New and Noteworthy Information—November 2014

Researchers found no long-term association of vaccines with multiple sclerosis (MS) or any other CNS demyelinating syndromes, according to a study published online ahead of print October 20 in JAMA Neurology. The investigators examined the relationship between vaccines and MS or other CNS demyelinating syndromes by using data from Kaiser Permanente Southern California members. The study authors identified 780 cases of CNS demyelinating syndromes and 3,885 controls; 92 cases and 459 controls were females between the ages of 9 and 26, which is the indicated age range for human papillomavirus (HPV) vaccination. The researchers found no associations between HepB vaccinations, HPV vaccination, or any vaccination and the risk of MS or CNS demyelinating syndromes for as long as three years later. Vaccination of any type was associated with increased risk of a CNS demyelinating syndrome onset within the first 30 days after vaccination only in patients younger than 50, but this association was not evident after 30 days.

Bariatric surgery is a potential risk factor for spontaneous intracranial hypotension, according to a study published online ahead of print October 22 in Neurology. Researchers compared a group of 338 patients with spontaneous intracranial hypotension to a control group of 245 people with unruptured intracranial aneurysms. Eleven of the 338 (3.3%) people with spontaneous intracranial hypotension had previously had bariatric surgery, compared with two of the 245 (0.8%) people with intracranial aneurysms. Of the 11 people with bariatric surgery and spontaneous intracranial hypotension, nine had no more symptoms after treatment, while symptoms persisted for two. The symptoms started from three months to 20 years after the bariatric surgery, and participants had lost an average of 116 pounds during that time.

Longitudinal measures of cortical atrophy were widely correlated with sleep quality, according to a study published September 9 in Neurology. The study included 147 adults, ages 20 and 84. Researchers examined the link between sleep difficulties, such as having trouble falling asleep or staying asleep at night, and brain volume. All participants underwent two MRI brain scans, an average of 3.5 years apart, before completing a questionnaire about their sleep habits. A total of 35% of the participants met the criteria for poor sleep quality, scoring an average of 8.5 out of 21 points on the sleep assessment. The researchers found that sleep difficulties were linked with a more rapid decline in brain volume during the course of the study in various brain regions, including within frontal, temporal, and parietal areas. The results were more pronounced in people older than 60.

An international group of researchers has established the first standardized guidelines for the collection of blood to test for early Alzheimer’s disease, as reported online ahead of print September 27 in Alzheimer’s & Dementia. These guidelines will be used in research for blood-based biomarkers of Alzheimer’s disease and will ensure that every laboratory is following the same protocol when collecting blood. The lack of readily available biomarkers is a significant hindrance toward progressing to effective therapeutic and preventative strategies for Alzheimer’s disease. Researchers have worked with representatives from the United States, Germany, Australia, England, and other countries to create these standards. “You can create a blood test in the lab, but if you don’t have a systemized way for collecting the blood, the test will never go into practice,” said the investigators.

A new study suggests a cause of amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print October 14 in Proceedings of the National Academy of Sciences. Researchers used advanced biophysical methods to probe how different superoxide dismutase 1(SOD1) gene mutations in a genetic ALS hotspot affect SOD protein stability. Investigators examined how the aggregation dynamics of mutant SOD G93A differed from that of nonmutant SOD. They developed a method for gradually inducing SOD aggregation, which was measured with SAXS, a structural imaging system. The G93-mutant SODs appear to have looser, floppier structures that are more likely to drop their copper ions and are more likely to misfold and stick together in aggregates. “Our work supports a common theme whereby loss of protein stability leads to disease,” investigators said.

Long-term functional outcome and risk of fatal or disabling stroke are similar for stenting and endarterectomy for symptomatic carotid stenosis, according to a study published online ahead of print October 14 in the Lancet. Researchers followed 1,713 patients with carotid artery disease, of whom 855 were assigned to stenting and 858 to endarterectomy, for as long as 10 years. The median follow-up was 4.2 years. Both techniques were found to be equally good at preventing fatal and disabling strokes, but stented patients were slightly more likely to have minor strokes without long-term effects. The risk of any stroke in five years was 15.2% in the stenting group, compared with 9.4% in the endarterectomy group, but the additional strokes were minor and had no impact on long-term quality of life.

Researchers have found Class II evidence that serum metabolite profiles accurately distinguish patients with different subtypes and stages of multiple sclerosis (MS), according to a study published October 21 in Neurology. Investigators obtained serum samples from patients with primary progressive MS, secondary-progressive MS, and relapsing-remitting MS, patients with other neurodegenerative conditions, and from age-matched controls. Samples were analyzed by nuclear magnetic resonance, and partial least squares discriminant analysis models were derived to separate disease groups. The partial least squares discriminant analysis models for serum samples from patients with MS enabled reliable differentiation between relapsing-remitting MS and secondary-progressive MS. This approach identified significant differences between the metabolite profiles of each of the MS groups and the healthy controls, as well as predicting disease group membership with high sensitivity and specificity.

Parkinson’s disease pathogenic mutations have an age-dependent penetrance that could be ameliorated or exacerbated by modifier genes or environmental factors in different populations, according to a study published online ahead of print October 20 in JAMA Neurology. The investigators examined 49 previously published studies that included 709 participants and were found in ISI Web of Science and PubMed. They also analyzed extracted information about the number of mutation carriers within families and sporadic cases worldwide for pathogenic mutations in SNCA, LRRK2, VPS35, EIF4G1, and DNAJC13. The end-of-search date was January 31, 2014. In particular, penetrance of SNCA duplications were comparable to point mutations and driven by inclusion of SNCA p.A53T (mean age at onset, 45.9). Each penetrance estimate was given separately with 95% confidence intervals.

Spreading depolarizations can be measured after traumatic brain injury (TBI) by the placement of EEG electrodes on the scalp, according to a study published online ahead of print August 25 in Annals of Neurology. Eighteen patients requiring surgical treatment for TBI were monitored by invasive electrocorticography (ECoG) and noninvasive scalp EEG during intensive care. Spreading depolarizations were first identified in subdural recordings, and EEGs were then examined visually and quantitatively to identify correlates. A total of 455 spreading depolarizations occurred during 65.9 days of simultaneous ECoG and EEG monitoring. For 179 of 455 events (39%), depolarizations caused temporally isolated, transient depressions of spontaneous EEG amplitudes to 57% (median) of baseline power. For 62 of 179 (35%) events, isolated depressions showed a clear spread of depression between EEG channels with delays of 17 minutes (median).

A diet that includes walnuts may have a beneficial effect on reducing the risk, delaying the onset, and slowing the progression of, or preventing, Alzheimer’s disease, according to a study published October 21 in the Journal of Alzheimer’s Disease. The research group examined the effects of dietary supplementation on mice with 6% or 9% walnuts, which is equivalent to 1 ounce and 1.5 ounces per day, respectively, of walnuts in humans. The investigators found significant improvement in learning skills, memory, reducing anxiety, and motor development in mice fed a walnut-enriched diet. “These findings are very promising and help lay the groundwork for future human studies on walnuts and Alzheimer’s disease,” the investigators said.

Dopamine receptor agonist drugs are associated with impulse control disorders, such as pathologic gambling, hypersexuality, and compulsive shopping, according to a study that was published online ahead of print October 20 in JAMA Internal Medicine. Researchers conducted a retrospective disproportionality analysis that was based on the 2.7 million serious domestic and foreign adverse drug event reports between 2003 and 2012 that were extracted from the FDA Adverse Event Reporting System. The investigators identified 1,580 events indicating impulse control disorders from the United States and 21 other countries (710 for dopamine receptor agonist drugs and 870 for other drugs). The dopamine receptor agonist drugs had a strong signal associated with these impulse control disorders. The association was strongest for the dopamine agonists pramipexole and ropinirole, with preferential affinity for the dopamine D3 receptor. A signal was also seen for aripiprazole.

—Kimberly D. Williams

Researchers found no long-term association of vaccines with multiple sclerosis (MS) or any other CNS demyelinating syndromes, according to a study published online ahead of print October 20 in JAMA Neurology. The investigators examined the relationship between vaccines and MS or other CNS demyelinating syndromes by using data from Kaiser Permanente Southern California members. The study authors identified 780 cases of CNS demyelinating syndromes and 3,885 controls; 92 cases and 459 controls were females between the ages of 9 and 26, which is the indicated age range for human papillomavirus (HPV) vaccination. The researchers found no associations between HepB vaccinations, HPV vaccination, or any vaccination and the risk of MS or CNS demyelinating syndromes for as long as three years later. Vaccination of any type was associated with increased risk of a CNS demyelinating syndrome onset within the first 30 days after vaccination only in patients younger than 50, but this association was not evident after 30 days.

Bariatric surgery is a potential risk factor for spontaneous intracranial hypotension, according to a study published online ahead of print October 22 in Neurology. Researchers compared a group of 338 patients with spontaneous intracranial hypotension to a control group of 245 people with unruptured intracranial aneurysms. Eleven of the 338 (3.3%) people with spontaneous intracranial hypotension had previously had bariatric surgery, compared with two of the 245 (0.8%) people with intracranial aneurysms. Of the 11 people with bariatric surgery and spontaneous intracranial hypotension, nine had no more symptoms after treatment, while symptoms persisted for two. The symptoms started from three months to 20 years after the bariatric surgery, and participants had lost an average of 116 pounds during that time.

Longitudinal measures of cortical atrophy were widely correlated with sleep quality, according to a study published September 9 in Neurology. The study included 147 adults, ages 20 and 84. Researchers examined the link between sleep difficulties, such as having trouble falling asleep or staying asleep at night, and brain volume. All participants underwent two MRI brain scans, an average of 3.5 years apart, before completing a questionnaire about their sleep habits. A total of 35% of the participants met the criteria for poor sleep quality, scoring an average of 8.5 out of 21 points on the sleep assessment. The researchers found that sleep difficulties were linked with a more rapid decline in brain volume during the course of the study in various brain regions, including within frontal, temporal, and parietal areas. The results were more pronounced in people older than 60.

An international group of researchers has established the first standardized guidelines for the collection of blood to test for early Alzheimer’s disease, as reported online ahead of print September 27 in Alzheimer’s & Dementia. These guidelines will be used in research for blood-based biomarkers of Alzheimer’s disease and will ensure that every laboratory is following the same protocol when collecting blood. The lack of readily available biomarkers is a significant hindrance toward progressing to effective therapeutic and preventative strategies for Alzheimer’s disease. Researchers have worked with representatives from the United States, Germany, Australia, England, and other countries to create these standards. “You can create a blood test in the lab, but if you don’t have a systemized way for collecting the blood, the test will never go into practice,” said the investigators.

A new study suggests a cause of amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print October 14 in Proceedings of the National Academy of Sciences. Researchers used advanced biophysical methods to probe how different superoxide dismutase 1(SOD1) gene mutations in a genetic ALS hotspot affect SOD protein stability. Investigators examined how the aggregation dynamics of mutant SOD G93A differed from that of nonmutant SOD. They developed a method for gradually inducing SOD aggregation, which was measured with SAXS, a structural imaging system. The G93-mutant SODs appear to have looser, floppier structures that are more likely to drop their copper ions and are more likely to misfold and stick together in aggregates. “Our work supports a common theme whereby loss of protein stability leads to disease,” investigators said.

Long-term functional outcome and risk of fatal or disabling stroke are similar for stenting and endarterectomy for symptomatic carotid stenosis, according to a study published online ahead of print October 14 in the Lancet. Researchers followed 1,713 patients with carotid artery disease, of whom 855 were assigned to stenting and 858 to endarterectomy, for as long as 10 years. The median follow-up was 4.2 years. Both techniques were found to be equally good at preventing fatal and disabling strokes, but stented patients were slightly more likely to have minor strokes without long-term effects. The risk of any stroke in five years was 15.2% in the stenting group, compared with 9.4% in the endarterectomy group, but the additional strokes were minor and had no impact on long-term quality of life.

Researchers have found Class II evidence that serum metabolite profiles accurately distinguish patients with different subtypes and stages of multiple sclerosis (MS), according to a study published October 21 in Neurology. Investigators obtained serum samples from patients with primary progressive MS, secondary-progressive MS, and relapsing-remitting MS, patients with other neurodegenerative conditions, and from age-matched controls. Samples were analyzed by nuclear magnetic resonance, and partial least squares discriminant analysis models were derived to separate disease groups. The partial least squares discriminant analysis models for serum samples from patients with MS enabled reliable differentiation between relapsing-remitting MS and secondary-progressive MS. This approach identified significant differences between the metabolite profiles of each of the MS groups and the healthy controls, as well as predicting disease group membership with high sensitivity and specificity.

Parkinson’s disease pathogenic mutations have an age-dependent penetrance that could be ameliorated or exacerbated by modifier genes or environmental factors in different populations, according to a study published online ahead of print October 20 in JAMA Neurology. The investigators examined 49 previously published studies that included 709 participants and were found in ISI Web of Science and PubMed. They also analyzed extracted information about the number of mutation carriers within families and sporadic cases worldwide for pathogenic mutations in SNCA, LRRK2, VPS35, EIF4G1, and DNAJC13. The end-of-search date was January 31, 2014. In particular, penetrance of SNCA duplications were comparable to point mutations and driven by inclusion of SNCA p.A53T (mean age at onset, 45.9). Each penetrance estimate was given separately with 95% confidence intervals.

Spreading depolarizations can be measured after traumatic brain injury (TBI) by the placement of EEG electrodes on the scalp, according to a study published online ahead of print August 25 in Annals of Neurology. Eighteen patients requiring surgical treatment for TBI were monitored by invasive electrocorticography (ECoG) and noninvasive scalp EEG during intensive care. Spreading depolarizations were first identified in subdural recordings, and EEGs were then examined visually and quantitatively to identify correlates. A total of 455 spreading depolarizations occurred during 65.9 days of simultaneous ECoG and EEG monitoring. For 179 of 455 events (39%), depolarizations caused temporally isolated, transient depressions of spontaneous EEG amplitudes to 57% (median) of baseline power. For 62 of 179 (35%) events, isolated depressions showed a clear spread of depression between EEG channels with delays of 17 minutes (median).

A diet that includes walnuts may have a beneficial effect on reducing the risk, delaying the onset, and slowing the progression of, or preventing, Alzheimer’s disease, according to a study published October 21 in the Journal of Alzheimer’s Disease. The research group examined the effects of dietary supplementation on mice with 6% or 9% walnuts, which is equivalent to 1 ounce and 1.5 ounces per day, respectively, of walnuts in humans. The investigators found significant improvement in learning skills, memory, reducing anxiety, and motor development in mice fed a walnut-enriched diet. “These findings are very promising and help lay the groundwork for future human studies on walnuts and Alzheimer’s disease,” the investigators said.

Dopamine receptor agonist drugs are associated with impulse control disorders, such as pathologic gambling, hypersexuality, and compulsive shopping, according to a study that was published online ahead of print October 20 in JAMA Internal Medicine. Researchers conducted a retrospective disproportionality analysis that was based on the 2.7 million serious domestic and foreign adverse drug event reports between 2003 and 2012 that were extracted from the FDA Adverse Event Reporting System. The investigators identified 1,580 events indicating impulse control disorders from the United States and 21 other countries (710 for dopamine receptor agonist drugs and 870 for other drugs). The dopamine receptor agonist drugs had a strong signal associated with these impulse control disorders. The association was strongest for the dopamine agonists pramipexole and ropinirole, with preferential affinity for the dopamine D3 receptor. A signal was also seen for aripiprazole.

—Kimberly D. Williams

Researchers found no long-term association of vaccines with multiple sclerosis (MS) or any other CNS demyelinating syndromes, according to a study published online ahead of print October 20 in JAMA Neurology. The investigators examined the relationship between vaccines and MS or other CNS demyelinating syndromes by using data from Kaiser Permanente Southern California members. The study authors identified 780 cases of CNS demyelinating syndromes and 3,885 controls; 92 cases and 459 controls were females between the ages of 9 and 26, which is the indicated age range for human papillomavirus (HPV) vaccination. The researchers found no associations between HepB vaccinations, HPV vaccination, or any vaccination and the risk of MS or CNS demyelinating syndromes for as long as three years later. Vaccination of any type was associated with increased risk of a CNS demyelinating syndrome onset within the first 30 days after vaccination only in patients younger than 50, but this association was not evident after 30 days.

Bariatric surgery is a potential risk factor for spontaneous intracranial hypotension, according to a study published online ahead of print October 22 in Neurology. Researchers compared a group of 338 patients with spontaneous intracranial hypotension to a control group of 245 people with unruptured intracranial aneurysms. Eleven of the 338 (3.3%) people with spontaneous intracranial hypotension had previously had bariatric surgery, compared with two of the 245 (0.8%) people with intracranial aneurysms. Of the 11 people with bariatric surgery and spontaneous intracranial hypotension, nine had no more symptoms after treatment, while symptoms persisted for two. The symptoms started from three months to 20 years after the bariatric surgery, and participants had lost an average of 116 pounds during that time.

Longitudinal measures of cortical atrophy were widely correlated with sleep quality, according to a study published September 9 in Neurology. The study included 147 adults, ages 20 and 84. Researchers examined the link between sleep difficulties, such as having trouble falling asleep or staying asleep at night, and brain volume. All participants underwent two MRI brain scans, an average of 3.5 years apart, before completing a questionnaire about their sleep habits. A total of 35% of the participants met the criteria for poor sleep quality, scoring an average of 8.5 out of 21 points on the sleep assessment. The researchers found that sleep difficulties were linked with a more rapid decline in brain volume during the course of the study in various brain regions, including within frontal, temporal, and parietal areas. The results were more pronounced in people older than 60.

An international group of researchers has established the first standardized guidelines for the collection of blood to test for early Alzheimer’s disease, as reported online ahead of print September 27 in Alzheimer’s & Dementia. These guidelines will be used in research for blood-based biomarkers of Alzheimer’s disease and will ensure that every laboratory is following the same protocol when collecting blood. The lack of readily available biomarkers is a significant hindrance toward progressing to effective therapeutic and preventative strategies for Alzheimer’s disease. Researchers have worked with representatives from the United States, Germany, Australia, England, and other countries to create these standards. “You can create a blood test in the lab, but if you don’t have a systemized way for collecting the blood, the test will never go into practice,” said the investigators.

A new study suggests a cause of amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print October 14 in Proceedings of the National Academy of Sciences. Researchers used advanced biophysical methods to probe how different superoxide dismutase 1(SOD1) gene mutations in a genetic ALS hotspot affect SOD protein stability. Investigators examined how the aggregation dynamics of mutant SOD G93A differed from that of nonmutant SOD. They developed a method for gradually inducing SOD aggregation, which was measured with SAXS, a structural imaging system. The G93-mutant SODs appear to have looser, floppier structures that are more likely to drop their copper ions and are more likely to misfold and stick together in aggregates. “Our work supports a common theme whereby loss of protein stability leads to disease,” investigators said.

Long-term functional outcome and risk of fatal or disabling stroke are similar for stenting and endarterectomy for symptomatic carotid stenosis, according to a study published online ahead of print October 14 in the Lancet. Researchers followed 1,713 patients with carotid artery disease, of whom 855 were assigned to stenting and 858 to endarterectomy, for as long as 10 years. The median follow-up was 4.2 years. Both techniques were found to be equally good at preventing fatal and disabling strokes, but stented patients were slightly more likely to have minor strokes without long-term effects. The risk of any stroke in five years was 15.2% in the stenting group, compared with 9.4% in the endarterectomy group, but the additional strokes were minor and had no impact on long-term quality of life.

Researchers have found Class II evidence that serum metabolite profiles accurately distinguish patients with different subtypes and stages of multiple sclerosis (MS), according to a study published October 21 in Neurology. Investigators obtained serum samples from patients with primary progressive MS, secondary-progressive MS, and relapsing-remitting MS, patients with other neurodegenerative conditions, and from age-matched controls. Samples were analyzed by nuclear magnetic resonance, and partial least squares discriminant analysis models were derived to separate disease groups. The partial least squares discriminant analysis models for serum samples from patients with MS enabled reliable differentiation between relapsing-remitting MS and secondary-progressive MS. This approach identified significant differences between the metabolite profiles of each of the MS groups and the healthy controls, as well as predicting disease group membership with high sensitivity and specificity.

Parkinson’s disease pathogenic mutations have an age-dependent penetrance that could be ameliorated or exacerbated by modifier genes or environmental factors in different populations, according to a study published online ahead of print October 20 in JAMA Neurology. The investigators examined 49 previously published studies that included 709 participants and were found in ISI Web of Science and PubMed. They also analyzed extracted information about the number of mutation carriers within families and sporadic cases worldwide for pathogenic mutations in SNCA, LRRK2, VPS35, EIF4G1, and DNAJC13. The end-of-search date was January 31, 2014. In particular, penetrance of SNCA duplications were comparable to point mutations and driven by inclusion of SNCA p.A53T (mean age at onset, 45.9). Each penetrance estimate was given separately with 95% confidence intervals.

Spreading depolarizations can be measured after traumatic brain injury (TBI) by the placement of EEG electrodes on the scalp, according to a study published online ahead of print August 25 in Annals of Neurology. Eighteen patients requiring surgical treatment for TBI were monitored by invasive electrocorticography (ECoG) and noninvasive scalp EEG during intensive care. Spreading depolarizations were first identified in subdural recordings, and EEGs were then examined visually and quantitatively to identify correlates. A total of 455 spreading depolarizations occurred during 65.9 days of simultaneous ECoG and EEG monitoring. For 179 of 455 events (39%), depolarizations caused temporally isolated, transient depressions of spontaneous EEG amplitudes to 57% (median) of baseline power. For 62 of 179 (35%) events, isolated depressions showed a clear spread of depression between EEG channels with delays of 17 minutes (median).

A diet that includes walnuts may have a beneficial effect on reducing the risk, delaying the onset, and slowing the progression of, or preventing, Alzheimer’s disease, according to a study published October 21 in the Journal of Alzheimer’s Disease. The research group examined the effects of dietary supplementation on mice with 6% or 9% walnuts, which is equivalent to 1 ounce and 1.5 ounces per day, respectively, of walnuts in humans. The investigators found significant improvement in learning skills, memory, reducing anxiety, and motor development in mice fed a walnut-enriched diet. “These findings are very promising and help lay the groundwork for future human studies on walnuts and Alzheimer’s disease,” the investigators said.

Dopamine receptor agonist drugs are associated with impulse control disorders, such as pathologic gambling, hypersexuality, and compulsive shopping, according to a study that was published online ahead of print October 20 in JAMA Internal Medicine. Researchers conducted a retrospective disproportionality analysis that was based on the 2.7 million serious domestic and foreign adverse drug event reports between 2003 and 2012 that were extracted from the FDA Adverse Event Reporting System. The investigators identified 1,580 events indicating impulse control disorders from the United States and 21 other countries (710 for dopamine receptor agonist drugs and 870 for other drugs). The dopamine receptor agonist drugs had a strong signal associated with these impulse control disorders. The association was strongest for the dopamine agonists pramipexole and ropinirole, with preferential affinity for the dopamine D3 receptor. A signal was also seen for aripiprazole.

—Kimberly D. Williams