New and Noteworthy Information—December

A majority of patients with mild traumatic brain injury (mTBI) have evidence of chronic traumatic encephalopathy (CTE), according to research published in the online December 2 Brain. Of 85 participants with a history of mTBI, 68 (80%) showed postmortem evidence of the degenerative brain disease. The persons with CTE were all males ages 17 to 98, most of whom were athletes and military veterans. The researchers used a four-stage system to classify CTE, and symptoms ranged from headache and concentration difficulties in stage one to dementia, aggression, and difficulty with words in stage four. Among American football players, stage of CTE correlated with increased duration of football play, survival after football, and age of death. “There is an ordered and predictable progression of hyperphosphorylated tau abnormalities through the nervous system in CTE that occurs in conjunction with widespread axonal disruption and loss,” the researchers said.
Persons who experience traumatic brain injury (TBI) and have also been exposed to the pesticide paraquat have triple the risk of developing Parkinson’s disease, according to research published in the November 13 Neurology. From 2001 to 2011, investigators examined 357 persons with idiopathic Parkinson’s disease and 754 population controls. A validated geographic information system based on records of pesticide application was used to assess paraquat exposure, while TBI was assessed through self-report of all head injuries that involved loss of consciousness for greater than five minutes. According to the researchers, exposure to paraquat and TBI each moderately increase the risk of Parkinson’s disease. However, the risk of developing Parkinson’s disease was threefold higher in study participants with both TBI and exposure to paraquat than in participants exposed to neither risk factor, the investigators said.
Preterm-born children have a significantly reduced capacity for cortical neuroplasticity, which affects learning and memory, researchers reported in the November 14 Journal of Neuroscience. The investigators used a noninvasive magnetic brain stimulation technique to induce long-term depressionlike neuroplasticity in groups of adolescents born after early preterm, late preterm, and term gestations. “Compared with term-born adolescents, both early and late preterm adolescents had reduced long-term depressionlike neuroplasticity in response to brain stimulation that was also associated with low salivary cortisol levels,” said the study authors, adding that these findings may show a potential mechanistic link between the brain physiology of preterm birth and behavioral deficits in learning and memory. Altered hypothalamic-pituitary-adrenal axis function may modulate the altered neuroplasticity and may offer options for therapeutic interventions, the researchers concluded.
MRI scans show that patients with mild traumatic brain injury (mTBI) have abnormal default-mode network connectivity patterns, researchers reported in the December Radiology. The study used resting-state functional MRI to characterize the default-mode network and included 18 healthy controls and 23 patients with mTBI who had post-traumatic symptoms less than two months after injury. Compared with controls, patients with mTBI showed significantly reduced connectivity in the posterior cingulate complex and parietal regions, which correlated positively with neurocognitive dysfunction. Patients with mTBI also showed increased frontal connectivity around the medial prefrontal cortex, which correlated with post-traumatic symptoms such as depression, anxiety, fatigue, and postconcussion syndrome. According to the researchers, the results may “provide insight into how neuronal communication and information integration are disrupted among default-mode network key structures after mild head injury.”

Increased concentration of phosphorylated neurofilament heavy subunit (pNF-H) in the plasma, serum, and CSF of patients with amyotrophic lateral sclerosis (ALS) may be associated with faster disease progression, according to research published in the online October 31 Journal of Neurology, Neurosurgery & Psychiatry. Investigators measured pNF-H concentration in the plasma and CSF of patients with ALS from the Mayo Clinic Florida and Emory University, as well as plasma from an earlier pilot study of 20 patients with ALS. Analysis showed that higher levels of pNF-H in plasma, serum, and CSF were linked with greater decline for ALS patients. The researchers also noted that patients with bulbar onset might have higher pNF-H concentration in plasma than those with spinal onset, though the results require confirmation. “These data support further study of pNF-H in CSF, serum, and plasma as a potential ALS biomarker,” the study authors said.
Paralyzed dogs who received intraspinal transplantation of cells derived from olfactory mucosal cultures regained some movement, researchers reported in the November Brain. The investigators conducted a randomized, double-blind clinical trial in which dogs with severe chronic thoracolumbar spinal injuries received an injection of either intraspinal autologous cells derived from olfactory mucosal cultures or cell transport medium alone. Dogs who received the olfactory mucosal transplants showed significantly better fore–hind coordination than those who received only the cell transport medium. “We conclude that intraspinal olfactory mucosal cell transplantation improves communication across the damaged region of the injured spinal cord, even in chronically injured individuals. However, we find no evidence for concomitant improvement in long tract function,” the researchers said.
Suvorexant, an orexin receptor antagonist, may offer a novel approach to treating insomnia, researchers reported in the December Neurology. In a randomized, double-blind, placebo-controlled study that took place during two periods of four weeks, patients received 10 mg, 20 mg, 40 mg, or 80 mg of suvorexant in one period and placebo in the other period. Coprimary end points were sleep efficiency on night one and at the end of week four. Patients receiving suvorexant showed significant dose-related improvements on both of the primary end points compared with those receiving placebo. “Dose-related effects were also observed for sleep induction (latency to persistent sleep) and maintenance (wake after sleep onset). Suvorexant was generally well tolerated,” the researchers said.
Persons born in April have significantly more risk of developing multiple sclerosis (MS) than those born in October and November, according to research published in the online November 14 Journal of Neurology, Neurosurgery & Psychiatry. The study was a meta-analysis of previously published data on month of birth of 151,978 patients with MS. According to the researchers, the month of birth effect is “likely to be due to ultraviolet light exposure and maternal vitamin D levels.” In a separate study published in the November 20 Neurology, investigators observed an association between high levels of vitamin D in the years prior to disease onset and a decreased risk of MS. However, there was no association between gestational levels of vitamin D and MS risk in the offspring. Decreasing levels of vitamin D in the population might help explain the increase in MS cases suggested from epidemiologic studies, the study authors said.
Mutations of the immune system gene TREM2 may be linked to an increased risk of Alzheimer’s disease, researchers reported in two studies in the online November 14 New England Journal of Medicine. In one study, investigators analyzed the genetic variability in TREM2 and performed a meta-analysis on imputed data for the TREM2 variant rs75932628, which is predicted to cause a R47H substitution. The R47H mutation was highly significantly associated with Alzheimer’s disease, said the authors. In the second study, researchers examined genome sequences of 2,261 Icelanders and found that the TREM2 mutation rs75932628-T conferred a significant risk of Alzheimer’s disease (odds ratio, 2.92). “Given the reported anti-inflammatory role of TREM2 in the brain, the R47H substitution may lead to an increased predisposition to Alzheimer’s disease through impaired containment of inflammatory processes,” the investigators concluded.
Exposure to traffic-related air pollution during pregnancy and the first year of life is associated with autism, according to a study published in the online November Archives of General Psychiatry. Researchers conducted a population-based case-control study that included data from 279 children with autism and 245 control children with typical development. Compared with controls, those with autism were more likely to live in areas with the highest quartile of exposure to traffic-related air pollution during gestation and during the first year of life. Exposure to particulate matter and nitrogen dioxide were also linked with autism. “Further epidemiological and toxicological examinations of likely biological pathways will help determine whether these associations are causal,” the researchers concluded.
Consumption of fish and long-chain omega 3 fatty acids may moderately reduce cerebrovascular risk, but fish oil supplements may not have the same beneficial effect, according to research published in the October 30 BMJ. The systemic review and meta-analysis examined 26 prospective cohort studies and 12 randomized controlled trials with aggregate data on 794,000 participants and 34,817 cerebrovascular outcomes. Results showed that persons who ate two to four servings of fish per week and those who ate five or more servings a week had a lower risk of cerebrovascular disease, compared with persons who ate one serving a week. However, no association was observed between risk for cerebrovascular disease and long-chain omega 3 fatty acids measured as circulating biomarkers in observational studies or supplements in primary and secondary prevention trials.
Depression is the most important factor affecting the health status of patients with Parkinson’s disease, according to early findings released as part of the Parkinson’s Outcome Project, a longitudinal study examining which treatments produce the best outcomes. The study, which began in 2009, includes data from more than 5,500 patients with Parkinson’s disease. Based on this research, the National Parkinson Foundation recommends screening patients for depression at least once a year and encouraging patients to discuss any mood change with a health care professional, particularly the physician treating them for Parkinson’s disease. Patients may also benefit from bringing a family member to doctor’s appointments and asking the family member to share any changes in the patient’s mood.                          

A majority of patients with mild traumatic brain injury (mTBI) have evidence of chronic traumatic encephalopathy (CTE), according to research published in the online December 2 Brain. Of 85 participants with a history of mTBI, 68 (80%) showed postmortem evidence of the degenerative brain disease. The persons with CTE were all males ages 17 to 98, most of whom were athletes and military veterans. The researchers used a four-stage system to classify CTE, and symptoms ranged from headache and concentration difficulties in stage one to dementia, aggression, and difficulty with words in stage four. Among American football players, stage of CTE correlated with increased duration of football play, survival after football, and age of death. “There is an ordered and predictable progression of hyperphosphorylated tau abnormalities through the nervous system in CTE that occurs in conjunction with widespread axonal disruption and loss,” the researchers said.
Persons who experience traumatic brain injury (TBI) and have also been exposed to the pesticide paraquat have triple the risk of developing Parkinson’s disease, according to research published in the November 13 Neurology. From 2001 to 2011, investigators examined 357 persons with idiopathic Parkinson’s disease and 754 population controls. A validated geographic information system based on records of pesticide application was used to assess paraquat exposure, while TBI was assessed through self-report of all head injuries that involved loss of consciousness for greater than five minutes. According to the researchers, exposure to paraquat and TBI each moderately increase the risk of Parkinson’s disease. However, the risk of developing Parkinson’s disease was threefold higher in study participants with both TBI and exposure to paraquat than in participants exposed to neither risk factor, the investigators said.
Preterm-born children have a significantly reduced capacity for cortical neuroplasticity, which affects learning and memory, researchers reported in the November 14 Journal of Neuroscience. The investigators used a noninvasive magnetic brain stimulation technique to induce long-term depressionlike neuroplasticity in groups of adolescents born after early preterm, late preterm, and term gestations. “Compared with term-born adolescents, both early and late preterm adolescents had reduced long-term depressionlike neuroplasticity in response to brain stimulation that was also associated with low salivary cortisol levels,” said the study authors, adding that these findings may show a potential mechanistic link between the brain physiology of preterm birth and behavioral deficits in learning and memory. Altered hypothalamic-pituitary-adrenal axis function may modulate the altered neuroplasticity and may offer options for therapeutic interventions, the researchers concluded.
MRI scans show that patients with mild traumatic brain injury (mTBI) have abnormal default-mode network connectivity patterns, researchers reported in the December Radiology. The study used resting-state functional MRI to characterize the default-mode network and included 18 healthy controls and 23 patients with mTBI who had post-traumatic symptoms less than two months after injury. Compared with controls, patients with mTBI showed significantly reduced connectivity in the posterior cingulate complex and parietal regions, which correlated positively with neurocognitive dysfunction. Patients with mTBI also showed increased frontal connectivity around the medial prefrontal cortex, which correlated with post-traumatic symptoms such as depression, anxiety, fatigue, and postconcussion syndrome. According to the researchers, the results may “provide insight into how neuronal communication and information integration are disrupted among default-mode network key structures after mild head injury.”

Increased concentration of phosphorylated neurofilament heavy subunit (pNF-H) in the plasma, serum, and CSF of patients with amyotrophic lateral sclerosis (ALS) may be associated with faster disease progression, according to research published in the online October 31 Journal of Neurology, Neurosurgery & Psychiatry. Investigators measured pNF-H concentration in the plasma and CSF of patients with ALS from the Mayo Clinic Florida and Emory University, as well as plasma from an earlier pilot study of 20 patients with ALS. Analysis showed that higher levels of pNF-H in plasma, serum, and CSF were linked with greater decline for ALS patients. The researchers also noted that patients with bulbar onset might have higher pNF-H concentration in plasma than those with spinal onset, though the results require confirmation. “These data support further study of pNF-H in CSF, serum, and plasma as a potential ALS biomarker,” the study authors said.
Paralyzed dogs who received intraspinal transplantation of cells derived from olfactory mucosal cultures regained some movement, researchers reported in the November Brain. The investigators conducted a randomized, double-blind clinical trial in which dogs with severe chronic thoracolumbar spinal injuries received an injection of either intraspinal autologous cells derived from olfactory mucosal cultures or cell transport medium alone. Dogs who received the olfactory mucosal transplants showed significantly better fore–hind coordination than those who received only the cell transport medium. “We conclude that intraspinal olfactory mucosal cell transplantation improves communication across the damaged region of the injured spinal cord, even in chronically injured individuals. However, we find no evidence for concomitant improvement in long tract function,” the researchers said.
Suvorexant, an orexin receptor antagonist, may offer a novel approach to treating insomnia, researchers reported in the December Neurology. In a randomized, double-blind, placebo-controlled study that took place during two periods of four weeks, patients received 10 mg, 20 mg, 40 mg, or 80 mg of suvorexant in one period and placebo in the other period. Coprimary end points were sleep efficiency on night one and at the end of week four. Patients receiving suvorexant showed significant dose-related improvements on both of the primary end points compared with those receiving placebo. “Dose-related effects were also observed for sleep induction (latency to persistent sleep) and maintenance (wake after sleep onset). Suvorexant was generally well tolerated,” the researchers said.
Persons born in April have significantly more risk of developing multiple sclerosis (MS) than those born in October and November, according to research published in the online November 14 Journal of Neurology, Neurosurgery & Psychiatry. The study was a meta-analysis of previously published data on month of birth of 151,978 patients with MS. According to the researchers, the month of birth effect is “likely to be due to ultraviolet light exposure and maternal vitamin D levels.” In a separate study published in the November 20 Neurology, investigators observed an association between high levels of vitamin D in the years prior to disease onset and a decreased risk of MS. However, there was no association between gestational levels of vitamin D and MS risk in the offspring. Decreasing levels of vitamin D in the population might help explain the increase in MS cases suggested from epidemiologic studies, the study authors said.
Mutations of the immune system gene TREM2 may be linked to an increased risk of Alzheimer’s disease, researchers reported in two studies in the online November 14 New England Journal of Medicine. In one study, investigators analyzed the genetic variability in TREM2 and performed a meta-analysis on imputed data for the TREM2 variant rs75932628, which is predicted to cause a R47H substitution. The R47H mutation was highly significantly associated with Alzheimer’s disease, said the authors. In the second study, researchers examined genome sequences of 2,261 Icelanders and found that the TREM2 mutation rs75932628-T conferred a significant risk of Alzheimer’s disease (odds ratio, 2.92). “Given the reported anti-inflammatory role of TREM2 in the brain, the R47H substitution may lead to an increased predisposition to Alzheimer’s disease through impaired containment of inflammatory processes,” the investigators concluded.
Exposure to traffic-related air pollution during pregnancy and the first year of life is associated with autism, according to a study published in the online November Archives of General Psychiatry. Researchers conducted a population-based case-control study that included data from 279 children with autism and 245 control children with typical development. Compared with controls, those with autism were more likely to live in areas with the highest quartile of exposure to traffic-related air pollution during gestation and during the first year of life. Exposure to particulate matter and nitrogen dioxide were also linked with autism. “Further epidemiological and toxicological examinations of likely biological pathways will help determine whether these associations are causal,” the researchers concluded.
Consumption of fish and long-chain omega 3 fatty acids may moderately reduce cerebrovascular risk, but fish oil supplements may not have the same beneficial effect, according to research published in the October 30 BMJ. The systemic review and meta-analysis examined 26 prospective cohort studies and 12 randomized controlled trials with aggregate data on 794,000 participants and 34,817 cerebrovascular outcomes. Results showed that persons who ate two to four servings of fish per week and those who ate five or more servings a week had a lower risk of cerebrovascular disease, compared with persons who ate one serving a week. However, no association was observed between risk for cerebrovascular disease and long-chain omega 3 fatty acids measured as circulating biomarkers in observational studies or supplements in primary and secondary prevention trials.
Depression is the most important factor affecting the health status of patients with Parkinson’s disease, according to early findings released as part of the Parkinson’s Outcome Project, a longitudinal study examining which treatments produce the best outcomes. The study, which began in 2009, includes data from more than 5,500 patients with Parkinson’s disease. Based on this research, the National Parkinson Foundation recommends screening patients for depression at least once a year and encouraging patients to discuss any mood change with a health care professional, particularly the physician treating them for Parkinson’s disease. Patients may also benefit from bringing a family member to doctor’s appointments and asking the family member to share any changes in the patient’s mood.                          

A majority of patients with mild traumatic brain injury (mTBI) have evidence of chronic traumatic encephalopathy (CTE), according to research published in the online December 2 Brain. Of 85 participants with a history of mTBI, 68 (80%) showed postmortem evidence of the degenerative brain disease. The persons with CTE were all males ages 17 to 98, most of whom were athletes and military veterans. The researchers used a four-stage system to classify CTE, and symptoms ranged from headache and concentration difficulties in stage one to dementia, aggression, and difficulty with words in stage four. Among American football players, stage of CTE correlated with increased duration of football play, survival after football, and age of death. “There is an ordered and predictable progression of hyperphosphorylated tau abnormalities through the nervous system in CTE that occurs in conjunction with widespread axonal disruption and loss,” the researchers said.
Persons who experience traumatic brain injury (TBI) and have also been exposed to the pesticide paraquat have triple the risk of developing Parkinson’s disease, according to research published in the November 13 Neurology. From 2001 to 2011, investigators examined 357 persons with idiopathic Parkinson’s disease and 754 population controls. A validated geographic information system based on records of pesticide application was used to assess paraquat exposure, while TBI was assessed through self-report of all head injuries that involved loss of consciousness for greater than five minutes. According to the researchers, exposure to paraquat and TBI each moderately increase the risk of Parkinson’s disease. However, the risk of developing Parkinson’s disease was threefold higher in study participants with both TBI and exposure to paraquat than in participants exposed to neither risk factor, the investigators said.
Preterm-born children have a significantly reduced capacity for cortical neuroplasticity, which affects learning and memory, researchers reported in the November 14 Journal of Neuroscience. The investigators used a noninvasive magnetic brain stimulation technique to induce long-term depressionlike neuroplasticity in groups of adolescents born after early preterm, late preterm, and term gestations. “Compared with term-born adolescents, both early and late preterm adolescents had reduced long-term depressionlike neuroplasticity in response to brain stimulation that was also associated with low salivary cortisol levels,” said the study authors, adding that these findings may show a potential mechanistic link between the brain physiology of preterm birth and behavioral deficits in learning and memory. Altered hypothalamic-pituitary-adrenal axis function may modulate the altered neuroplasticity and may offer options for therapeutic interventions, the researchers concluded.
MRI scans show that patients with mild traumatic brain injury (mTBI) have abnormal default-mode network connectivity patterns, researchers reported in the December Radiology. The study used resting-state functional MRI to characterize the default-mode network and included 18 healthy controls and 23 patients with mTBI who had post-traumatic symptoms less than two months after injury. Compared with controls, patients with mTBI showed significantly reduced connectivity in the posterior cingulate complex and parietal regions, which correlated positively with neurocognitive dysfunction. Patients with mTBI also showed increased frontal connectivity around the medial prefrontal cortex, which correlated with post-traumatic symptoms such as depression, anxiety, fatigue, and postconcussion syndrome. According to the researchers, the results may “provide insight into how neuronal communication and information integration are disrupted among default-mode network key structures after mild head injury.”

Increased concentration of phosphorylated neurofilament heavy subunit (pNF-H) in the plasma, serum, and CSF of patients with amyotrophic lateral sclerosis (ALS) may be associated with faster disease progression, according to research published in the online October 31 Journal of Neurology, Neurosurgery & Psychiatry. Investigators measured pNF-H concentration in the plasma and CSF of patients with ALS from the Mayo Clinic Florida and Emory University, as well as plasma from an earlier pilot study of 20 patients with ALS. Analysis showed that higher levels of pNF-H in plasma, serum, and CSF were linked with greater decline for ALS patients. The researchers also noted that patients with bulbar onset might have higher pNF-H concentration in plasma than those with spinal onset, though the results require confirmation. “These data support further study of pNF-H in CSF, serum, and plasma as a potential ALS biomarker,” the study authors said.
Paralyzed dogs who received intraspinal transplantation of cells derived from olfactory mucosal cultures regained some movement, researchers reported in the November Brain. The investigators conducted a randomized, double-blind clinical trial in which dogs with severe chronic thoracolumbar spinal injuries received an injection of either intraspinal autologous cells derived from olfactory mucosal cultures or cell transport medium alone. Dogs who received the olfactory mucosal transplants showed significantly better fore–hind coordination than those who received only the cell transport medium. “We conclude that intraspinal olfactory mucosal cell transplantation improves communication across the damaged region of the injured spinal cord, even in chronically injured individuals. However, we find no evidence for concomitant improvement in long tract function,” the researchers said.
Suvorexant, an orexin receptor antagonist, may offer a novel approach to treating insomnia, researchers reported in the December Neurology. In a randomized, double-blind, placebo-controlled study that took place during two periods of four weeks, patients received 10 mg, 20 mg, 40 mg, or 80 mg of suvorexant in one period and placebo in the other period. Coprimary end points were sleep efficiency on night one and at the end of week four. Patients receiving suvorexant showed significant dose-related improvements on both of the primary end points compared with those receiving placebo. “Dose-related effects were also observed for sleep induction (latency to persistent sleep) and maintenance (wake after sleep onset). Suvorexant was generally well tolerated,” the researchers said.
Persons born in April have significantly more risk of developing multiple sclerosis (MS) than those born in October and November, according to research published in the online November 14 Journal of Neurology, Neurosurgery & Psychiatry. The study was a meta-analysis of previously published data on month of birth of 151,978 patients with MS. According to the researchers, the month of birth effect is “likely to be due to ultraviolet light exposure and maternal vitamin D levels.” In a separate study published in the November 20 Neurology, investigators observed an association between high levels of vitamin D in the years prior to disease onset and a decreased risk of MS. However, there was no association between gestational levels of vitamin D and MS risk in the offspring. Decreasing levels of vitamin D in the population might help explain the increase in MS cases suggested from epidemiologic studies, the study authors said.
Mutations of the immune system gene TREM2 may be linked to an increased risk of Alzheimer’s disease, researchers reported in two studies in the online November 14 New England Journal of Medicine. In one study, investigators analyzed the genetic variability in TREM2 and performed a meta-analysis on imputed data for the TREM2 variant rs75932628, which is predicted to cause a R47H substitution. The R47H mutation was highly significantly associated with Alzheimer’s disease, said the authors. In the second study, researchers examined genome sequences of 2,261 Icelanders and found that the TREM2 mutation rs75932628-T conferred a significant risk of Alzheimer’s disease (odds ratio, 2.92). “Given the reported anti-inflammatory role of TREM2 in the brain, the R47H substitution may lead to an increased predisposition to Alzheimer’s disease through impaired containment of inflammatory processes,” the investigators concluded.
Exposure to traffic-related air pollution during pregnancy and the first year of life is associated with autism, according to a study published in the online November Archives of General Psychiatry. Researchers conducted a population-based case-control study that included data from 279 children with autism and 245 control children with typical development. Compared with controls, those with autism were more likely to live in areas with the highest quartile of exposure to traffic-related air pollution during gestation and during the first year of life. Exposure to particulate matter and nitrogen dioxide were also linked with autism. “Further epidemiological and toxicological examinations of likely biological pathways will help determine whether these associations are causal,” the researchers concluded.
Consumption of fish and long-chain omega 3 fatty acids may moderately reduce cerebrovascular risk, but fish oil supplements may not have the same beneficial effect, according to research published in the October 30 BMJ. The systemic review and meta-analysis examined 26 prospective cohort studies and 12 randomized controlled trials with aggregate data on 794,000 participants and 34,817 cerebrovascular outcomes. Results showed that persons who ate two to four servings of fish per week and those who ate five or more servings a week had a lower risk of cerebrovascular disease, compared with persons who ate one serving a week. However, no association was observed between risk for cerebrovascular disease and long-chain omega 3 fatty acids measured as circulating biomarkers in observational studies or supplements in primary and secondary prevention trials.
Depression is the most important factor affecting the health status of patients with Parkinson’s disease, according to early findings released as part of the Parkinson’s Outcome Project, a longitudinal study examining which treatments produce the best outcomes. The study, which began in 2009, includes data from more than 5,500 patients with Parkinson’s disease. Based on this research, the National Parkinson Foundation recommends screening patients for depression at least once a year and encouraging patients to discuss any mood change with a health care professional, particularly the physician treating them for Parkinson’s disease. Patients may also benefit from bringing a family member to doctor’s appointments and asking the family member to share any changes in the patient’s mood.