that they called CCSVI (J. Neurol. Neurosurg. Psychiatry 2009;80:392–9). They also suggested that blood flow is detoured around obstructions and that reversed blood flow might initiate the inflammation and immune-mediated brain damage characteristic of MS.

The investigators had used advanced ultrasound techniques to evaluate blood outflow in 65 people with MS and in 235 controls who were either healthy or had other neurologic disorders.

Later last year, in December, the group reported on the safety and preliminary outcomes of surgical intervention using percutaneous transluminal angioplasty in 35 patients with relapsing-remitting, secondary progressive, and primary progressive multiple sclerosis (J. Vasc. Surg. 2009;50:1348–58).

Some positive effects were described—significant reduction of relapses and active lesions, improved function and quality of life, and less fatigue—although a high rate of restenosis was reported. The group issued a call for larger, controlled trials.

Dr. Robert Zivadinov, director of the Buffalo (N.Y.) Neuroimaging Analysis Center, was another featured speaker. He and his group are exploring the prevalence of venous obstruction in 1,700 children and adults with MS, healthy controls, autoimmune-vascular disorders, and other neurologic diseases using a combination of transcranial and extracranial venous Doppler methods.

They released their preliminary results earlier this year, and Dr. Zivadinov unveiled the results of phase I of the Combined Transcranial and Extracranial Venous Doppler Evaluation Study during the forum. In these first 500 patients, 62.5% of MS patients met CCSVI diagnostic criteria, compared with 25.5% of healthy controls and 45.8% of those with other neurologic diseases. Although there was an increased likelihood that MS patients would meet the criteria for CCSVI (odds ratio, 4.85; P less than 0.001), compared with healthy controls, CCSVI seemed to be present in a proportion of healthy controls as well—in contradiction to Dr. Zamboni's hypothesis.

By late 2009, patients and their families began asking for more information about CCSVI as a possible cause of MS, and endovascular stent treatment as a possible cure. At Stanford (Calif.) University, vascular specialist Dr. Michael D. Dake embarked on a program to insert stents into the internal jugular veins of MS patients based on Dr. Zamboni's reports—a program that was terminated in December because the procedure was deemed experimental.

Complications included the death of one of Dr. Dake's patients who had been on coumadin and a dislodged stent that required surgical removal in another patient.

With research reports published in reputable medical publications and calls from patients for more information, the MS Society decided to take an active role in evaluating “this interesting hypothesis that needed to be further explored: whether there is an association between CCSVI and MS,” said Patricia A. O'Looney, Ph.D., the vice president of biomedical research for the society.

She cited previous research programs in gender differences in MS, genetics, and myelin repair mechanisms, as examples of the society's role in encouraging research in “underexplored” areas.

On Dec. 16, 2009, the society invited researchers worldwide to submit applications for funding and proposals for further research on CCSVI in MS. The deadline for submissions was Feb. 9, and decisions are expected mid-June.

In an interview, Dr. O'Looney declined to specify how much money has been allocated by the society. She said that she expects more than one project to be funded and that the hope is that definitive information about the CCSVI-MS association would be available within 2 years.

“We felt that answering this question was critical before patients underwent interventional treatment, which carries its own risks,” Dr. O'Looney said.

Dr. Zivadinov (left), Dr. Miller (third from left), and Dr. Zamboni (standing) discuss CCSVI in a forum held at the AAN meeting.

Source Courtesy National MS Society

TORONTO — People who act out their dreams as a result of having REM Sleep Behavior Disorder have an increased risk of developing mild cognitive impairment or parkinsonism within 3 years of follow-up, according to researchers affiliated with the Mayo Clinic Study of Aging.

Evidence also suggests that knowledge of a REM sleep behavior disorder (RBD) diagnosis might enhance the accuracy of diagnosing associated dementia, in addition to predicting future cognitive or motor impairment.

“We already knew from studies of clinic-based samples that between 45% and 85% of patients with RBD develop one of the synucleinopathies [Parkinson's disease, Parkinson's disease with dementia, dementia with Lewy bodies (DLB), or multiple system atrophy],” said Dr. Brendon P. Boot, a fellow at the Mayo Clinic in Rochester, Minn. “We were interested to know what the risk is for the elderly living in the community.”

The synucleinopathies are a group of neurodegenerative disorders characterized by aggregation of alpha-synuclein, a protein normally found in neuronal synapses.

Diagnosing RBD requires polysomnographic testing. However, the researchers used the Mayo Sleep Questionnaire (MSQ) to screen for RBD by asking the subject's bed partner: Has your spouse ever “acted out his or her dreams” while sleeping? This includes punching or flailing arms in the air or shouting or screaming.

In one of the Mayo Clinic studies presented at the annual meeting of the American Academy of Neurology, Dr. Boot reported that the MSQ has a sensitivity of 100% and a specificity of 95% for the diagnosis of RBD, based on testing of 96 cognitively normal, 29 mildly cognitively impaired, and 3 mildly demented community-dwelling elderly individuals from Olmsted County, Minn.

Dr. Boot and his colleagues then administered the MSQ in another study of 543 cognitively normal individuals between 70 and 89 years old and found that 44 had probable RBD. After a median follow-up of 33 months, 1 of these 44 patients developed Parkinson's disease and 13 developed mild cognitive impairment (MCI).

Those with MCI are at increased risk of developing dementia, and so RBD plus MCI may represent an early sign of a synucleinopathy. After adjustment for age, sex, education, and medical comorbidity, patients with probable RBD had 2.5 times greater risk of developing MCI or a synucleinopathy than did those without RBD.

In a related study, these investigators found that older, cognitively normal people with probable RBD had significantly worse olfaction than those without probable RBD, using the University of Pennsylvania Brief Smell Identification Test.

Hyposmia frequently precedes other symptoms of the synucleinopathies, Dr. Boot said.

In another study, Tanis J. Ferman, Ph.D., from the Mayo Clinic in Jacksonville, Fla., explored the diagnostic value of RBD in 82 patients with DLB and 64 patients with Alzheimer's disease.

According to the 2005 Consensus Criteria, diagnosis of DLB requires dementia plus one or more core clinical features fluctuating alertness and cognition, visual hallucinations, and parkinsonism. The criteria were modified in 2005 to include RBD as a suggestive feature, where the presence of RBD plus one core feature yields a diagnosis of probable DLB (Neurology 2005;65:1863–72).

In autopsy examinations of patients with dementia, the presence of RBD was associated with nearly sixfold higher odds of having DLB rather than Alzheimer's disease.

RBD appears to be a useful early clinical indicator of DLB, Dr. Ferman said.

Dr. Boot and Dr. Ferman said they had no relevant disclosures.

TORONTO — People who act out their dreams as a result of having REM Sleep Behavior Disorder have an increased risk of developing mild cognitive impairment or parkinsonism within 3 years of follow-up, according to researchers affiliated with the Mayo Clinic Study of Aging.

Evidence also suggests that knowledge of a REM sleep behavior disorder (RBD) diagnosis might enhance the accuracy of diagnosing associated dementia, in addition to predicting future cognitive or motor impairment.

“We already knew from studies of clinic-based samples that between 45% and 85% of patients with RBD develop one of the synucleinopathies [Parkinson's disease, Parkinson's disease with dementia, dementia with Lewy bodies (DLB), or multiple system atrophy],” said Dr. Brendon P. Boot, a fellow at the Mayo Clinic in Rochester, Minn. “We were interested to know what the risk is for the elderly living in the community.”

The synucleinopathies are a group of neurodegenerative disorders characterized by aggregation of alpha-synuclein, a protein normally found in neuronal synapses.

Diagnosing RBD requires polysomnographic testing. However, the researchers used the Mayo Sleep Questionnaire (MSQ) to screen for RBD by asking the subject's bed partner: Has your spouse ever “acted out his or her dreams” while sleeping? This includes punching or flailing arms in the air or shouting or screaming.

In one of the Mayo Clinic studies presented at the annual meeting of the American Academy of Neurology, Dr. Boot reported that the MSQ has a sensitivity of 100% and a specificity of 95% for the diagnosis of RBD, based on testing of 96 cognitively normal, 29 mildly cognitively impaired, and 3 mildly demented community-dwelling elderly individuals from Olmsted County, Minn.

Dr. Boot and his colleagues then administered the MSQ in another study of 543 cognitively normal individuals between 70 and 89 years old and found that 44 had probable RBD. After a median follow-up of 33 months, 1 of these 44 patients developed Parkinson's disease and 13 developed mild cognitive impairment (MCI).

Those with MCI are at increased risk of developing dementia, and so RBD plus MCI may represent an early sign of a synucleinopathy. After adjustment for age, sex, education, and medical comorbidity, patients with probable RBD had 2.5 times greater risk of developing MCI or a synucleinopathy than did those without RBD.

In a related study, these investigators found that older, cognitively normal people with probable RBD had significantly worse olfaction than those without probable RBD, using the University of Pennsylvania Brief Smell Identification Test.

Hyposmia frequently precedes other symptoms of the synucleinopathies, Dr. Boot said.

In another study, Tanis J. Ferman, Ph.D., from the Mayo Clinic in Jacksonville, Fla., explored the diagnostic value of RBD in 82 patients with DLB and 64 patients with Alzheimer's disease.

According to the 2005 Consensus Criteria, diagnosis of DLB requires dementia plus one or more core clinical features fluctuating alertness and cognition, visual hallucinations, and parkinsonism. The criteria were modified in 2005 to include RBD as a suggestive feature, where the presence of RBD plus one core feature yields a diagnosis of probable DLB (Neurology 2005;65:1863–72).

In autopsy examinations of patients with dementia, the presence of RBD was associated with nearly sixfold higher odds of having DLB rather than Alzheimer's disease.

RBD appears to be a useful early clinical indicator of DLB, Dr. Ferman said.

Dr. Boot and Dr. Ferman said they had no relevant disclosures.

TORONTO — People who act out their dreams as a result of having REM Sleep Behavior Disorder have an increased risk of developing mild cognitive impairment or parkinsonism within 3 years of follow-up, according to researchers affiliated with the Mayo Clinic Study of Aging.

Evidence also suggests that knowledge of a REM sleep behavior disorder (RBD) diagnosis might enhance the accuracy of diagnosing associated dementia, in addition to predicting future cognitive or motor impairment.

“We already knew from studies of clinic-based samples that between 45% and 85% of patients with RBD develop one of the synucleinopathies [Parkinson's disease, Parkinson's disease with dementia, dementia with Lewy bodies (DLB), or multiple system atrophy],” said Dr. Brendon P. Boot, a fellow at the Mayo Clinic in Rochester, Minn. “We were interested to know what the risk is for the elderly living in the community.”

The synucleinopathies are a group of neurodegenerative disorders characterized by aggregation of alpha-synuclein, a protein normally found in neuronal synapses.

Diagnosing RBD requires polysomnographic testing. However, the researchers used the Mayo Sleep Questionnaire (MSQ) to screen for RBD by asking the subject's bed partner: Has your spouse ever “acted out his or her dreams” while sleeping? This includes punching or flailing arms in the air or shouting or screaming.

In one of the Mayo Clinic studies presented at the annual meeting of the American Academy of Neurology, Dr. Boot reported that the MSQ has a sensitivity of 100% and a specificity of 95% for the diagnosis of RBD, based on testing of 96 cognitively normal, 29 mildly cognitively impaired, and 3 mildly demented community-dwelling elderly individuals from Olmsted County, Minn.

Dr. Boot and his colleagues then administered the MSQ in another study of 543 cognitively normal individuals between 70 and 89 years old and found that 44 had probable RBD. After a median follow-up of 33 months, 1 of these 44 patients developed Parkinson's disease and 13 developed mild cognitive impairment (MCI).

Those with MCI are at increased risk of developing dementia, and so RBD plus MCI may represent an early sign of a synucleinopathy. After adjustment for age, sex, education, and medical comorbidity, patients with probable RBD had 2.5 times greater risk of developing MCI or a synucleinopathy than did those without RBD.

In a related study, these investigators found that older, cognitively normal people with probable RBD had significantly worse olfaction than those without probable RBD, using the University of Pennsylvania Brief Smell Identification Test.

Hyposmia frequently precedes other symptoms of the synucleinopathies, Dr. Boot said.

In another study, Tanis J. Ferman, Ph.D., from the Mayo Clinic in Jacksonville, Fla., explored the diagnostic value of RBD in 82 patients with DLB and 64 patients with Alzheimer's disease.

According to the 2005 Consensus Criteria, diagnosis of DLB requires dementia plus one or more core clinical features fluctuating alertness and cognition, visual hallucinations, and parkinsonism. The criteria were modified in 2005 to include RBD as a suggestive feature, where the presence of RBD plus one core feature yields a diagnosis of probable DLB (Neurology 2005;65:1863–72).

In autopsy examinations of patients with dementia, the presence of RBD was associated with nearly sixfold higher odds of having DLB rather than Alzheimer's disease.

RBD appears to be a useful early clinical indicator of DLB, Dr. Ferman said.

Dr. Boot and Dr. Ferman said they had no relevant disclosures.

NEW YORK — New evidence that children with the systemic form of juvenile idiopathic arthritis respond better to treatment with anakinra than do those with other types of arthritis lends credence to the hypothesis that a different pathway underlies systemic disease, according to Dr. Norman T. Ilowite.

In an open-label study, the response rate was 73% (11 of 15) for children with systemic juvenile idiopathic arthritis (JIA), compared with 67% (6 of 9) for children with pauciarticular and 52% (29 of 56) for children with polyarticular JIA.

The overall response rate was 58% (46 of 80), according to Dr. Ilowite, who reported his findings at a rheumatology meeting sponsored by New York University.

“These observations are in contradistinction to those seen in most studies of [tumor necrosis factor] therapies in JIA, where those with systemic disease didn't do as well as those with polyarticular or oligoarticular disease,” said Dr. Ilowite, chief of pediatric rheumatology at Children's Hospital at Montefiore Medical Center and professor of pediatrics at the Albert Einstein College of Medicine, both in New York.

Anakinra is similar to a naturally occurring interleukin-1 (IL-1) receptor antagonist that has been approved for the management of signs and symptoms of rheumatoid arthritis in adults. It has not received approval for use in children with arthritis.

It has been proposed that inflammation in systemic JIA is mediated by IL-1, and thus that the inhibition of IL-1's proinflammatory effects would be an attractive therapeutic strategy.

Systemic JIA appears to be similar to other autoinflammatory syndromes in which IL-1 inhibition has been used successfully as therapy, including neonatal-onset multisystem inflammatory disease (NOMID) and cryopyrin-associated periodic syndromes (CAPS), said Dr. Ilowite.

Although the number of patients enrolled was small, Dr. Ilowite also presented data suggesting that anakinra was safe and reduced the number of disease flares across all subtypes of JIA, compared with placebo (Clin. Rheumatol. 2009;28:129–37).

Systemic JIA affects about 10% of children who have JIA, said Dr. Ilowite. It is the only subtype that causes fever, and arthritis usually ensues within 6 months of fever onset. It begins with mostly extra-articular manifestations, and is the only subtype with no strong HLA, sex, or age predilections.

The course is highly variable, with about 40% following a uniphasic course that fades within about 2 years, about 55% following a persistent course that progresses rapidly with serious systemic manifestations, and about 5% having intermittent exacerbations and remissions. Extra-articular manifestations include daily fever with two spikes a day, hepatosplenomegaly, lymphadenopathy, and rash.

Macrophage activation syndrome, a potentially fatal complication, occurs in about 7% of children with systemic JIA, according to Dr. Ilowite.

Other studies also suggest a preferential importance of IL-1 pathway activation in systemic JIA.

Anakinra was effective in a retrospective study of 33 patients with systemic JIA (J. Clin. Rheumatol. 2009;15:161–4). Furthermore, a characteristic IL-1 signature was reversed among systemic JIA patients who were treated with anakinra (J. Exp. Med. 2005;201:1479–86).

Disclosures: Dr. Ilowite had nothing to disclose. His study is reporting on unapproved indications for anakinra.

NEW YORK — New evidence that children with the systemic form of juvenile idiopathic arthritis respond better to treatment with anakinra than do those with other types of arthritis lends credence to the hypothesis that a different pathway underlies systemic disease, according to Dr. Norman T. Ilowite.

In an open-label study, the response rate was 73% (11 of 15) for children with systemic juvenile idiopathic arthritis (JIA), compared with 67% (6 of 9) for children with pauciarticular and 52% (29 of 56) for children with polyarticular JIA.

The overall response rate was 58% (46 of 80), according to Dr. Ilowite, who reported his findings at a rheumatology meeting sponsored by New York University.

“These observations are in contradistinction to those seen in most studies of [tumor necrosis factor] therapies in JIA, where those with systemic disease didn't do as well as those with polyarticular or oligoarticular disease,” said Dr. Ilowite, chief of pediatric rheumatology at Children's Hospital at Montefiore Medical Center and professor of pediatrics at the Albert Einstein College of Medicine, both in New York.

Anakinra is similar to a naturally occurring interleukin-1 (IL-1) receptor antagonist that has been approved for the management of signs and symptoms of rheumatoid arthritis in adults. It has not received approval for use in children with arthritis.

It has been proposed that inflammation in systemic JIA is mediated by IL-1, and thus that the inhibition of IL-1's proinflammatory effects would be an attractive therapeutic strategy.

Systemic JIA appears to be similar to other autoinflammatory syndromes in which IL-1 inhibition has been used successfully as therapy, including neonatal-onset multisystem inflammatory disease (NOMID) and cryopyrin-associated periodic syndromes (CAPS), said Dr. Ilowite.

Although the number of patients enrolled was small, Dr. Ilowite also presented data suggesting that anakinra was safe and reduced the number of disease flares across all subtypes of JIA, compared with placebo (Clin. Rheumatol. 2009;28:129–37).

Systemic JIA affects about 10% of children who have JIA, said Dr. Ilowite. It is the only subtype that causes fever, and arthritis usually ensues within 6 months of fever onset. It begins with mostly extra-articular manifestations, and is the only subtype with no strong HLA, sex, or age predilections.

The course is highly variable, with about 40% following a uniphasic course that fades within about 2 years, about 55% following a persistent course that progresses rapidly with serious systemic manifestations, and about 5% having intermittent exacerbations and remissions. Extra-articular manifestations include daily fever with two spikes a day, hepatosplenomegaly, lymphadenopathy, and rash.

Macrophage activation syndrome, a potentially fatal complication, occurs in about 7% of children with systemic JIA, according to Dr. Ilowite.

Other studies also suggest a preferential importance of IL-1 pathway activation in systemic JIA.

Anakinra was effective in a retrospective study of 33 patients with systemic JIA (J. Clin. Rheumatol. 2009;15:161–4). Furthermore, a characteristic IL-1 signature was reversed among systemic JIA patients who were treated with anakinra (J. Exp. Med. 2005;201:1479–86).

Disclosures: Dr. Ilowite had nothing to disclose. His study is reporting on unapproved indications for anakinra.

NEW YORK — New evidence that children with the systemic form of juvenile idiopathic arthritis respond better to treatment with anakinra than do those with other types of arthritis lends credence to the hypothesis that a different pathway underlies systemic disease, according to Dr. Norman T. Ilowite.

In an open-label study, the response rate was 73% (11 of 15) for children with systemic juvenile idiopathic arthritis (JIA), compared with 67% (6 of 9) for children with pauciarticular and 52% (29 of 56) for children with polyarticular JIA.

The overall response rate was 58% (46 of 80), according to Dr. Ilowite, who reported his findings at a rheumatology meeting sponsored by New York University.

“These observations are in contradistinction to those seen in most studies of [tumor necrosis factor] therapies in JIA, where those with systemic disease didn't do as well as those with polyarticular or oligoarticular disease,” said Dr. Ilowite, chief of pediatric rheumatology at Children's Hospital at Montefiore Medical Center and professor of pediatrics at the Albert Einstein College of Medicine, both in New York.

Anakinra is similar to a naturally occurring interleukin-1 (IL-1) receptor antagonist that has been approved for the management of signs and symptoms of rheumatoid arthritis in adults. It has not received approval for use in children with arthritis.

It has been proposed that inflammation in systemic JIA is mediated by IL-1, and thus that the inhibition of IL-1's proinflammatory effects would be an attractive therapeutic strategy.

Systemic JIA appears to be similar to other autoinflammatory syndromes in which IL-1 inhibition has been used successfully as therapy, including neonatal-onset multisystem inflammatory disease (NOMID) and cryopyrin-associated periodic syndromes (CAPS), said Dr. Ilowite.

Although the number of patients enrolled was small, Dr. Ilowite also presented data suggesting that anakinra was safe and reduced the number of disease flares across all subtypes of JIA, compared with placebo (Clin. Rheumatol. 2009;28:129–37).

Systemic JIA affects about 10% of children who have JIA, said Dr. Ilowite. It is the only subtype that causes fever, and arthritis usually ensues within 6 months of fever onset. It begins with mostly extra-articular manifestations, and is the only subtype with no strong HLA, sex, or age predilections.

The course is highly variable, with about 40% following a uniphasic course that fades within about 2 years, about 55% following a persistent course that progresses rapidly with serious systemic manifestations, and about 5% having intermittent exacerbations and remissions. Extra-articular manifestations include daily fever with two spikes a day, hepatosplenomegaly, lymphadenopathy, and rash.

Macrophage activation syndrome, a potentially fatal complication, occurs in about 7% of children with systemic JIA, according to Dr. Ilowite.

Other studies also suggest a preferential importance of IL-1 pathway activation in systemic JIA.

Anakinra was effective in a retrospective study of 33 patients with systemic JIA (J. Clin. Rheumatol. 2009;15:161–4). Furthermore, a characteristic IL-1 signature was reversed among systemic JIA patients who were treated with anakinra (J. Exp. Med. 2005;201:1479–86).

Disclosures: Dr. Ilowite had nothing to disclose. His study is reporting on unapproved indications for anakinra.

NEW YORK — Almost half of children with “growing pains” have not outgrown them 5 years later.

Those children who continued to have growing pains had significantly lower pain thresholds than did controls or patients whose pains had resolved, said Dr. Lisa F. Imundo, referring to recently published data by other investigators (J. Pediatr. 2010 [doi:10.1016/j.jpeds.2009.11.078

Chronic and idiopathic pain complaints are responsible for 7% of referrals to pediatric rheumatology centers, said Dr. Imundo, director of pediatric rheumatology at the Morgan Stanley Children's Hospital of New York–Presbyterian. Idiopathic pain syndromes in children include growing pains, benign hypermobility, reflex sympathetic dystrophy, fibromyalgia syndrome, chronic fatigue, chronic Lyme disease, and Munchausen and conversion disorders.

Growing pains are generally considered to be a temporary, benign condition that affects children aged 2-6 years. Affected children may wake up crying from a deep sleep, rubbing one or both legs. Episodes tend to occur only at night, when children may be awakened for several nights in a row, followed by days or weeks of uninterrupted sleep, explained Dr. Imundo.

To see what actually happens to children with growing pains as they age, investigators examined 35 of the 44 patients in the original cohort. At the time of the reevaluation, the mean age of the children was 13.4 years, and 51% (18 of 35) said they no longer had pain.

In all, 17 patients (49%) reported persistent growing pains. Of these, 14 patients currently had fewer pain episodes, compared with the time of their first diagnosis, whereas 3 patients said the pains were more frequent. Most (94%) of the persistent-pain patients had pain in the lower extremities, and about one-quarter had pain in the upper extremities. Pain was symmetric for 88% of this group. Nine children used analgesics regularly to relieve pain. None reported missing school because of pain.

One of the study's objectives was to determine whether children with growing pains develop other pain syndromes in adolescence. Of the 35 in the original growing-pain cohort, 5 children (14%) reported symptoms of other pain syndromes, such as migrainelike headaches (9%) or recurrent abdominal pain (6%). No patients developed arthritis or fibromyalgia.

Pain thresholds were assessed in predefined body areas using a Fischer-type dolorimeter. Pressure was gradually increased in increments of 1 kg/sec until the patient reported feeling pain. The threshold was measured in 18 predefined pressure points of fibromyalgia, 3 control points, and in the mid–anterior tibia where these patients commonly report pain.

Children with persistent pains had lower pain thresholds than did 38 age- and sex-matched controls (P less than .05) or patients with resolved growing pains (P less than .02). Such heightened pain sensitivity of children with continued growing pains was seen for the fibromyalgia points, the control points, and the tibia point (P less than .01 for each).

Dr. Imundo does not recommend opioids or NSAIDs for conditions that are associated with central pain-processing syndromes. Instead, she suggests that antidepressants or anticonvulsants may be more effective.

Disclosures: Dr. Imundo had nothing to disclose. This report contains information on the use of medications that are not approved for the use of growing pains.

NEW YORK — Almost half of children with “growing pains” have not outgrown them 5 years later.

Those children who continued to have growing pains had significantly lower pain thresholds than did controls or patients whose pains had resolved, said Dr. Lisa F. Imundo, referring to recently published data by other investigators (J. Pediatr. 2010 [doi:10.1016/j.jpeds.2009.11.078

Chronic and idiopathic pain complaints are responsible for 7% of referrals to pediatric rheumatology centers, said Dr. Imundo, director of pediatric rheumatology at the Morgan Stanley Children's Hospital of New York–Presbyterian. Idiopathic pain syndromes in children include growing pains, benign hypermobility, reflex sympathetic dystrophy, fibromyalgia syndrome, chronic fatigue, chronic Lyme disease, and Munchausen and conversion disorders.

Growing pains are generally considered to be a temporary, benign condition that affects children aged 2-6 years. Affected children may wake up crying from a deep sleep, rubbing one or both legs. Episodes tend to occur only at night, when children may be awakened for several nights in a row, followed by days or weeks of uninterrupted sleep, explained Dr. Imundo.

To see what actually happens to children with growing pains as they age, investigators examined 35 of the 44 patients in the original cohort. At the time of the reevaluation, the mean age of the children was 13.4 years, and 51% (18 of 35) said they no longer had pain.

In all, 17 patients (49%) reported persistent growing pains. Of these, 14 patients currently had fewer pain episodes, compared with the time of their first diagnosis, whereas 3 patients said the pains were more frequent. Most (94%) of the persistent-pain patients had pain in the lower extremities, and about one-quarter had pain in the upper extremities. Pain was symmetric for 88% of this group. Nine children used analgesics regularly to relieve pain. None reported missing school because of pain.

One of the study's objectives was to determine whether children with growing pains develop other pain syndromes in adolescence. Of the 35 in the original growing-pain cohort, 5 children (14%) reported symptoms of other pain syndromes, such as migrainelike headaches (9%) or recurrent abdominal pain (6%). No patients developed arthritis or fibromyalgia.

Pain thresholds were assessed in predefined body areas using a Fischer-type dolorimeter. Pressure was gradually increased in increments of 1 kg/sec until the patient reported feeling pain. The threshold was measured in 18 predefined pressure points of fibromyalgia, 3 control points, and in the mid–anterior tibia where these patients commonly report pain.

Children with persistent pains had lower pain thresholds than did 38 age- and sex-matched controls (P less than .05) or patients with resolved growing pains (P less than .02). Such heightened pain sensitivity of children with continued growing pains was seen for the fibromyalgia points, the control points, and the tibia point (P less than .01 for each).

Dr. Imundo does not recommend opioids or NSAIDs for conditions that are associated with central pain-processing syndromes. Instead, she suggests that antidepressants or anticonvulsants may be more effective.

Disclosures: Dr. Imundo had nothing to disclose. This report contains information on the use of medications that are not approved for the use of growing pains.

NEW YORK — Almost half of children with “growing pains” have not outgrown them 5 years later.

Those children who continued to have growing pains had significantly lower pain thresholds than did controls or patients whose pains had resolved, said Dr. Lisa F. Imundo, referring to recently published data by other investigators (J. Pediatr. 2010 [doi:10.1016/j.jpeds.2009.11.078

Chronic and idiopathic pain complaints are responsible for 7% of referrals to pediatric rheumatology centers, said Dr. Imundo, director of pediatric rheumatology at the Morgan Stanley Children's Hospital of New York–Presbyterian. Idiopathic pain syndromes in children include growing pains, benign hypermobility, reflex sympathetic dystrophy, fibromyalgia syndrome, chronic fatigue, chronic Lyme disease, and Munchausen and conversion disorders.

Growing pains are generally considered to be a temporary, benign condition that affects children aged 2-6 years. Affected children may wake up crying from a deep sleep, rubbing one or both legs. Episodes tend to occur only at night, when children may be awakened for several nights in a row, followed by days or weeks of uninterrupted sleep, explained Dr. Imundo.

To see what actually happens to children with growing pains as they age, investigators examined 35 of the 44 patients in the original cohort. At the time of the reevaluation, the mean age of the children was 13.4 years, and 51% (18 of 35) said they no longer had pain.

In all, 17 patients (49%) reported persistent growing pains. Of these, 14 patients currently had fewer pain episodes, compared with the time of their first diagnosis, whereas 3 patients said the pains were more frequent. Most (94%) of the persistent-pain patients had pain in the lower extremities, and about one-quarter had pain in the upper extremities. Pain was symmetric for 88% of this group. Nine children used analgesics regularly to relieve pain. None reported missing school because of pain.

One of the study's objectives was to determine whether children with growing pains develop other pain syndromes in adolescence. Of the 35 in the original growing-pain cohort, 5 children (14%) reported symptoms of other pain syndromes, such as migrainelike headaches (9%) or recurrent abdominal pain (6%). No patients developed arthritis or fibromyalgia.

Pain thresholds were assessed in predefined body areas using a Fischer-type dolorimeter. Pressure was gradually increased in increments of 1 kg/sec until the patient reported feeling pain. The threshold was measured in 18 predefined pressure points of fibromyalgia, 3 control points, and in the mid–anterior tibia where these patients commonly report pain.

Children with persistent pains had lower pain thresholds than did 38 age- and sex-matched controls (P less than .05) or patients with resolved growing pains (P less than .02). Such heightened pain sensitivity of children with continued growing pains was seen for the fibromyalgia points, the control points, and the tibia point (P less than .01 for each).

Dr. Imundo does not recommend opioids or NSAIDs for conditions that are associated with central pain-processing syndromes. Instead, she suggests that antidepressants or anticonvulsants may be more effective.

Disclosures: Dr. Imundo had nothing to disclose. This report contains information on the use of medications that are not approved for the use of growing pains.

Many physicians who care for children say that selective cyclo-oxygenase–2 nonsteroidal anti-inflammatory agents have equivalent or greater safety, efficacy, or tolerability and fewer side effects than do traditional NSAIDs. However, in the years since the voluntary withdrawal of rofecoxib and valdecoxib from the market, few practitioners aside from rheumatologists prescribe selective COX-2 NSAIDs for children, according to survey results.

The aim of the survey was to examine the prescribing habits of NSAIDs among pediatric medical and surgical practitioners, and to examine concerns and barriers to their use. A link to a 22-question Web-based survey that could be completed in 10-15 minutes was sent to 1,289 pediatricians, pediatric rheumatologists, sports medicine physicians, pediatric surgeons, and pediatric orthopedic surgeons Eighty-four e-mails were returned as “undeliverable.”

Only 338 (28%) of the 1,205 e-mail recipients completed the surveys. The highest response rates were from pediatric rheumatologists (100 of 247, 40%) and the lowest from sports medicine specialists (12 of 106, 11%).

Indeed, one limitation of the study was that it was skewed to include a large percentage of pediatric rheumatologists, according to Dr. Deborah M. Levy, a pediatric rheumatologist at the Hospital for Sick Children in Toronto, and Dr. Lisa F. Imundo, a pediatric rheumatologist at the Morgan Stanley Children's Hospital of New York–Presbyterian, Columbia University.

Of the pediatricians and pediatric subspecialists, 98% indicated they had prescribed an NSAID for a child. The most common reasons given for ever prescribing an NSAID were musculoskeletal pain, soft-tissue injury, fever, arthritis, fracture, and headache.

Nonrheumatologists frequently (more than once a week) prescribed ibuprofen, naproxen, and ketorolac, but they rarely prescribed any other NSAID. Rheumatologists used a wider variety of medications, most notably ibuprofen, diclofenac, indomethacin, naproxen, celecoxib, and rofecoxib.

About half of the respondents (164 of 330) had never prescribed a selective COX-2 NSAID. By specialty, 72% of pediatricians, 52% of orthopedic surgeons, 79% of pediatric surgeons, and 4% of rheumatologists had never prescribed a selective COX-2 NSAID. The most common reasons for prescribing a selective COX-2 NSAID were for arthritis, musculoskeletal pain, soft-tissue injury, and fracture. Use of these agents was more likely after failure of one or more traditional NSAIDS.

Responses from pediatric rheumatologists showed that certain adverse events were more common with conventional NSAIDs than with selective COX-2 agents. Specifically, abdominal pain (81% vs. 23%), epistaxis (13% vs. 2%), easy bruising (64% vs. 8%), headaches (21% vs. 1%), and fatigue (12% vs. 1%) were more common with traditional NSAIDs (n = 99) compared with the selective COX-2 medications (n = 95).

COX-2 NSAIDs were rated as equivalent or superior to traditional NSAIDs for safety (66%), pain relief (72%), relief of inflammation (74%), and tolerability (83%).

Eleven physicians reported that one or more patients had a cardiovascular event while taking an NSAID. The events were attributed to the patients' underlying diseases, and not to the use of either a traditional or selective COX-2 NSAID, according to the investigators.

Rofecoxib was voluntarily withdrawn from the market in September 2004 and valdecoxib was withdrawn in April of 2005, and these events affected physician prescribing habits. For pediatric rheumatologists, 57% said they prescribed selective COX-2 NSAIDs less frequently and 26% said they no longer prescribed them. Consequently, 44% increased their prescriptions of traditional NSAIDs.

Nine traditional NSAIDs (aspirin, etodolac, ibuprofen, indomethacin, ketorolac, meloxicam, naproxen, oxaprozin, and tolmetin) and one selective COX-2 NSAID (celecoxib) currently have Food and Drug Administration–approved pediatric indications. At the time of the survey, no COX-2 NSAID had a pediatric indication.

Disclosures: Dr. Levy received support through an independent research grant from Pfizer, manufacturer of valdecoxib. Dr. Imundo reported that she has no financial conflicts of interest.

Many physicians who care for children say that selective cyclo-oxygenase–2 nonsteroidal anti-inflammatory agents have equivalent or greater safety, efficacy, or tolerability and fewer side effects than do traditional NSAIDs. However, in the years since the voluntary withdrawal of rofecoxib and valdecoxib from the market, few practitioners aside from rheumatologists prescribe selective COX-2 NSAIDs for children, according to survey results.

The aim of the survey was to examine the prescribing habits of NSAIDs among pediatric medical and surgical practitioners, and to examine concerns and barriers to their use. A link to a 22-question Web-based survey that could be completed in 10-15 minutes was sent to 1,289 pediatricians, pediatric rheumatologists, sports medicine physicians, pediatric surgeons, and pediatric orthopedic surgeons Eighty-four e-mails were returned as “undeliverable.”

Only 338 (28%) of the 1,205 e-mail recipients completed the surveys. The highest response rates were from pediatric rheumatologists (100 of 247, 40%) and the lowest from sports medicine specialists (12 of 106, 11%).

Indeed, one limitation of the study was that it was skewed to include a large percentage of pediatric rheumatologists, according to Dr. Deborah M. Levy, a pediatric rheumatologist at the Hospital for Sick Children in Toronto, and Dr. Lisa F. Imundo, a pediatric rheumatologist at the Morgan Stanley Children's Hospital of New York–Presbyterian, Columbia University.

Of the pediatricians and pediatric subspecialists, 98% indicated they had prescribed an NSAID for a child. The most common reasons given for ever prescribing an NSAID were musculoskeletal pain, soft-tissue injury, fever, arthritis, fracture, and headache.

Nonrheumatologists frequently (more than once a week) prescribed ibuprofen, naproxen, and ketorolac, but they rarely prescribed any other NSAID. Rheumatologists used a wider variety of medications, most notably ibuprofen, diclofenac, indomethacin, naproxen, celecoxib, and rofecoxib.

About half of the respondents (164 of 330) had never prescribed a selective COX-2 NSAID. By specialty, 72% of pediatricians, 52% of orthopedic surgeons, 79% of pediatric surgeons, and 4% of rheumatologists had never prescribed a selective COX-2 NSAID. The most common reasons for prescribing a selective COX-2 NSAID were for arthritis, musculoskeletal pain, soft-tissue injury, and fracture. Use of these agents was more likely after failure of one or more traditional NSAIDS.

Responses from pediatric rheumatologists showed that certain adverse events were more common with conventional NSAIDs than with selective COX-2 agents. Specifically, abdominal pain (81% vs. 23%), epistaxis (13% vs. 2%), easy bruising (64% vs. 8%), headaches (21% vs. 1%), and fatigue (12% vs. 1%) were more common with traditional NSAIDs (n = 99) compared with the selective COX-2 medications (n = 95).

COX-2 NSAIDs were rated as equivalent or superior to traditional NSAIDs for safety (66%), pain relief (72%), relief of inflammation (74%), and tolerability (83%).

Eleven physicians reported that one or more patients had a cardiovascular event while taking an NSAID. The events were attributed to the patients' underlying diseases, and not to the use of either a traditional or selective COX-2 NSAID, according to the investigators.

Rofecoxib was voluntarily withdrawn from the market in September 2004 and valdecoxib was withdrawn in April of 2005, and these events affected physician prescribing habits. For pediatric rheumatologists, 57% said they prescribed selective COX-2 NSAIDs less frequently and 26% said they no longer prescribed them. Consequently, 44% increased their prescriptions of traditional NSAIDs.

Nine traditional NSAIDs (aspirin, etodolac, ibuprofen, indomethacin, ketorolac, meloxicam, naproxen, oxaprozin, and tolmetin) and one selective COX-2 NSAID (celecoxib) currently have Food and Drug Administration–approved pediatric indications. At the time of the survey, no COX-2 NSAID had a pediatric indication.

Disclosures: Dr. Levy received support through an independent research grant from Pfizer, manufacturer of valdecoxib. Dr. Imundo reported that she has no financial conflicts of interest.

Many physicians who care for children say that selective cyclo-oxygenase–2 nonsteroidal anti-inflammatory agents have equivalent or greater safety, efficacy, or tolerability and fewer side effects than do traditional NSAIDs. However, in the years since the voluntary withdrawal of rofecoxib and valdecoxib from the market, few practitioners aside from rheumatologists prescribe selective COX-2 NSAIDs for children, according to survey results.

The aim of the survey was to examine the prescribing habits of NSAIDs among pediatric medical and surgical practitioners, and to examine concerns and barriers to their use. A link to a 22-question Web-based survey that could be completed in 10-15 minutes was sent to 1,289 pediatricians, pediatric rheumatologists, sports medicine physicians, pediatric surgeons, and pediatric orthopedic surgeons Eighty-four e-mails were returned as “undeliverable.”

Only 338 (28%) of the 1,205 e-mail recipients completed the surveys. The highest response rates were from pediatric rheumatologists (100 of 247, 40%) and the lowest from sports medicine specialists (12 of 106, 11%).

Indeed, one limitation of the study was that it was skewed to include a large percentage of pediatric rheumatologists, according to Dr. Deborah M. Levy, a pediatric rheumatologist at the Hospital for Sick Children in Toronto, and Dr. Lisa F. Imundo, a pediatric rheumatologist at the Morgan Stanley Children's Hospital of New York–Presbyterian, Columbia University.

Of the pediatricians and pediatric subspecialists, 98% indicated they had prescribed an NSAID for a child. The most common reasons given for ever prescribing an NSAID were musculoskeletal pain, soft-tissue injury, fever, arthritis, fracture, and headache.

Nonrheumatologists frequently (more than once a week) prescribed ibuprofen, naproxen, and ketorolac, but they rarely prescribed any other NSAID. Rheumatologists used a wider variety of medications, most notably ibuprofen, diclofenac, indomethacin, naproxen, celecoxib, and rofecoxib.

About half of the respondents (164 of 330) had never prescribed a selective COX-2 NSAID. By specialty, 72% of pediatricians, 52% of orthopedic surgeons, 79% of pediatric surgeons, and 4% of rheumatologists had never prescribed a selective COX-2 NSAID. The most common reasons for prescribing a selective COX-2 NSAID were for arthritis, musculoskeletal pain, soft-tissue injury, and fracture. Use of these agents was more likely after failure of one or more traditional NSAIDS.

Responses from pediatric rheumatologists showed that certain adverse events were more common with conventional NSAIDs than with selective COX-2 agents. Specifically, abdominal pain (81% vs. 23%), epistaxis (13% vs. 2%), easy bruising (64% vs. 8%), headaches (21% vs. 1%), and fatigue (12% vs. 1%) were more common with traditional NSAIDs (n = 99) compared with the selective COX-2 medications (n = 95).

COX-2 NSAIDs were rated as equivalent or superior to traditional NSAIDs for safety (66%), pain relief (72%), relief of inflammation (74%), and tolerability (83%).

Eleven physicians reported that one or more patients had a cardiovascular event while taking an NSAID. The events were attributed to the patients' underlying diseases, and not to the use of either a traditional or selective COX-2 NSAID, according to the investigators.

Rofecoxib was voluntarily withdrawn from the market in September 2004 and valdecoxib was withdrawn in April of 2005, and these events affected physician prescribing habits. For pediatric rheumatologists, 57% said they prescribed selective COX-2 NSAIDs less frequently and 26% said they no longer prescribed them. Consequently, 44% increased their prescriptions of traditional NSAIDs.

Nine traditional NSAIDs (aspirin, etodolac, ibuprofen, indomethacin, ketorolac, meloxicam, naproxen, oxaprozin, and tolmetin) and one selective COX-2 NSAID (celecoxib) currently have Food and Drug Administration–approved pediatric indications. At the time of the survey, no COX-2 NSAID had a pediatric indication.

Disclosures: Dr. Levy received support through an independent research grant from Pfizer, manufacturer of valdecoxib. Dr. Imundo reported that she has no financial conflicts of interest.