ICYMI Multiple Sclerosis

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SAN DIEGO—Patients with multiple sclerosis (MS) and cognitive impairment may benefit from increasing their cognitive reserve and from rehabilitation techniques such as self-generated learning, spaced learning, and spaced retrieval, researchers reported at the Fourth Cooperative Meeting of the Consortium of MS Centers and Americas Committee for Treatment and Research in MS.

Approximately two-thirds of patients with MS have cognitive impairment, and patients cite cognition as a critically important issue, said John DeLuca, PhD, Vice President for Research at the Kessler Foundation Research Center in West Orange, New Jersey, and Professor of Physical Medicine and Rehabilitation and Neurology and Neuroscience at the University of Medicine and Dentistry of New Jersey–New Jersey Medical School in Newark. “It’s something we should be paying a lot more attention to in MS clinics throughout the country,” he told Neurology Reviews.

Assessing Impairment
According to Dr. DeLuca, rehabilitation techniques are most effective when preceded by an accurate assessment of a patient’s impairment, but many impairment assessments rely on self-report. “The accuracy of self-reported cognitive problems can be a significant issue,” he said. “You cannot treat a cognitive problem unless you know what it is.”

To further explore this issue, he and his colleagues ran a series of studies examining “actual reality,” a technique that measures actual everyday life activity, in this case using an Internet task in which people were asked to book an airline ticket to Florida. “This is an actual behavior. You can do it at home or in the lab, in New York City, or in China,” said Dr. DeLuca.

The investigators examined whether the actual performance of healthy controls and patients with MS correlated with self-reports and with performance on cognitive tasks. Results showed that self-report did not correlate with actual performance of an actual task in everyday life, but objective memory and composite scores of cognition predicted actual, everyday life performance. Dr. DeLuca believes more formalized assessment of cognitive problems is necessary to devise appropriate treatment plans that can improve everyday life functional activity.

Learning and Memory
Treatment is also enhanced by accurately assessing the cause of memory problems in patients with MS. “People always talk about persons with MS having a memory problem. Well, there is no memory without learning. If you don’t learn something, you can’t remember it,” said Dr. DeLuca.

After studying memory and learning problems in patients with MS, he and his colleagues found that the patients had difficulty with the learning of new information but were able to accurately retrieve newly learned information. That is, the major problem is not in retrieval from long-term storage, but in difficulty in the acquisition of new knowledge. “It wasn’t so much a memory problem—it was a learning problem,” he stated. “Our treatment should be, let’s make sure they learn to begin with.”

Several techniques might address acquisition issues, including one approach called self-generated learning. Research has shown that patients who generate their own answers to questions remember information better than those who are simply presented with material. “Self-generating provides stronger encoding, which makes it easier to retrieve the information,” Dr. DeLuca explained.

Spaced learning also benefits patients with MS. Dr. DeLuca cited a study in which participants studied a newspaper article three times in a row versus three times that were spaced apart. The patients remembered significantly more information when the learning trials were spaced apart, he noted.

Furthermore, research has shown that individuals improve retrieval of information by studying material on one trial and then being tested on a second trial, rather than studying the information twice. This finding—known as spaced retrieval or the testing effect—is counterintuitive, as most people would opt to study material several times. However, the act of testing increases the strength of the encoding of information, which makes it easier to retrieve.

When cognitive techniques such as spaced retrieval, self-generation, and spaced learning are used in conjunction with one another, they can significantly improve learning in patients with MS. “We found that if you made sure that people learned, their recall and recognition—their retrieval from long-term storage—was as good as that of healthy individuals,” said Dr. DeLuca.

Cognitive Reserve
Researchers have sought to explain why some patients with MS show little or no cognitive impairment, while others with the same degree of MRI disease progression show significant cognitive impairment. The cognitive reserve hypothesis might explain this disparity, said Dr. DeLuca, as well as provide an avenue for cognitive rehabilitation. According to the hypothesis, individuals who lead an intellectually stimulating life may develop greater cerebral efficiency, which, in turn, provides protection from MS disease expression (ie, cognitive impairment).

Dr. DeLuca added that patients with MS who have low cognitive reserve show greater impairment in cognition than those with high cognitive reserve, despite displaying similar levels of brain atrophy on MRI. “People who develop a brain that’s more resistant to the expression of MS will be much less likely to show these cognitive problems,” he said.

This finding has significant implications for the cognitive rehabilitation of patients with MS. Patients might build cognitive reserve through intellectual hobbies such as reading, art, and music, as well as by engaging in aerobic exercise.

For a young person diagnosed with MS, “building a cognitive reserve is going to be the very backbone of cognitive rehabilitation,” said Dr. DeLuca. “It may not be protective against disease progression, but it could be protective against the expression of the disease.”

Dr. DeLuca emphasized that cognitive rehabilitation influences the family life, employment, social relationships, and everyday life of patients. “Cognitive interventions can have a profound effect on the life of persons with MS, and that’s something we really need to focus on,” he concluded.                                           

Click here to listen to an accompanying audio interview.

SAN DIEGO—Patients with multiple sclerosis (MS) and cognitive impairment may benefit from increasing their cognitive reserve and from rehabilitation techniques such as self-generated learning, spaced learning, and spaced retrieval, researchers reported at the Fourth Cooperative Meeting of the Consortium of MS Centers and Americas Committee for Treatment and Research in MS.

Approximately two-thirds of patients with MS have cognitive impairment, and patients cite cognition as a critically important issue, said John DeLuca, PhD, Vice President for Research at the Kessler Foundation Research Center in West Orange, New Jersey, and Professor of Physical Medicine and Rehabilitation and Neurology and Neuroscience at the University of Medicine and Dentistry of New Jersey–New Jersey Medical School in Newark. “It’s something we should be paying a lot more attention to in MS clinics throughout the country,” he told Neurology Reviews.

Assessing Impairment
According to Dr. DeLuca, rehabilitation techniques are most effective when preceded by an accurate assessment of a patient’s impairment, but many impairment assessments rely on self-report. “The accuracy of self-reported cognitive problems can be a significant issue,” he said. “You cannot treat a cognitive problem unless you know what it is.”

To further explore this issue, he and his colleagues ran a series of studies examining “actual reality,” a technique that measures actual everyday life activity, in this case using an Internet task in which people were asked to book an airline ticket to Florida. “This is an actual behavior. You can do it at home or in the lab, in New York City, or in China,” said Dr. DeLuca.

The investigators examined whether the actual performance of healthy controls and patients with MS correlated with self-reports and with performance on cognitive tasks. Results showed that self-report did not correlate with actual performance of an actual task in everyday life, but objective memory and composite scores of cognition predicted actual, everyday life performance. Dr. DeLuca believes more formalized assessment of cognitive problems is necessary to devise appropriate treatment plans that can improve everyday life functional activity.

Learning and Memory
Treatment is also enhanced by accurately assessing the cause of memory problems in patients with MS. “People always talk about persons with MS having a memory problem. Well, there is no memory without learning. If you don’t learn something, you can’t remember it,” said Dr. DeLuca.

After studying memory and learning problems in patients with MS, he and his colleagues found that the patients had difficulty with the learning of new information but were able to accurately retrieve newly learned information. That is, the major problem is not in retrieval from long-term storage, but in difficulty in the acquisition of new knowledge. “It wasn’t so much a memory problem—it was a learning problem,” he stated. “Our treatment should be, let’s make sure they learn to begin with.”

Several techniques might address acquisition issues, including one approach called self-generated learning. Research has shown that patients who generate their own answers to questions remember information better than those who are simply presented with material. “Self-generating provides stronger encoding, which makes it easier to retrieve the information,” Dr. DeLuca explained.

Spaced learning also benefits patients with MS. Dr. DeLuca cited a study in which participants studied a newspaper article three times in a row versus three times that were spaced apart. The patients remembered significantly more information when the learning trials were spaced apart, he noted.

Furthermore, research has shown that individuals improve retrieval of information by studying material on one trial and then being tested on a second trial, rather than studying the information twice. This finding—known as spaced retrieval or the testing effect—is counterintuitive, as most people would opt to study material several times. However, the act of testing increases the strength of the encoding of information, which makes it easier to retrieve.

When cognitive techniques such as spaced retrieval, self-generation, and spaced learning are used in conjunction with one another, they can significantly improve learning in patients with MS. “We found that if you made sure that people learned, their recall and recognition—their retrieval from long-term storage—was as good as that of healthy individuals,” said Dr. DeLuca.

Cognitive Reserve
Researchers have sought to explain why some patients with MS show little or no cognitive impairment, while others with the same degree of MRI disease progression show significant cognitive impairment. The cognitive reserve hypothesis might explain this disparity, said Dr. DeLuca, as well as provide an avenue for cognitive rehabilitation. According to the hypothesis, individuals who lead an intellectually stimulating life may develop greater cerebral efficiency, which, in turn, provides protection from MS disease expression (ie, cognitive impairment).

Dr. DeLuca added that patients with MS who have low cognitive reserve show greater impairment in cognition than those with high cognitive reserve, despite displaying similar levels of brain atrophy on MRI. “People who develop a brain that’s more resistant to the expression of MS will be much less likely to show these cognitive problems,” he said.

This finding has significant implications for the cognitive rehabilitation of patients with MS. Patients might build cognitive reserve through intellectual hobbies such as reading, art, and music, as well as by engaging in aerobic exercise.

For a young person diagnosed with MS, “building a cognitive reserve is going to be the very backbone of cognitive rehabilitation,” said Dr. DeLuca. “It may not be protective against disease progression, but it could be protective against the expression of the disease.”

Dr. DeLuca emphasized that cognitive rehabilitation influences the family life, employment, social relationships, and everyday life of patients. “Cognitive interventions can have a profound effect on the life of persons with MS, and that’s something we really need to focus on,” he concluded.                                           

Click here to listen to an accompanying audio interview.

SAN DIEGO—Patients with multiple sclerosis (MS) and cognitive impairment may benefit from increasing their cognitive reserve and from rehabilitation techniques such as self-generated learning, spaced learning, and spaced retrieval, researchers reported at the Fourth Cooperative Meeting of the Consortium of MS Centers and Americas Committee for Treatment and Research in MS.

Approximately two-thirds of patients with MS have cognitive impairment, and patients cite cognition as a critically important issue, said John DeLuca, PhD, Vice President for Research at the Kessler Foundation Research Center in West Orange, New Jersey, and Professor of Physical Medicine and Rehabilitation and Neurology and Neuroscience at the University of Medicine and Dentistry of New Jersey–New Jersey Medical School in Newark. “It’s something we should be paying a lot more attention to in MS clinics throughout the country,” he told Neurology Reviews.

Assessing Impairment
According to Dr. DeLuca, rehabilitation techniques are most effective when preceded by an accurate assessment of a patient’s impairment, but many impairment assessments rely on self-report. “The accuracy of self-reported cognitive problems can be a significant issue,” he said. “You cannot treat a cognitive problem unless you know what it is.”

To further explore this issue, he and his colleagues ran a series of studies examining “actual reality,” a technique that measures actual everyday life activity, in this case using an Internet task in which people were asked to book an airline ticket to Florida. “This is an actual behavior. You can do it at home or in the lab, in New York City, or in China,” said Dr. DeLuca.

The investigators examined whether the actual performance of healthy controls and patients with MS correlated with self-reports and with performance on cognitive tasks. Results showed that self-report did not correlate with actual performance of an actual task in everyday life, but objective memory and composite scores of cognition predicted actual, everyday life performance. Dr. DeLuca believes more formalized assessment of cognitive problems is necessary to devise appropriate treatment plans that can improve everyday life functional activity.

Learning and Memory
Treatment is also enhanced by accurately assessing the cause of memory problems in patients with MS. “People always talk about persons with MS having a memory problem. Well, there is no memory without learning. If you don’t learn something, you can’t remember it,” said Dr. DeLuca.

After studying memory and learning problems in patients with MS, he and his colleagues found that the patients had difficulty with the learning of new information but were able to accurately retrieve newly learned information. That is, the major problem is not in retrieval from long-term storage, but in difficulty in the acquisition of new knowledge. “It wasn’t so much a memory problem—it was a learning problem,” he stated. “Our treatment should be, let’s make sure they learn to begin with.”

Several techniques might address acquisition issues, including one approach called self-generated learning. Research has shown that patients who generate their own answers to questions remember information better than those who are simply presented with material. “Self-generating provides stronger encoding, which makes it easier to retrieve the information,” Dr. DeLuca explained.

Spaced learning also benefits patients with MS. Dr. DeLuca cited a study in which participants studied a newspaper article three times in a row versus three times that were spaced apart. The patients remembered significantly more information when the learning trials were spaced apart, he noted.

Furthermore, research has shown that individuals improve retrieval of information by studying material on one trial and then being tested on a second trial, rather than studying the information twice. This finding—known as spaced retrieval or the testing effect—is counterintuitive, as most people would opt to study material several times. However, the act of testing increases the strength of the encoding of information, which makes it easier to retrieve.

When cognitive techniques such as spaced retrieval, self-generation, and spaced learning are used in conjunction with one another, they can significantly improve learning in patients with MS. “We found that if you made sure that people learned, their recall and recognition—their retrieval from long-term storage—was as good as that of healthy individuals,” said Dr. DeLuca.

Cognitive Reserve
Researchers have sought to explain why some patients with MS show little or no cognitive impairment, while others with the same degree of MRI disease progression show significant cognitive impairment. The cognitive reserve hypothesis might explain this disparity, said Dr. DeLuca, as well as provide an avenue for cognitive rehabilitation. According to the hypothesis, individuals who lead an intellectually stimulating life may develop greater cerebral efficiency, which, in turn, provides protection from MS disease expression (ie, cognitive impairment).

Dr. DeLuca added that patients with MS who have low cognitive reserve show greater impairment in cognition than those with high cognitive reserve, despite displaying similar levels of brain atrophy on MRI. “People who develop a brain that’s more resistant to the expression of MS will be much less likely to show these cognitive problems,” he said.

This finding has significant implications for the cognitive rehabilitation of patients with MS. Patients might build cognitive reserve through intellectual hobbies such as reading, art, and music, as well as by engaging in aerobic exercise.

For a young person diagnosed with MS, “building a cognitive reserve is going to be the very backbone of cognitive rehabilitation,” said Dr. DeLuca. “It may not be protective against disease progression, but it could be protective against the expression of the disease.”

Dr. DeLuca emphasized that cognitive rehabilitation influences the family life, employment, social relationships, and everyday life of patients. “Cognitive interventions can have a profound effect on the life of persons with MS, and that’s something we really need to focus on,” he concluded.                                           

Click here to listen to an accompanying audio interview.

NEW ORLEANS—Now that testing for John Cunningham virus (JCV) antibody status is recommended for all patients with multiple sclerosis (MS) receiving infusions of natalizumab, the decision of whether to switch to another agent if the antibody status is positive might seem straightforward. However, the potential for relapsing and worsening MS might cause some patients to weigh the risks of natalizumab treatment, including progressive multifocal leukoencephalopathy (PML), a bit differently.

Researchers from Winthrop Comprehensive MS Care Center in Mineola, New York, presented findings from a study on patient decision-making and JCV antibody status at the 64th Annual Meeting of the American Academy of Neurology. Malcolm Gottesman, MD, and colleagues studied 71 patients who had initiated natalizumab therapy without knowing their JCV status. After antibody testing, patients were followed for six months and evaluated based on whether they elected to continue or discontinue natalizumab therapy. Of the 39 patients who were JCV negative, all continued on therapy and two (5%) experienced a relapse within the six-month period. Of the 32 patients who tested positive for JCV, nine elected to stop natalizumab therapy, but five patients (56%) had a relapse during the follow-up period. Of the 23 who continued, one patient (4%) relapsed. Of the nine patients who discontinued natalizumab after learning their JCV status, all but one (80%) resumed the treatment after they experienced an MS relapse.

In an interview with Neurology Reviews, coinvestigator Denise Cheng, RN, explained that personal acceptance of risk seemed to be the most relevant factor in patients’ decision of whether to stay on therapy after learning of a positive JCV assay. No other patient characteristics, such as age or gender, stood out among the groups. Although none of the patients treated at the clinic has developed a case of PML, Ms. Cheng advocated maintaining a close relationship with patients receiving infusions of natalizumab, as well as their families, to monitor for early signs that may indicate PML onset. Some of these signs, including cognitive, language, or visual impairment, are difficult to distinguish from MS symptoms.

As many as 50% to 70% of the population carries antibodies to JCV. The FDA confirmed in January 2012 that testing positive for anti-JCV antibodies has been identified as a risk factor for PML, stating, “The risks and benefits of continuing treatment [with natalizumab] should be carefully considered in patients who are found to be anti-JCV antibody positive and have one or more of the other known risk factors for PML.” The other two risk factors are treatment with natalizumab for more than two years and prior treatment with immunosuppressive medications. Prior immunosuppressive treatment has been shown to increase PML risk twofold to fourfold. People with all three known risk factors have an estimated risk of PML of 11 in 1,000 users.      

NEW ORLEANS—Now that testing for John Cunningham virus (JCV) antibody status is recommended for all patients with multiple sclerosis (MS) receiving infusions of natalizumab, the decision of whether to switch to another agent if the antibody status is positive might seem straightforward. However, the potential for relapsing and worsening MS might cause some patients to weigh the risks of natalizumab treatment, including progressive multifocal leukoencephalopathy (PML), a bit differently.

Researchers from Winthrop Comprehensive MS Care Center in Mineola, New York, presented findings from a study on patient decision-making and JCV antibody status at the 64th Annual Meeting of the American Academy of Neurology. Malcolm Gottesman, MD, and colleagues studied 71 patients who had initiated natalizumab therapy without knowing their JCV status. After antibody testing, patients were followed for six months and evaluated based on whether they elected to continue or discontinue natalizumab therapy. Of the 39 patients who were JCV negative, all continued on therapy and two (5%) experienced a relapse within the six-month period. Of the 32 patients who tested positive for JCV, nine elected to stop natalizumab therapy, but five patients (56%) had a relapse during the follow-up period. Of the 23 who continued, one patient (4%) relapsed. Of the nine patients who discontinued natalizumab after learning their JCV status, all but one (80%) resumed the treatment after they experienced an MS relapse.

In an interview with Neurology Reviews, coinvestigator Denise Cheng, RN, explained that personal acceptance of risk seemed to be the most relevant factor in patients’ decision of whether to stay on therapy after learning of a positive JCV assay. No other patient characteristics, such as age or gender, stood out among the groups. Although none of the patients treated at the clinic has developed a case of PML, Ms. Cheng advocated maintaining a close relationship with patients receiving infusions of natalizumab, as well as their families, to monitor for early signs that may indicate PML onset. Some of these signs, including cognitive, language, or visual impairment, are difficult to distinguish from MS symptoms.

As many as 50% to 70% of the population carries antibodies to JCV. The FDA confirmed in January 2012 that testing positive for anti-JCV antibodies has been identified as a risk factor for PML, stating, “The risks and benefits of continuing treatment [with natalizumab] should be carefully considered in patients who are found to be anti-JCV antibody positive and have one or more of the other known risk factors for PML.” The other two risk factors are treatment with natalizumab for more than two years and prior treatment with immunosuppressive medications. Prior immunosuppressive treatment has been shown to increase PML risk twofold to fourfold. People with all three known risk factors have an estimated risk of PML of 11 in 1,000 users.      

NEW ORLEANS—Now that testing for John Cunningham virus (JCV) antibody status is recommended for all patients with multiple sclerosis (MS) receiving infusions of natalizumab, the decision of whether to switch to another agent if the antibody status is positive might seem straightforward. However, the potential for relapsing and worsening MS might cause some patients to weigh the risks of natalizumab treatment, including progressive multifocal leukoencephalopathy (PML), a bit differently.

Researchers from Winthrop Comprehensive MS Care Center in Mineola, New York, presented findings from a study on patient decision-making and JCV antibody status at the 64th Annual Meeting of the American Academy of Neurology. Malcolm Gottesman, MD, and colleagues studied 71 patients who had initiated natalizumab therapy without knowing their JCV status. After antibody testing, patients were followed for six months and evaluated based on whether they elected to continue or discontinue natalizumab therapy. Of the 39 patients who were JCV negative, all continued on therapy and two (5%) experienced a relapse within the six-month period. Of the 32 patients who tested positive for JCV, nine elected to stop natalizumab therapy, but five patients (56%) had a relapse during the follow-up period. Of the 23 who continued, one patient (4%) relapsed. Of the nine patients who discontinued natalizumab after learning their JCV status, all but one (80%) resumed the treatment after they experienced an MS relapse.

In an interview with Neurology Reviews, coinvestigator Denise Cheng, RN, explained that personal acceptance of risk seemed to be the most relevant factor in patients’ decision of whether to stay on therapy after learning of a positive JCV assay. No other patient characteristics, such as age or gender, stood out among the groups. Although none of the patients treated at the clinic has developed a case of PML, Ms. Cheng advocated maintaining a close relationship with patients receiving infusions of natalizumab, as well as their families, to monitor for early signs that may indicate PML onset. Some of these signs, including cognitive, language, or visual impairment, are difficult to distinguish from MS symptoms.

As many as 50% to 70% of the population carries antibodies to JCV. The FDA confirmed in January 2012 that testing positive for anti-JCV antibodies has been identified as a risk factor for PML, stating, “The risks and benefits of continuing treatment [with natalizumab] should be carefully considered in patients who are found to be anti-JCV antibody positive and have one or more of the other known risk factors for PML.” The other two risk factors are treatment with natalizumab for more than two years and prior treatment with immunosuppressive medications. Prior immunosuppressive treatment has been shown to increase PML risk twofold to fourfold. People with all three known risk factors have an estimated risk of PML of 11 in 1,000 users.      

Treatment with interferon beta (1a or 1b) was not associated with reduced progression of disability among patients with relapsing–remitting multiple sclerosis (MS), according to research published in the July 18 JAMA.

The observed outcome rates for reaching a sustained Expanded Disability Status Scale score of 6, which was the study’s main outcome measure, were 10.8% for treated patients, 5.3% for the contemporary control cohort, and 23.1% for the historical control cohort. After adjusting for potential baseline confounders such as sex, age, and disease duration, researchers found no statistically significant difference in this rate between cohorts. Further adjustment did not alter the results.

Afsaneh Shirani, MD, a postdoctoral research fellow at the University of British Columbia’s Pharmacoepidemiology in Multiple Sclerosis Research Group in Vancouver, and colleagues prospectively collected data on 2,656 patients with relapsing–remitting MS. Of these patients, 868 registered with a British Columbia clinic when interferon beta was available and underwent treatment, 829 registered during the same period but did not undergo treatment, and 959 registered before the availability of interferon beta and remained unexposed to the drug. Gender ratio and mean age of disease onset were similar for all cohorts.

“The ultimate goal of treatment for MS is to prevent or delay long-term disability,” stated Dr. Shirani and colleagues. “Our findings bring into question the routine use of interferon beta drugs to achieve this goal in MS. It is, however, possible that a subgroup of patients benefit from interferon beta treatment and that this association would not be discernable in our comprehensive ‘real-world’ study. Our findings also encourage the investigation of novel therapeutics for MS.”

“The differing directions of the hazard ratios found in these comparisons—although neither was statistically significant—are compatible with the assumption that the contemporary cohort included a high number of patients who did not qualify for treatment because their disease was relatively benign, thus introducing a bias against interferon treatment,” said Tobias Derfuss, MD, Professor of Biomedicine at University Hospital Basel in Switzerland, and Ludwig Kappos, MD, Professor of Biomedicine at the University of Basel in Switzerland, in an accompanying editorial. The study, however, “reinforce[s] the conclusion that the associations between use of interferons and long-term disability, although plausible, remain unproven,” they concluded.
Shirani A, Zhao Y, Karim ME, et al. Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis. JAMA. 2012;308(3):247-256.
Derfuss T, Kappos L. Evaluating the potential benefit of interferon treatment in multiple sclerosis. JAMA. 2012;308(3):290-291.

Treatment with interferon beta (1a or 1b) was not associated with reduced progression of disability among patients with relapsing–remitting multiple sclerosis (MS), according to research published in the July 18 JAMA.

The observed outcome rates for reaching a sustained Expanded Disability Status Scale score of 6, which was the study’s main outcome measure, were 10.8% for treated patients, 5.3% for the contemporary control cohort, and 23.1% for the historical control cohort. After adjusting for potential baseline confounders such as sex, age, and disease duration, researchers found no statistically significant difference in this rate between cohorts. Further adjustment did not alter the results.

Afsaneh Shirani, MD, a postdoctoral research fellow at the University of British Columbia’s Pharmacoepidemiology in Multiple Sclerosis Research Group in Vancouver, and colleagues prospectively collected data on 2,656 patients with relapsing–remitting MS. Of these patients, 868 registered with a British Columbia clinic when interferon beta was available and underwent treatment, 829 registered during the same period but did not undergo treatment, and 959 registered before the availability of interferon beta and remained unexposed to the drug. Gender ratio and mean age of disease onset were similar for all cohorts.

“The ultimate goal of treatment for MS is to prevent or delay long-term disability,” stated Dr. Shirani and colleagues. “Our findings bring into question the routine use of interferon beta drugs to achieve this goal in MS. It is, however, possible that a subgroup of patients benefit from interferon beta treatment and that this association would not be discernable in our comprehensive ‘real-world’ study. Our findings also encourage the investigation of novel therapeutics for MS.”

“The differing directions of the hazard ratios found in these comparisons—although neither was statistically significant—are compatible with the assumption that the contemporary cohort included a high number of patients who did not qualify for treatment because their disease was relatively benign, thus introducing a bias against interferon treatment,” said Tobias Derfuss, MD, Professor of Biomedicine at University Hospital Basel in Switzerland, and Ludwig Kappos, MD, Professor of Biomedicine at the University of Basel in Switzerland, in an accompanying editorial. The study, however, “reinforce[s] the conclusion that the associations between use of interferons and long-term disability, although plausible, remain unproven,” they concluded.
Shirani A, Zhao Y, Karim ME, et al. Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis. JAMA. 2012;308(3):247-256.
Derfuss T, Kappos L. Evaluating the potential benefit of interferon treatment in multiple sclerosis. JAMA. 2012;308(3):290-291.

Treatment with interferon beta (1a or 1b) was not associated with reduced progression of disability among patients with relapsing–remitting multiple sclerosis (MS), according to research published in the July 18 JAMA.

The observed outcome rates for reaching a sustained Expanded Disability Status Scale score of 6, which was the study’s main outcome measure, were 10.8% for treated patients, 5.3% for the contemporary control cohort, and 23.1% for the historical control cohort. After adjusting for potential baseline confounders such as sex, age, and disease duration, researchers found no statistically significant difference in this rate between cohorts. Further adjustment did not alter the results.

Afsaneh Shirani, MD, a postdoctoral research fellow at the University of British Columbia’s Pharmacoepidemiology in Multiple Sclerosis Research Group in Vancouver, and colleagues prospectively collected data on 2,656 patients with relapsing–remitting MS. Of these patients, 868 registered with a British Columbia clinic when interferon beta was available and underwent treatment, 829 registered during the same period but did not undergo treatment, and 959 registered before the availability of interferon beta and remained unexposed to the drug. Gender ratio and mean age of disease onset were similar for all cohorts.

“The ultimate goal of treatment for MS is to prevent or delay long-term disability,” stated Dr. Shirani and colleagues. “Our findings bring into question the routine use of interferon beta drugs to achieve this goal in MS. It is, however, possible that a subgroup of patients benefit from interferon beta treatment and that this association would not be discernable in our comprehensive ‘real-world’ study. Our findings also encourage the investigation of novel therapeutics for MS.”

“The differing directions of the hazard ratios found in these comparisons—although neither was statistically significant—are compatible with the assumption that the contemporary cohort included a high number of patients who did not qualify for treatment because their disease was relatively benign, thus introducing a bias against interferon treatment,” said Tobias Derfuss, MD, Professor of Biomedicine at University Hospital Basel in Switzerland, and Ludwig Kappos, MD, Professor of Biomedicine at the University of Basel in Switzerland, in an accompanying editorial. The study, however, “reinforce[s] the conclusion that the associations between use of interferons and long-term disability, although plausible, remain unproven,” they concluded.
Shirani A, Zhao Y, Karim ME, et al. Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis. JAMA. 2012;308(3):247-256.
Derfuss T, Kappos L. Evaluating the potential benefit of interferon treatment in multiple sclerosis. JAMA. 2012;308(3):290-291.

SAN DIEGO—At 21 years, treatment with interferon beta-1b reduced the risk of death by approximately 47%, compared with placebo, for patients with multiple sclerosis (MS). Presented at the Fourth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis, the data reflect the longest period of follow-up for a treatment-exposed MS population.

A Multicenter Observational Study
Anthony Reder, MD, Professor of Neurology at the University of Chicago Medical Center, and colleagues conducted a multicenter observational study to evaluate the effects of interferon beta-1b on the clinical outcomes of patients with MS 21 years after the initiation of randomized treatment.

All patients enrolled in the 1988 pivotal randomized controlled trial of interferon beta-1b were eligible. In this trial, 125 patients received 50 µg of interferon beta-1b, 124 patients received 250 µg of interferon beta-1b, and 123 received placebo, every other day. Patients remained on randomized treatment for as long as 5.1 years, after which use of disease-modifying therapies was open label and at their own and their physicians’ discretion.

At the beginning of the trial, all patients were treatment naïve and between the ages of 18 and 50. Eligible patients’ Expanded Disability Status Scale score was 5.5 or less, and patients had had at least two clinical exacerbations during the previous two years.

A High Rate of Ascertainment
Approximately 21 years after enrollment in the initial trial, investigators identified 366 of the original 372 patients for follow-up. A total of 81 of the identified patients had died, including 37 patients randomized to placebo, 22 patients randomized to 50 µg of interferon beta-1b, and 22 patients randomized to 250 µg of interferon beta-1b. Compared with placebo, patients randomized to 250 µg of interferon beta-1b had a 46.8% reduction in the hazard rate of dying. Patients randomized to 50 µg of interferon beta-1b had a 46% lower hazard rate of dying than patients randomized to placebo.

An adjudication committee determined the relationship between MS and death in 69 of the 81 deaths. Approximately 78% of adjudicated deaths were considered to be MS-related. The excess deaths observed in the placebo group were largely explained by MS-related causes. Pulmonary infections secondary to MS were the most common cause of death.

The instances of cancer, heart attacks, and all other medical conditions that caused death were similar among patients receiving interferon beta-1b and patients receiving placebo, Dr. Reder told Neurology Reviews. Disability outcomes also were similar between groups. 

In other trials, missing patients could affect the analysis. “Trials with information on less than 90% of the patients could miss important information on number of deaths and causes of death,” but this study achieved a 98% rate of ascertainment, Dr. Reder added.

Overall, 60% of patients stopped working because of MS. Nearly 31% of patients randomized to placebo accumulated enough disability to prevent them from maintaining employment, compared with 23% of patients randomized to 250 µg of interferon beta-1b and 32.7% of patients randomized to 50 µg of interferon beta-1b. A subset of 93 patients underwent cognitive assessment. Approximately 46% of patients showed no cognitive impairment, but nearly 29% of patients were cognitively impaired.              

To listen to an accompanying audiocast, please click here.

SAN DIEGO—At 21 years, treatment with interferon beta-1b reduced the risk of death by approximately 47%, compared with placebo, for patients with multiple sclerosis (MS). Presented at the Fourth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis, the data reflect the longest period of follow-up for a treatment-exposed MS population.

A Multicenter Observational Study
Anthony Reder, MD, Professor of Neurology at the University of Chicago Medical Center, and colleagues conducted a multicenter observational study to evaluate the effects of interferon beta-1b on the clinical outcomes of patients with MS 21 years after the initiation of randomized treatment.

All patients enrolled in the 1988 pivotal randomized controlled trial of interferon beta-1b were eligible. In this trial, 125 patients received 50 µg of interferon beta-1b, 124 patients received 250 µg of interferon beta-1b, and 123 received placebo, every other day. Patients remained on randomized treatment for as long as 5.1 years, after which use of disease-modifying therapies was open label and at their own and their physicians’ discretion.

At the beginning of the trial, all patients were treatment naïve and between the ages of 18 and 50. Eligible patients’ Expanded Disability Status Scale score was 5.5 or less, and patients had had at least two clinical exacerbations during the previous two years.

A High Rate of Ascertainment
Approximately 21 years after enrollment in the initial trial, investigators identified 366 of the original 372 patients for follow-up. A total of 81 of the identified patients had died, including 37 patients randomized to placebo, 22 patients randomized to 50 µg of interferon beta-1b, and 22 patients randomized to 250 µg of interferon beta-1b. Compared with placebo, patients randomized to 250 µg of interferon beta-1b had a 46.8% reduction in the hazard rate of dying. Patients randomized to 50 µg of interferon beta-1b had a 46% lower hazard rate of dying than patients randomized to placebo.

An adjudication committee determined the relationship between MS and death in 69 of the 81 deaths. Approximately 78% of adjudicated deaths were considered to be MS-related. The excess deaths observed in the placebo group were largely explained by MS-related causes. Pulmonary infections secondary to MS were the most common cause of death.

The instances of cancer, heart attacks, and all other medical conditions that caused death were similar among patients receiving interferon beta-1b and patients receiving placebo, Dr. Reder told Neurology Reviews. Disability outcomes also were similar between groups. 

In other trials, missing patients could affect the analysis. “Trials with information on less than 90% of the patients could miss important information on number of deaths and causes of death,” but this study achieved a 98% rate of ascertainment, Dr. Reder added.

Overall, 60% of patients stopped working because of MS. Nearly 31% of patients randomized to placebo accumulated enough disability to prevent them from maintaining employment, compared with 23% of patients randomized to 250 µg of interferon beta-1b and 32.7% of patients randomized to 50 µg of interferon beta-1b. A subset of 93 patients underwent cognitive assessment. Approximately 46% of patients showed no cognitive impairment, but nearly 29% of patients were cognitively impaired.              

To listen to an accompanying audiocast, please click here.

SAN DIEGO—At 21 years, treatment with interferon beta-1b reduced the risk of death by approximately 47%, compared with placebo, for patients with multiple sclerosis (MS). Presented at the Fourth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis, the data reflect the longest period of follow-up for a treatment-exposed MS population.

A Multicenter Observational Study
Anthony Reder, MD, Professor of Neurology at the University of Chicago Medical Center, and colleagues conducted a multicenter observational study to evaluate the effects of interferon beta-1b on the clinical outcomes of patients with MS 21 years after the initiation of randomized treatment.

All patients enrolled in the 1988 pivotal randomized controlled trial of interferon beta-1b were eligible. In this trial, 125 patients received 50 µg of interferon beta-1b, 124 patients received 250 µg of interferon beta-1b, and 123 received placebo, every other day. Patients remained on randomized treatment for as long as 5.1 years, after which use of disease-modifying therapies was open label and at their own and their physicians’ discretion.

At the beginning of the trial, all patients were treatment naïve and between the ages of 18 and 50. Eligible patients’ Expanded Disability Status Scale score was 5.5 or less, and patients had had at least two clinical exacerbations during the previous two years.

A High Rate of Ascertainment
Approximately 21 years after enrollment in the initial trial, investigators identified 366 of the original 372 patients for follow-up. A total of 81 of the identified patients had died, including 37 patients randomized to placebo, 22 patients randomized to 50 µg of interferon beta-1b, and 22 patients randomized to 250 µg of interferon beta-1b. Compared with placebo, patients randomized to 250 µg of interferon beta-1b had a 46.8% reduction in the hazard rate of dying. Patients randomized to 50 µg of interferon beta-1b had a 46% lower hazard rate of dying than patients randomized to placebo.

An adjudication committee determined the relationship between MS and death in 69 of the 81 deaths. Approximately 78% of adjudicated deaths were considered to be MS-related. The excess deaths observed in the placebo group were largely explained by MS-related causes. Pulmonary infections secondary to MS were the most common cause of death.

The instances of cancer, heart attacks, and all other medical conditions that caused death were similar among patients receiving interferon beta-1b and patients receiving placebo, Dr. Reder told Neurology Reviews. Disability outcomes also were similar between groups. 

In other trials, missing patients could affect the analysis. “Trials with information on less than 90% of the patients could miss important information on number of deaths and causes of death,” but this study achieved a 98% rate of ascertainment, Dr. Reder added.

Overall, 60% of patients stopped working because of MS. Nearly 31% of patients randomized to placebo accumulated enough disability to prevent them from maintaining employment, compared with 23% of patients randomized to 250 µg of interferon beta-1b and 32.7% of patients randomized to 50 µg of interferon beta-1b. A subset of 93 patients underwent cognitive assessment. Approximately 46% of patients showed no cognitive impairment, but nearly 29% of patients were cognitively impaired.              

To listen to an accompanying audiocast, please click here.

Severe influenza is associated with greater odds of Parkinson’s disease, while measles reduces the odds of Parkinson’s disease, researchers reported in the July 2 online Movement Disorders. In this population-based, case-control study, the investigators examined 403 cases of Parkinson’s disease and 405 controls. Although there was an association between severe influenza and Parkinson’s disease (odds ratio, 2.01%), this effect was weaker when influenza reports were limited to those occurring 10 or more years before diagnosis. Conversely, childhood illness,  particularly red measles (odds ratio, 0.65%), was associated with a lower risk of Parkinson’s disease. In addition, several animal exposures were linked with developing Parkinson’s disease, and these effects were statistically significant for exposure to cats (odds ratio, 2.06) and cattle (odds ratio, 2.23), the researchers noted.
Shift work is associated with an increased risk of vascular events such as heart attack and stroke, researchers reported in the July 26 online BMJ. The investigators conducted a meta-analysis of 34 studies that assessed risk ratios for vascular morbidity, vascular mortality, or all-cause mortality in relation to shift work. More than two million participants were included in the studies, in which 6,598 persons had myocardial infarctions, 17,359 had coronary events, and 1,854 had ischemic stroke. Results showed that shift work correlated with myocardial infarction (risk ratio,1.23), ischemic stroke (risk ratio, 1.05), and coronary events (risk ratio, 1.24), and these risks remained the same after adjustment for socioeconomic status and smoking. However, shift work was not associated with increased rates of overall mortality or mortality due to vascular causes.
Persons with higher levels of certain species of serum ceramides may have a greater risk of Alzheimer’s disease, according to research published in the online July 18 Neurology. The study included 99 women ages 70 to 79 who did not have dementia. Researchers recorded baseline levels of serum ceramides and sphingomyelins, as well as lipids, and followed the women for up to six visits over nine years, during which 27 women had incident dementia and 18 were diagnosed with probable Alzheimer’s disease. Analysis showed that higher baseline serum ceramides correlated with an increased risk of Alzheimer’s disease, while higher levels of sphingomyelins, total and high-density lipoprotein cholesterol, and triglycerides did not show a correlation with dementia or Alzheimer’s disease. The researchers noted that the study was preliminary and that the results warrant continued examination in larger studies.

Persons with advanced forms of relapsing–remitting multiple sclerosis (RRMS) show increasing levels of sodium concentration in their brains as the disease progresses, according to research published in the online July 17 Radiology. Using sodium 23 MRI, investigators measured brain sodium accumulations in 14 patients with early RRMS, 12 with advanced RRMS, and 15 controls. They found that total sodium concentrations increased inside demyelinating lesions in both groups of patients, but only patients with advanced RRMS showed increased total sodium concentrations in normal-appearing white matter and gray matter. Furthermore, increased total sodium concentration inside gray matter correlated with disability. Thus, brain sodium MRI may be helpful for monitoring the occurrence of tissue injury and disability, the researchers concluded.
The FDA has approved Gammagard liquid 10% (Immune Globulin Infusion [Human]) for treatment of multifocal motor neuropathy (MMN). The drug is the first immunoglobulin treatment approved in the US for patients with MMN, and its efficacy, safety, and tolerability were evaluated in a randomized, double-blind, placebo-controlled study. The study’s two coprimary end points were grip strength and disability in the more affected hand. According to the investigators, patients showed a relative change of 22.94% in mean grip strength in the more affected hand, compared with placebo. Furthermore, during the placebo period, most patients had functional deterioration and subsequently required an accelerated switch to Gammagard liquid. Although no study participants died or experienced unexpected serious adverse events, some patients had treatment-related pulmonary embolism and blurred vision.
The potassium channel KIR4.1 is the target of an autoantibody response in persons with multiple sclerosis (MS) and may serve as a potential diagnostic marker for MS, according to a study published in the July 12 New England Journal of Medicine. After screening serum IgG from patients with MS, researchers observed specific binding of IgG to glial cells in a subgroup of patients. The ATP-sensitive inward rectifying potassium channel KIR4.1 was identified as the target of the antibodies, and analysis of combined datasets showed that 186 of 397 persons with MS had the antibodies (46.9%), compared with three of 329 persons with other neurologic diseases (0.9%), and none of 59 healthy donors. “Serum levels of antibodies to KIR4.1 were higher in persons with MS than in persons with other neurologic diseases and healthy donors,” the researchers stated.
Fetal exposure to the pandemic influenza A[H1N1]pdm09 vaccine does not significantly increase the risk of adverse outcomes for infants, although adults exposed to the H1N1 vaccination have a small but significant risk of Guillain-Barré syndrome. Researchers reported these results in two studies published in the July 11 JAMA. The first study included data from all liveborn singleton infants in Denmark. Of those infants, 53,432 were exposed to the H1N1 vaccine in utero, and exposure was not associated with a significantly increased risk of major birth defects, preterm birth, or fetal growth restriction. The second study followed up on an immunization campaign in Quebec in which 57% of the 7.8 million residents were vaccinated. There were 83 cases of Guillain-Barré identified during a six-month period. According to investigators, approximately two cases of Guillain-Barré syndrome were attributable to vaccination per one million doses. However, they noted that the benefits of immunization likely outweigh the risks.
A 24-week treatment period of stress management therapy reduces new gadolinium-enhancing brain lesions in patients with relapsing forms of multiple sclerosis (MS) while they are in treatment, researchers reported in the July 11 online Neurology. The study included 121 patients who were randomized to a wait-list control condition or to stress management therapy for MS (SMT-MS), which consisted of 16 individual treatment sessions for 24 weeks, followed by a 24-week post-treatment period. The primary outcome was the cumulative number of new gadolinium-enhancing lesions on MRI at weeks 8, 16, and 24.  Compared with controls, more patients who received SMT-MS remained free of new lesions, and these patients also showed a reduction in new lesions compared with controls. However, the positive effects of SMT-MS were not detectable during the 24-week post-treatment period. Researchers concluded that SMT-MS may be useful in reducing the development of new brain lesions during treatment.
Patients with stroke who are admitted to the hospital on the weekend are less likely to receive urgent care and more likely to have worse overall outcomes, according to a study in the July 9 online Archives of Neurology. Researchers retrospectively evaluated data from 93,621 patients with stroke who were admitted to hospitals from April 1, 2009, to March 31, 2010. Logistic regression was used to measure six indicators of hospital care, and results showed significantly lower performance on weekends across five of the six measures. For example, rates of same-day brain scans were 43.1% on weekends and 47.6% on weekdays, and the rate of seven-day in-hospital mortality for Sunday admissions was 11.0% versus 8.9% for weekday admissions. Replicating weekday performance on weekends is likely to improve patient outcomes, the researchers concluded.
A coding mutation in the amyloid-b precursor protein (APP) gene protects against cognitive decline in older persons who do not have Alzheimer’s disease, according to a study published in the online July 11 Nature. Researchers identified the beneficial coding mutation (A673T) in the APP gene after studying coding variants in APP in a set of whole-genome sequence data from 1,795 Icelanders. The mutation leads to an approximately 40% reduction in the formation of amyloidogenic peptides in vitro, and it provides support for the hypothesis that reducing b-cleavage of APP may protect against Alzheimer’s disease. “As the A673T allele also protects against cognitive decline in the elderly without Alzheimer’s disease, the two may be mediated through the same or similar mechanisms,” the study authors wrote.     

Severe influenza is associated with greater odds of Parkinson’s disease, while measles reduces the odds of Parkinson’s disease, researchers reported in the July 2 online Movement Disorders. In this population-based, case-control study, the investigators examined 403 cases of Parkinson’s disease and 405 controls. Although there was an association between severe influenza and Parkinson’s disease (odds ratio, 2.01%), this effect was weaker when influenza reports were limited to those occurring 10 or more years before diagnosis. Conversely, childhood illness,  particularly red measles (odds ratio, 0.65%), was associated with a lower risk of Parkinson’s disease. In addition, several animal exposures were linked with developing Parkinson’s disease, and these effects were statistically significant for exposure to cats (odds ratio, 2.06) and cattle (odds ratio, 2.23), the researchers noted.
Shift work is associated with an increased risk of vascular events such as heart attack and stroke, researchers reported in the July 26 online BMJ. The investigators conducted a meta-analysis of 34 studies that assessed risk ratios for vascular morbidity, vascular mortality, or all-cause mortality in relation to shift work. More than two million participants were included in the studies, in which 6,598 persons had myocardial infarctions, 17,359 had coronary events, and 1,854 had ischemic stroke. Results showed that shift work correlated with myocardial infarction (risk ratio,1.23), ischemic stroke (risk ratio, 1.05), and coronary events (risk ratio, 1.24), and these risks remained the same after adjustment for socioeconomic status and smoking. However, shift work was not associated with increased rates of overall mortality or mortality due to vascular causes.
Persons with higher levels of certain species of serum ceramides may have a greater risk of Alzheimer’s disease, according to research published in the online July 18 Neurology. The study included 99 women ages 70 to 79 who did not have dementia. Researchers recorded baseline levels of serum ceramides and sphingomyelins, as well as lipids, and followed the women for up to six visits over nine years, during which 27 women had incident dementia and 18 were diagnosed with probable Alzheimer’s disease. Analysis showed that higher baseline serum ceramides correlated with an increased risk of Alzheimer’s disease, while higher levels of sphingomyelins, total and high-density lipoprotein cholesterol, and triglycerides did not show a correlation with dementia or Alzheimer’s disease. The researchers noted that the study was preliminary and that the results warrant continued examination in larger studies.

Persons with advanced forms of relapsing–remitting multiple sclerosis (RRMS) show increasing levels of sodium concentration in their brains as the disease progresses, according to research published in the online July 17 Radiology. Using sodium 23 MRI, investigators measured brain sodium accumulations in 14 patients with early RRMS, 12 with advanced RRMS, and 15 controls. They found that total sodium concentrations increased inside demyelinating lesions in both groups of patients, but only patients with advanced RRMS showed increased total sodium concentrations in normal-appearing white matter and gray matter. Furthermore, increased total sodium concentration inside gray matter correlated with disability. Thus, brain sodium MRI may be helpful for monitoring the occurrence of tissue injury and disability, the researchers concluded.
The FDA has approved Gammagard liquid 10% (Immune Globulin Infusion [Human]) for treatment of multifocal motor neuropathy (MMN). The drug is the first immunoglobulin treatment approved in the US for patients with MMN, and its efficacy, safety, and tolerability were evaluated in a randomized, double-blind, placebo-controlled study. The study’s two coprimary end points were grip strength and disability in the more affected hand. According to the investigators, patients showed a relative change of 22.94% in mean grip strength in the more affected hand, compared with placebo. Furthermore, during the placebo period, most patients had functional deterioration and subsequently required an accelerated switch to Gammagard liquid. Although no study participants died or experienced unexpected serious adverse events, some patients had treatment-related pulmonary embolism and blurred vision.
The potassium channel KIR4.1 is the target of an autoantibody response in persons with multiple sclerosis (MS) and may serve as a potential diagnostic marker for MS, according to a study published in the July 12 New England Journal of Medicine. After screening serum IgG from patients with MS, researchers observed specific binding of IgG to glial cells in a subgroup of patients. The ATP-sensitive inward rectifying potassium channel KIR4.1 was identified as the target of the antibodies, and analysis of combined datasets showed that 186 of 397 persons with MS had the antibodies (46.9%), compared with three of 329 persons with other neurologic diseases (0.9%), and none of 59 healthy donors. “Serum levels of antibodies to KIR4.1 were higher in persons with MS than in persons with other neurologic diseases and healthy donors,” the researchers stated.
Fetal exposure to the pandemic influenza A[H1N1]pdm09 vaccine does not significantly increase the risk of adverse outcomes for infants, although adults exposed to the H1N1 vaccination have a small but significant risk of Guillain-Barré syndrome. Researchers reported these results in two studies published in the July 11 JAMA. The first study included data from all liveborn singleton infants in Denmark. Of those infants, 53,432 were exposed to the H1N1 vaccine in utero, and exposure was not associated with a significantly increased risk of major birth defects, preterm birth, or fetal growth restriction. The second study followed up on an immunization campaign in Quebec in which 57% of the 7.8 million residents were vaccinated. There were 83 cases of Guillain-Barré identified during a six-month period. According to investigators, approximately two cases of Guillain-Barré syndrome were attributable to vaccination per one million doses. However, they noted that the benefits of immunization likely outweigh the risks.
A 24-week treatment period of stress management therapy reduces new gadolinium-enhancing brain lesions in patients with relapsing forms of multiple sclerosis (MS) while they are in treatment, researchers reported in the July 11 online Neurology. The study included 121 patients who were randomized to a wait-list control condition or to stress management therapy for MS (SMT-MS), which consisted of 16 individual treatment sessions for 24 weeks, followed by a 24-week post-treatment period. The primary outcome was the cumulative number of new gadolinium-enhancing lesions on MRI at weeks 8, 16, and 24.  Compared with controls, more patients who received SMT-MS remained free of new lesions, and these patients also showed a reduction in new lesions compared with controls. However, the positive effects of SMT-MS were not detectable during the 24-week post-treatment period. Researchers concluded that SMT-MS may be useful in reducing the development of new brain lesions during treatment.
Patients with stroke who are admitted to the hospital on the weekend are less likely to receive urgent care and more likely to have worse overall outcomes, according to a study in the July 9 online Archives of Neurology. Researchers retrospectively evaluated data from 93,621 patients with stroke who were admitted to hospitals from April 1, 2009, to March 31, 2010. Logistic regression was used to measure six indicators of hospital care, and results showed significantly lower performance on weekends across five of the six measures. For example, rates of same-day brain scans were 43.1% on weekends and 47.6% on weekdays, and the rate of seven-day in-hospital mortality for Sunday admissions was 11.0% versus 8.9% for weekday admissions. Replicating weekday performance on weekends is likely to improve patient outcomes, the researchers concluded.
A coding mutation in the amyloid-b precursor protein (APP) gene protects against cognitive decline in older persons who do not have Alzheimer’s disease, according to a study published in the online July 11 Nature. Researchers identified the beneficial coding mutation (A673T) in the APP gene after studying coding variants in APP in a set of whole-genome sequence data from 1,795 Icelanders. The mutation leads to an approximately 40% reduction in the formation of amyloidogenic peptides in vitro, and it provides support for the hypothesis that reducing b-cleavage of APP may protect against Alzheimer’s disease. “As the A673T allele also protects against cognitive decline in the elderly without Alzheimer’s disease, the two may be mediated through the same or similar mechanisms,” the study authors wrote.     

Severe influenza is associated with greater odds of Parkinson’s disease, while measles reduces the odds of Parkinson’s disease, researchers reported in the July 2 online Movement Disorders. In this population-based, case-control study, the investigators examined 403 cases of Parkinson’s disease and 405 controls. Although there was an association between severe influenza and Parkinson’s disease (odds ratio, 2.01%), this effect was weaker when influenza reports were limited to those occurring 10 or more years before diagnosis. Conversely, childhood illness,  particularly red measles (odds ratio, 0.65%), was associated with a lower risk of Parkinson’s disease. In addition, several animal exposures were linked with developing Parkinson’s disease, and these effects were statistically significant for exposure to cats (odds ratio, 2.06) and cattle (odds ratio, 2.23), the researchers noted.
Shift work is associated with an increased risk of vascular events such as heart attack and stroke, researchers reported in the July 26 online BMJ. The investigators conducted a meta-analysis of 34 studies that assessed risk ratios for vascular morbidity, vascular mortality, or all-cause mortality in relation to shift work. More than two million participants were included in the studies, in which 6,598 persons had myocardial infarctions, 17,359 had coronary events, and 1,854 had ischemic stroke. Results showed that shift work correlated with myocardial infarction (risk ratio,1.23), ischemic stroke (risk ratio, 1.05), and coronary events (risk ratio, 1.24), and these risks remained the same after adjustment for socioeconomic status and smoking. However, shift work was not associated with increased rates of overall mortality or mortality due to vascular causes.
Persons with higher levels of certain species of serum ceramides may have a greater risk of Alzheimer’s disease, according to research published in the online July 18 Neurology. The study included 99 women ages 70 to 79 who did not have dementia. Researchers recorded baseline levels of serum ceramides and sphingomyelins, as well as lipids, and followed the women for up to six visits over nine years, during which 27 women had incident dementia and 18 were diagnosed with probable Alzheimer’s disease. Analysis showed that higher baseline serum ceramides correlated with an increased risk of Alzheimer’s disease, while higher levels of sphingomyelins, total and high-density lipoprotein cholesterol, and triglycerides did not show a correlation with dementia or Alzheimer’s disease. The researchers noted that the study was preliminary and that the results warrant continued examination in larger studies.

Persons with advanced forms of relapsing–remitting multiple sclerosis (RRMS) show increasing levels of sodium concentration in their brains as the disease progresses, according to research published in the online July 17 Radiology. Using sodium 23 MRI, investigators measured brain sodium accumulations in 14 patients with early RRMS, 12 with advanced RRMS, and 15 controls. They found that total sodium concentrations increased inside demyelinating lesions in both groups of patients, but only patients with advanced RRMS showed increased total sodium concentrations in normal-appearing white matter and gray matter. Furthermore, increased total sodium concentration inside gray matter correlated with disability. Thus, brain sodium MRI may be helpful for monitoring the occurrence of tissue injury and disability, the researchers concluded.
The FDA has approved Gammagard liquid 10% (Immune Globulin Infusion [Human]) for treatment of multifocal motor neuropathy (MMN). The drug is the first immunoglobulin treatment approved in the US for patients with MMN, and its efficacy, safety, and tolerability were evaluated in a randomized, double-blind, placebo-controlled study. The study’s two coprimary end points were grip strength and disability in the more affected hand. According to the investigators, patients showed a relative change of 22.94% in mean grip strength in the more affected hand, compared with placebo. Furthermore, during the placebo period, most patients had functional deterioration and subsequently required an accelerated switch to Gammagard liquid. Although no study participants died or experienced unexpected serious adverse events, some patients had treatment-related pulmonary embolism and blurred vision.
The potassium channel KIR4.1 is the target of an autoantibody response in persons with multiple sclerosis (MS) and may serve as a potential diagnostic marker for MS, according to a study published in the July 12 New England Journal of Medicine. After screening serum IgG from patients with MS, researchers observed specific binding of IgG to glial cells in a subgroup of patients. The ATP-sensitive inward rectifying potassium channel KIR4.1 was identified as the target of the antibodies, and analysis of combined datasets showed that 186 of 397 persons with MS had the antibodies (46.9%), compared with three of 329 persons with other neurologic diseases (0.9%), and none of 59 healthy donors. “Serum levels of antibodies to KIR4.1 were higher in persons with MS than in persons with other neurologic diseases and healthy donors,” the researchers stated.
Fetal exposure to the pandemic influenza A[H1N1]pdm09 vaccine does not significantly increase the risk of adverse outcomes for infants, although adults exposed to the H1N1 vaccination have a small but significant risk of Guillain-Barré syndrome. Researchers reported these results in two studies published in the July 11 JAMA. The first study included data from all liveborn singleton infants in Denmark. Of those infants, 53,432 were exposed to the H1N1 vaccine in utero, and exposure was not associated with a significantly increased risk of major birth defects, preterm birth, or fetal growth restriction. The second study followed up on an immunization campaign in Quebec in which 57% of the 7.8 million residents were vaccinated. There were 83 cases of Guillain-Barré identified during a six-month period. According to investigators, approximately two cases of Guillain-Barré syndrome were attributable to vaccination per one million doses. However, they noted that the benefits of immunization likely outweigh the risks.
A 24-week treatment period of stress management therapy reduces new gadolinium-enhancing brain lesions in patients with relapsing forms of multiple sclerosis (MS) while they are in treatment, researchers reported in the July 11 online Neurology. The study included 121 patients who were randomized to a wait-list control condition or to stress management therapy for MS (SMT-MS), which consisted of 16 individual treatment sessions for 24 weeks, followed by a 24-week post-treatment period. The primary outcome was the cumulative number of new gadolinium-enhancing lesions on MRI at weeks 8, 16, and 24.  Compared with controls, more patients who received SMT-MS remained free of new lesions, and these patients also showed a reduction in new lesions compared with controls. However, the positive effects of SMT-MS were not detectable during the 24-week post-treatment period. Researchers concluded that SMT-MS may be useful in reducing the development of new brain lesions during treatment.
Patients with stroke who are admitted to the hospital on the weekend are less likely to receive urgent care and more likely to have worse overall outcomes, according to a study in the July 9 online Archives of Neurology. Researchers retrospectively evaluated data from 93,621 patients with stroke who were admitted to hospitals from April 1, 2009, to March 31, 2010. Logistic regression was used to measure six indicators of hospital care, and results showed significantly lower performance on weekends across five of the six measures. For example, rates of same-day brain scans were 43.1% on weekends and 47.6% on weekdays, and the rate of seven-day in-hospital mortality for Sunday admissions was 11.0% versus 8.9% for weekday admissions. Replicating weekday performance on weekends is likely to improve patient outcomes, the researchers concluded.
A coding mutation in the amyloid-b precursor protein (APP) gene protects against cognitive decline in older persons who do not have Alzheimer’s disease, according to a study published in the online July 11 Nature. Researchers identified the beneficial coding mutation (A673T) in the APP gene after studying coding variants in APP in a set of whole-genome sequence data from 1,795 Icelanders. The mutation leads to an approximately 40% reduction in the formation of amyloidogenic peptides in vitro, and it provides support for the hypothesis that reducing b-cleavage of APP may protect against Alzheimer’s disease. “As the A673T allele also protects against cognitive decline in the elderly without Alzheimer’s disease, the two may be mediated through the same or similar mechanisms,” the study authors wrote.     

NEW ORLEANS—Exposure to disease-modifying multiple sclerosis (MS) drugs could adversely affect the fetus, according to a study that was presented at the 64th Annual Meeting of the American Academy of Neurology.

In addition, women with MS who took interferon beta before conception or during pregnancy had an increased risk of preterm birth (ie, at a gestational age of less than 37 weeks). Babies born to these women also had an increased risk of lower birth weight and shorter birth length. Both measures were still within the normal range for the general population, however.

In utero exposure to mitoxantrone, in particular, could harm offspring. Although no controlled human studies of mitoxantrone’s effects on unborn children have been performed to date, animal studies and human case reports suggest a risk of fetal harm after the mother or father is exposed to the drug, reported Ellen Lu, a PhD student at the University of British Columbia in Vancouver.

A Retrospective Evaluation of the Safety of MS Drugs for Fetuses
Ms. Lu and her colleagues reviewed the literature published before February 2012 to assess the effects of periconceptional or in utero exposure to interferon beta, glatiramer acetate, natalizumab, mitoxantrone, or fingolimod on perinatal and developmental outcomes in the children of patients with MS. The researchers evaluated the level and quality of evidence in the studies by examining their study designs and methods of data collection.

A total of 15 studies identified 761 pregnancies exposed to interferon beta, 97 exposed to glatiramer acetate, and 35 exposed to natalizumab. The quality of the studies ranged from poor to good. No study was considered excellent, and small sample sizes limited most of the studies. The researchers assigned each drug a Class of Recommendation regarding its use during pregnancy according to international guidelines.

Should MS Drugs Be Discontinued Before Conception?
The researchers concluded that mitoxantrone was harmful to the fetus during pregnancy, and that interferon beta may be harmful. Further studies of glatiramer acetate, natalizumab, and fingolimod are necessary because limited data were available for these drugs. In addition, no peer-reviewed studies on fingolimod have been published because the drug entered the market in 2011.

“Women with MS should be advised to discontinue disease-modifying drugs before conceiving,” said the researchers. Women also should consider discontinuing disease-modifying drugs if they are unintentionally exposed to them during pregnancy, they added.

Future research should explore birth outcomes following periconceptional exposure to disease-modifying drugs in fathers with MS and long-term development in offspring exposed to disease-modifying drugs, they concluded.   

NEW ORLEANS—Exposure to disease-modifying multiple sclerosis (MS) drugs could adversely affect the fetus, according to a study that was presented at the 64th Annual Meeting of the American Academy of Neurology.

In addition, women with MS who took interferon beta before conception or during pregnancy had an increased risk of preterm birth (ie, at a gestational age of less than 37 weeks). Babies born to these women also had an increased risk of lower birth weight and shorter birth length. Both measures were still within the normal range for the general population, however.

In utero exposure to mitoxantrone, in particular, could harm offspring. Although no controlled human studies of mitoxantrone’s effects on unborn children have been performed to date, animal studies and human case reports suggest a risk of fetal harm after the mother or father is exposed to the drug, reported Ellen Lu, a PhD student at the University of British Columbia in Vancouver.

A Retrospective Evaluation of the Safety of MS Drugs for Fetuses
Ms. Lu and her colleagues reviewed the literature published before February 2012 to assess the effects of periconceptional or in utero exposure to interferon beta, glatiramer acetate, natalizumab, mitoxantrone, or fingolimod on perinatal and developmental outcomes in the children of patients with MS. The researchers evaluated the level and quality of evidence in the studies by examining their study designs and methods of data collection.

A total of 15 studies identified 761 pregnancies exposed to interferon beta, 97 exposed to glatiramer acetate, and 35 exposed to natalizumab. The quality of the studies ranged from poor to good. No study was considered excellent, and small sample sizes limited most of the studies. The researchers assigned each drug a Class of Recommendation regarding its use during pregnancy according to international guidelines.

Should MS Drugs Be Discontinued Before Conception?
The researchers concluded that mitoxantrone was harmful to the fetus during pregnancy, and that interferon beta may be harmful. Further studies of glatiramer acetate, natalizumab, and fingolimod are necessary because limited data were available for these drugs. In addition, no peer-reviewed studies on fingolimod have been published because the drug entered the market in 2011.

“Women with MS should be advised to discontinue disease-modifying drugs before conceiving,” said the researchers. Women also should consider discontinuing disease-modifying drugs if they are unintentionally exposed to them during pregnancy, they added.

Future research should explore birth outcomes following periconceptional exposure to disease-modifying drugs in fathers with MS and long-term development in offspring exposed to disease-modifying drugs, they concluded.   

NEW ORLEANS—Exposure to disease-modifying multiple sclerosis (MS) drugs could adversely affect the fetus, according to a study that was presented at the 64th Annual Meeting of the American Academy of Neurology.

In addition, women with MS who took interferon beta before conception or during pregnancy had an increased risk of preterm birth (ie, at a gestational age of less than 37 weeks). Babies born to these women also had an increased risk of lower birth weight and shorter birth length. Both measures were still within the normal range for the general population, however.

In utero exposure to mitoxantrone, in particular, could harm offspring. Although no controlled human studies of mitoxantrone’s effects on unborn children have been performed to date, animal studies and human case reports suggest a risk of fetal harm after the mother or father is exposed to the drug, reported Ellen Lu, a PhD student at the University of British Columbia in Vancouver.

A Retrospective Evaluation of the Safety of MS Drugs for Fetuses
Ms. Lu and her colleagues reviewed the literature published before February 2012 to assess the effects of periconceptional or in utero exposure to interferon beta, glatiramer acetate, natalizumab, mitoxantrone, or fingolimod on perinatal and developmental outcomes in the children of patients with MS. The researchers evaluated the level and quality of evidence in the studies by examining their study designs and methods of data collection.

A total of 15 studies identified 761 pregnancies exposed to interferon beta, 97 exposed to glatiramer acetate, and 35 exposed to natalizumab. The quality of the studies ranged from poor to good. No study was considered excellent, and small sample sizes limited most of the studies. The researchers assigned each drug a Class of Recommendation regarding its use during pregnancy according to international guidelines.

Should MS Drugs Be Discontinued Before Conception?
The researchers concluded that mitoxantrone was harmful to the fetus during pregnancy, and that interferon beta may be harmful. Further studies of glatiramer acetate, natalizumab, and fingolimod are necessary because limited data were available for these drugs. In addition, no peer-reviewed studies on fingolimod have been published because the drug entered the market in 2011.

“Women with MS should be advised to discontinue disease-modifying drugs before conceiving,” said the researchers. Women also should consider discontinuing disease-modifying drugs if they are unintentionally exposed to them during pregnancy, they added.

Future research should explore birth outcomes following periconceptional exposure to disease-modifying drugs in fathers with MS and long-term development in offspring exposed to disease-modifying drugs, they concluded.