Michele G. Sullivan

BANGKOK, THAILAND – Patients with multiple sclerosis who abruptly discontinue natalizumab treatment may develop a sudden surge in the number of gadolinium enhancing lesions apparent on imaging, which seems to resolve by 9 months.

The phenomenon is probably a reaction to the sudden resurgence of lymphocytes into the brain–a central nervous system form of immune reconstitution inflammatory syndrome, Dr. Omar Khan said at the World Congress of Neurology.

Although the dramatic imaging changes aren't accompanied by clinical deterioration, about 22% of the lesions did develop into nonenhancing T1 hypointensities, said Dr. Khan, director of the Wayne State University Multiple Sclerosis Clinical Research Center and Radiology Image Analysis Laboratory, Detroit. “Some patients may accumulate a lot of irreversible neuronal damage in this short period of time. And although it's too soon to know for sure, my gut feeling is that over 3 or 4 years, there might be some consequences,” he noted.

Dr. Khan presented a case series of 11 patients with MS who had received natalizumab infusions before stopping the treatment abruptly. The reasons that were given for discontinuation included infusion site reactions, the development of neutralizing antibodies, changes in insurance coverage, and patient concerns about developing progressive multifocal leukoencephalopathy.

The patients' mean age was 36 years. They had undergone a mean of 13 natalizumab infusions, although that number ranged from 8 to 21. Before taking natalizumab, their mean relapse rate was 1.6/year; the mean relapse rate at discontinuation of the drug was 0.1/year. All patients were negative for John Cunningham virus.

Before beginning natalizumab, the patients had a mean of 12 T2 lesions, two T1 lesions, and 20 gadolinium-enhancing lesions on MRI. Three months after stopping the drug, the numbers of lesions increased significantly, to 17 T2 lesions, 13 T1 lesions, and 137 gadolinium-enhancing lesions. Overall, 93 of the lesions appeared in brain areas that were previously normal-appearing on imaging.

Before natalizumab discontinuation, the mean magnetization transfer ratio value of the gadolinium-enhancing lesions was 31%; at month 3, the mean value had dropped to 19%. “This is a pretty impressive decline, something telling us there might be some fairly intense inflammatory injury on these sites,” Dr. Khan said.

Despite the “alarming” scans, Dr. Khan said, the patients did not show corresponding clinical deterioration. Their mean Expanded Disability Status Scale (EDSS) was 3.2 at discontinuation, and did not increase significantly by 3 months.

By 9 months, however, the scans had almost universally improved. The mean number of T2, T1, and gadolinium-enhancing lesions had dropped and were not significantly different from the number of lesions seen at baseline.

Clinically, the patients remained stable, Dr. Khan said. Their mean EDSS at 9 months was 4.0–not significantly worse than it was at natalizumab discontinuation. The mean relapse rate also was not significantly different.

Dr. Khan said the study was independently funded and he did not have any financial declarations to make.

When this 43-year-old woman discontinued natalizumab after the 17th infusion of the drug, she developed many areas of gadolinium enhancement, which were visible 3 months after discontinuation. Most areas of enhancement appeared in areas that previously were normal on T2 or FLAIR sequences before the patient started on the natalizumab treatment.

Source COURTESY DR. OMAR KHAN

BANGKOK, THAILAND – Patients with multiple sclerosis who abruptly discontinue natalizumab treatment may develop a sudden surge in the number of gadolinium enhancing lesions apparent on imaging, which seems to resolve by 9 months.

The phenomenon is probably a reaction to the sudden resurgence of lymphocytes into the brain–a central nervous system form of immune reconstitution inflammatory syndrome, Dr. Omar Khan said at the World Congress of Neurology.

Although the dramatic imaging changes aren't accompanied by clinical deterioration, about 22% of the lesions did develop into nonenhancing T1 hypointensities, said Dr. Khan, director of the Wayne State University Multiple Sclerosis Clinical Research Center and Radiology Image Analysis Laboratory, Detroit. “Some patients may accumulate a lot of irreversible neuronal damage in this short period of time. And although it's too soon to know for sure, my gut feeling is that over 3 or 4 years, there might be some consequences,” he noted.

Dr. Khan presented a case series of 11 patients with MS who had received natalizumab infusions before stopping the treatment abruptly. The reasons that were given for discontinuation included infusion site reactions, the development of neutralizing antibodies, changes in insurance coverage, and patient concerns about developing progressive multifocal leukoencephalopathy.

The patients' mean age was 36 years. They had undergone a mean of 13 natalizumab infusions, although that number ranged from 8 to 21. Before taking natalizumab, their mean relapse rate was 1.6/year; the mean relapse rate at discontinuation of the drug was 0.1/year. All patients were negative for John Cunningham virus.

Before beginning natalizumab, the patients had a mean of 12 T2 lesions, two T1 lesions, and 20 gadolinium-enhancing lesions on MRI. Three months after stopping the drug, the numbers of lesions increased significantly, to 17 T2 lesions, 13 T1 lesions, and 137 gadolinium-enhancing lesions. Overall, 93 of the lesions appeared in brain areas that were previously normal-appearing on imaging.

Before natalizumab discontinuation, the mean magnetization transfer ratio value of the gadolinium-enhancing lesions was 31%; at month 3, the mean value had dropped to 19%. “This is a pretty impressive decline, something telling us there might be some fairly intense inflammatory injury on these sites,” Dr. Khan said.

Despite the “alarming” scans, Dr. Khan said, the patients did not show corresponding clinical deterioration. Their mean Expanded Disability Status Scale (EDSS) was 3.2 at discontinuation, and did not increase significantly by 3 months.

By 9 months, however, the scans had almost universally improved. The mean number of T2, T1, and gadolinium-enhancing lesions had dropped and were not significantly different from the number of lesions seen at baseline.

Clinically, the patients remained stable, Dr. Khan said. Their mean EDSS at 9 months was 4.0–not significantly worse than it was at natalizumab discontinuation. The mean relapse rate also was not significantly different.

Dr. Khan said the study was independently funded and he did not have any financial declarations to make.

When this 43-year-old woman discontinued natalizumab after the 17th infusion of the drug, she developed many areas of gadolinium enhancement, which were visible 3 months after discontinuation. Most areas of enhancement appeared in areas that previously were normal on T2 or FLAIR sequences before the patient started on the natalizumab treatment.

Source COURTESY DR. OMAR KHAN

BANGKOK, THAILAND – Patients with multiple sclerosis who abruptly discontinue natalizumab treatment may develop a sudden surge in the number of gadolinium enhancing lesions apparent on imaging, which seems to resolve by 9 months.

The phenomenon is probably a reaction to the sudden resurgence of lymphocytes into the brain–a central nervous system form of immune reconstitution inflammatory syndrome, Dr. Omar Khan said at the World Congress of Neurology.

Although the dramatic imaging changes aren't accompanied by clinical deterioration, about 22% of the lesions did develop into nonenhancing T1 hypointensities, said Dr. Khan, director of the Wayne State University Multiple Sclerosis Clinical Research Center and Radiology Image Analysis Laboratory, Detroit. “Some patients may accumulate a lot of irreversible neuronal damage in this short period of time. And although it's too soon to know for sure, my gut feeling is that over 3 or 4 years, there might be some consequences,” he noted.

Dr. Khan presented a case series of 11 patients with MS who had received natalizumab infusions before stopping the treatment abruptly. The reasons that were given for discontinuation included infusion site reactions, the development of neutralizing antibodies, changes in insurance coverage, and patient concerns about developing progressive multifocal leukoencephalopathy.

The patients' mean age was 36 years. They had undergone a mean of 13 natalizumab infusions, although that number ranged from 8 to 21. Before taking natalizumab, their mean relapse rate was 1.6/year; the mean relapse rate at discontinuation of the drug was 0.1/year. All patients were negative for John Cunningham virus.

Before beginning natalizumab, the patients had a mean of 12 T2 lesions, two T1 lesions, and 20 gadolinium-enhancing lesions on MRI. Three months after stopping the drug, the numbers of lesions increased significantly, to 17 T2 lesions, 13 T1 lesions, and 137 gadolinium-enhancing lesions. Overall, 93 of the lesions appeared in brain areas that were previously normal-appearing on imaging.

Before natalizumab discontinuation, the mean magnetization transfer ratio value of the gadolinium-enhancing lesions was 31%; at month 3, the mean value had dropped to 19%. “This is a pretty impressive decline, something telling us there might be some fairly intense inflammatory injury on these sites,” Dr. Khan said.

Despite the “alarming” scans, Dr. Khan said, the patients did not show corresponding clinical deterioration. Their mean Expanded Disability Status Scale (EDSS) was 3.2 at discontinuation, and did not increase significantly by 3 months.

By 9 months, however, the scans had almost universally improved. The mean number of T2, T1, and gadolinium-enhancing lesions had dropped and were not significantly different from the number of lesions seen at baseline.

Clinically, the patients remained stable, Dr. Khan said. Their mean EDSS at 9 months was 4.0–not significantly worse than it was at natalizumab discontinuation. The mean relapse rate also was not significantly different.

Dr. Khan said the study was independently funded and he did not have any financial declarations to make.

When this 43-year-old woman discontinued natalizumab after the 17th infusion of the drug, she developed many areas of gadolinium enhancement, which were visible 3 months after discontinuation. Most areas of enhancement appeared in areas that previously were normal on T2 or FLAIR sequences before the patient started on the natalizumab treatment.

Source COURTESY DR. OMAR KHAN

BANGKOK, THAILAND – Far from affecting only white matter, multiple sclerosis seems to strike at gray matter as well, causing atrophy of brain structures that correlates with disease duration and declining cognitive function.

“Traditionally, multiple sclerosis has been considered a white matter disease, but recent literature suggests an involvement of the gray matter as well, causing atrophy of particular brain regions,” Asaf Achiron said at the World Congress of Neurology.

Mr. Achiron, a fifth-year medical student, presented the results of an imaging study of 38 adults with relapsing-remitting multiple sclerosis, in which he tracked volumetric changes in specific brain regions as the disease progressed. The research was part of the Arrow Project, a student/professor collaboration in Tel Aviv University. Mr. Achiron's mentor, Dr. Ida Sarova-Pinhas, is a neurologist at The Chaim Sheba Medical Center, Tel Hashomer, Israel, and at Tel Aviv University.

The collaborators used a computerized imaging program called FreeSurfer to determine thickness and volume of the cerebral cortices, thalami, and hippocampi of their subjects. FreeSurfer is a set of automated tools that can reconstruct the brain's cortical surface from structural MRI data and overlay functional MRI data onto the reconstructed surface.

The study group consisted of 38 patients with relapsing-remitting MS, 24 of whom were women. Those with short disease duration (fewer than 5 years) were an average age of 33 years, with an average disease duration of 2 years. Those with longer disease duration (more than 5 years) were an average age of 36 years with an average disease duration of 11 years. Significant differences were found in the neurologic disability of those with shorter compared with longer disease duration.

In addition to undergoing MRI studies, the patients completed an online cognitive assessment called the Neurotrax Mindstreams Computerized Cognitive Battery (www.neurotrax.com

Mr. Achiron and Dr. Sarova-Pinhas found that, compared with patients with longer disease duration, patients with shorter duration disease had significantly larger volumetric measurements of the right cerebral cortex (274 vs. 245 cc) and left cerebral cortex (276 vs. 247 cc) and the right and left hippocampi (both 4.7 vs. 4.3 cc). While the differences were not significant, the right thalamus was larger in the group with shorter disease duration (7.4 vs. 7.0 cc), as was the left thalamus (7.8 vs. 7.4 cc).

“My feeling is that if we had a larger group, we might have reached significance,” in thalamic volume difference, Mr. Achiron said.

In the cognitive testing, patients with short duration of disease had significantly better scores in global cognition, visual spatial perception, and executive function than did those with longer disease duration.

“This loss of gray matter is a complement of the axonal loss and the genesis of symptomatic progression in MS,” Mr. Achiron said. “Identification of these specific areas of loss has clinical relevance for understanding the associated cognitive changes.”

FreeSurfer software, developed by the National Institutes of Health, is available for free download at http://surfer.nmr.mgh.harvard.edu/

The Arrow Project is a research program for medical students held in the Multiple Sclerosis Center at Sheba Medical Center, Tel Hashomer. Its aim is to strengthen students' knowledge and practice, and train them to be better physicians and researchers. Students are matched with a mentor and together, they choose a study topic and work on its design, literature review, and methodology.

This year, 10 students, including Mr. Achiron, are involved in the program (http://medical-students.ny.sheba.co.il/

◊ To watch a video interview of Mr. Achiron, go to www.youtube.com/watch?v=2gfzYiwacaw

Vitals

Major Finding: Volumetric measurements of the cerebral cortex and hippocampus declined with disease duration in multiple sclerosis.

Data Source: Imaging study of 38 adults with relapsing-remitting multiple sclerosis.

Disclosures: None.

BANGKOK, THAILAND – Far from affecting only white matter, multiple sclerosis seems to strike at gray matter as well, causing atrophy of brain structures that correlates with disease duration and declining cognitive function.

“Traditionally, multiple sclerosis has been considered a white matter disease, but recent literature suggests an involvement of the gray matter as well, causing atrophy of particular brain regions,” Asaf Achiron said at the World Congress of Neurology.

Mr. Achiron, a fifth-year medical student, presented the results of an imaging study of 38 adults with relapsing-remitting multiple sclerosis, in which he tracked volumetric changes in specific brain regions as the disease progressed. The research was part of the Arrow Project, a student/professor collaboration in Tel Aviv University. Mr. Achiron's mentor, Dr. Ida Sarova-Pinhas, is a neurologist at The Chaim Sheba Medical Center, Tel Hashomer, Israel, and at Tel Aviv University.

The collaborators used a computerized imaging program called FreeSurfer to determine thickness and volume of the cerebral cortices, thalami, and hippocampi of their subjects. FreeSurfer is a set of automated tools that can reconstruct the brain's cortical surface from structural MRI data and overlay functional MRI data onto the reconstructed surface.

The study group consisted of 38 patients with relapsing-remitting MS, 24 of whom were women. Those with short disease duration (fewer than 5 years) were an average age of 33 years, with an average disease duration of 2 years. Those with longer disease duration (more than 5 years) were an average age of 36 years with an average disease duration of 11 years. Significant differences were found in the neurologic disability of those with shorter compared with longer disease duration.

In addition to undergoing MRI studies, the patients completed an online cognitive assessment called the Neurotrax Mindstreams Computerized Cognitive Battery (www.neurotrax.com

Mr. Achiron and Dr. Sarova-Pinhas found that, compared with patients with longer disease duration, patients with shorter duration disease had significantly larger volumetric measurements of the right cerebral cortex (274 vs. 245 cc) and left cerebral cortex (276 vs. 247 cc) and the right and left hippocampi (both 4.7 vs. 4.3 cc). While the differences were not significant, the right thalamus was larger in the group with shorter disease duration (7.4 vs. 7.0 cc), as was the left thalamus (7.8 vs. 7.4 cc).

“My feeling is that if we had a larger group, we might have reached significance,” in thalamic volume difference, Mr. Achiron said.

In the cognitive testing, patients with short duration of disease had significantly better scores in global cognition, visual spatial perception, and executive function than did those with longer disease duration.

“This loss of gray matter is a complement of the axonal loss and the genesis of symptomatic progression in MS,” Mr. Achiron said. “Identification of these specific areas of loss has clinical relevance for understanding the associated cognitive changes.”

FreeSurfer software, developed by the National Institutes of Health, is available for free download at http://surfer.nmr.mgh.harvard.edu/

The Arrow Project is a research program for medical students held in the Multiple Sclerosis Center at Sheba Medical Center, Tel Hashomer. Its aim is to strengthen students' knowledge and practice, and train them to be better physicians and researchers. Students are matched with a mentor and together, they choose a study topic and work on its design, literature review, and methodology.

This year, 10 students, including Mr. Achiron, are involved in the program (http://medical-students.ny.sheba.co.il/

◊ To watch a video interview of Mr. Achiron, go to www.youtube.com/watch?v=2gfzYiwacaw

Vitals

Major Finding: Volumetric measurements of the cerebral cortex and hippocampus declined with disease duration in multiple sclerosis.

Data Source: Imaging study of 38 adults with relapsing-remitting multiple sclerosis.

Disclosures: None.

BANGKOK, THAILAND – Far from affecting only white matter, multiple sclerosis seems to strike at gray matter as well, causing atrophy of brain structures that correlates with disease duration and declining cognitive function.

“Traditionally, multiple sclerosis has been considered a white matter disease, but recent literature suggests an involvement of the gray matter as well, causing atrophy of particular brain regions,” Asaf Achiron said at the World Congress of Neurology.

Mr. Achiron, a fifth-year medical student, presented the results of an imaging study of 38 adults with relapsing-remitting multiple sclerosis, in which he tracked volumetric changes in specific brain regions as the disease progressed. The research was part of the Arrow Project, a student/professor collaboration in Tel Aviv University. Mr. Achiron's mentor, Dr. Ida Sarova-Pinhas, is a neurologist at The Chaim Sheba Medical Center, Tel Hashomer, Israel, and at Tel Aviv University.

The collaborators used a computerized imaging program called FreeSurfer to determine thickness and volume of the cerebral cortices, thalami, and hippocampi of their subjects. FreeSurfer is a set of automated tools that can reconstruct the brain's cortical surface from structural MRI data and overlay functional MRI data onto the reconstructed surface.

The study group consisted of 38 patients with relapsing-remitting MS, 24 of whom were women. Those with short disease duration (fewer than 5 years) were an average age of 33 years, with an average disease duration of 2 years. Those with longer disease duration (more than 5 years) were an average age of 36 years with an average disease duration of 11 years. Significant differences were found in the neurologic disability of those with shorter compared with longer disease duration.

In addition to undergoing MRI studies, the patients completed an online cognitive assessment called the Neurotrax Mindstreams Computerized Cognitive Battery (www.neurotrax.com

Mr. Achiron and Dr. Sarova-Pinhas found that, compared with patients with longer disease duration, patients with shorter duration disease had significantly larger volumetric measurements of the right cerebral cortex (274 vs. 245 cc) and left cerebral cortex (276 vs. 247 cc) and the right and left hippocampi (both 4.7 vs. 4.3 cc). While the differences were not significant, the right thalamus was larger in the group with shorter disease duration (7.4 vs. 7.0 cc), as was the left thalamus (7.8 vs. 7.4 cc).

“My feeling is that if we had a larger group, we might have reached significance,” in thalamic volume difference, Mr. Achiron said.

In the cognitive testing, patients with short duration of disease had significantly better scores in global cognition, visual spatial perception, and executive function than did those with longer disease duration.

“This loss of gray matter is a complement of the axonal loss and the genesis of symptomatic progression in MS,” Mr. Achiron said. “Identification of these specific areas of loss has clinical relevance for understanding the associated cognitive changes.”

FreeSurfer software, developed by the National Institutes of Health, is available for free download at http://surfer.nmr.mgh.harvard.edu/

The Arrow Project is a research program for medical students held in the Multiple Sclerosis Center at Sheba Medical Center, Tel Hashomer. Its aim is to strengthen students' knowledge and practice, and train them to be better physicians and researchers. Students are matched with a mentor and together, they choose a study topic and work on its design, literature review, and methodology.

This year, 10 students, including Mr. Achiron, are involved in the program (http://medical-students.ny.sheba.co.il/

◊ To watch a video interview of Mr. Achiron, go to www.youtube.com/watch?v=2gfzYiwacaw

Vitals

Major Finding: Volumetric measurements of the cerebral cortex and hippocampus declined with disease duration in multiple sclerosis.

Data Source: Imaging study of 38 adults with relapsing-remitting multiple sclerosis.

Disclosures: None.

VIENNA – Statin treatment may reduce the risk of later dementia by more than 50%, a national Finnish study has determined.

“Disturbances in cholesterol metabolism have previously been linked to dementia development,” Dr. Alina Solomon wrote in a poster presented at the International Conference on Alzheimer's Disease. However, she noted not all studies have concluded that statins confer a protective effect against dementia onset.

Dr. Solomon, of the University of Kuopio, Finland, and her colleagues examined this question using data from the national FINRISK study, a large, population-based survey of cardiovascular risk factors in Finnish citizens. The survey began in 1972 and is conducted every 5 years. The substudy of FINRISK included data on 17,257 citizens who were included in the 1997 and 2002 cohorts and who were at least 60 years old in 1995, when statins became available in Finland.

By the study's end at 2007, 1,551 subjects had developed dementia and 15,706 had not. Of those who developed dementia, 18% had taken at least 1 year of statin therapy, while 37% of those without dementia had taken a statin–a significant difference.

No significant associations were found between dementia and the use of other cholesterol-lowering medications, Dr. Solomon said, suggesting that “the effect of statins in dementia is partly independent of their cholesterol-lowering effect.”

Those who developed dementia also had significantly higher baseline total cholesterol and baseline systolic and diastolic blood pressure. But a multivariate regression model controlling for age, gender, education, weight, cholesterol, and blood pressure still found that statins conferred a 57% risk reduction for dementia over the study period.

The finding does not prove that statins prevent dementia, but it does suggest further studies should explore the idea, focusing on statin types, dosages, and duration of treatment, Dr. Solomon said at the meeting, which was sponsored by the Alzheimer's Association. None of the researchers had any potential conflicts to declare.

VIENNA – Statin treatment may reduce the risk of later dementia by more than 50%, a national Finnish study has determined.

“Disturbances in cholesterol metabolism have previously been linked to dementia development,” Dr. Alina Solomon wrote in a poster presented at the International Conference on Alzheimer's Disease. However, she noted not all studies have concluded that statins confer a protective effect against dementia onset.

Dr. Solomon, of the University of Kuopio, Finland, and her colleagues examined this question using data from the national FINRISK study, a large, population-based survey of cardiovascular risk factors in Finnish citizens. The survey began in 1972 and is conducted every 5 years. The substudy of FINRISK included data on 17,257 citizens who were included in the 1997 and 2002 cohorts and who were at least 60 years old in 1995, when statins became available in Finland.

By the study's end at 2007, 1,551 subjects had developed dementia and 15,706 had not. Of those who developed dementia, 18% had taken at least 1 year of statin therapy, while 37% of those without dementia had taken a statin–a significant difference.

No significant associations were found between dementia and the use of other cholesterol-lowering medications, Dr. Solomon said, suggesting that “the effect of statins in dementia is partly independent of their cholesterol-lowering effect.”

Those who developed dementia also had significantly higher baseline total cholesterol and baseline systolic and diastolic blood pressure. But a multivariate regression model controlling for age, gender, education, weight, cholesterol, and blood pressure still found that statins conferred a 57% risk reduction for dementia over the study period.

The finding does not prove that statins prevent dementia, but it does suggest further studies should explore the idea, focusing on statin types, dosages, and duration of treatment, Dr. Solomon said at the meeting, which was sponsored by the Alzheimer's Association. None of the researchers had any potential conflicts to declare.

VIENNA – Statin treatment may reduce the risk of later dementia by more than 50%, a national Finnish study has determined.

“Disturbances in cholesterol metabolism have previously been linked to dementia development,” Dr. Alina Solomon wrote in a poster presented at the International Conference on Alzheimer's Disease. However, she noted not all studies have concluded that statins confer a protective effect against dementia onset.

Dr. Solomon, of the University of Kuopio, Finland, and her colleagues examined this question using data from the national FINRISK study, a large, population-based survey of cardiovascular risk factors in Finnish citizens. The survey began in 1972 and is conducted every 5 years. The substudy of FINRISK included data on 17,257 citizens who were included in the 1997 and 2002 cohorts and who were at least 60 years old in 1995, when statins became available in Finland.

By the study's end at 2007, 1,551 subjects had developed dementia and 15,706 had not. Of those who developed dementia, 18% had taken at least 1 year of statin therapy, while 37% of those without dementia had taken a statin–a significant difference.

No significant associations were found between dementia and the use of other cholesterol-lowering medications, Dr. Solomon said, suggesting that “the effect of statins in dementia is partly independent of their cholesterol-lowering effect.”

Those who developed dementia also had significantly higher baseline total cholesterol and baseline systolic and diastolic blood pressure. But a multivariate regression model controlling for age, gender, education, weight, cholesterol, and blood pressure still found that statins conferred a 57% risk reduction for dementia over the study period.

The finding does not prove that statins prevent dementia, but it does suggest further studies should explore the idea, focusing on statin types, dosages, and duration of treatment, Dr. Solomon said at the meeting, which was sponsored by the Alzheimer's Association. None of the researchers had any potential conflicts to declare.

BANGKOK, THAILAND — Magnetic resonance imaging of the brain should be considered every 1–2 years for patients with a confirmed diagnosis of multiple sclerosis, with more frequent imaging if symptoms worsen unexpectedly.

“If a patient has a clinical deterioration that is out of keeping with their disease, you will want to look for a complication of treatment, such as progressive multifocal leukoencephalopathy, or a different issue, such as a stroke in an elderly patient,” said Dr. Anthony Traboulsee, who is a coauthor of updates to the MRI Protocol for the Diagnosis and Follow-Up of Multiple Sclerosis, issued by the Consortium of MS Centers.

The consortium is an international group of neurologists and radiologists, including members of the American Academy of Neurology and the American Society of Neuroradiology. It first released its imaging recommendations in 2003. The new guidelines replace previous revisions from 2006.

The goal of the document is to establish a uniform, internationally practical imaging protocol for MS patients, said Dr. Traboulsee of the University of British Columbia, Vancouver. “The whole point of developing guidelines is practicality, so that anywhere you are in the world, if you have access to MRI, you can get good imaging for your MS patients.”

The document outlines recommendations for the initial imaging procedure in patients with a clinically isolated syndrome suggestive of the disease, and for follow-up imaging in patients with a confirmed diagnosis.

Patients with a clinically isolated syndrome and suspected MS should have, at the minimum, a brain MRI with gadolinium. A spinal cord MRI may be called for if there is persistent uncertainty about the diagnosis, equivocal findings on the brain MRI, or presenting symptoms at the spinal cord level.

To make the best use of both time and money, the guidelines recommend performing as much of the imaging as possible in a single session. This allows completion of both brain and spinal imaging on a single dose of gadolinium.

The protocol recommends a slice thickness of no more than 3 mm for brain and spinal cord. Core sequences of the brain should include sagittal and axial Fluid Attenuated Inversion Recovery (FLAIR); axial T2; and axial T1 both pre- and post-gadolinium.

Renal function should always be assessed before giving gadolinium, Dr. Traboulsee said at the World Congress of Neurology. “We recommend this because there have been rare cases of poor outcomes following exposure in patients with impaired renal function.” The gadolinium dose should be a single infusion of 0.1 mmol/kg given over 30 seconds, with a minimum 5-minute delay before obtaining post-gadolinium T1 images. The FLAIR or T2 studies can be done during this delay.

The guidelines recommend two types of sequences for spinal cord, he said. “Don't just rely on the sagittal T2, but try variations like proton density or Short Tau Inversion Recovery (STIR).”

There are two indications for follow-up MRI in patients with an established diagnosis: acute clinical deterioration, which may be related to treatment reaction or the onset of a concomitant disorder, and planned reassessment.

“How often we should be doing follow-up MRIs—particularly in the early disease course—is where the challenge comes in, because there is not a perfect relationship of new lesions and disease outcome,” Dr. Traboulsee said. However, the expert panel recommended that physicians consider annual or biannual studies.

A brain MRI with gadolinium should also be performed to reassess disease before starting or modifying medical therapy.

The guidelines are available at www.mscare.org/cmsc/images/pdf/mriprotocol2009.pdf

BANGKOK, THAILAND — Magnetic resonance imaging of the brain should be considered every 1–2 years for patients with a confirmed diagnosis of multiple sclerosis, with more frequent imaging if symptoms worsen unexpectedly.

“If a patient has a clinical deterioration that is out of keeping with their disease, you will want to look for a complication of treatment, such as progressive multifocal leukoencephalopathy, or a different issue, such as a stroke in an elderly patient,” said Dr. Anthony Traboulsee, who is a coauthor of updates to the MRI Protocol for the Diagnosis and Follow-Up of Multiple Sclerosis, issued by the Consortium of MS Centers.

The consortium is an international group of neurologists and radiologists, including members of the American Academy of Neurology and the American Society of Neuroradiology. It first released its imaging recommendations in 2003. The new guidelines replace previous revisions from 2006.

The goal of the document is to establish a uniform, internationally practical imaging protocol for MS patients, said Dr. Traboulsee of the University of British Columbia, Vancouver. “The whole point of developing guidelines is practicality, so that anywhere you are in the world, if you have access to MRI, you can get good imaging for your MS patients.”

The document outlines recommendations for the initial imaging procedure in patients with a clinically isolated syndrome suggestive of the disease, and for follow-up imaging in patients with a confirmed diagnosis.

Patients with a clinically isolated syndrome and suspected MS should have, at the minimum, a brain MRI with gadolinium. A spinal cord MRI may be called for if there is persistent uncertainty about the diagnosis, equivocal findings on the brain MRI, or presenting symptoms at the spinal cord level.

To make the best use of both time and money, the guidelines recommend performing as much of the imaging as possible in a single session. This allows completion of both brain and spinal imaging on a single dose of gadolinium.

The protocol recommends a slice thickness of no more than 3 mm for brain and spinal cord. Core sequences of the brain should include sagittal and axial Fluid Attenuated Inversion Recovery (FLAIR); axial T2; and axial T1 both pre- and post-gadolinium.

Renal function should always be assessed before giving gadolinium, Dr. Traboulsee said at the World Congress of Neurology. “We recommend this because there have been rare cases of poor outcomes following exposure in patients with impaired renal function.” The gadolinium dose should be a single infusion of 0.1 mmol/kg given over 30 seconds, with a minimum 5-minute delay before obtaining post-gadolinium T1 images. The FLAIR or T2 studies can be done during this delay.

The guidelines recommend two types of sequences for spinal cord, he said. “Don't just rely on the sagittal T2, but try variations like proton density or Short Tau Inversion Recovery (STIR).”

There are two indications for follow-up MRI in patients with an established diagnosis: acute clinical deterioration, which may be related to treatment reaction or the onset of a concomitant disorder, and planned reassessment.

“How often we should be doing follow-up MRIs—particularly in the early disease course—is where the challenge comes in, because there is not a perfect relationship of new lesions and disease outcome,” Dr. Traboulsee said. However, the expert panel recommended that physicians consider annual or biannual studies.

A brain MRI with gadolinium should also be performed to reassess disease before starting or modifying medical therapy.

The guidelines are available at www.mscare.org/cmsc/images/pdf/mriprotocol2009.pdf

BANGKOK, THAILAND — Magnetic resonance imaging of the brain should be considered every 1–2 years for patients with a confirmed diagnosis of multiple sclerosis, with more frequent imaging if symptoms worsen unexpectedly.

“If a patient has a clinical deterioration that is out of keeping with their disease, you will want to look for a complication of treatment, such as progressive multifocal leukoencephalopathy, or a different issue, such as a stroke in an elderly patient,” said Dr. Anthony Traboulsee, who is a coauthor of updates to the MRI Protocol for the Diagnosis and Follow-Up of Multiple Sclerosis, issued by the Consortium of MS Centers.

The consortium is an international group of neurologists and radiologists, including members of the American Academy of Neurology and the American Society of Neuroradiology. It first released its imaging recommendations in 2003. The new guidelines replace previous revisions from 2006.

The goal of the document is to establish a uniform, internationally practical imaging protocol for MS patients, said Dr. Traboulsee of the University of British Columbia, Vancouver. “The whole point of developing guidelines is practicality, so that anywhere you are in the world, if you have access to MRI, you can get good imaging for your MS patients.”

The document outlines recommendations for the initial imaging procedure in patients with a clinically isolated syndrome suggestive of the disease, and for follow-up imaging in patients with a confirmed diagnosis.

Patients with a clinically isolated syndrome and suspected MS should have, at the minimum, a brain MRI with gadolinium. A spinal cord MRI may be called for if there is persistent uncertainty about the diagnosis, equivocal findings on the brain MRI, or presenting symptoms at the spinal cord level.

To make the best use of both time and money, the guidelines recommend performing as much of the imaging as possible in a single session. This allows completion of both brain and spinal imaging on a single dose of gadolinium.

The protocol recommends a slice thickness of no more than 3 mm for brain and spinal cord. Core sequences of the brain should include sagittal and axial Fluid Attenuated Inversion Recovery (FLAIR); axial T2; and axial T1 both pre- and post-gadolinium.

Renal function should always be assessed before giving gadolinium, Dr. Traboulsee said at the World Congress of Neurology. “We recommend this because there have been rare cases of poor outcomes following exposure in patients with impaired renal function.” The gadolinium dose should be a single infusion of 0.1 mmol/kg given over 30 seconds, with a minimum 5-minute delay before obtaining post-gadolinium T1 images. The FLAIR or T2 studies can be done during this delay.

The guidelines recommend two types of sequences for spinal cord, he said. “Don't just rely on the sagittal T2, but try variations like proton density or Short Tau Inversion Recovery (STIR).”

There are two indications for follow-up MRI in patients with an established diagnosis: acute clinical deterioration, which may be related to treatment reaction or the onset of a concomitant disorder, and planned reassessment.

“How often we should be doing follow-up MRIs—particularly in the early disease course—is where the challenge comes in, because there is not a perfect relationship of new lesions and disease outcome,” Dr. Traboulsee said. However, the expert panel recommended that physicians consider annual or biannual studies.

A brain MRI with gadolinium should also be performed to reassess disease before starting or modifying medical therapy.

The guidelines are available at www.mscare.org/cmsc/images/pdf/mriprotocol2009.pdf

BANGKOK, THAILAND — Long-term antiepileptic drug therapy is associated with worsening bone health in premenopausal women.

Dr. Rungsan Chaisewikul of Siriraj Hospital, Bangkok, included 50 women with epilepsy and 51 matched controls in his study, presented during the meeting's poster session. All the women were premenopausal, with a mean age of 33 years. Patients had been receiving antiepileptic drugs (AEDs) for at least 3 years. Most (62%) were taking more than one drug, and most (84%) were taking an enzyme-inducing AED. All participants had bone mineral density (BMD) measured at the lumbar spine, left femur, and left radius.

Compared with controls, patients had significantly lower T-scores at the femoral neck (0.30 vs. −0.08). BMD at the lumbar spine was lower, but not significantly lower, in patients than in controls, as was BMD at the radius.

With measurements at the femoral neck and lumbar spine significantly more patients than controls were rated as having osteopenia and osteoporosis. More patients than controls also were rated as osteopenic or osteoporotic when considering the radius measurement, although the difference was not statistically significant.

BANGKOK, THAILAND — Long-term antiepileptic drug therapy is associated with worsening bone health in premenopausal women.

Dr. Rungsan Chaisewikul of Siriraj Hospital, Bangkok, included 50 women with epilepsy and 51 matched controls in his study, presented during the meeting's poster session. All the women were premenopausal, with a mean age of 33 years. Patients had been receiving antiepileptic drugs (AEDs) for at least 3 years. Most (62%) were taking more than one drug, and most (84%) were taking an enzyme-inducing AED. All participants had bone mineral density (BMD) measured at the lumbar spine, left femur, and left radius.

Compared with controls, patients had significantly lower T-scores at the femoral neck (0.30 vs. −0.08). BMD at the lumbar spine was lower, but not significantly lower, in patients than in controls, as was BMD at the radius.

With measurements at the femoral neck and lumbar spine significantly more patients than controls were rated as having osteopenia and osteoporosis. More patients than controls also were rated as osteopenic or osteoporotic when considering the radius measurement, although the difference was not statistically significant.

BANGKOK, THAILAND — Long-term antiepileptic drug therapy is associated with worsening bone health in premenopausal women.

Dr. Rungsan Chaisewikul of Siriraj Hospital, Bangkok, included 50 women with epilepsy and 51 matched controls in his study, presented during the meeting's poster session. All the women were premenopausal, with a mean age of 33 years. Patients had been receiving antiepileptic drugs (AEDs) for at least 3 years. Most (62%) were taking more than one drug, and most (84%) were taking an enzyme-inducing AED. All participants had bone mineral density (BMD) measured at the lumbar spine, left femur, and left radius.

Compared with controls, patients had significantly lower T-scores at the femoral neck (0.30 vs. −0.08). BMD at the lumbar spine was lower, but not significantly lower, in patients than in controls, as was BMD at the radius.

With measurements at the femoral neck and lumbar spine significantly more patients than controls were rated as having osteopenia and osteoporosis. More patients than controls also were rated as osteopenic or osteoporotic when considering the radius measurement, although the difference was not statistically significant.

As long as they have received the proper training, nonanesthesiologist physicians and nurses can administer propofol sedation to low-risk patients safely during elective endoscopic procedures, according to a new consensus statement issued jointly by four national gastroenterology and hepatology groups.

The statement—prepared by the American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy—is based on a review of 25 studies comprising almost 470,000 cases in which propofol sedation was administered by nonanesthesiologists during endoscopic procedures.

When administered by properly trained medical professionals, such sedation is safe as well as both cost effective and clinically effective, wrote Dr. John J. Vargo and his coauthors. “Most studies show that nonanesthesiologist–administered propofol sedation is superior to standard sedation regimens regarding time to sedation and time to recovery,” wrote Dr. Vargo of the Cleveland Clinic and his colleagues.

“Patient satisfaction with propofol sedation ranges from equivalent to slightly superior when compared to standard sedation. The use of anesthesiologist-administered propofol for healthy individuals undergoing elective endoscopy without risk factors for sedation-related complications is very costly, with no demonstrated improvement in patient safety or procedural outcome.”

The statement was published in the December issue of Gastroenterology.

As long as they have received the proper training, nonanesthesiologist physicians and nurses can administer propofol sedation to low-risk patients safely during elective endoscopic procedures, according to a new consensus statement issued jointly by four national gastroenterology and hepatology groups.

The statement—prepared by the American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy—is based on a review of 25 studies comprising almost 470,000 cases in which propofol sedation was administered by nonanesthesiologists during endoscopic procedures.

When administered by properly trained medical professionals, such sedation is safe as well as both cost effective and clinically effective, wrote Dr. John J. Vargo and his coauthors. “Most studies show that nonanesthesiologist–administered propofol sedation is superior to standard sedation regimens regarding time to sedation and time to recovery,” wrote Dr. Vargo of the Cleveland Clinic and his colleagues.

“Patient satisfaction with propofol sedation ranges from equivalent to slightly superior when compared to standard sedation. The use of anesthesiologist-administered propofol for healthy individuals undergoing elective endoscopy without risk factors for sedation-related complications is very costly, with no demonstrated improvement in patient safety or procedural outcome.”

The statement was published in the December issue of Gastroenterology.

As long as they have received the proper training, nonanesthesiologist physicians and nurses can administer propofol sedation to low-risk patients safely during elective endoscopic procedures, according to a new consensus statement issued jointly by four national gastroenterology and hepatology groups.

The statement—prepared by the American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy—is based on a review of 25 studies comprising almost 470,000 cases in which propofol sedation was administered by nonanesthesiologists during endoscopic procedures.

When administered by properly trained medical professionals, such sedation is safe as well as both cost effective and clinically effective, wrote Dr. John J. Vargo and his coauthors. “Most studies show that nonanesthesiologist–administered propofol sedation is superior to standard sedation regimens regarding time to sedation and time to recovery,” wrote Dr. Vargo of the Cleveland Clinic and his colleagues.

“Patient satisfaction with propofol sedation ranges from equivalent to slightly superior when compared to standard sedation. The use of anesthesiologist-administered propofol for healthy individuals undergoing elective endoscopy without risk factors for sedation-related complications is very costly, with no demonstrated improvement in patient safety or procedural outcome.”

The statement was published in the December issue of Gastroenterology.

BAN, THAILAND — Expressive and receptive language abilities are significantly lower in 3-year-olds who were exposed to sodium valproate in utero than they are in children who were exposed to other individual antiepileptic drugs during gestation, according to a subanalysis of the Neurodevelopmental Effects of Antiepileptic Drugs study.

Valproate exposure was associated with a 10-point difference on both language measures compared with exposure to phenytoin, carbamazepine, or lamotrigine—a difference that is not only statistically significant, but clinically important as well, Gus A. Baker, Ph.D., said at the World Congress of Neurology.

The differences apparent in these 3-year-old subjects will likely expand as the groups grow older, said Dr. Baker, director of the division of neurosciences at the Walton Centre for Neurology and Neurosurgery in Liverpool, England and professor of clinical neuropsychology at the University of Liverpool.

“We can expect the difference in the magnitude to get greater and not smaller with age,” he said. Already, Dr. Baker noted, valproate-exposed 3-year-olds in the U.K. portion of the study are lagging behind a group of matched controls. “Well over a third of those exposed to valproate have been referred for speech therapy, so we see that this 10-point difference has real meaning in terms of day-to-day practice.”

The prospective, observational Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study included 303 pregnant women who were taking sodium valproate, carbamazepine, lamotrigine, or phenytoin as monotherapy. Enrollment occurred during 1999-2004 in 25 epilepsy centers in the United States and the United Kingdom. Separate investigations in the two countries were later combined. The primary outcome is cognitive performance of the children at 6 years of age.

Dr. Baker presented the results of the drugs' effect on expressive and receptive language development among 234 children who were 3 years old at the time of assessment.

The children all underwent testing of verbal and nonverbal communication, including expressive and receptive language, visual motor construction, and nonverbal intellectual ability. The children's abilities in these areas were determined by calculating subscores on screening tests called the Differential Ability Scales (Second Edition) and the Preschool Language Scale (Fourth Edition). The scores were adjusted for factors known to affect child intellect, including maternal IQ, maternal age, gestational age, antiepileptic drug (AED) dose, and prenatal exposure to folate.

“We saw that maternal IQ, AED dose, maternal age, gestational age, and preconceptional exposure to folate were significant factors predicting the scores, as we would expect,” Dr. Baker said. “But we also showed that overall, the scores for valproate-exposed children were significantly lower than all other drugs and the magnitude of the effect was greater for verbal than nonverbal language.”

Testing showed that the children exposed to valproate scored significantly lower on measures of expressive language (mean score of 91 vs. 102 for carbamazepine, 104 for lamotrigine, and 101 for phenytoin); and receptive language (mean score of 89 vs. 97 for carbamazepine, 101 for lamotrigine, and 101 for phenytoin). On visual motor construction and nonverbal intellectual ability, children exposed to valproate scored lower, but not significantly lower, than children exposed to the other drugs.

In terms of developmental milestones, this finding could bode ill for the valproate-exposed children, said Dr. Baker.

Unlike the physical results of in utero valproate exposure, which can be surgically corrected to at least some degree, the cognitive effects cannot be erased, he pointed out.

The study confirms earlier NEAD findings, which strongly suggest that women of childbearing age who need AED therapy should avoid valproate if possible.

“For women for whom sodium valproate is the first choice because of the nature of their seizures, we should be thinking about reducing the dose to the least possible effective level,” Dr. Baker said.

The NEAD study is funded by the National Institutes of Health. Dr. Baker had no financial disclosures relevant to the study.

BAN, THAILAND — Expressive and receptive language abilities are significantly lower in 3-year-olds who were exposed to sodium valproate in utero than they are in children who were exposed to other individual antiepileptic drugs during gestation, according to a subanalysis of the Neurodevelopmental Effects of Antiepileptic Drugs study.

Valproate exposure was associated with a 10-point difference on both language measures compared with exposure to phenytoin, carbamazepine, or lamotrigine—a difference that is not only statistically significant, but clinically important as well, Gus A. Baker, Ph.D., said at the World Congress of Neurology.

The differences apparent in these 3-year-old subjects will likely expand as the groups grow older, said Dr. Baker, director of the division of neurosciences at the Walton Centre for Neurology and Neurosurgery in Liverpool, England and professor of clinical neuropsychology at the University of Liverpool.

“We can expect the difference in the magnitude to get greater and not smaller with age,” he said. Already, Dr. Baker noted, valproate-exposed 3-year-olds in the U.K. portion of the study are lagging behind a group of matched controls. “Well over a third of those exposed to valproate have been referred for speech therapy, so we see that this 10-point difference has real meaning in terms of day-to-day practice.”

The prospective, observational Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study included 303 pregnant women who were taking sodium valproate, carbamazepine, lamotrigine, or phenytoin as monotherapy. Enrollment occurred during 1999-2004 in 25 epilepsy centers in the United States and the United Kingdom. Separate investigations in the two countries were later combined. The primary outcome is cognitive performance of the children at 6 years of age.

Dr. Baker presented the results of the drugs' effect on expressive and receptive language development among 234 children who were 3 years old at the time of assessment.

The children all underwent testing of verbal and nonverbal communication, including expressive and receptive language, visual motor construction, and nonverbal intellectual ability. The children's abilities in these areas were determined by calculating subscores on screening tests called the Differential Ability Scales (Second Edition) and the Preschool Language Scale (Fourth Edition). The scores were adjusted for factors known to affect child intellect, including maternal IQ, maternal age, gestational age, antiepileptic drug (AED) dose, and prenatal exposure to folate.

“We saw that maternal IQ, AED dose, maternal age, gestational age, and preconceptional exposure to folate were significant factors predicting the scores, as we would expect,” Dr. Baker said. “But we also showed that overall, the scores for valproate-exposed children were significantly lower than all other drugs and the magnitude of the effect was greater for verbal than nonverbal language.”

Testing showed that the children exposed to valproate scored significantly lower on measures of expressive language (mean score of 91 vs. 102 for carbamazepine, 104 for lamotrigine, and 101 for phenytoin); and receptive language (mean score of 89 vs. 97 for carbamazepine, 101 for lamotrigine, and 101 for phenytoin). On visual motor construction and nonverbal intellectual ability, children exposed to valproate scored lower, but not significantly lower, than children exposed to the other drugs.

In terms of developmental milestones, this finding could bode ill for the valproate-exposed children, said Dr. Baker.

Unlike the physical results of in utero valproate exposure, which can be surgically corrected to at least some degree, the cognitive effects cannot be erased, he pointed out.

The study confirms earlier NEAD findings, which strongly suggest that women of childbearing age who need AED therapy should avoid valproate if possible.

“For women for whom sodium valproate is the first choice because of the nature of their seizures, we should be thinking about reducing the dose to the least possible effective level,” Dr. Baker said.

The NEAD study is funded by the National Institutes of Health. Dr. Baker had no financial disclosures relevant to the study.

BAN, THAILAND — Expressive and receptive language abilities are significantly lower in 3-year-olds who were exposed to sodium valproate in utero than they are in children who were exposed to other individual antiepileptic drugs during gestation, according to a subanalysis of the Neurodevelopmental Effects of Antiepileptic Drugs study.

Valproate exposure was associated with a 10-point difference on both language measures compared with exposure to phenytoin, carbamazepine, or lamotrigine—a difference that is not only statistically significant, but clinically important as well, Gus A. Baker, Ph.D., said at the World Congress of Neurology.

The differences apparent in these 3-year-old subjects will likely expand as the groups grow older, said Dr. Baker, director of the division of neurosciences at the Walton Centre for Neurology and Neurosurgery in Liverpool, England and professor of clinical neuropsychology at the University of Liverpool.

“We can expect the difference in the magnitude to get greater and not smaller with age,” he said. Already, Dr. Baker noted, valproate-exposed 3-year-olds in the U.K. portion of the study are lagging behind a group of matched controls. “Well over a third of those exposed to valproate have been referred for speech therapy, so we see that this 10-point difference has real meaning in terms of day-to-day practice.”

The prospective, observational Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study included 303 pregnant women who were taking sodium valproate, carbamazepine, lamotrigine, or phenytoin as monotherapy. Enrollment occurred during 1999-2004 in 25 epilepsy centers in the United States and the United Kingdom. Separate investigations in the two countries were later combined. The primary outcome is cognitive performance of the children at 6 years of age.

Dr. Baker presented the results of the drugs' effect on expressive and receptive language development among 234 children who were 3 years old at the time of assessment.

The children all underwent testing of verbal and nonverbal communication, including expressive and receptive language, visual motor construction, and nonverbal intellectual ability. The children's abilities in these areas were determined by calculating subscores on screening tests called the Differential Ability Scales (Second Edition) and the Preschool Language Scale (Fourth Edition). The scores were adjusted for factors known to affect child intellect, including maternal IQ, maternal age, gestational age, antiepileptic drug (AED) dose, and prenatal exposure to folate.

“We saw that maternal IQ, AED dose, maternal age, gestational age, and preconceptional exposure to folate were significant factors predicting the scores, as we would expect,” Dr. Baker said. “But we also showed that overall, the scores for valproate-exposed children were significantly lower than all other drugs and the magnitude of the effect was greater for verbal than nonverbal language.”

Testing showed that the children exposed to valproate scored significantly lower on measures of expressive language (mean score of 91 vs. 102 for carbamazepine, 104 for lamotrigine, and 101 for phenytoin); and receptive language (mean score of 89 vs. 97 for carbamazepine, 101 for lamotrigine, and 101 for phenytoin). On visual motor construction and nonverbal intellectual ability, children exposed to valproate scored lower, but not significantly lower, than children exposed to the other drugs.

In terms of developmental milestones, this finding could bode ill for the valproate-exposed children, said Dr. Baker.

Unlike the physical results of in utero valproate exposure, which can be surgically corrected to at least some degree, the cognitive effects cannot be erased, he pointed out.

The study confirms earlier NEAD findings, which strongly suggest that women of childbearing age who need AED therapy should avoid valproate if possible.

“For women for whom sodium valproate is the first choice because of the nature of their seizures, we should be thinking about reducing the dose to the least possible effective level,” Dr. Baker said.

The NEAD study is funded by the National Institutes of Health. Dr. Baker had no financial disclosures relevant to the study.

VIENNA – Pesticide exposure might increase the risk of later dementia by as much as 70%.

“Exposure to pesticides may have long-term damaging effects on the nervous system that contribute to the development of Alzheimer's or other dementias,” Kathleen M. Hayden, Ph.D., said at the International Conference on Alzheimer's Disease. “We need more research to fully characterize the increased risks associated with different types of pesticides, and the duration of their use.”

Dr. Hayden of Duke University Medical Center, Durham, N.C., based her study on data from the Cache County Study of Memory, Health, and Aging. The ongoing study began in 1995, and includes 5,092 subjects, who are assessed every 3 years. The study participants were given a questionnaire that focused on pesticide exposure.

The study population was a good one for examining the impact of pesticides because, Dr. Hayden said, the subjects live in a rural area, the economy of which relies heavily on growing wheat, soybeans, apples, corn, and hay.

Dr. Hayden and her colleagues assessed the risk of new-onset dementia and Alzheimer's disease in 4,012 subjects who were free of dementia at baseline. Her logistic regression analysis was based on 6 years of follow-up, and controlled for age, sex, education, and apolipoprotein-E status.

At baseline, the subjects were a mean of 75 years old. Pesticide exposure had occurred in 19% (743). The exposed group was primarily male (89%). After 6 years of follow-up, there were 412 new cases of dementia; 85 of these subjects (21%) reported some degree of pesticide exposure on their baseline assessment.

The analysis found consistent significant relationships between new-onset dementia and exposure to both organophosphates and organochlorines. Any pesticide exposure increased the risk of dementia and Alzheimer's disease by 56%. Exposure to organophosphate compounds increased the risk of dementia by 36% and Alzheimer's by 59%. Exposure to organochlorines increased the risk of dementia by 60% and Alzheimer's by 70%.

The study did not take into account duration or extent of exposure, and does not prove a causal link between pesticides and dementia, Dr. Hayden cautioned. But it does suggest that more study is necessary. “Some pesticides do alter the level of neurotransmitters, and their use has increased drastically in the past 50 years,” she said. “According to the Environmental Protection Agency, there are more than 18,000 pesticides licensed for use in the U.S., and each year, more than 2 million pounds are applied to our crops, parks, homes, and forests.”

More than 18,000 pesticides are licensed for use in the U.S.

Source ©4loops/iStockphoto.com

VIENNA – Pesticide exposure might increase the risk of later dementia by as much as 70%.

“Exposure to pesticides may have long-term damaging effects on the nervous system that contribute to the development of Alzheimer's or other dementias,” Kathleen M. Hayden, Ph.D., said at the International Conference on Alzheimer's Disease. “We need more research to fully characterize the increased risks associated with different types of pesticides, and the duration of their use.”

Dr. Hayden of Duke University Medical Center, Durham, N.C., based her study on data from the Cache County Study of Memory, Health, and Aging. The ongoing study began in 1995, and includes 5,092 subjects, who are assessed every 3 years. The study participants were given a questionnaire that focused on pesticide exposure.

The study population was a good one for examining the impact of pesticides because, Dr. Hayden said, the subjects live in a rural area, the economy of which relies heavily on growing wheat, soybeans, apples, corn, and hay.

Dr. Hayden and her colleagues assessed the risk of new-onset dementia and Alzheimer's disease in 4,012 subjects who were free of dementia at baseline. Her logistic regression analysis was based on 6 years of follow-up, and controlled for age, sex, education, and apolipoprotein-E status.

At baseline, the subjects were a mean of 75 years old. Pesticide exposure had occurred in 19% (743). The exposed group was primarily male (89%). After 6 years of follow-up, there were 412 new cases of dementia; 85 of these subjects (21%) reported some degree of pesticide exposure on their baseline assessment.

The analysis found consistent significant relationships between new-onset dementia and exposure to both organophosphates and organochlorines. Any pesticide exposure increased the risk of dementia and Alzheimer's disease by 56%. Exposure to organophosphate compounds increased the risk of dementia by 36% and Alzheimer's by 59%. Exposure to organochlorines increased the risk of dementia by 60% and Alzheimer's by 70%.

The study did not take into account duration or extent of exposure, and does not prove a causal link between pesticides and dementia, Dr. Hayden cautioned. But it does suggest that more study is necessary. “Some pesticides do alter the level of neurotransmitters, and their use has increased drastically in the past 50 years,” she said. “According to the Environmental Protection Agency, there are more than 18,000 pesticides licensed for use in the U.S., and each year, more than 2 million pounds are applied to our crops, parks, homes, and forests.”

More than 18,000 pesticides are licensed for use in the U.S.

Source ©4loops/iStockphoto.com

VIENNA – Pesticide exposure might increase the risk of later dementia by as much as 70%.

“Exposure to pesticides may have long-term damaging effects on the nervous system that contribute to the development of Alzheimer's or other dementias,” Kathleen M. Hayden, Ph.D., said at the International Conference on Alzheimer's Disease. “We need more research to fully characterize the increased risks associated with different types of pesticides, and the duration of their use.”

Dr. Hayden of Duke University Medical Center, Durham, N.C., based her study on data from the Cache County Study of Memory, Health, and Aging. The ongoing study began in 1995, and includes 5,092 subjects, who are assessed every 3 years. The study participants were given a questionnaire that focused on pesticide exposure.

The study population was a good one for examining the impact of pesticides because, Dr. Hayden said, the subjects live in a rural area, the economy of which relies heavily on growing wheat, soybeans, apples, corn, and hay.

Dr. Hayden and her colleagues assessed the risk of new-onset dementia and Alzheimer's disease in 4,012 subjects who were free of dementia at baseline. Her logistic regression analysis was based on 6 years of follow-up, and controlled for age, sex, education, and apolipoprotein-E status.

At baseline, the subjects were a mean of 75 years old. Pesticide exposure had occurred in 19% (743). The exposed group was primarily male (89%). After 6 years of follow-up, there were 412 new cases of dementia; 85 of these subjects (21%) reported some degree of pesticide exposure on their baseline assessment.

The analysis found consistent significant relationships between new-onset dementia and exposure to both organophosphates and organochlorines. Any pesticide exposure increased the risk of dementia and Alzheimer's disease by 56%. Exposure to organophosphate compounds increased the risk of dementia by 36% and Alzheimer's by 59%. Exposure to organochlorines increased the risk of dementia by 60% and Alzheimer's by 70%.

The study did not take into account duration or extent of exposure, and does not prove a causal link between pesticides and dementia, Dr. Hayden cautioned. But it does suggest that more study is necessary. “Some pesticides do alter the level of neurotransmitters, and their use has increased drastically in the past 50 years,” she said. “According to the Environmental Protection Agency, there are more than 18,000 pesticides licensed for use in the U.S., and each year, more than 2 million pounds are applied to our crops, parks, homes, and forests.”

More than 18,000 pesticides are licensed for use in the U.S.

Source ©4loops/iStockphoto.com

VIENNA – Dementia does not appear to spare the oldest old, contrary to findings of prior studies suggesting that the incidence tapers off after age 85.

Studies presented at the International Conference on Alzheimer's Disease suggest that dementia rates continue their linear increase even as people approach 100, with a doubling of incidence every 5 years.

“We believe there is now convincing evidence that, unfortunately, this disorder does not go down with age,” Dr. Claudia H. Kawas said at the meeting, which was sponsored by the Alzheimer's Association. The findings are especially important, given that the population of those 90 years and older will increase 10-fold by the middle of this century, said Dr. Kawas, the Al and Trish Nichols Chair in Clinical Neuroscience at the University of California, Irvine. “As more individuals live to these extreme ages, dementia in the oldest old could become an epidemic with enormous public health impact.”

Dr. Kawas and her colleagues presented data from The 90+ Study, a population-based study established in the early 1980s in a California retirement community. Out of the original 14,000 enrolled, her substudy comprised 330 who were aged 90 years or older at the beginning of 2003, available for in-person interviews, and nondemented.

At baseline, the participants ranged in age from 90–108 years; the mean age was 94 years. Most (54%) were still living alone; 29% were living at home with a relative; and 17% were in a group facility or nursing home. Seventy percent were women.

Assessments occurred every 6 months through Jan. 1, 2008, and included a neurologic exam, neuropsychiatric testing, informative questionnaires, and medical records. The mean follow-up time was a little longer than 2 years; almost 400 person-years of follow-up data were collected overall, with 50 person-years of data on those who were 100 years or older. “As far as I know, this is the largest study of dementia in centenarians ever done,” Dr. Kawas said.

By the end of the study, 140 cases of dementia had developed: 49 in those aged 90–94; 71 in those aged 95–99; and 20 in those aged 100 and older. The rate was 18% for both men and women.

The investigators found that the risk of dementia doubled every 5 years, from 10% for the 90- to 94-year-olds to 20% for the 95- to 99-year-olds, and 41% for those 100 and older.

An Italian study that examined dementia rates in people 80 years and older came to similar conclusions. “Although not increasing exponentially, the overall prevalence and incidence rates of dementia continue to rise in very old age,” Dr. Ugo Lucca of Istituto di Ricerche Farmacologiche “Mario Negri,” Milan, wrote in his poster.

Dr. Lucca and his colleagues examined the rate of new-onset dementia in subjects older than 80 years, who were followed for a mean of 3 years. The Monzino 80-plus Study gathered baseline information on 2,138 residents of eight municipalities in Varese province, Italy. Most of the assessment information was gathered at a first visit that occurred at the subjects' residence.

The assessment included neuropsychiatric testing, functional status, and mood and behavioral assessments. Those who screened positive for dementia received additional testing to make a more specific determination of their cognitive status.

VIENNA – Dementia does not appear to spare the oldest old, contrary to findings of prior studies suggesting that the incidence tapers off after age 85.

Studies presented at the International Conference on Alzheimer's Disease suggest that dementia rates continue their linear increase even as people approach 100, with a doubling of incidence every 5 years.

“We believe there is now convincing evidence that, unfortunately, this disorder does not go down with age,” Dr. Claudia H. Kawas said at the meeting, which was sponsored by the Alzheimer's Association. The findings are especially important, given that the population of those 90 years and older will increase 10-fold by the middle of this century, said Dr. Kawas, the Al and Trish Nichols Chair in Clinical Neuroscience at the University of California, Irvine. “As more individuals live to these extreme ages, dementia in the oldest old could become an epidemic with enormous public health impact.”

Dr. Kawas and her colleagues presented data from The 90+ Study, a population-based study established in the early 1980s in a California retirement community. Out of the original 14,000 enrolled, her substudy comprised 330 who were aged 90 years or older at the beginning of 2003, available for in-person interviews, and nondemented.

At baseline, the participants ranged in age from 90–108 years; the mean age was 94 years. Most (54%) were still living alone; 29% were living at home with a relative; and 17% were in a group facility or nursing home. Seventy percent were women.

Assessments occurred every 6 months through Jan. 1, 2008, and included a neurologic exam, neuropsychiatric testing, informative questionnaires, and medical records. The mean follow-up time was a little longer than 2 years; almost 400 person-years of follow-up data were collected overall, with 50 person-years of data on those who were 100 years or older. “As far as I know, this is the largest study of dementia in centenarians ever done,” Dr. Kawas said.

By the end of the study, 140 cases of dementia had developed: 49 in those aged 90–94; 71 in those aged 95–99; and 20 in those aged 100 and older. The rate was 18% for both men and women.

The investigators found that the risk of dementia doubled every 5 years, from 10% for the 90- to 94-year-olds to 20% for the 95- to 99-year-olds, and 41% for those 100 and older.

An Italian study that examined dementia rates in people 80 years and older came to similar conclusions. “Although not increasing exponentially, the overall prevalence and incidence rates of dementia continue to rise in very old age,” Dr. Ugo Lucca of Istituto di Ricerche Farmacologiche “Mario Negri,” Milan, wrote in his poster.

Dr. Lucca and his colleagues examined the rate of new-onset dementia in subjects older than 80 years, who were followed for a mean of 3 years. The Monzino 80-plus Study gathered baseline information on 2,138 residents of eight municipalities in Varese province, Italy. Most of the assessment information was gathered at a first visit that occurred at the subjects' residence.

The assessment included neuropsychiatric testing, functional status, and mood and behavioral assessments. Those who screened positive for dementia received additional testing to make a more specific determination of their cognitive status.

VIENNA – Dementia does not appear to spare the oldest old, contrary to findings of prior studies suggesting that the incidence tapers off after age 85.

Studies presented at the International Conference on Alzheimer's Disease suggest that dementia rates continue their linear increase even as people approach 100, with a doubling of incidence every 5 years.

“We believe there is now convincing evidence that, unfortunately, this disorder does not go down with age,” Dr. Claudia H. Kawas said at the meeting, which was sponsored by the Alzheimer's Association. The findings are especially important, given that the population of those 90 years and older will increase 10-fold by the middle of this century, said Dr. Kawas, the Al and Trish Nichols Chair in Clinical Neuroscience at the University of California, Irvine. “As more individuals live to these extreme ages, dementia in the oldest old could become an epidemic with enormous public health impact.”

Dr. Kawas and her colleagues presented data from The 90+ Study, a population-based study established in the early 1980s in a California retirement community. Out of the original 14,000 enrolled, her substudy comprised 330 who were aged 90 years or older at the beginning of 2003, available for in-person interviews, and nondemented.

At baseline, the participants ranged in age from 90–108 years; the mean age was 94 years. Most (54%) were still living alone; 29% were living at home with a relative; and 17% were in a group facility or nursing home. Seventy percent were women.

Assessments occurred every 6 months through Jan. 1, 2008, and included a neurologic exam, neuropsychiatric testing, informative questionnaires, and medical records. The mean follow-up time was a little longer than 2 years; almost 400 person-years of follow-up data were collected overall, with 50 person-years of data on those who were 100 years or older. “As far as I know, this is the largest study of dementia in centenarians ever done,” Dr. Kawas said.

By the end of the study, 140 cases of dementia had developed: 49 in those aged 90–94; 71 in those aged 95–99; and 20 in those aged 100 and older. The rate was 18% for both men and women.

The investigators found that the risk of dementia doubled every 5 years, from 10% for the 90- to 94-year-olds to 20% for the 95- to 99-year-olds, and 41% for those 100 and older.

An Italian study that examined dementia rates in people 80 years and older came to similar conclusions. “Although not increasing exponentially, the overall prevalence and incidence rates of dementia continue to rise in very old age,” Dr. Ugo Lucca of Istituto di Ricerche Farmacologiche “Mario Negri,” Milan, wrote in his poster.

Dr. Lucca and his colleagues examined the rate of new-onset dementia in subjects older than 80 years, who were followed for a mean of 3 years. The Monzino 80-plus Study gathered baseline information on 2,138 residents of eight municipalities in Varese province, Italy. Most of the assessment information was gathered at a first visit that occurred at the subjects' residence.

The assessment included neuropsychiatric testing, functional status, and mood and behavioral assessments. Those who screened positive for dementia received additional testing to make a more specific determination of their cognitive status.

VIENNA – Valproate treatment over 2 years does nothing to delay the onset of agitation or psychosis in patients with Alzheimer's disease, and patients taking the anticonvulsant showed significantly more brain volume loss on MRI at year 1 than did those taking placebo.

But because the changes in brain volume did not correlate with any clinical differences between the groups, it's difficult to know just what to make of the observed volume loss, Dr. Pierre Tariot said at the International Conference on Alzheimer's Disease.

“Interpretation of these results really isn't possible at this juncture,” said Dr. Tariot of the Banner Alzheimer's Institute, Phoenix, in an interview. “It could theoretically represent damage to the brain, but that seems unlikely due to the absence of correlation with clinical decline that is seen in natural history studies. There are case reports of 'pseudoatrophy' associated with valproate use, which may be relevant here. We have an ongoing analysis, and the full details will be presented at a later time.”

The trial randomized 313 patients with mild-moderate Alzheimer's disease who lacked agitation or psychosis at baseline to either placebo or an extended-release form of divalproex sodium (Depakote ER) at a dose of 10–12 mg/kg per day. The primary outcome was time until the emergence of agitation and/or psychosis. The symptoms had to last at least 2 weeks, and had to be clinically significant in the opinion of the site physician.

Secondary end points included changes in the Neuropsychiatric Inventory (NPI) score the Cohen-Mansfield Agitation Inventory (CMAI), Mini-Mental State Exam (MMSE), the Alzheimer's Disease Assessment Scale–Cognitive (ADAS-Cog) domain, and the Alzheimer's Disease Cooperative Study activities of daily living (ADCS-ADL) domain. MRI of the brain was performed on a subset of 90 patients at baseline and 1 year.

The patients' mean age was 75 years; their mean MMSE at baseline was 17 and the mean NPI score was 3. Most of the patients (70%) were positive for the high-risk apolipoprotein E e4 (ApoE e4) allele.

There were no between-group differences in time to agitation or psychosis. In fact, although the study assumed an incidence of 50% by the end of the trial, only 17% of the entire cohort developed either of these symptoms, said Dr. Tariot, who received consulting fees and research funding from Abbott Laboratories, which manufactures Depakote ER. Abbott supplied the drugs for the trial and funded the MRI portion of the trial.

There also were no between-group differences in any of the secondary end points, confirming that valproate confers no clinically discernible neuroprotective benefit. Patients taking placebo had a slightly better score on the ADCS-ADL at 24 months, Dr. Tariot said, but that difference did not reach significance after adjustment for multiple comparisons.

Consistent with known effects of the medication, patients taking valproate had significantly more central nervous system and gastrointestinal side effects. Patients in the active treatment group also experienced mild decreases in neutrophils and platelets.

The conference was sponsored by the Alzheimer's Association.

'There are case reports of “pseudoatrophy” associated with valproate use, which may be relevant here.'

Source DR. TARIOT

VIENNA – Valproate treatment over 2 years does nothing to delay the onset of agitation or psychosis in patients with Alzheimer's disease, and patients taking the anticonvulsant showed significantly more brain volume loss on MRI at year 1 than did those taking placebo.

But because the changes in brain volume did not correlate with any clinical differences between the groups, it's difficult to know just what to make of the observed volume loss, Dr. Pierre Tariot said at the International Conference on Alzheimer's Disease.

“Interpretation of these results really isn't possible at this juncture,” said Dr. Tariot of the Banner Alzheimer's Institute, Phoenix, in an interview. “It could theoretically represent damage to the brain, but that seems unlikely due to the absence of correlation with clinical decline that is seen in natural history studies. There are case reports of 'pseudoatrophy' associated with valproate use, which may be relevant here. We have an ongoing analysis, and the full details will be presented at a later time.”

The trial randomized 313 patients with mild-moderate Alzheimer's disease who lacked agitation or psychosis at baseline to either placebo or an extended-release form of divalproex sodium (Depakote ER) at a dose of 10–12 mg/kg per day. The primary outcome was time until the emergence of agitation and/or psychosis. The symptoms had to last at least 2 weeks, and had to be clinically significant in the opinion of the site physician.

Secondary end points included changes in the Neuropsychiatric Inventory (NPI) score the Cohen-Mansfield Agitation Inventory (CMAI), Mini-Mental State Exam (MMSE), the Alzheimer's Disease Assessment Scale–Cognitive (ADAS-Cog) domain, and the Alzheimer's Disease Cooperative Study activities of daily living (ADCS-ADL) domain. MRI of the brain was performed on a subset of 90 patients at baseline and 1 year.

The patients' mean age was 75 years; their mean MMSE at baseline was 17 and the mean NPI score was 3. Most of the patients (70%) were positive for the high-risk apolipoprotein E e4 (ApoE e4) allele.

There were no between-group differences in time to agitation or psychosis. In fact, although the study assumed an incidence of 50% by the end of the trial, only 17% of the entire cohort developed either of these symptoms, said Dr. Tariot, who received consulting fees and research funding from Abbott Laboratories, which manufactures Depakote ER. Abbott supplied the drugs for the trial and funded the MRI portion of the trial.

There also were no between-group differences in any of the secondary end points, confirming that valproate confers no clinically discernible neuroprotective benefit. Patients taking placebo had a slightly better score on the ADCS-ADL at 24 months, Dr. Tariot said, but that difference did not reach significance after adjustment for multiple comparisons.

Consistent with known effects of the medication, patients taking valproate had significantly more central nervous system and gastrointestinal side effects. Patients in the active treatment group also experienced mild decreases in neutrophils and platelets.

The conference was sponsored by the Alzheimer's Association.

'There are case reports of “pseudoatrophy” associated with valproate use, which may be relevant here.'

Source DR. TARIOT

VIENNA – Valproate treatment over 2 years does nothing to delay the onset of agitation or psychosis in patients with Alzheimer's disease, and patients taking the anticonvulsant showed significantly more brain volume loss on MRI at year 1 than did those taking placebo.

But because the changes in brain volume did not correlate with any clinical differences between the groups, it's difficult to know just what to make of the observed volume loss, Dr. Pierre Tariot said at the International Conference on Alzheimer's Disease.

“Interpretation of these results really isn't possible at this juncture,” said Dr. Tariot of the Banner Alzheimer's Institute, Phoenix, in an interview. “It could theoretically represent damage to the brain, but that seems unlikely due to the absence of correlation with clinical decline that is seen in natural history studies. There are case reports of 'pseudoatrophy' associated with valproate use, which may be relevant here. We have an ongoing analysis, and the full details will be presented at a later time.”

The trial randomized 313 patients with mild-moderate Alzheimer's disease who lacked agitation or psychosis at baseline to either placebo or an extended-release form of divalproex sodium (Depakote ER) at a dose of 10–12 mg/kg per day. The primary outcome was time until the emergence of agitation and/or psychosis. The symptoms had to last at least 2 weeks, and had to be clinically significant in the opinion of the site physician.

Secondary end points included changes in the Neuropsychiatric Inventory (NPI) score the Cohen-Mansfield Agitation Inventory (CMAI), Mini-Mental State Exam (MMSE), the Alzheimer's Disease Assessment Scale–Cognitive (ADAS-Cog) domain, and the Alzheimer's Disease Cooperative Study activities of daily living (ADCS-ADL) domain. MRI of the brain was performed on a subset of 90 patients at baseline and 1 year.

The patients' mean age was 75 years; their mean MMSE at baseline was 17 and the mean NPI score was 3. Most of the patients (70%) were positive for the high-risk apolipoprotein E e4 (ApoE e4) allele.

There were no between-group differences in time to agitation or psychosis. In fact, although the study assumed an incidence of 50% by the end of the trial, only 17% of the entire cohort developed either of these symptoms, said Dr. Tariot, who received consulting fees and research funding from Abbott Laboratories, which manufactures Depakote ER. Abbott supplied the drugs for the trial and funded the MRI portion of the trial.

There also were no between-group differences in any of the secondary end points, confirming that valproate confers no clinically discernible neuroprotective benefit. Patients taking placebo had a slightly better score on the ADCS-ADL at 24 months, Dr. Tariot said, but that difference did not reach significance after adjustment for multiple comparisons.

Consistent with known effects of the medication, patients taking valproate had significantly more central nervous system and gastrointestinal side effects. Patients in the active treatment group also experienced mild decreases in neutrophils and platelets.

The conference was sponsored by the Alzheimer's Association.

'There are case reports of “pseudoatrophy” associated with valproate use, which may be relevant here.'

Source DR. TARIOT