News Roundup: New and Noteworthy Information

Premature birth may increase the risk of epilepsy as an adult, according to a study published in the October 4 Neurology. Investigators observed rates of hospitalization for epilepsy and prescription of antiepileptic drugs during a four-year period in 630,090 adults (including 27,953 who were born preterm). “We found a strong association between preterm birth and epilepsy that increased by earlier gestational age,” the researchers stated. After adjusting for fetal growth and potential confounders, the investigators found that individuals who were born at 23 to 31 weeks were almost five times more likely to be hospitalized for epilepsy than those who were born full-term. The odds ratios for those born at 32 to 34 weeks and 35 to 36 weeks were 1.98 and 1.76, respectively. “These associations persisted after excluding individuals with cerebral palsy, inflammatory diseases of the CNS, cerebrovascular disease, and brain tumors,” the investigators noted.

The use of attention-deficit/hyperactivity disorder (ADHD) medications is not associated with an increased risk of serious cardiovascular events, as some adverse-event reports have suggested, according to a report published online November 1 in the New England Journal of Medicine. A group of researchers estimated the risk of serious cardiovascular events (sudden cardiac death, acute myocardial infarction, and stroke) among more than 1 million children and young adults (age range, 2 to 24). There were 81 cardiovascular events among the cohort members and seven serious cardiovascular events in current users. “Current users of ADHD drugs were not at increased risk for serious cardiovascular events (hazard ratio, 0.75),” the investigators reported. “Risk was not increased for any of the individual end points, or for current users as compared with former users (hazard ratio, 0.70).”

Researchers have identified several genetic variants that contribute to early stent thrombosis, as reported in the October 26 JAMA. Twenty-three genetic variants were examined in 15 different genes in a population of patients undergoing percutaneous coronary intervention. “Among the 23 genetic variants investigated in 15 different genes, the significant determinants of early stent thrombosis were CYP2C19 metabolic status (odds ratio, 1.99), ABCB1 3435 TT genotype (odds ratio, 2.16), and ITGB3 PLA2 carriage (odds ratio, 0.52),” the investigators reported. The researchers also found that certain nongenetic factors (including use of proton pump inhibitors and higher clopidogrel loading doses) were associated with early stent thrombosis. “Future studies are needed to validate the prognostic accuracy of these risk factors in prospective cohorts,” the investigators concluded.

Changes in the blurring of the cortical gray and white matter border were associated with lower verbal expression abilities, according to a study that was published in the October 26 issue of the Journal of Neuroscience. Healthy participants underwent MRI to determine their gray and white matter contrast (GWC), and they also completed measures of verbal expression and verbal working memory. The investigators found that blurring in the participants’ left hemisphere inferior frontal cortex and temporal pole was associated with reduced verbal expression abilities, and that reduced verbal working memory was associated with blurring in widespread left frontal and temporal cortices. “Such lateralized and focal results provide support for GWC as a measure of regional functional integrity and highlight its potential role in probing the neuroanatomic substrates of cognition in healthy and diseased populations,” the researchers concluded.

The FDA has approved ONFI (clobazam) for use as an adjunctive therapy for seizures that are associated with Lennox-Gastaut syndrome in patients who are two years and older. ONFI (Lundbeck, Inc; Deerfield, Illinois) is an oral antiepileptic drug and is a derivative of benzodiazepine. The drug will be available in 5-, 10-, and 20-mg tablets. The exact mechanism of action of clobazam is not fully understood, but it is thought to involve potentiation of GABA-ergic neurotransmission resulting from binding at the benzodiazepine site of the GABA A receptor. The FDA’s approval was based on the results of two multicenter controlled studies, including a phase 3 trial involving 238 patients with Lennox-Gastaut syndrome who experienced a significant reduction in the weekly frequency of drop seizures. The most common side effects of clobazam include sleepiness, fever, drooling, aggressive behavior, irritability, and lack of coordination.

People who rate their health as poor or fair may be significantly more likely to develop Alzheimer’s disease or vascular dementia, compared with those who rate their health as good, according to a study that was published in the October 11 issue of Neurology. Study participants rated their health status at baseline (as “good,” “fair,” or “poor”) and were followed for a median of 6.7 years for the incidence of dementia. During the follow-up period, 618 participants developed dementia, and risk of dementia was increased among participants with poor (hazard ratio, 1.70) or fair (hazard ratio, 1.34) self-rated health, compared with participants with good self-rated health. “Self-rated health could help raise awareness of medical doctors about a patient’s risk of dementia, especially in those without conditions indicative of potential cognitive impairment,” the investigators concluded.

Diffusion-weighted imaging (DWI) had a higher predictive value than fluid-attenuated inversion recovery (FLAIR) MRI for detecting patients within the recommended time window for thrombolysis, according to a study that was published in the November issue of Lancet Neurology. Researchers analyzed the clinical and MRI data from patients with acute stroke who had undergone DWI and FLAIR imaging within 12 hours of symptom onset, and they determined that patients with an acute ischemic lesion detected with DWI but not with FLAIR imaging are likely to be within a time window for which thrombolysis is safe and effective. “DWI-FLAIR mismatch identified patients within four to five hours of symptom onset with 62% sensitivity, 78% specificity, 83% positive predictive value, and 54% negative predictive value,” the investigators stated. “These findings lend support to the use of DWI-FLAIR mismatch for selection of patients in a future randomized trial of thrombolysis in patients with unknown time of symptom onset.”

Older adults who were taking statins before sustaining moderate or severe head injury had improved survival and functional outcomes, according to the results of a study that was published in the October issue of the Journal of Trauma. “Of 523 eligible individuals, 117 (22%) used statins at the time of injury,” the investigators wrote. “Statin use was associated with a 76% lower adjusted risk of in-hospital death.” Patients who took the cholesterol-lowering drugs were also 13% more likely to have a good recovery at 12 months postinjury, compared with patients who did not use statins. However, individuals with cardiovascular comorbidities lose this benefit, the investigators noted. “Statins, as possible protective agents in head trauma, warrant further study,” the study authors concluded.

A neuron’s inability to secrete beta-amyloid (Aß) plays a major role in the pathogenesis of Alzheimer’s disease, a finding that contradicts the dominant theory in Alzheimer’s disease pathology, according to a study in the October 26 Journal of Neuroscience. By studying neurons in Alzheimer’s disease–transgenic and wild-type mice, the investigators found that an increase in intracellular Aß occurred early in the beginning stages of the disease, and that this accumulation of Aß inside the neuron was caused by the neuron’s inability to properly secrete Aß. “We demonstrate that synaptic activity promotes an increase in the Aß-degrading protease neprilysin at the cell surface and a concomitant increase in colocalization with Aß42,” the investigators stated. “Remarkably, Alzheimer’s disease–transgenic but not wild-type neurons show reduced levels of neprilysin with time in culture. This impaired ability to secrete Ab and reduce intraneuronal Aß has important implications for the pathogenesis and treatment of Alzheimer’s disease.”

Long-term estrogen deprivation in aging rats is associated with a decrease in estrogen receptors in the brain, and with a loss of the hormone’s neuroprotective effects, according to a study that was published in the August 30 issue of the Proceedings of the National Academy of Sciences. Researchers studied estrogen levels in middle-aged rats that had undergone long periods of estrogen deprivation and observed an enhanced interaction between estrogen receptors and the CHIP enzyme (a carboxyl terminus of Hsc70-interacting protein), which contributed to the decrease of estrogen receptors in the hippocampus. They also found that administration of 17b-estradiol (E2) replacement therapy shortly before, but not after, the drop in hormone levels prevented degradation of estrogen receptors in the brain, and preserved estrogen’s neuroprotective effects. “As a whole, the study provides support for a ‘critical period’ for E2 neuroprotection of the hippocampus and provides important insight into the mechanism underlying the critical period,” the researchers concluded.

Premature birth may increase the risk of epilepsy as an adult, according to a study published in the October 4 Neurology. Investigators observed rates of hospitalization for epilepsy and prescription of antiepileptic drugs during a four-year period in 630,090 adults (including 27,953 who were born preterm). “We found a strong association between preterm birth and epilepsy that increased by earlier gestational age,” the researchers stated. After adjusting for fetal growth and potential confounders, the investigators found that individuals who were born at 23 to 31 weeks were almost five times more likely to be hospitalized for epilepsy than those who were born full-term. The odds ratios for those born at 32 to 34 weeks and 35 to 36 weeks were 1.98 and 1.76, respectively. “These associations persisted after excluding individuals with cerebral palsy, inflammatory diseases of the CNS, cerebrovascular disease, and brain tumors,” the investigators noted.

The use of attention-deficit/hyperactivity disorder (ADHD) medications is not associated with an increased risk of serious cardiovascular events, as some adverse-event reports have suggested, according to a report published online November 1 in the New England Journal of Medicine. A group of researchers estimated the risk of serious cardiovascular events (sudden cardiac death, acute myocardial infarction, and stroke) among more than 1 million children and young adults (age range, 2 to 24). There were 81 cardiovascular events among the cohort members and seven serious cardiovascular events in current users. “Current users of ADHD drugs were not at increased risk for serious cardiovascular events (hazard ratio, 0.75),” the investigators reported. “Risk was not increased for any of the individual end points, or for current users as compared with former users (hazard ratio, 0.70).”

Researchers have identified several genetic variants that contribute to early stent thrombosis, as reported in the October 26 JAMA. Twenty-three genetic variants were examined in 15 different genes in a population of patients undergoing percutaneous coronary intervention. “Among the 23 genetic variants investigated in 15 different genes, the significant determinants of early stent thrombosis were CYP2C19 metabolic status (odds ratio, 1.99), ABCB1 3435 TT genotype (odds ratio, 2.16), and ITGB3 PLA2 carriage (odds ratio, 0.52),” the investigators reported. The researchers also found that certain nongenetic factors (including use of proton pump inhibitors and higher clopidogrel loading doses) were associated with early stent thrombosis. “Future studies are needed to validate the prognostic accuracy of these risk factors in prospective cohorts,” the investigators concluded.

Changes in the blurring of the cortical gray and white matter border were associated with lower verbal expression abilities, according to a study that was published in the October 26 issue of the Journal of Neuroscience. Healthy participants underwent MRI to determine their gray and white matter contrast (GWC), and they also completed measures of verbal expression and verbal working memory. The investigators found that blurring in the participants’ left hemisphere inferior frontal cortex and temporal pole was associated with reduced verbal expression abilities, and that reduced verbal working memory was associated with blurring in widespread left frontal and temporal cortices. “Such lateralized and focal results provide support for GWC as a measure of regional functional integrity and highlight its potential role in probing the neuroanatomic substrates of cognition in healthy and diseased populations,” the researchers concluded.

The FDA has approved ONFI (clobazam) for use as an adjunctive therapy for seizures that are associated with Lennox-Gastaut syndrome in patients who are two years and older. ONFI (Lundbeck, Inc; Deerfield, Illinois) is an oral antiepileptic drug and is a derivative of benzodiazepine. The drug will be available in 5-, 10-, and 20-mg tablets. The exact mechanism of action of clobazam is not fully understood, but it is thought to involve potentiation of GABA-ergic neurotransmission resulting from binding at the benzodiazepine site of the GABA A receptor. The FDA’s approval was based on the results of two multicenter controlled studies, including a phase 3 trial involving 238 patients with Lennox-Gastaut syndrome who experienced a significant reduction in the weekly frequency of drop seizures. The most common side effects of clobazam include sleepiness, fever, drooling, aggressive behavior, irritability, and lack of coordination.

People who rate their health as poor or fair may be significantly more likely to develop Alzheimer’s disease or vascular dementia, compared with those who rate their health as good, according to a study that was published in the October 11 issue of Neurology. Study participants rated their health status at baseline (as “good,” “fair,” or “poor”) and were followed for a median of 6.7 years for the incidence of dementia. During the follow-up period, 618 participants developed dementia, and risk of dementia was increased among participants with poor (hazard ratio, 1.70) or fair (hazard ratio, 1.34) self-rated health, compared with participants with good self-rated health. “Self-rated health could help raise awareness of medical doctors about a patient’s risk of dementia, especially in those without conditions indicative of potential cognitive impairment,” the investigators concluded.

Diffusion-weighted imaging (DWI) had a higher predictive value than fluid-attenuated inversion recovery (FLAIR) MRI for detecting patients within the recommended time window for thrombolysis, according to a study that was published in the November issue of Lancet Neurology. Researchers analyzed the clinical and MRI data from patients with acute stroke who had undergone DWI and FLAIR imaging within 12 hours of symptom onset, and they determined that patients with an acute ischemic lesion detected with DWI but not with FLAIR imaging are likely to be within a time window for which thrombolysis is safe and effective. “DWI-FLAIR mismatch identified patients within four to five hours of symptom onset with 62% sensitivity, 78% specificity, 83% positive predictive value, and 54% negative predictive value,” the investigators stated. “These findings lend support to the use of DWI-FLAIR mismatch for selection of patients in a future randomized trial of thrombolysis in patients with unknown time of symptom onset.”

Older adults who were taking statins before sustaining moderate or severe head injury had improved survival and functional outcomes, according to the results of a study that was published in the October issue of the Journal of Trauma. “Of 523 eligible individuals, 117 (22%) used statins at the time of injury,” the investigators wrote. “Statin use was associated with a 76% lower adjusted risk of in-hospital death.” Patients who took the cholesterol-lowering drugs were also 13% more likely to have a good recovery at 12 months postinjury, compared with patients who did not use statins. However, individuals with cardiovascular comorbidities lose this benefit, the investigators noted. “Statins, as possible protective agents in head trauma, warrant further study,” the study authors concluded.

A neuron’s inability to secrete beta-amyloid (Aß) plays a major role in the pathogenesis of Alzheimer’s disease, a finding that contradicts the dominant theory in Alzheimer’s disease pathology, according to a study in the October 26 Journal of Neuroscience. By studying neurons in Alzheimer’s disease–transgenic and wild-type mice, the investigators found that an increase in intracellular Aß occurred early in the beginning stages of the disease, and that this accumulation of Aß inside the neuron was caused by the neuron’s inability to properly secrete Aß. “We demonstrate that synaptic activity promotes an increase in the Aß-degrading protease neprilysin at the cell surface and a concomitant increase in colocalization with Aß42,” the investigators stated. “Remarkably, Alzheimer’s disease–transgenic but not wild-type neurons show reduced levels of neprilysin with time in culture. This impaired ability to secrete Ab and reduce intraneuronal Aß has important implications for the pathogenesis and treatment of Alzheimer’s disease.”

Long-term estrogen deprivation in aging rats is associated with a decrease in estrogen receptors in the brain, and with a loss of the hormone’s neuroprotective effects, according to a study that was published in the August 30 issue of the Proceedings of the National Academy of Sciences. Researchers studied estrogen levels in middle-aged rats that had undergone long periods of estrogen deprivation and observed an enhanced interaction between estrogen receptors and the CHIP enzyme (a carboxyl terminus of Hsc70-interacting protein), which contributed to the decrease of estrogen receptors in the hippocampus. They also found that administration of 17b-estradiol (E2) replacement therapy shortly before, but not after, the drop in hormone levels prevented degradation of estrogen receptors in the brain, and preserved estrogen’s neuroprotective effects. “As a whole, the study provides support for a ‘critical period’ for E2 neuroprotection of the hippocampus and provides important insight into the mechanism underlying the critical period,” the researchers concluded.

Premature birth may increase the risk of epilepsy as an adult, according to a study published in the October 4 Neurology. Investigators observed rates of hospitalization for epilepsy and prescription of antiepileptic drugs during a four-year period in 630,090 adults (including 27,953 who were born preterm). “We found a strong association between preterm birth and epilepsy that increased by earlier gestational age,” the researchers stated. After adjusting for fetal growth and potential confounders, the investigators found that individuals who were born at 23 to 31 weeks were almost five times more likely to be hospitalized for epilepsy than those who were born full-term. The odds ratios for those born at 32 to 34 weeks and 35 to 36 weeks were 1.98 and 1.76, respectively. “These associations persisted after excluding individuals with cerebral palsy, inflammatory diseases of the CNS, cerebrovascular disease, and brain tumors,” the investigators noted.

The use of attention-deficit/hyperactivity disorder (ADHD) medications is not associated with an increased risk of serious cardiovascular events, as some adverse-event reports have suggested, according to a report published online November 1 in the New England Journal of Medicine. A group of researchers estimated the risk of serious cardiovascular events (sudden cardiac death, acute myocardial infarction, and stroke) among more than 1 million children and young adults (age range, 2 to 24). There were 81 cardiovascular events among the cohort members and seven serious cardiovascular events in current users. “Current users of ADHD drugs were not at increased risk for serious cardiovascular events (hazard ratio, 0.75),” the investigators reported. “Risk was not increased for any of the individual end points, or for current users as compared with former users (hazard ratio, 0.70).”

Researchers have identified several genetic variants that contribute to early stent thrombosis, as reported in the October 26 JAMA. Twenty-three genetic variants were examined in 15 different genes in a population of patients undergoing percutaneous coronary intervention. “Among the 23 genetic variants investigated in 15 different genes, the significant determinants of early stent thrombosis were CYP2C19 metabolic status (odds ratio, 1.99), ABCB1 3435 TT genotype (odds ratio, 2.16), and ITGB3 PLA2 carriage (odds ratio, 0.52),” the investigators reported. The researchers also found that certain nongenetic factors (including use of proton pump inhibitors and higher clopidogrel loading doses) were associated with early stent thrombosis. “Future studies are needed to validate the prognostic accuracy of these risk factors in prospective cohorts,” the investigators concluded.

Changes in the blurring of the cortical gray and white matter border were associated with lower verbal expression abilities, according to a study that was published in the October 26 issue of the Journal of Neuroscience. Healthy participants underwent MRI to determine their gray and white matter contrast (GWC), and they also completed measures of verbal expression and verbal working memory. The investigators found that blurring in the participants’ left hemisphere inferior frontal cortex and temporal pole was associated with reduced verbal expression abilities, and that reduced verbal working memory was associated with blurring in widespread left frontal and temporal cortices. “Such lateralized and focal results provide support for GWC as a measure of regional functional integrity and highlight its potential role in probing the neuroanatomic substrates of cognition in healthy and diseased populations,” the researchers concluded.

The FDA has approved ONFI (clobazam) for use as an adjunctive therapy for seizures that are associated with Lennox-Gastaut syndrome in patients who are two years and older. ONFI (Lundbeck, Inc; Deerfield, Illinois) is an oral antiepileptic drug and is a derivative of benzodiazepine. The drug will be available in 5-, 10-, and 20-mg tablets. The exact mechanism of action of clobazam is not fully understood, but it is thought to involve potentiation of GABA-ergic neurotransmission resulting from binding at the benzodiazepine site of the GABA A receptor. The FDA’s approval was based on the results of two multicenter controlled studies, including a phase 3 trial involving 238 patients with Lennox-Gastaut syndrome who experienced a significant reduction in the weekly frequency of drop seizures. The most common side effects of clobazam include sleepiness, fever, drooling, aggressive behavior, irritability, and lack of coordination.

People who rate their health as poor or fair may be significantly more likely to develop Alzheimer’s disease or vascular dementia, compared with those who rate their health as good, according to a study that was published in the October 11 issue of Neurology. Study participants rated their health status at baseline (as “good,” “fair,” or “poor”) and were followed for a median of 6.7 years for the incidence of dementia. During the follow-up period, 618 participants developed dementia, and risk of dementia was increased among participants with poor (hazard ratio, 1.70) or fair (hazard ratio, 1.34) self-rated health, compared with participants with good self-rated health. “Self-rated health could help raise awareness of medical doctors about a patient’s risk of dementia, especially in those without conditions indicative of potential cognitive impairment,” the investigators concluded.

Diffusion-weighted imaging (DWI) had a higher predictive value than fluid-attenuated inversion recovery (FLAIR) MRI for detecting patients within the recommended time window for thrombolysis, according to a study that was published in the November issue of Lancet Neurology. Researchers analyzed the clinical and MRI data from patients with acute stroke who had undergone DWI and FLAIR imaging within 12 hours of symptom onset, and they determined that patients with an acute ischemic lesion detected with DWI but not with FLAIR imaging are likely to be within a time window for which thrombolysis is safe and effective. “DWI-FLAIR mismatch identified patients within four to five hours of symptom onset with 62% sensitivity, 78% specificity, 83% positive predictive value, and 54% negative predictive value,” the investigators stated. “These findings lend support to the use of DWI-FLAIR mismatch for selection of patients in a future randomized trial of thrombolysis in patients with unknown time of symptom onset.”

Older adults who were taking statins before sustaining moderate or severe head injury had improved survival and functional outcomes, according to the results of a study that was published in the October issue of the Journal of Trauma. “Of 523 eligible individuals, 117 (22%) used statins at the time of injury,” the investigators wrote. “Statin use was associated with a 76% lower adjusted risk of in-hospital death.” Patients who took the cholesterol-lowering drugs were also 13% more likely to have a good recovery at 12 months postinjury, compared with patients who did not use statins. However, individuals with cardiovascular comorbidities lose this benefit, the investigators noted. “Statins, as possible protective agents in head trauma, warrant further study,” the study authors concluded.

A neuron’s inability to secrete beta-amyloid (Aß) plays a major role in the pathogenesis of Alzheimer’s disease, a finding that contradicts the dominant theory in Alzheimer’s disease pathology, according to a study in the October 26 Journal of Neuroscience. By studying neurons in Alzheimer’s disease–transgenic and wild-type mice, the investigators found that an increase in intracellular Aß occurred early in the beginning stages of the disease, and that this accumulation of Aß inside the neuron was caused by the neuron’s inability to properly secrete Aß. “We demonstrate that synaptic activity promotes an increase in the Aß-degrading protease neprilysin at the cell surface and a concomitant increase in colocalization with Aß42,” the investigators stated. “Remarkably, Alzheimer’s disease–transgenic but not wild-type neurons show reduced levels of neprilysin with time in culture. This impaired ability to secrete Ab and reduce intraneuronal Aß has important implications for the pathogenesis and treatment of Alzheimer’s disease.”

Long-term estrogen deprivation in aging rats is associated with a decrease in estrogen receptors in the brain, and with a loss of the hormone’s neuroprotective effects, according to a study that was published in the August 30 issue of the Proceedings of the National Academy of Sciences. Researchers studied estrogen levels in middle-aged rats that had undergone long periods of estrogen deprivation and observed an enhanced interaction between estrogen receptors and the CHIP enzyme (a carboxyl terminus of Hsc70-interacting protein), which contributed to the decrease of estrogen receptors in the hippocampus. They also found that administration of 17b-estradiol (E2) replacement therapy shortly before, but not after, the drop in hormone levels prevented degradation of estrogen receptors in the brain, and preserved estrogen’s neuroprotective effects. “As a whole, the study provides support for a ‘critical period’ for E2 neuroprotection of the hippocampus and provides important insight into the mechanism underlying the critical period,” the researchers concluded.